COVID-19 Evidence Support Team EVIDENCE SEARCH REPORT
Review Question: How effective are COVID-19 vaccines? Context: Benefits following dose/second dose; how well it prevents infections; evidence of limiting viral replication or spread; preventing hospitalization; preventing ventilation; preventing “long COVID” (long term symptoms), duration of immunity (natural and vaccinated). FDA cold chain changes. Effectiveness against any and all variants. Booster doses for variants. Mixing vaccine types.
Does not include vaccine willingness/acceptance (to be run as a separate search) Review Code: INF031801v4 ESR Complete Date: May 14, 2021
Cite As: Miller, L. Howell-Spooner, B.. How effective are COVID-19 vaccines? 2021 May 14, Document no.: INF031801v4 ESR. In: COVID-19 Rapid Evidence Reviews [Internet]. SK: SK COVID Evidence Support Team, c2021. 98 p. (CEST evidence search report).
Librarian Notes & Comment
There were 204 references to journal articles & preprints found since the last search (April 30, 2021).
Link to Online Zotero library (Requires a Zotero login/account. Contact Lukas for access)
There has been some duplication from the prior report. This is unavoidable as some are updates of duplicate references, with abstracts/indexing terms changed or added after the initial entry.
Sincerely,
Lukas & Brianna
Search Results: Guidelines, Summaries & Other Grey Literature
Disclaimer This information is provided as a service by the Saskatchewan Health Authority and University of Saskatchewan Libraries. Professional librarians conduct searches of the literature. Results are subject to the limitations of the databases and the specificity, broadness and appropriateness of the search parameters presented by the requester. The Libraries do not represent in any matter that retrieved citations are complete, accurate or otherwise to be relied upon. The se arch results are only valid as of the date and time at which the search is conducted. The Libraries do not accept responsibility for any loss or damage aris ing from the use of, or reliance on, search results.
Government CDC Demographic and Social Factors Associated with COVID-19 Vaccination Initiation Among Adults Aged 65 Years – United States, December 14, 2020-April 10, 2021. May 14, 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7019e4.htm?s_cid=mm7019e4_x Modeling of Future COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Rates and Nonpharmaceutical Intervention Scenarios – United States, April-September, 2021. May 14, 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7019e3.htm?s_cid=mm7019e3_w How CDC Is Making COVID-19 Vaccine Recommendations. May 12, 2021. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations-process.html Information about COVID-19 Vaccines for People who Are Pregnant or Breastfeeding. May 11, 2021. https://www.cdc.gov/coronavirus/2019- ncov/vaccines/recommendations/pregnancy.html Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Among Hospitalized Adults Aged 65 Years – United States, January-March, 2021. May 7, 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7018e1.htm?s_cid=mm7018e1_w Updated Recommendations from the Advisory Committee on Immunization Practice for Use of the Janssen (Johnson & Johnson) COVID-19 Vaccine After Reports of Thrombosis with Thrombocytopenia Syndrome Among Recipients – United States, April 2021. April 30, 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7017e4.htm?s_cid=mm7017e4_w
FDA Coronavirus (COVID-19) Update: FDA Authorizes Pfizer-BioNTech COVID-19 Vaccine for Emergency Use in Adolescents in Another Important Action in Fight Against Pandemic. May 10, 2021. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update- fda-authorizes-pfizer-biontech-covid-19-vaccine-emergency-use FDA In Brief: FDA to Hold Meeting of its Vaccines and Related Biological Products Advisory Committee to Discuss Pediatric Use of COVID-19 Vaccines. May 10, 2021. https://www.fda.gov/news-events/press-announcements/fda-brief-fda-hold-meeting-its- vaccines-and-related-biological-products-advisory-committee-discuss
Health Canada Health Canada authorizes the use of the Pfizer-BioNTech COVID-19 vaccine in children 12 to 15 years of age. May 5, 2021. https://www.canada.ca/en/health-canada/news/2021/05/health- canada-authorizes-use-of-the-pfizer-biontech-covid-19-vaccine-in-children-12-to-15-years-of- age.html
Public Health England COVID-19 vaccines: further evidence of success. May 10, 2021. https://www.gov.uk/government/news/covid-19-vaccines-further-evidence-of-success PHE monitoring of the effectiveness of COVID-19 vaccination. May 10, 2021. https://www.gov.uk/government/publications/phe-monitoring-of-the-effectiveness-of-covid- 19-vaccination
UK Government International Severe Acute Respiratory Infection Consortium Clinical Characterisation Protocol (ISARIC4C) and COVID-19 Clinical Information Network (CO-CIN).
Evidence Search Report: INF031801v4 ESR 2 o ISARIC4C and CO-CIN: Hospitalised patients stratified by vaccination tier in second wave, 22 April 2021. April 30, 2021. https://www.gov.uk/government/publications/isaric4c- and-co-cin-hospitalised-patients-stratified-by-vaccination-tier-in-second-wave-22-april- 2021 o ISARIC4C and CO-CIN: Hospitalised vaccinated patients during the second wave - update April 2021, 22 April 2021. April 30, 2021. https://www.gov.uk/government/publications/isaric4c-and-co-cin-hospitalised- vaccinated-patients-during-the-second-wave-update-april-2021-22-april-2021
Agencies WHO The Sinopharm COVID-19 vaccine: What do you need to know. May 10, 2021. https://www.who.int/news-room/feature-stories/detail/the-sinopharm-covid-19-vaccine-what- you-need-to-know Estimating COVID-19 vaccine effectiveness against severe acute respiratory infections (SARI) hospitalizations associated with laboratory-confirmed SARS-CoV-2: an evaluation using the test negative design. May 6, 2021. https://www.who.int/publications/i/item/WHO-EURO-2021- 2481-42237-58308
Research Centres COVID-END COVID-19 Living Evidence Synthesis #6 – What is the efficacy and effectiveness of available COVID-19 vaccines in general and specifically for variants of concern?. May 7, 2021. https://www.mcmasterforum.org/docs/default-source/product-documents/living-evidence- syntheses/covid-19-living-evidence-synthesis-6.4---what-is-the-efficacy-and-effectiveness-of- available-covid-19-vaccines-in-general-and-specifically-for-variants-of- concern.pdf?sfvrsn=26dbc572_5 COVID-19 Living Evidence Synthesis #6 – What is the efficacy and effectiveness of available COVID-19 vaccines in general and specifically for variants of concern?. April 30. 2021. https://www.mcmasterforum.org/docs/default-source/product-documents/living-evidence- syntheses/covid-19-living-evidence-synthesis-6.3---what-is-the-efficacy-and-effectiveness-of- available-covid-19-vaccines-in-general-and-specifically-for-variants-of- concern.pdf?sfvrsn=42753ad6_5
Science Table (Ontario) Risk of Vaccine-Induced Thrombotic Thrombocytopenia (VITT) following the AstraZeneca/COVISHIELD Adenovirus Vector COVID-19 Vaccines. May 11, 2021. https://covid19- sciencetable.ca/sciencebrief/risk-of-vaccine-induced-thrombotic-thrombocytopenia-vitt- following-the-astrazeneca-covishield-adenovirus-vector-covid-19-vaccines/ Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) Following Adenovirus Vector COVID-19 Vaccination: Interim Guidance for Healthcare Professionals in Emergency Department and Inpatient Settings. May 10, 2021. https://covid19-sciencetable.ca/sciencebrief/vaccine- induced-immune-thrombotic-thrombocytopenia-vitt-following-adenovirus-vector-covid-19- vaccination-interim-guidance-for-healthcare-professionals-in-emergency-department-and- inpatient-settings/
Evidence Search Report: INF031801v4 ESR 3 Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) Following Adenovirus Vector COVID-19 Vaccination: Interim Guidance for Healthcare Professionals in the Outpatient Setting. May 10, 2021. https://covid19-sciencetable.ca/sciencebrief/vaccine-induced-immune- thrombotic-thrombocytopenia-vitt-following-adenovirus-vector-covid-19-vaccination-interim- guidance-for-healthcare-professionals-in-the-outpatient-setting/ Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) Following Adenovirus Vector COVID-19 Vaccination. May 7, 2021. https://covid19-sciencetable.ca/sciencebrief/vaccine- induced-immune-thrombotic-thrombocytopenia-vitt-following-adenovirus-vector-covid-19- vaccination/ Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) Following Adenovirus Vector COVID-19 Vaccination: Lay Summary. May 7, 2021. https://covid19- sciencetable.ca/sciencebrief/vaccine-induced-immune-thrombotic-thrombocytopenia-vitt- following-adenovirus-vector-covid-19-vaccination-lay-summary/
Search Results: News, Blogs, & Social Media
News CBC Mixing COVID-19 vaccine doses leads to more reactions, study finds, which may be ‘first sign of success’. May 12, 2021. https://www.cbc.ca/news/health/vaccines-mixing-doses-1.6023830 As some province halt the use of AstraZeneca, Canada confirms 655,00 more doses will arrive next week. May 12, 2021. https://www.cbc.ca/news/politics/astrazeneca-shots-delivery- 1.6024063 Future of AstraZeneca COVID-19 vaccine in question in Canada over blood clots, supply issues. May 12, 2021. https://www.cbc.ca/news/health/astrazeneca-vaccine-paused-canada-blood- clot-vitt-1.6022821 Sask. stops giving AstraZeneca as 1st dose over supply issues, considers Pfizer instead. May 12, 2021. https://www.cbc.ca/news/canada/saskatchewan/sask-stops-administering-astrazeneca- 1st-dose-considers-pfizer-2nd-1.6023098 Vaccines have been more than 99% effective against COVID-19 in Sask., top doctor says. May 12, 2021. https://www.cbc.ca/news/canada/saskatoon/saskatchewan-covid-19-vaccine- effectiveness-dr-saqib-shahab-1.6022879 N.S. pauses AstraZeneca rollout, citing concerns over blood clots. May 12, 2021. https://www.cbc.ca/news/canada/nova-scotia/nova-scotia-covid-19-update-wednesday-may- 12-2021-1.6023208 What happens when people get two difference vaccines?. May 11, 2021. https://www.cbc.ca/news/politics/vaccines-mix-and-match-1.6020986 Ontario will no longer give AstraZeneca COVID-19 vaccine as 1st dose due to blood clot risk. May 11, 2021. https://www.cbc.ca/news/canada/toronto/ontario-update-astrazeneca-vaccine- 1.6022545 U.K. to offer adults under 40 alternative vaccines to AstraZeneca-Oxford over blood clot concerns. May 7, 2021. https://www.cbc.ca/news/health/uk-astrazeneca-1.6017658 U.K. to offer adults under 40 alternative vaccines to AstraZeneca-Oxford over blood clot concerns. May 7, 2021. https://www.cbc.ca/news/health/uk-astrazeneca-1.6017658 Health Canada authorizes Pfizer vaccine for adolescents. May 5, 2021. https://www.cbc.ca/news/politics/health-canada-authorized-pfizer-12-16-1.6014551
Evidence Search Report: INF031801v4 ESR 4 Moderna booster increases antibodies against COVID-19 variants, early trials show. May 5, 2021. https://www.cbc.ca/news/health/moderna-booster-science-trials-1.6015405 Not available in Canada: A look at COVID-19 vaccine from China, India, and Cuba. May 4, 2021. https://www.cbc.ca/news/science/inactivated-conjugate-covid-19-vaccines-1.6011962 Pfizer-BioNTech vaccine not troubled by variants so far, says CEO. May 4, 2021. https://www.cbc.ca/news/politics/ugur-sahin-vaccine-pfizer-power-politics-1.6013818 Johnson & Johnson vaccine recommended for Canadians 30 and older despite risk of rare blood clots. May 3, 2021. https://www.cbc.ca/news/health/naci-johnson-and-johnson-vaccine-blood- clot-risk-covid-19-1.6012102 Why your first COVID-19 shot is more protective than you might think. May 1, 2021. https://www.cbc.ca/news/health/covid-19-vaccine-first-dose-protection-canada-1.6009822 Health Canada holding off on Johnson & Johnson COVID-19 vaccine distribution. April 30, 2021. https://www.cbc.ca/news/health/johnson-johnson-vaccine-hold-health-canada-1.6010065
CIDRAP CDC adviser green-light COVID vaccine in young teens. May 12, 2021. https://www.cidrap.umn.edu/news-perspective/2021/05/cdc-advisers-green-light-covid- vaccine-young-teens FDA paves way for COVID-19 vaccine in 12- to 15-year-olds. May 11, 2021. https://www.cidrap.umn.edu/news-perspective/2021/05/fda-paves-way-covid-19-vaccine-12- 15-year-olds WHO lists Sinopharm COVID-19 vaccine for emergency use. May 7, 2021 https://www.cidrap.umn.edu/news-perspective/2021/05/who-lists-sinopharm-covid-19- vaccine-emergency-use Real-world studies detail high Pfizer COVID vaccine protection. May 7, 2021. https://www.cidrap.umn.edu/news-perspective/2021/05/real-world-studies-detail-high-pfizer- covid-vaccine-protection Three vaccines show promise against COVID variants. May 6, 2021. https://www.cidrap.umn.edu/news-perspective/2021/05/three-vaccines-show-promise-against- covid-variants Data reveal fewer real-world COVID vaccine side effects. April 28, 2021. https://www.cidrap.umn.edu/news-perspective/2021/04/data-reveal-fewer-real-world-covid- vaccine-side-effects
Kaiser Health Network The Shock and Reality of Catching Covid After Being Vaccinated. April 16, 2021. https://khn.org/news/article/the-shock-and-reality-of-catching-covid-after-being-vaccinated/
Search Results: Journal Articles (includes preprints) Sorted by newest-oldest.
1. Aatif M, Muteeb G, Alsultan A, et al. Dieckol and Its Derivatives as Potential Inhibitors of SARS -CoV- 2 Spike Protein (UK Strain: VUI 202012/01): A Computational Study. Mar Drugs. 2021;19(5):25. DOI: 10.3390/md19050242
Evidence Search Report: INF031801v4 ESR 5 ABSTRACT: The high risk of morbidity and mortality associated with SARS-CoV-2 has accelerated the development of many potential vaccines. However, these vaccines are designed against SARS-CoV-2 isolated in Wuhan, China, and thereby may not be effective against other SARS-CoV-2 variants such as the United Kingdom variant (VUI-202012/01). The UK SARS-CoV-2 variant possesses D614G mutation in the Spike protein, which impart it a high rate of infection. Therefore, newer strategies are warranted to design novel vaccines and drug candidates specifically designed against the mutated forms of SARS-CoV- 2. One such strategy is to target ACE2 (angiotensin-converting enzyme2)-Spike protein RBD (receptor binding domain) interaction. Here, we generated a homology model of Spike protein RBD of SARS-CoV-2 UK strain and screened a marine seaweed database employing different computational approaches. On the basis of high-throughput virtual screening, standard precision, and extra precision molecular docking, we identified BE011 (Dieckol) as the most potent compounds against RBD. However, Dieckol did not display drug-like properties, and thus different derivatives of it were generated in silico and evaluated for binding potential and drug-like properties. One Dieckol derivative (DK07) displayed good binding affinity for RBD along with acceptable physicochemical, pharmacokinetic, drug-likeness, and ADMET properties. Analysis of the RBD-DK07 interaction suggested the formation of hydrogen bonds, electrostatic interactions, and hydrophobic interactions with key residues mediating the ACE2-RBD interaction. Molecular dynamics simulation confirmed the stability of the RBD-DK07 complex. Free energy calculations suggested the primary role of electrostatic and Van der Waals' interaction in stabilizing the RBD-DK07 complex. Thus, DK07 may be developed as a potential inhibitor of the RBD- ACE2 interaction. However, these results warrant further validation by in vitro and in vivo studies. URL: https://www.ncbi.nlm.nih.gov/pubmed/33922914 DOI: 10.3390/md19050242
2. Abbasi J. Researchers Tie Severe Immunosuppression to Chronic COVID-19 and Virus Variants. JAMA. 2021. DOI: 10.1001/jama.2021.7212 ABSTRACT: Last summer, a UK man in his 70s was admitted to Addenbrooke’s Hospital in Cambridge with COVID-19 pneumonia. He hadn’t been able to shake his illness since testing positive for SARS-CoV-2 more than a month earlier. Despite interventions including multiple rounds of the antiviral remdesivir and convalescent plasma, he died in the hospital’s intensive care unit about 9 weeks after his arrival.Throughout his hospitalization, the patient continued to test positive with a high viral load. This, along with his worsening illness, indicated that he was battling an ongoing infection with live, replicating virus for more than 100 days. URL: https://www.ncbi.nlm.nih.gov/pubmed/33950236 DOI: 10.1001/jama.2021.7212
3. Abid MB. Overlap of immunotherapy-related pneumonitis and COVID-19 pneumonia: diagnostic and vaccine considerations. J Immunother Cancer. 2021;9(4):04. DOI: 10.1136/jitc-2020-002307 ABSTRACT: The clinically indistinguishable overlap between pneumonitis caused due to immune checkpoint inhibition (ICI) and pneumonia associated with COVID-19 has posed considerable challenges for patients with cancer and oncologists alike. The cancer community continues to face the challenges that lay at the complex immunological intersection of immune-based cancer therapy and immune dysregulation that results from COVID-19. Is there compounded immune dysregulation that could lead to poor outcomes? Could ICIs, in fact, ameliorate SARS-CoV-2-driven T-cell exhaustion?A little more is known about the kinetics of the viral replication in immunocompromised patients now as compared with earlier during the pandemic. Working knowledge of the diagnostic and therapeutic nuances of SARS-CoV-2 infection in patients with active cancers, issues related to viability and replication potential of the virus, unclear role of corticosteroids among those with diminished or dysfunctional effector T-cell
Evidence Search Report: INF031801v4 ESR 6 repertoire, and the type of immunotherapy with differential risk of pneumonitis will inform decision making related to immunotherapy choices and decision for ICI continuation in the era of COVID-19. URL: https://www.ncbi.nlm.nih.gov/pubmed/33931473 DOI: 10.1136/jitc-2020-002307
4. Acuna-Zegarra MA, Diaz-Infante S, Baca-Carrasco D, et al. COVID-19 optimal vaccination policies: A modeling study on efficacy, natural and vaccine-induced immunity responses. Math Biosci. 2021:108614. DOI: 10.1016/j.mbs.2021.108614 ABSTRACT: About a year into the pandemic, COVID-19 accumulates more than two million deaths worldwide. Despite non-pharmaceutical interventions as social distance, mask-wearing, and restrictive lockdown, the daily confirmed cases remain growing. Vaccine developments from Pfizer, Moderna, and Gamaleya Institute reach more than 90% efficacy and sustain the vaccination campaigns in multiple countries. However, natural and vaccine-induced immunity responses remain poorly understood. There are great expectations, but the new SARS-CoV-2 variants demand to inquire if the vaccines will be highly protective or induce permanent immunity. Further, in the first quarter of 2021, vaccine supply is scarce. Consequently, some countries that are applying the Pfizer vaccine will delay its second required dose. Likewise, logistic supply, economic and political implications impose a set of grand challenges to develop vaccination policies. Therefore, health decision-makers require tools to evaluate hypothetical scenarios and evaluate admissible responses. Following some of the WHO-SAGE recommendations, we formulate an optimal control problem with mixed constraints to describe vaccination schedules. Our solution identifies vaccination policies that minimize the burden of COVID-19 quantified by the number of disability-adjusted years of life lost. These optimal policies ensure the vaccination coverage of a prescribed population fraction in a given time horizon and preserve hospitalization occupancy below a risk level. We explore via simulation plausible scenarios regarding efficacy, coverage, vaccine-induced, and natural immunity. Our simulations suggest that response regarding vaccine-induced immunity and reinfection periods would play a dominant role in mitigating COVID-19. URL: https://www.ncbi.nlm.nih.gov/pubmed/33961878 DOI: 10.1016/j.mbs.2021.108614
5. Aguilar TL, Gorry C. COVID-19 Requires Innovation, Regulation and Rigor: Amaylid Arteaga-Garcia MD MS Director, National Clinical Trials Coordinating Center (CENCEC). MEDICC Rev. 2021;23(2):9. DOI: 10.37757/MR2021.V23.N2.16 ABSTRACT: The effects and implications of COVID-19 are global, comprehensive and long-term. The pandemic has exposed inequities, the fragility of economic and political systems, and in many cases, skewed priorities. Population health, not to mention planetary health, is suffering as a result. Nevertheless, the global health crisis in which we are embroiled has provided opportunities for effective collaboration, scientific innovation and real dialog around health and equity. Dr Amaylid Arteaga-Garcia, director of Cuba's National Clinical Trials Coordinating Center (CENCEC), emphasized these opportunities when discussing Cuba's clinical trials in times of COVID-19. Founded in 1991 in response to the groundbreaking research emerging from the country's biopharmaceutical sector-including the first safe, effective vaccine against serogroup B meningococcal disease, VA-MENGOC-BC in 1989 and a recombinant vaccine against hepatitis B, Heberbiovac in 1990-CENCEC now coordinates some 100 clinical trials annually, many of them multi-site trials involving thousands of volunteers. Little did Dr Arteaga Garcia know what problems lurked when she became CENCEC director in 2019. In February 2020, Cuba implemented its National COVID-19 Prevention & Control Plan. This included a scientific Innovation Committee tasked with evaluating promising projects, products and research that might be used in the health system to control and treat COVID-19. This approach taps into two of Cuba's
Evidence Search Report: INF031801v4 ESR 7 strengths: biotechnology and primary health care. Given the volume and complexity of COVID-19 clinical trials, Dr Arteaga. URL: https://www.ncbi.nlm.nih.gov/pubmed/33974607 DOI: 10.37757/MR2021.V23.N2.16
6. Aguilar TL, Gorry C. Monoclonal Antibodies vs COVID-19: Eduardo Ojito-Magaz MS General Director, Molecular Immunology Center. MEDICC Rev. 2021;23(2):12. DOI: 10.37757/MR2021.V23.N2.17 ABSTRACT: Cuba has five COVID-19 vaccines in clinical trials and is on track to receive emergency use authorization from the country's regulatory agency to begin mass vaccination with two of those candidates: Abdala and SOBERANA 02. Results from phase 1 and 2 trials of these vaccines, the first developed and produced in Latin America, have been encouraging, both in terms of safety and immunogenicity. The ongoing phase 3 trials will continue to look at safety, together with efficacy; parallel intervention studies involving over a million people in Havana will begin generating data on effectiveness. Coordination between Cuba's biotechnology sector and its public health system- particularly throughout the different levels of primary care-to control and treat COVID-19 is a cornerstone of the Cuban strategy and one that could serve as a blueprint for future pandemics. Another Cuban product, itolizumab, is showing positive results mitigating cytokine release syndrome (CRS) in COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Developed in collaboration with Biocon (India), itolizumab is administered under an expanded access program to treat vulnerable populations in Cuba. Marshaling complementary capacities of dozens of institutions belonging to BioCubaFarma-the country's biotech conglomerate-and developing therapies, vaccines and medical technologies together, is another cornerstone of Cuba's strategy to combat COVID-19 and improve population health. The Molecular Immunology Center (CIM) is a key player in this strategy. Founded in 1992, CIM is a powerhouse in monoclonal antibody research and production, with 6 registered products and 22 in the pipeline. Known for several novel therapeutic cancer treatments, CIM has over two decades' experience producing complex recombinant proteins in mammalian cells on an industrial scale. Once Cuba's Innovation Committee (convened in January 2020 as part of the National COVID-19 Prevention & Control Plan) determined Cuban researchers would pursue protein subunit vaccine candidates, they turned to CIM to produce the required receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, among other responsibilities. CIM's General Director, Dr Eduardo Ojito- Magaz, is a chemical engineer and holds a master's degree in biotechnology. He spoke with MEDICC Review just days before 1.7 million Havana residents began participating in the country's largest intervention study with the COVID-19 vaccines his center helped make possible. URL: https://www.ncbi.nlm.nih.gov/pubmed/33974610 DOI: 10.37757/MR2021.V23.N2.17
7. Allen N, Ni Riain U, Conlon N, et al. Prevalence of Antibodies to SARS-CoV-2 in Irish Hospital Healthcare Workers. Epidemiol Infect. 2021:1-33. DOI: 10.1017/S0950268821000984 ABSTRACT: Hospital healthcare workers (HCW) are at increased risk of contracting COVID-19 infection. We aimed to determine the seroprevalence of SARS-CoV-2 antibodies in HCW in Ireland. Two tertiary referral hospitals in Irish cities with diverging community incidence and seroprevalence were identified; COVID-19 had been diagnosed in 10.2% and 1.8% of staff respectively by the time of the study (October 2020). All staff of both hospitals (N=9038) were invited to participate in an online questionnaire and blood sampling for SARS-CoV-2 antibody testing. Frequencies and percentages for positive SARS-CoV-2 antibody were calculated and adjusted relative risks (aRR) for participant characteristics were calculated using multivariable regression analysis. 5,788 HCW participated (64% response rate). Seroprevalence of antibodies to SARS-CoV-2 was 15% and 4.1% in Hospital 1 and 2, respectively. Thirty-nine percent of infections were previously undiagnosed. Risk for seropositivity was higher for healthcare assistants (aRR:
Evidence Search Report: INF031801v4 ESR 8 2.0, 95%CI:1.4 3.0), nurses (aRR: 1.6, 95%CI: 1.1 2.2), daily exposure to patients with COVID-19 (aRR: 1.6, 95%CI: 1.2-2.1), age 18-29 years (aRR: 1.4, 95%CI: 1.1-1.9), living with other HCW (aRR: 1.3, 95%CI: 1.1 1.5), Asian background (aRR: 1.3, 95%CI: 1.0-1.6), and male sex (aRR: 1.2, 95%CI 1.0-1.4). The HCW seroprevalence was six times higher than community seroprevalence. Risk was higher for those with close patient contact. The proportion of undiagnosed infections call for robust infection control guidance, easy access to testing and consideration of screening in asymptomatic HCW. With emerging evidence of reduction in transmission from vaccinated individuals, the authors strongly endorse rapid vaccination of all HCW.Copyright © 2021 Cambridge University Press. All rights reserved. URL: https://www.ncbi.nlm.nih.gov/pubmed/33902786 DOI: 10.1017/S0950268821000984
8. Alshogran OY, Altawalbeh SM, Al-Azzam SI, et al. Predictors of Covid-19 case fatality rate: An ecological study. Ann Med Surg (Lond). 2021;65:102319. DOI: 10.1016/j.amsu.2021.102319 ABSTRACT: Background: The outbreak of novel coronavirus (Covid-19) has a significant burden on global health and could be associated with significant mortality. Limited information exists about determinants of its fatality worldwide. Thus, this ecological study examined the association of various predictors with Covid-19 fatality. Methods: International data bases of Covid-19 statistics and health metrics available primarily at WHO were reviewed to collect information for 113 countries. The dependent variable was Covid-19 case fatality rate. Independent variables were demographic, social, clinical, economic, heath care and child health factors. Results: Case fatality rate of Covid-19 varies across countries with an average of 4.2 +/- 3.8%, and about half of countries had fatality rate >3.2% (median). Significant relationships were observed between Covid-19 fatality rate and socio-economic, clinical, and health variables at the unadjusted regression analysis. At the multivariate adjusted model, percentage of population with age>60 years was positively associated with Covid-19 fatality (B = 0.032, p = 0.005), while Polio-3 immunization at 1-year old was inversely related (B = -0.057, p = 0.017). Conclusions: This ecological investigation highlights the higher risk of death among elderly with Covid-19 pandemic and suggests that Polio-3 immunization coverage among 1-year-olds may be associated with better survival. Future research is warranted to validate these findings. URL: https://www.ncbi.nlm.nih.gov/pubmed/33936591 DOI: 10.1016/j.amsu.2021.102319
9. Anand P, Stahel VP. Review the safety of Covid-19 mRNA vaccines: a review. Patient Saf Surg. 2021;15(1):20. DOI: 10.1186/s13037-021-00291-9 ABSTRACT: The novel coronavirus disease 2019 (COVID-19) has infected more than 100 million people globally within the first year of the pandemic. With a death toll surpassing 500,000 in the United States alone, containing the pandemic is predicated on achieving herd immunity on a global scale. This implies that at least 70-80 % of the population must achieve active immunity against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), either as a result of a previous COVID-19 infection or by vaccination against SARS-CoV-2. In December 2020, the first two vaccines were approved by the FDA through emergency use authorization in the United States. These vaccines are based on the mRNA vaccine platform and were developed by Pfizer/BioNTech and Moderna. Published safety and efficacy trials reported high efficacy rates of 94-95 % after two interval doses, in conjunction with limited side effects and a low rate of adverse reactions. The rapid pace of vaccine development and the uncertainty of potential long-term adverse effects raised some level of hesitation against mRNA vaccines in the global community. A successful vaccination campaign is contingent on widespread access to the vaccine under appropriate storage conditions, deployment of a sufficient number of vaccinators, and the willingness of the population to be vaccinated. Thus, it is important to clarify the objective data related to vaccine safety, including known side effects and potential adverse reactions. The present review was
Evidence Search Report: INF031801v4 ESR 9 designed to provide an update on the current state of science related to the safety and efficacy of SARS- CoV-2 mRNA vaccines. URL: https://www.ncbi.nlm.nih.gov/pubmed/33933145 DOI: 10.1186/s13037-021-00291-9
10. Andrew MK, Schmader KE, Rockwood K, et al. Considering Frailty in SARS-CoV-2 Vaccine Development: How Geriatricians Can Assist. Clin Interv Aging. 2021;16:731-8. DOI: 10.2147/CIA.S295522 ABSTRACT: The COVID-19 pandemic has disproportionately impacted frail older adults, especially residents of long-term care (LTC) facilities. This has appropriately led to prioritization of frail older adults and LTC residents, and those who care for them, in the vaccination effort against COVID-19. Older adults have distinct immunological, clinical, and practical complexity, which can be understood through a lens of frailty. Even so, frailty has not been considered in studies of COVID-19 vaccines to date, leading to concerns that the vaccines have not been optimally tailored for and evaluated in this population even as vaccination programs are being implemented. This is an example of how vaccines are often not tested in Phase 1/2/3 clinical trials in the people most in need of protection. We argue that geriatricians, as frailty specialists, have much to contribute to the development, testing and implementation of COVID-19 vaccines in older adults. We discuss roles for geriatricians in ten stages of the vaccine development process, covering vaccine design, trial design, trial recruitment, establishment and interpretation of illness definitions, safety monitoring, consideration of relevant health measures such as frailty and function, analysis methods to account for frailty and differential vulnerability, contributions in regulatory and advisory roles, post-marketing surveillance, and program implementation and public health messaging. In presenting key recommendations pertinent to each stage, we hope to contribute to a dialogue on how to push the field of vaccinology to embrace the complexity of frailty. Making vaccines that can benefit frail older adults will benefit everyone in the fight against COVID-19. URL: https://www.ncbi.nlm.nih.gov/pubmed/33953551 DOI: 10.2147/CIA.S295522
11. Angel Y, Spitzer A, Henig O, et al. Association Between Vaccination With BNT162b2 and Incidence of Symptomatic and Asymptomatic SARS-CoV-2 Infections Among Health Care Workers. JAMA. 2021;06:06. DOI: 10.1001/jama.2021.7152 ABSTRACT: Importance: Randomized clinical trials have provided estimates of the effectiveness of the BNT162b2 vaccine against symptomatic SARS-CoV-2 infection, but its effect on asymptomatic infections remains unclear. Objective: To estimate the association of vaccination with the Pfizer-BioNTech BNT162b2 vaccine with symptomatic and asymptomatic SARS-CoV-2 infections among health care workers. Design, Setting, and Participants: This was a single-center, retrospective cohort study conducted at a tertiary medical center in Tel Aviv, Israel. Data were collected on symptomatic and asymptomatic SARS-CoV-2 infections confirmed via polymerase chain reaction (PCR) tests in health care workers undergoing regular screening with nasopharyngeal swabs between December 20, 2020, and February 25, 2021. Logistic regression was used to calculate incidence rate ratios (IRRs) comparing the incidence of infection between fully vaccinated and unvaccinated participants, controlling for demographics and the number of PCR tests performed. Exposures: Vaccination with the BNT162b2 vaccine vs unvaccinated status was ascertained from the employee health database. Full vaccination was defined as more than 7 days after receipt of the second vaccine dose. Main Outcomes and Measures: The primary outcome was the regression-adjusted IRR for symptomatic and asymptomatic SARS-CoV-2 infection of fully vaccinated vs unvaccinated health care workers. The secondary outcomes included IRRs for partially vaccinated health care workers (days 7-28 after first dose) and for those considered as late fully vaccinated (>21 days after second dose). Results: A total of 6710 health care
Evidence Search Report: INF031801v4 ESR 10 workers (mean [SD] age, 44.3 [12.5] years; 4465 [66.5%] women) were followed up for a median period of 63 days; 5953 health care workers (88.7%) received at least 1 dose of the BNT162b2 vaccine, 5517 (82.2%) received 2 doses, and 757 (11.3%) were not vaccinated. Vaccination was associated with older age compared with those who were not vaccinated (mean age, 44.8 vs 40.7 years, respectively) and male sex (31.4% vs 17.7%). Symptomatic SARS-CoV-2 infection occurred in 8 fully vaccinated health care workers and 38 unvaccinated health care workers (incidence rate, 4.7 vs 149.8 per 100000 person-days, respectively, adjusted IRR, 0.03 [95% CI, 0.01-0.06]). Asymptomatic SARS-CoV-2 infection occurred in 19 fully vaccinated health care workers and 17 unvaccinated health care workers (incidence rate, 11.3 vs 67.0 per 100000 person-days, respectively, adjusted IRR, 0.14 [95% CI, 0.07-0.31]). The results were qualitatively unchanged by the propensity score sensitivity analysis. Conclusions and Relevance: Among health care workers at a single center in Tel Aviv, Israel, receipt of the BNT162b2 vaccine compared with no vaccine was associated with a significantly lower incidence of symptomatic and asymptomatic SARS- CoV-2 infection more than 7 days after the second dose. Findings are limited by the observational design. URL: https://www.ncbi.nlm.nih.gov/pubmed/33956048 DOI: 10.1001/jama.2021.7152
12. Anonymous. FDA authorizes Johnson & Johnson COVID-19 vaccine. Med Lett Drugs Ther. 2021;63(1620):41-2. URL: https://www.ncbi.nlm.nih.gov/pubmed/33976088
13. Anonymous. In brief: Suspension of Johnson & Johnson COVID-19 vaccine lifted. Med Lett Drugs Ther. 2021;63(1624):e1. URL: https://www.ncbi.nlm.nih.gov/pubmed/33976095
14. Arling G, Blaser M, Cailas MD, et al. A Data Driven Approach for Prioritizing COVID-19 Vaccinations in the Midwestern United States. Online J Public Health Inform. 2021;13(1):e5. DOI: 10.5210/ojphi.v13i1.11621 ABSTRACT: Considering the potential for widespread adoption of social vulnerability indices (SVI) to prioritize COVID-19 vaccinations, there is a need to carefully assess them, particularly for correspondence with outcomes (such as loss of life) in the context of the COVID-19 pandemic. The University of Illinois at Chicago School of Public Health Public Health GIS team developed a methodology for assessing and deriving vulnerability indices based on the premise that these indices are, in the final analysis, classifiers. Application of this methodology to several Midwestern states with a commonly used SVI indicates that by using only the SVI rankings there is a risk of assigning a high priority to locations with the lowest mortality rates and low priority to locations with the highest mortality rates. Based on the findings, we propose using a two-dimensional approach to rationalize the distribution of vaccinations. This approach has the potential to account for areas with high vulnerability characteristics as well as to incorporate the areas that were hard hit by the pandemic. URL: https://www.ncbi.nlm.nih.gov/pubmed/33936526 DOI: 10.5210/ojphi.v13i1.11621
15. Aspatwar A, Gong W, Wang S, et al. Tuberculosis vaccine BCG: the magical effect of the old vaccine in the fight against the COVID-19 pandemic. Int Rev Immunol. 2021:1-14. DOI: 10.1080/08830185.2021.1922685 ABSTRACT: Bacillus Calmette-Guerin (BCG) is a live attenuated M. bovis vaccine that was developed about 100 years ago by Albert Calmette and Camille Guerin. Many countries have been using the vaccine for decades against tuberculosis (TB). The World Health Organization (WHO) recommends a
Evidence Search Report: INF031801v4 ESR 11 single dose of BCG for infants in TB endemic as well as leprosy high risk countries, and globally almost 130 million infants are vaccinated yearly. The role of BCG is well known in reducing neonatal and childhood death rates. Epidemiological and retrospective cross-sectional studies demonstrated that the BCG vaccination protects the children against respiratory tract infections and lowers the risk of malaria in children. In addition, BCG enhances IFN-gamma and IL-10 levels, thus providing immunity against respiratory tract infection even in elderly people. The BCG is also known to provide nonspecific innate immunity against viruses and parasites, through an innate immune mechanism termed 'trained immunity' and is defined as the immunological recall of the innate immune system by epigenetic reprogramming. Based on these studies it is suggested that the BCG has the potential to act as a protective agent against COVID-19. Further proven safety records of BCG in humans, its adjuvant activity and low-cost manufacturing make it an attractive option to stop the pandemic and reduce the COVID-19 related mortality. In this review we discuss the heterologous effects of BCG, induction of trained immunity and its implication in development of a potential vaccine against COVID-19 pandemic. URL: https://www.ncbi.nlm.nih.gov/pubmed/33960271 DOI: 10.1080/08830185.2021.1922685
16. Barrett JR, Belij-Rammerstorfer S, Dold C, et al. Author Correction: Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses. Nat Med. 2021;06:06. DOI: 10.1038/s41591-021-01372-z URL: https://www.ncbi.nlm.nih.gov/pubmed/33958800 DOI: 10.1038/s41591-021-01372-z
17. Beckman MF, Mougeot FB, Mougeot JC. Comorbidities and Susceptibility to COVID-19: A Generalized Gene Set Data Mining Approach. J Clin Med. 2021;10(8):13. DOI: 10.3390/jcm10081666 ABSTRACT: The COVID-19 pandemic has led to over 2.26 million deaths for almost 104 million confirmed cases worldwide, as of 4 February 2021 (WHO). Risk factors include pre-existing conditions such as cancer, cardiovascular disease, diabetes, and obesity. Although several vaccines have been deployed, there are few alternative anti-viral treatments available in the case of reduced or non-existent vaccine protection. Adopting a long-term holistic approach to cope with the COVID-19 pandemic appears critical with the emergence of novel and more infectious SARS-CoV-2 variants. Our objective was to identify comorbidity-associated single nucleotide polymorphisms (SNPs), potentially conferring increased susceptibility to SARS-CoV-2 infection using a computational meta-analysis approach. SNP datasets were downloaded from a publicly available genome-wide association studies (GWAS) catalog for 141 of 258 candidate COVID-19 comorbidities. Gene-level SNP analysis was performed to identify significant pathways by using the program MAGMA. An SNP annotation program was used to analyze MAGMA- identified genes. Differential gene expression was determined for significant genes across 30 general tissue types using the Functional and Annotation Mapping of GWAS online tool GENE2FUNC. COVID-19 comorbidities (n = 22) from six disease categories were found to have significant associated pathways, validated by Q-Q plots (p < 0.05). Protein-protein interactions of significant (p < 0.05) differentially expressed genes were visualized with the STRING program. Gene interaction networks were found to be relevant to SARS and influenza pathogenesis. In conclusion, we were able to identify the pathways potentially affected by or affecting SARS-CoV-2 infection in underlying medical conditions likely to confer susceptibility and/or the severity of COVID-19. Our findings have implications in future COVID-19 experimental research and treatment development. URL: https://www.ncbi.nlm.nih.gov/pubmed/33924631 DOI: 10.3390/jcm10081666
Evidence Search Report: INF031801v4 ESR 12 18. Bewley KR, Coombes NS, Gagnon L, et al. Quantification of SARS-CoV-2 neutralizing antibody by wild-type plaque reduction neutralization, microneutralization and pseudotyped virus neutralization assays. Nat Protoc. 2021. DOI: 10.1038/s41596-021-00536-y ABSTRACT: Virus neutralization assays measure neutralizing antibodies in serum and plasma, and the plaque reduction neutralization test (PRNT) is considered the gold standard for measuring levels of these antibodies for many viral diseases. We have developed procedures for the standard PRNT, microneutralization assay (MNA) and pseudotyped virus neutralization assay (PNA) for severe acute respiratory syndrome coronavirus 2. The MNA offers advantages over the PRNT by reducing assay time, allowing increased throughput and reducing operator workload while remaining dependent upon the use of wild-type virus. This ensures that all severe acute respiratory syndrome coronavirus 2 antigens are present, but Biosafety Level 3 facilities are required. In addition to the advantages of MNA, PNA can be performed with lower biocontainment (Biosafety Level 2 facilities) and allows for further increases in throughput. For each new vaccine, it is critical to ensure good correlation of the neutralizing activity measured using PNA against the PRNT or MNA. These assays have been used in the development and licensure of the ChAdOx1 nCoV-19 (AstraZeneca; Oxford University) and Ad26.COV2.S (Janssen) coronavirus disease 2019 vaccines and are critical for demonstrating bioequivalence of future vaccines. URL: https://www.ncbi.nlm.nih.gov/pubmed/33893470 DOI: 10.1038/s41596-021-00536-y
19. Bezbaruah R, Borah P, Kakoti BB, et al. Developmental Landscape of Potential Vaccine Candidates Based on Viral Vector for Prophylaxis of COVID-19. Front Mol Biosci. 2021;8:635337. DOI: 10.3389/fmolb.2021.635337 ABSTRACT: Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, arose at the end of 2019 as a zoonotic virus, which is the causative agent of the novel coronavirus outbreak COVID-19. Without any clear indications of abatement, the disease has become a major healthcare threat across the globe, owing to prolonged incubation period, high prevalence, and absence of existing drugs or vaccines. Development of COVID-19 vaccine is being considered as the most efficient strategy to curtail the ongoing pandemic. Following publication of genetic sequence of SARS-CoV-2, globally extensive research and development work has been in progress to develop a vaccine against the disease. The use of genetic engineering, recombinant technologies, and other computational tools has led to the expansion of several promising vaccine candidates. The range of technology platforms being evaluated, including virus-like particles, peptides, nucleic acid (DNA and RNA), recombinant proteins, inactivated virus, live attenuated viruses, and viral vectors (replicating and non-replicating) approaches, are striking features of the vaccine development strategies. Viral vectors, the next-generation vaccine platforms, provide a convenient method for delivering vaccine antigens into the host cell to induce antigenic proteins which can be tailored to arouse an assortment of immune responses, as evident from the success of smallpox vaccine and Ervebo vaccine against Ebola virus. As per the World Health Organization, till January 22, 2021, 14 viral vector vaccine candidates are under clinical development including 10 nonreplicating and four replicating types. Moreover, another 39 candidates based on viral vector platform are under preclinical evaluation. This review will outline the current developmental landscape and discuss issues that remain critical to the success or failure of viral vector vaccine candidates against COVID-19. URL: https://www.ncbi.nlm.nih.gov/pubmed/33937326 DOI: 10.3389/fmolb.2021.635337
20. Bhadoria SS, Shukla D, Joshi A. COVID-19 Pandemic: A Speed Breaker for Routine Immunisation. Journal of Clinical and Diagnostic Research. 2021;15(4):LC32-LC5. DOI: 10.7860/jcdr/2021/46875.14844
Evidence Search Report: INF031801v4 ESR 13 ABSTRACT: Introduction: Immunisation services are affected by Coronavirus Disease 2019 (COVID-19) pandemic due to lockdown and fear of COVID among public along with problems of workforce management and vaccine supply. All these factors have led to decrease in vaccination coverage. It may further lead to increase in risk of vaccine preventable diseases. Aim(s): To assess the overall trend and evaluate the vaccination coverage during COVID-19 pandemic in a tertiary care hospital in Gwalior district. Material(s) and Method(s): Record based secondary data from the immunisation OPD of the tertiary care hospital Gwalior, Madhya Pradesh, India, for the period of 01 February 2020 to 31 August 2020 was utilised in current study. Data were entered into Microsoft Excel version-2007 and analysed. Frequency, percentage, mean, and standard deviation were calculated as a descriptive measures and graphical presentation to show time trends. The p-value was calculated at 5% level of significance. Result(s): In the study, 817 children were included, with mean age of 7.46 +/-13.59 months. Total 61.1% (499) children were male and 38.9% (318) were female. During the study period, all the children were vaccinated for Bacille Calmette-Guerin (BCG) (10.6%) Pentavalent-1 series (36.4%), Pentavalent-2 series (17.4%), Pentavalent-3 series (12.2%), Measles-Rubella (MR-1) (6.5%), Booster-I (11.8%) and Booster-II (5.1%). Delayed vaccination was seen in 51(6.20%) children. The delay was observed for Pentavalent-2 series (43.1%), pentavalent-3 series (51.0%) and MR-1 (5.9%) and the difference is significant at p-value <0.05. Conclusion(s): Immunisation services were severely interrupted and completely suspended in April 2020. Certain amount of delay in various doses was also observed. Maintaining routine immunisation is essential in preventing an outbreak of vaccine preventable diseases.Copyright © 2021 Journal of Clinical and Diagnostic Research. All rights reserved. URL: https://www.jcdr.net/articles/PDF/14844/46875_CE[Ra1]_F[SK]_PF1(SC_SL)_PFA(Pr_KM)_PN(KM).pdf http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emedx&NEWS=N&AN=2011938755 DOI: 10.7860/jcdr/2021/46875.14844
21. Binagwaho A, Mathewos K, Davis S. Equitable and Effective Distribution of the COVID-19 Vaccines - A Scientific and Moral Obligation. Int J Health Policy Manag. 2021;26:26. DOI: 10.34172/ijhpm.2021.49 ABSTRACT: The rapid development of coronavirus disease 2019 (COVID-19) vaccines has not been met with the assurance of an effective and equitable global distribution mechanism. Low-income countries are especially at-risk, with the price of the vaccines and supply shortages limiting their ability to procure and distribute the vaccines. While the COVAX initiative is one of the solutions to these challenges, vaccine nationalism has resulted in the hoarding of vaccines and the signing of parallel bilateral deals, undermining this formerly promising initiative. Moreover, inequity in local distribution also remains a problem, with clear discrimination of minorities and lack of logistical preparation in some countries. As we continue to distribute the COVID-19 vaccines, pharmaceutical companies should share their technology to increase supply and reduce prices, governments should prioritize equitable distribution to the most at-risk in all nations and low-income countries should bolster their logistical capacity in preparation for mass vaccination campaigns. URL: https://www.ncbi.nlm.nih.gov/pubmed/33949818 DOI: 10.34172/ijhpm.2021.49
22. Bonet-Esteve A, Munoz-Miralles R, Gonzalez-Claramunt C, et al. Influenza vaccination during the coronavirus pandemic: intention to vaccinate among the at-risk population in the Central Catalonia Health Region (VAGCOVID). BMC Fam Pract. 2021;22(1):84. DOI: 10.1186/s12875-021-01434-8 ABSTRACT: BACKGROUND: Influenza is a major public health issue, with the primary preventive measure being an annual influenza vaccination. Nevertheless, vaccination coverage among the at-risk population is low. Our understanding of the behaviour of the influenza virus during the SARS-CoV-2 coronavirus
Evidence Search Report: INF031801v4 ESR 14 pandemic is limited, meaning influenza vaccination is still recommended for individuals at risk for severe complications due to influenza infection. The aim of the study is to determine the intention to vaccinate against seasonal influenza among the at-risk population in the 2020-21 campaign during the SARS-CoV-2 pandemic and to analyse the factors which influence such intention. METHODS: Cross-sectional telephone survey of adults (aged over 18) with risk factors in central Catalonia where the need for the Seasonal Influenza Vaccine (SIV) was recommended. RESULTS: A total of 434 participants responded to the survey, 43.3% of whom intended to be vaccinated against influenza for the 2020-2021 influenza season, 40.8% had no intention to be vaccinated and 15.9% were uncertain or did not express their opinion. The intention to get vaccinated against influenza is associated with having dependents, the individual's perception of the risk of being infected with influenza and the perceived risk of transmission to dependents. It is also associated with age, whether the individual had received influenza vaccine the previous season or any other season before. The best predictors of the intention to vaccinate are the individual's perception of the risk of catching influenza and whether the individual had been vaccinated in the previous season. CONCLUSIONS: Intention to vaccinate can be a good predictor of individual behaviour in relation to vaccination. During the current SARS-CoV-2 pandemic many individuals are hesitant to influenza vaccination. In order to improve influenza vaccination coverage in people included in risk groups, it is necessary to promote educational actions, especially among those who express doubts. URL: https://www.ncbi.nlm.nih.gov/pubmed/33931039 DOI: 10.1186/s12875-021-01434-8
23. Boyarsky BJ, Ou MT, Greenberg RS, et al. Safety of the First Dose of SARS-CoV-2 Vaccination in Solid Organ Transplant Recipients. Transplantation. 2021;105(5):e56-e7. DOI: 10.1097/TP.0000000000003654 URL: https://www.ncbi.nlm.nih.gov/pubmed/33560728 DOI: 10.1097/TP.0000000000003654
24. Brodziak A, Sigorski D, Osmola M, et al. Attitudes of Patients with Cancer towards Vaccinations- Results of Online Survey with Special Focus on the Vaccination against COVID-19. Vaccines (Basel). 2021;9(5):21. DOI: 10.3390/vaccines9050411 ABSTRACT: Recently developed COVID-19 vaccines significantly reduce the risk of severe coronavirus disease, which is essential in the particularly vulnerable cancer patient population. There is a growing anti-vaccine concern that may affect the success of the fight against the SARS-CoV2 pandemic. To evaluate opinions and attitudes toward vaccination, we conducted an anonymous online survey among Polish patients diagnosed with cancer. We analyzed how socio-demographic factors, type of cancer, comorbidities, previous influenza vaccinations, and information sources affect the general willingness and opinions about vaccinations, emphasizing vaccination against COVID-19. Six hundred thirty-five patients (80.2% female) participated in the study. A positive attitude towards vaccination was presented by 73.7%, neutral by 17.8%, while negative by 8.5%. Willingness to get vaccinated was declared by 60.3%, 23.5% were unwilling, and 16.2% were undecided. Significant predictors of willingness were education, marital status, active anti-cancer treatment, previous influenza vaccination, and positive attitude towards vaccinations. Patients with cancer have concerns regarding safety, effectiveness, and the process of development of the COVID-19 vaccine. Overall, patients with cancer present positive attitudes towards COVID-19 vaccination but required sufficient information on its efficacy and side effects. URL: https://www.ncbi.nlm.nih.gov/pubmed/33919048 DOI: 10.3390/vaccines9050411
Evidence Search Report: INF031801v4 ESR 15 25. Broniatowski DA, Dredze M, Ayers JW. "First Do No Harm": Effective Communication About COVID-19 Vaccines. Am J Public Health. 2021;111(6):1055-7. DOI: 10.2105/AJPH.2021.306288 URL: https://www.ncbi.nlm.nih.gov/pubmed/33950727 DOI: 10.2105/AJPH.2021.306288
26. Bruchfeld A, Kronbichler A, Alberici F, et al. COVID-19 and ANCA-associated vasculitis - recommendations for vaccine preparedness and the use of rituximab. Nephrol Dial Transplant. 2021;03:03. DOI: 10.1093/ndt/gfab174 URL: https://www.ncbi.nlm.nih.gov/pubmed/33944946 DOI: 10.1093/ndt/gfab174
27. Brussow H. COVID-19: Vaccination problems. Environ Microbiol. 2021;29:29. DOI: 10.1111/1462- 2920.15549 ABSTRACT: This minireview addresses problems of financing the vaccine development, regulatory questions, the ethics and efficacy of vaccine prioritization strategies, and the coverage of variant viruses by current vaccines. Serious adverse effects observed with adenovirus vectored vaccines and mRNA vaccines in mass vaccination campaigns are reported. The ethical problems of continuing with placebo controlled vaccine trials and alternative clinical trial protocols are discussed as well as concrete vaccination issues such as the splitting of doses, the delaying of the second dose, the immunization with two different vaccine types, and the need of vaccinating seropositive subjects. Strategies to increase vaccine acceptance in the population are shortly mentioned. This article is protected by copyright. All rights reserved. URL: https://www.ncbi.nlm.nih.gov/pubmed/33928745 DOI: 10.1111/1462-2920.15549
28. Butter S, McGlinchey E, Berry E, et al. Psychological, social, and situational factors associated with COVID-19 vaccination intentions: A study of UK key workers and non-key workers. Br J Health Psychol. 2021;05:05. DOI: 10.1111/bjhp.12530 ABSTRACT: OBJECTIVES: Vaccine hesitancy is a growing concern and threat to public health. This research will begin to examine the relative influence of relevant psychological, social, and situational factors on intent to engage with a hypothetical COVID-19 vaccine among key workers and non-key workers. DESIGN: Cross-sectional. METHODS: The study utilized a sample of UK adults who completed the 1-month follow-up of The COVID-19 Psychological Wellbeing Study during April/May 2020 and indicated having not been previously diagnosed with COVID-19 (key workers n = 584; not key workers n = 1,021). These groups were compared in relation to their intentions to vaccinate, perceived risk of infection, and symptom severity. Binary logistic regression was used to examine predictors of vaccine hesitancy. RESULTS: Overall, 74.2% of the sample (76.2% key workers, 73.1% non-key workers) indicated they would accept a COVID-19 vaccine in future. Key workers (in particular health and social care workers) had a higher perceived risk of becoming infected in the coming months. For key workers, being female and perceiving oneself as having relatively low infection risk in the next 6 months was associated with increased likelihood of vaccine hesitancy. For non-key workers, however, being aged 25-54, having a low or average income and not knowing someone diagnosed with COVID-19 were associated with hesitancy. CONCLUSIONS: The proportion of individuals willing to accept a vaccine is encouraging but there is much room for improvement. Given the unique predictors of vaccine hesitancy in each group, public health campaigns may benefit from targeted messaging. URL: https://www.ncbi.nlm.nih.gov/pubmed/33949038 DOI: 10.1111/bjhp.12530
Evidence Search Report: INF031801v4 ESR 16 29. Calzetta L, Ritondo BL, Coppola A, et al. Factors Influencing the Efficacy of COVID-19 Vaccines: A Quantitative Synthesis of Phase III Trials. Vaccines (Basel). 2021;9(4):01. DOI: 10.3390/vaccines9040341 ABSTRACT: To date, there is still a paucity of data from Phase III trials concerning the efficacy of vaccines against COVID-19. Furthermore, no studies investigated the variables that may modulate the efficacy of vaccination. The aim of this analysis was to assess whether there are modifying factors that may potentially influence the clinical efficacy of COVID-19 vaccines. A quantitative synthesis of data from Phase III trials was performed via pairwise and network meta-analyses, along with meta-regression analysis. Data from Phase III trials are currently available only for AZD1222, BNT162b2, mRNA-1237, and Sputnik V. Vaccination resulted to be generally effective (90.0%, 95%CI 72.6-96.4; p < 0.001), although the efficacy of AZD1222 (62.1%) introduced a significant level of heterogeneity in the meta-analysis (I(2) 92.17%, p < 0.001). No significant modifying factors resulted from the meta-regression analysis. However, considering the mRNA-based vaccines, a trend toward significance (p = 0.081) resulted for age. The network meta-analysis provided the following rank of effectiveness: BNT162b2 approximately mRNA-1273 > Sputnik V >> AZD1222. In conclusion, no modifying factors seem to modulate the efficacy of vaccines against COVID-19. This quantitative synthesis will need to be updated as soon as further clinical results on the efficacy profile are available from Phase III trials for further licensed COVID-19 vaccines. URL: https://www.ncbi.nlm.nih.gov/pubmed/33916222 DOI: 10.3390/vaccines9040341
30. Carnell GW, Ciazynska KA, Wells DA, et al. SARS-CoV-2 spike protein stabilized in the closed state induces potent neutralizing responses. J Virol. 2021;07:07. DOI: 10.1128/JVI.00203-21 ABSTRACT: The majority of SARS-CoV-2 vaccines in use or advanced development are based on the viral spike protein (S) as their immunogen. S is present on virions as pre-fusion trimers in which the receptor binding domain (RBD) is stochastically open or closed. Neutralizing antibodies have been described against both open and closed conformations. The long-term success of vaccination strategies depends upon inducing antibodies that provide long-lasting broad immunity against evolving SARS-CoV-2 strains. Here we have assessed the results of immunization in a mouse model using an S protein trimer stabilized in the closed state to prevent full exposure of the receptor binding site and therefore interaction with receptor. We compared this with other modified S protein constructs, including representatives used in current vaccines. We found that all trimeric S proteins induced a T cell response and long-lived, strongly neutralizing antibody responses against 2019 SARS-CoV-2 and variants of concern B.1.248 and B.1.351. Notably, the protein binding properties of sera induced by the closed spike differed from those induced by standard S protein constructs. Closed S proteins induced more potent neutralizing responses than expected based on the degree to which they inhibit interactions between the RBD and ACE2. These observations suggest that closed spikes recruit different, but equally potent, immune responses than open spikes, and that this is likely to include neutralizing antibodies against conformational epitopes present in the closed conformation. Together with their improved stability and storage properties we suggest that closed spikes may be a valuable component of refined, next- generation vaccines.ImportanceVaccines in use against SARS-CoV-2 induce immune responses against the spike protein. There is intense interest in whether the antibody response induced by vaccines will be robust against new variants, as well as in next-generation vaccines for use in previously infected or immunized individuals. We assessed the use as an immunogen of a spike protein engineered to be conformationally stabilized in the closed state where the receptor binding site is occluded. Despite occlusion of the receptor binding site, the spike induces potently neutralizing sera against multiple SARS- CoV-2 variants. Antibodies are raised against a different pattern of epitopes to those induced by other
Evidence Search Report: INF031801v4 ESR 17 spike constructs, preferring conformational epitopes present in the closed conformation. Closed spikes, or mRNA vaccines based on their sequence, can be a valuable component of next generation vaccines. URL: https://www.ncbi.nlm.nih.gov/pubmed/33963055 DOI: 10.1128/JVI.00203-21
31. Caron B, Neuville E, Peyrin-Biroulet L. Inflammatory Bowel Disease and COVID-19 Vaccination: A Patients' Survey. Dig Dis Sci. 2021;12:12. DOI: 10.1007/s10620-021-07040-z ABSTRACT: BACKGROUND: Vaccination against COVID-19 is a major public health challenge, including the community of patients with inflammatory bowel disease. Vaccination coverage is suboptimal in inflammatory bowel disease population. It is of paramount importance to ensure an effective and rapid vaccination program with the adherence of the largest number of well-informed patients. AIMS: We assessed the acceptance of COVID-19 vaccination among inflammatory bowel disease patients. METHODS: We performed a survey as part of routine practice, between January 8th and February 22nd, 2021. All consecutive adult patients followed at Nancy University Hospital for inflammatory bowel disease were included. Patients completed a self-administered, structured, paper-based questionnaire. Demographic data, medical history, knowledge, and perceptions of COVID-19 vaccination were collected. RESULTS: Among the 104 patients who responded to the survey, 57 patients (54.8%) had intent to receive the COVID-19 vaccine. Vaccine efficacy, social responsibility, herd immunity, and desire to return to normal life were associated with self-reported willingness to receive a vaccine (20.2%, 20.2%, 11.5%, and 15.4%, respectively). Unknown long-term safety, risk of adverse reaction to vaccine and concern that the vaccine is being developed too quickly were the most commonly reported reasons for non-uptake (27.9%, 15.4%, and 12.5%, respectively). CONCLUSION: Half of the patients with inflammatory bowel disease would like to be vaccinated against SARS-CoV-2. This rate is similar to that reported in the French general population. Despite some concerns, patients with inflammatory bowel disease understood the necessity to be vaccinated against COVID-19. URL: https://www.ncbi.nlm.nih.gov/pubmed/33977419 DOI: 10.1007/s10620-021-07040-z
32. Catma S, Reindl D. Parents' willingness to pay for a COVID-19 vaccine for themselves and their children in the United States. Hum Vaccin Immunother. 2021:1-7. DOI: 10.1080/21645515.2021.1919453 ABSTRACT: Differences in obtaining a vaccine vary based on a multitude of factors including perceptions of vaccine safety, efficacy and willingness to pay (WTP). This study focuses on parent perceptions toward a vaccine for COVID-19 including their WTP decisions for their children and themselves. A mixed methods design using a cross-sectional survey was used to assess the perceptions of US parents, with children under 18, in response to the COVID-19 pandemic. The survey was administered online in November 2020 and 584 final responses were collected. The questionnaire consisted of approximately 37 closed and open-ended questions regarding personal background information; awareness, knowledge, and experience of the virus; perception toward vaccines and COVID-19; and the contingent valuation of a hypothetical COVID-19 vaccine. WTP was found to be higher for children and a direct relationship between the number of children and WTP was observed. Parents were willing to pay US$228-$291 for a vaccine for themselves and US$243-US$321 for their children. A positive impact on WTP was found with self-reported parent health status but not children. The findings of this study have important implications for policy programs which require detailed cost-benefit analyses. WTP for a COVID-19 vaccine is crucial to determine the partial benefits of vaccinating to reduce the risk of repetitive widespread outbreaks. URL: https://www.ncbi.nlm.nih.gov/pubmed/33929290 DOI: 10.1080/21645515.2021.1919453
Evidence Search Report: INF031801v4 ESR 18
33. Cerda AA, Garcia LY. Hesitation and Refusal Factors in Individuals' Decision-Making Processes Regarding a Coronavirus Disease 2019 Vaccination. Front Public Health. 2021;9:626852. DOI: 10.3389/fpubh.2021.626852 ABSTRACT: Introduction: Considering the global prevalence of coronavirus disease 2019 (COVID-19), a vaccine is being developed to control the disease as a complementary solution to hygiene measures-and better, in social terms, than social distancing. Given that a vaccine will eventually be produced, information will be needed to support a potential campaign to promote vaccination. Objective: The aim of this study was to determine the variables affecting the likelihood of refusal and indecision toward a vaccine against COVID-19 and to determine the acceptance of the vaccine for different scenarios of effectiveness and side effects. Materials and Methods: A multinomial logistic regression method based on the Health Belief Model was used to estimate the current methodology, using data obtained by an online anonymous survey of 370 respondents in Chile. Results: The results indicate that 49% of respondents were willing to be vaccinated, with 28% undecided or 77% of individuals who would potentially be willing to be inoculated. The main variables that explained the probability of rejection or indecision were associated with the severity of COVID-19, such as, the side effects and effectiveness of the vaccine; perceived benefits, including immunity, decreased fear of contagion, and the protection of oneself and the environment; action signals, such as, responses from ones' family and the government, available information, and specialists' recommendations; and susceptibility, including the contagion rate per 1,000 inhabitants and relatives with COVID-19, among others. Our analysis of hypothetical vaccine scenarios revealed that individuals preferred less risky vaccines in terms of fewer side effects, rather than effectiveness. Additionally, the variables that explained the indecision toward or rejection of a potential COVID-19 vaccine could be used in designing public health policies. Conclusions: We discovered that it is necessary to formulate specific, differentiated vaccination-promotion strategies for the anti-vaccine and undecided groups based on the factors that explain the probability of individuals refusing or expressing hesitation toward vaccination. URL: https://www.ncbi.nlm.nih.gov/pubmed/33968880 DOI: 10.3389/fpubh.2021.626852
34. Chen X, Chen Z, Azman AS, et al. Comprehensive mapping of neutralizing antibodies against SARS - CoV-2 variants induced by natural infection or vaccination. medRxiv. 2021;05:05. DOI: 10.1101/2021.05.03.21256506 ABSTRACT: Background: Immunity after SARS-CoV-2 infection or vaccination has been threatened by recently emerged SARS-CoV-2 variants. A systematic summary of the landscape of neutralizing antibodies against emerging variants is needed. Methods: We systematically searched PubMed, Embase, Web of Science, and 3 pre-print servers for studies that evaluated neutralizing antibodies titers induced by previous infection or vaccination against SARS-CoV-2 variants and comprehensively collected individual data. We calculated lineage-specific GMTs across different study participants and types of neutralization assays. Findings: We identified 56 studies, including 2,483 individuals and 8,590 neutralization tests, meeting the eligibility criteria. Compared with lineage B, we estimate a 1.5-fold (95% CI: 1.0-2.2) reduction in neutralization against the B.1.1.7, 8.7-fold (95% CI: 6.5-11.7) reduction against B.1.351 and 5.0-fold (95% CI: 4.0-6.2) reduction against P.1. The estimated neutralization reductions for B.1.351 compared to lineage B were 240.2-fold (95% CI: 124.0-465.6) reduction for non- replicating vector platform, 4.6-fold (95% CI: 4.0-5.2) reduction for RNA platform, and 1.6-fold (95% CI: 1.2-2.1) reduction for protein subunit platform. The neutralizing antibodies induced by administration of inactivated vaccines and mRNA vaccines against lineage P.1 were also remarkably reduced by an average of 5.9-fold (95% CI: 3.7-9.3) and 1.5-fold (95% CI: 1.2-1.9). Interpretation: Our findings indicate that the antibody response established by natural infection or vaccination might be able to effectively
Evidence Search Report: INF031801v4 ESR 19 neutralize B.1.1.7, but neutralizing titers against B.1.351 and P.1 suffered large reductions. Standardized protocols for neutralization assays, as well as updating immune-based prevention and treatment, are needed. Funding: Chinese National Science Fund for Distinguished Young Scholars. Research in context: Evidence before this study: Several newly emerged SARS-CoV-2 variants have raised significant concerns globally, and there is concern that SARS-CoV-2 variants can evade immune responses that are based on the prototype strain. It is not known to what extent do emerging SARS-CoV-2 variants escape the immune response induced by previous infection or vaccination. However, existing studies of neutralizing potency against SARS-CoV-2 variants are based on limited numbers of samples and lack comparability between different laboratory methods. Furthermore, there are no studies providing whole picture of neutralizing antibodies induced by prior infections or vaccination against emerging variants. Therefore, we systematically reviewed and quantitively synthesized evidence on the degree to which antibodies from previous SARS-CoV-2 infection or vaccination effectively neutralize variants.Added value of this study: In this study, 56 studies, including 2,483 individuals and 8,590 neutralization tests, were identified. Antibodies from natural infection or vaccination are likely to effectively neutralize B.1.1.7, but neutralizing titers against B.1.351 and P.1 suffered large reductions. Lineage B.1.351 escaped natural- infection-mediated neutralization the most, with GMT of 79.2 (95% CI: 68.5-91.6), while neutralizing antibody titers against the B.1.1.7 variant were largely preserved (254.6, 95% CI: 214.1-302.8). Compared with lineage B, we estimate a 1.5-fold (95% CI: 1.0-2.2) reduction in neutralization against the B.1.1.7, 8.7-fold (95% CI: 6.5-11.7) reduction against B.1.351 and 5.0-fold (95% CI: 4.0-6.2) reduction against P.1. The neutralizing antibody response after vaccinating with non-replicating vector vaccines against lineage B.1.351 was worse than responses elicited by vaccines on other platforms, with levels lower than that of individuals who were previously infected. The neutralizing antibodies induced by administration of inactivated vaccines and mRNA vaccines against lineage P.1 were also remarkably reduced by an average of 5.9-fold (95% CI: 3.7-9.3) and 1.5-fold (95% CI: 1.2-1.9).Implications of all the available evidence: Our findings indicate that antibodies from natural infection of the parent lineage of SARS-CoV-2 or vaccination may be less able to neutralize some emerging variants, and antibody-based therapies may need to be updated. Furthermore, standardized protocols for neutralizing antibody testing against SARS-CoV-2 are needed to reduce lab-to-lab variations, thus facilitating comparability and interpretability across studies. URL: https://www.ncbi.nlm.nih.gov/pubmed/33972950 DOI: 10.1101/2021.05.03.21256506
35. Chiozzini C, Manfredi F, Ferrantelli F, et al. The C-Terminal Domain of Nef(mut) Is Dispensable for the CD8(+) T Cell Immunogenicity of In Vivo Engineered Extracellular Vesicles. Vaccines (Basel). 2021;9(4):12. DOI: 10.3390/vaccines9040373 ABSTRACT: Intramuscular injection of DNA vectors expressing the extracellular vesicle (EV)-anchoring protein Nef(mut) fused at its C-terminus to viral and tumor antigens elicit a potent, effective, and anti- tolerogenic CD8(+) T cell immunity against the heterologous antigen. The immune response is induced through the production of EVs incorporating Nef(mut)-derivatives released by muscle cells. In the perspective of a possible translation into the clinic of the Nef(mut)-based vaccine platform, we aimed at increasing its safety profile by identifying the minimal part of Nef(mut) retaining the EV-anchoring protein property. We found that a C-terminal deletion of 29-amino acids did not affect the ability of Nef(mut) to associate with EVs. The EV-anchoring function was also preserved when antigens from both HPV16 (i.e., E6 and E7) and SARS-CoV-2 (i.e., S1 and S2) were fused to its C-terminus. Most important, the Nef(mut) C-terminal deletion did not affect levels, quality, and diffusion at distal sites of the antigen- specific CD8(+) T immunity. We concluded that the C-terminal Nef(mut) truncation does not influence stability, EV-anchoring, and CD8(+) T cell immunogenicity of the fused antigen. Hence, the C-terminal deleted Nef(mut) may represent a safer alternative to the full-length isoform for vaccines in humans.
Evidence Search Report: INF031801v4 ESR 20 URL: https://www.ncbi.nlm.nih.gov/pubmed/33921215 DOI: 10.3390/vaccines9040373
36. Chudasama DY, Flannagan J, Collin SM, et al. Household clustering of SARS-CoV-2 variant of concern B.1.1.7 (VOC-202012-01) in England. J Infect. 2021. DOI: 10.1016/j.jinf.2021.04.029 URL: https://www.ncbi.nlm.nih.gov/pubmed/33933529 DOI: 10.1016/j.jinf.2021.04.029
37. Collier AY, McMahan K, Yu J, et al. Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women. JAMA. 2021;13:13. DOI: 10.1001/jama.2021.7563 ABSTRACT: Importance: Pregnant women are at increased risk of morbidity and mortality from COVID- 19 but have been excluded from the phase 3 COVID-19 vaccine trials. Data on vaccine safety and immunogenicity in these populations are therefore limited. Objective: To evaluate the immunogenicity of COVID-19 messenger RNA (mRNA) vaccines in pregnant and lactating women, including against emerging SARS-CoV-2 variants of concern. Design, Setting, and Participants: An exploratory, descriptive, prospective cohort study enrolled 103 women who received a COVID-19 vaccine from December 2020 through March 2021 and 28 women who had confirmed SARS-CoV-2 infection from April 2020 through March 2021 (the last follow-up date was March 26, 2021). This study enrolled 30 pregnant, 16 lactating, and 57 neither pregnant nor lactating women who received either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines and 22 pregnant and 6 nonpregnant unvaccinated women with SARS-CoV-2 infection. Main Outcomes and Measures: SARS-CoV-2 receptor binding domain binding, neutralizing, and functional nonneutralizing antibody responses from pregnant, lactating, and nonpregnant women were assessed following vaccination. Spike-specific T-cell responses were evaluated using IFN-gamma enzyme-linked immunospot and multiparameter intracellular cytokine- staining assays. Humoral and cellular immune responses were determined against the original SARS- CoV-2 USA-WA1/2020 strain as well as against the B.1.1.7 and B.1.351 variants. Results: This study enrolled 103 women aged 18 to 45 years (66% non-Hispanic White) who received a COVID-19 mRNA vaccine. After the second vaccine dose, fever was reported in 4 pregnant women (14%; SD, 6%), 7 lactating women (44%; SD, 12%), and 27 nonpregnant women (52%; SD, 7%). Binding, neutralizing, and functional nonneutralizing antibody responses as well as CD4 and CD8 T-cell responses were present in pregnant, lactating, and nonpregnant women following vaccination. Binding and neutralizing antibodies were also observed in infant cord blood and breast milk. Binding and neutralizing antibody titers against the SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern were reduced, but T-cell responses were preserved against viral variants. Conclusion and Relevance: In this exploratory analysis of a convenience sample, receipt of a COVID-19 mRNA vaccine was immunogenic in pregnant women, and vaccine- elicited antibodies were transported to infant cord blood and breast milk. Pregnant and nonpregnant women who were vaccinated developed cross-reactive antibody responses and T-cell responses against SARS-CoV-2 variants of concern. URL: https://www.ncbi.nlm.nih.gov/pubmed/33983379 DOI: 10.1001/jama.2021.7563
38. Cordina M, Lauri MA, Lauri J. Attitudes towards COVID-19 vaccination, vaccine hesitancy and intention to take the vaccine. Pharm Pract (Granada). 2021;19(1):2317. DOI: 10.18549/PharmPract.2021.1.2317 ABSTRACT: Background: The pandemic is at a paradoxical stage, with vaccine roll out initiated but a significantly elevated level of infection and death. Hope for recovery lies in high equitable vaccine uptake. Objective: The study aimed to: i) explore attitudes and factors influencing attitudes, towards the COVID-19 vaccine amongst people living in Malta, ii) identify the reasons as to why individuals are
Evidence Search Report: INF031801v4 ESR 21 unsure or unwilling to take the vaccine. Methods: Two consecutive, short, anonymous online surveys using social media platforms were used to gather data from adult individuals. The first study was open to residents in Malta, while the second study invited international participation. Study 1 consisted of 17 questions inspired by the Theories of Planned Behaviour and Reasoned Action. Study 2 asked participates whether they were willing, unwilling or unsure of taking the vaccine and their reasons for being unsure or unwilling. Results: A total of 2,529 individuals participated in Study 1 and 834 in Study 2. In both studies respondents were predominantly female having a tertiary education. Over 50% declared that they were willing to take the vaccine, with males being more willing (t=5.83, df=1164.2, p<0.00005). Opinions of significant others- family and friends (r=0.22, p<0.005) and health professionals (r=0.74, p<0.005) were associated with willingness to take the vaccine. Vaccine hesitancy was present in the study population with 32.6% being unsure and 15.6% declaring that they were not willing to take the vaccine. Females were more likely to be unsure (Chi-squared=14.63, df=4, p=0.006). Lack of vaccine safety was the main reason cited for unwillingness to take the vaccine. Predictors for willingness to take the vaccine were: i) The belief that the COVID-19 vaccine will protect the health of the people who take it; ii) Valuing the advice of health professionals regarding the effectiveness of COVID-19 vaccine; iii) Having taken the influenza vaccine last year and; iv) Encouraging their elderly parents to take the vaccine. Conclusions: COVID-19 vaccination information campaigns should promote group strategies, focusing on emphasising the safety of the vaccine and offer reassurance, especially to women. URL: https://www.ncbi.nlm.nih.gov/pubmed/33828623 DOI: 10.18549/PharmPract.2021.1.2317
39. Covidsurg Collaborative GC. SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study. Br J Surg. 2021:1-8. DOI: 10.1093/bjs/znab101 ABSTRACT: BACKGROUND: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. METHODS: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. RESULTS: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS- CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. CONCLUSION: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population. URL: https://www.ncbi.nlm.nih.gov/pubmed/33761533 DOI: 10.1093/bjs/znab101
40. Cromer D, Juno JA, Khoury D, et al. Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection. Nat Rev Immunol. 2021;29:29. DOI: 10.1038/s41577-021-00550-x ABSTRACT: Immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is central to long-term control of the current pandemic. Despite our rapidly advancing knowledge of immune memory to SARS-CoV-2, understanding how these responses translate into protection against reinfection at both the individual and population levels remains a major challenge. An ideal outcome
Evidence Search Report: INF031801v4 ESR 22 following infection or after vaccination would be a highly protective and durable immunity that allows for the establishment of high levels of population immunity. However, current studies suggest a decay of neutralizing antibody responses in convalescent patients, and documented cases of SARS-CoV-2 reinfection are increasing. Understanding the dynamics of memory responses to SARS-CoV-2 and the mechanisms of immune control are crucial for the rational design and deployment of vaccines and for understanding the possible future trajectories of the pandemic. Here, we summarize our current understanding of immune responses to and immune control of SARS-CoV-2 and the implications for prevention of reinfection. URL: https://www.ncbi.nlm.nih.gov/pubmed/33927374 DOI: 10.1038/s41577-021-00550-x
41. Cruwys T, Stevens M, Donaldson JL, et al. Perceived COVID-19 risk is attenuated by ingroup trust: evidence from three empirical studies. BMC Public Health. 2021;21(1):869. DOI: 10.1186/s12889-021- 10925-3 ABSTRACT: BACKGROUND: The social identity model of risk taking proposes that people take more risks with ingroup members because they trust them more. While this can be beneficial in some circumstances, in the context of the COVID-19 pandemic it has the potential to undermine an effective public health response if people underestimate the risk of contagion posed by ingroup members, or overestimate the risk of vaccines or treatments developed by outgroup members. METHODS: Three studies (two prospective surveys, one experiment) with community-based adults tested the potential for the social identity model of risk taking to explain risk perception and risk taking in the context of COVID- 19. RESULTS: Study 1 was a two-wave study with a pre-COVID baseline, and found that people who identified more strongly as a member of their neighborhood pre-COVID tended to trust their neighbors more, and perceive interacting with them during COVID-19 lockdown to be less risky. Study 2 (N = 2033) replicated these findings in a two-wave nationally representative Australian sample. Study 3 (N = 216) was a pre-registered experiment which found that people indicated greater willingness to take a vaccine, and perceived it to be less risky, when it was developed by an ingroup compared to an outgroup source. We interpret this as evidence that the tendency to trust ingroup members more could be harnessed to enhance the COVID-19 response. CONCLUSIONS: Across all three studies, ingroup members were trusted more and were perceived to pose less health risk. These findings are discussed with a focus on how group processes can be more effectively incorporated into public health policy, both for the current pandemic and for future contagious disease threats. URL: https://www.ncbi.nlm.nih.gov/pubmed/33952235 DOI: 10.1186/s12889-021-10925-3
42. Dages KN, Pitlick MM, Joshi AY, et al. Risk of allergic reaction in patients with atopic disease and recent COVID-19 vaccination. Ann Allergy Asthma Immunol. 2021;04:04. DOI: 10.1016/j.anai.2021.04.024 URL: https://www.ncbi.nlm.nih.gov/pubmed/33962029 DOI: 10.1016/j.anai.2021.04.024
43. D'Agostino V, Caranci F, Negro A, et al. A Rare Case of Cerebral Venous Thrombosis and Disseminated Intravascular Coagulation Temporally Associated to the COVID-19 Vaccine Administration. J Pers Med. 2021;11(4):08. DOI: 10.3390/jpm11040285 ABSTRACT: Globally, at the time of writing (20 March 2021), 121.759.109 confirmed COVID-19 cases have been reported to the WHO, including 2.690.731 deaths. Globally, on 18 March 2021, a total of 364.184.603 vaccine doses have been administered. In Italy, 3.306.711 confirmed COVID-19 cases with 103.855 deaths have been reported to WHO. In Italy, on 9 March 2021, a total of 6.634.450 vaccine
Evidence Search Report: INF031801v4 ESR 23 doses have been administered. On 15 March 2021, Italian Medicines Agency (AIFA) decided to temporarily suspend the use of the AstraZeneca COVID-19 vaccine throughout the country as a precaution, pending the rulings of the European Medicines Agency (EMA). This decision was taken in line with similar measures adopted by other European countries due to the death of vaccinated people. On 18 March 2021, EMA's safety committee concluded its preliminary review about thromboembolic events in people vaccinated with COVID-19 Vaccine AstraZeneca at its extraordinary meeting, confirming the benefits of the vaccine continue to outweigh the risk of side effects, however, the vaccine may be associated with very rare cases of blood clots associated with thrombocytopenia, i.e., low levels of blood platelets with or without bleeding, including rare cases of cerebral venous thrombosis (CVT). We report the case of a 54-year-old woman who developed disseminated intravascular coagulation (DIC) with multi-district thrombosis 12 days after the AstraZeneca COVID-19 vaccine administration. A brain computed tomography (CT) scan showed multiple subacute intra-axial hemorrhages in atypical locations, including the right frontal and the temporal lobes. A plain old balloon angioplasty (POBA) of the right coronary artery was performed, without stent implantation, with restoration of distal flow, but with persistence of extensive thrombosis of the vessel. A successive thorax angio-CT added the findings of multiple contrast filling defects with multi-vessel involvement: at the level of the left upper lobe segmental branches, of left interlobar artery, of the right middle lobe segmental branches and of the right interlobar artery. A brain magnetic resonance imaging (MRI) in the same day showed the presence of an acute basilar thrombosis associated with the superior sagittal sinus thrombosis. An abdomen angio-CT showed filling defects at the level of left portal branch and at the level of right suprahepatic vein. Bilaterally, it was adrenal hemorrhage and blood in the pelvis. An evaluation of coagulation factors did not show genetic alterations so as the nasopharyngeal swab ruled out a COVID-19 infection. The patient died after 5 days of hospitalization in intensive care. URL: https://www.ncbi.nlm.nih.gov/pubmed/33917902 DOI: 10.3390/jpm11040285
44. Dal-Re R, Orenstein W, Caplan AL. Being fair to participants in placebo-controlled COVID-19 vaccine trials. Nat Med. 2021. DOI: 10.1038/s41591-021-01338-1 URL: https://www.ncbi.nlm.nih.gov/pubmed/33903751 DOI: 10.1038/s41591-021-01338-1
45. De Miguel Beriain I, Rueda J. Vaccination certificates, immunity passports, and test-based travel licences: ethical, legal, and public health issues. Travel Med Infect Dis. 2021:102079. DOI: 10.1016/j.tmaid.2021.102079 URL: https://www.ncbi.nlm.nih.gov/pubmed/33971334 DOI: 10.1016/j.tmaid.2021.102079
46. Dosanjh A. Pediatric Vaccine Hesitancy and the Utilization of Antibody Measurements: A Novel Strategy with Implications for COVID 19. J Asthma Allergy. 2021;14:427-31. DOI: 10.2147/JAA.S303309 ABSTRACT: Vaccine hesitancy is a well researched area with implications for both public health and the health of children and their families The factors leading to vaccine hesitancy are often complex and involve fear of the healthcare system and the process of vaccine development, cultural viewpoints and experiences. Pediatric patients often rely on parental guidance and decision making, and this may result in a lack of immunization for some children. The availability of the COVID 19 vaccine has been widely anticipated, yet not all individuals will seek the vaccine. Once vaccines are available for children under the age of 16 years, this long-standing pediatric management issue may again emerge and impact public health. The clinical trial efficacy and safety data for children and adolescents less than 16 years of age are not yet available. A traditional approach is to discuss the concerns of the parent in relationship to
Evidence Search Report: INF031801v4 ESR 24 presentation and review of American Association of Pediatrics (AAP) and CDC guidelines in the framework of medical and scientific explanations. This includes the presentation of efficacy and safety data. Therefore, the use of lab-based antibody testing adds scientific evidence and emphasizes the need for vaccination against SARS CoV-2 and other pathogens. The purpose of this commentary is to propose lab-based testing as a potential adjunctive strategy in addressing this public health concern. Further study of a pediatric population is required to assess the impact of the selective use of lab-based testing in improving vaccination rates among a pediatric population. URL: https://www.ncbi.nlm.nih.gov/pubmed/33935504 DOI: 10.2147/JAA.S303309
47. DuPre NC, Karimi S, Zhang CH, et al. County-level demographic, social, economic, and lifestyle correlates of COVID-19 infection and death trajectories during the first wave of the pandemic in the United States. Sci Total Environ. 2021;786:147495. DOI: 10.1016/j.scitotenv.2021.147495 ABSTRACT: BACKGROUND: The US COVID-19 epidemic impacted counties differently across space and time, though large-scale transmission dynamics are unclear. The study's objective was to group counties with similar trajectories of COVID-19 cases and deaths and identify county-level correlates of the distinct trajectory groups. METHODS: Daily COVID-19 cases and deaths were obtained from 3141 US counties from January through June 2020. Clusters of epidemic curve trajectories of COVID-19 cases and deaths per 100,000 people were identified with Proc Traj. We utilized polytomous logistic regression to estimate Odds Ratios for trajectory group membership in relation to county-level demographics, socioeconomic factors, school enrollment, employment and lifestyle data. RESULTS: Six COVID-19 case trajectory groups and five death trajectory groups were identified. Younger counties, counties with a greater proportion of females, Black and Hispanic populations, and greater employment in private sectors had higher odds of being in worse case and death trajectories. Percentage of counties enrolled in grades 1-8 was associated with earlier-start case trajectories. Counties with more educated adult populations had lower odds of being in worse case trajectories but were generally not associated with worse death trajectories. Counties with higher poverty rates, higher uninsured, and more living in non- family households had lower odds of being in worse case and death trajectories. Counties with higher smoking rates had higher odds of being in worse death trajectory counties. DISCUSSION: In the absence of clear guidelines and personal protection, smoking, racial and ethnic groups, younger populations, social, and economic factors were correlated with worse COVID-19 epidemics that may reflect population transmission dynamics during January-June 2020. After vaccination of high-risk individuals, communities with higher proportions of youth, communities of color, smokers, and workers in healthcare, service and goods industries can reduce viral spread by targeting vaccination programs to these populations and increasing access and education on non-pharmaceutical interventions. URL: https://www.ncbi.nlm.nih.gov/pubmed/33971599 DOI: 10.1016/j.scitotenv.2021.147495
48. Dzieciolowska S, Hamel D, Gadio S, et al. Covid-19 Vaccine Acceptance, Hesitancy and Refusal among Canadian Healthcare Workers: a Multicenter Survey. Am J Infect Control. 2021;27:27. DOI: 10.1016/j.ajic.2021.04.079 ABSTRACT: BACKGROUND: Determinants of COVID-19 vaccine acceptance among healthcare workers (HCW) remains poorly understood. We assessed HCWs' willingness to be vaccinated and reasons underlying hesitancy. METHODS: Cross-sectional survey across 17 healthcare institutions. HCWs eligible for vaccination (Pfizer-BioNTech mRNA) in December 2020 were invited to receive immunization. Multivariate logistic regression was performed to identify predictors of acceptance. Reasons for refusal among those who never intended to be vaccinated (i.e. firm refusers) and those who preferred delaying vaccination (i.e. vaccine hesitants) were assessed. RESULTS: Among 2761 respondents (72% female,
Evidence Search Report: INF031801v4 ESR 25 average age, 44), 2233 (80.9%) accepted the vaccine. Physicians, environmental services workers and healthcare managers were more likely to accept vaccination compared to nurses. Male sex, age over 50, rehabilitation center workers, and occupational COVID-19 exposure were independently associated with vaccine acceptance by multivariate analysis. Factors for refusal included vaccine novelty, wanting others to receive it first, and insufficient time for decision-making. Among those who declined, 74% reported they may accept future vaccination. Vaccine firm refusers were more likely than vaccine hesitants to distrust pharmaceutical companies and to prefer developing a natural immunity by getting COVID-19. CONCLUSIONS: Vaccine hesitancy exists among HCWs. Our findings provide useful information to plan future interventions and improve acceptance. URL: https://www.ncbi.nlm.nih.gov/pubmed/33930516 DOI: 10.1016/j.ajic.2021.04.079
49. Eibensteiner F, Ritschl V, Nawaz FA, et al. People's Willingness to Vaccinate Against COVID-19 Despite Their Safety Concerns: Twitter Poll Analysis. J Med Internet Res. 2021;23(4):e28973. DOI: 10.2196/28973 ABSTRACT: BACKGROUND: On January 30, 2020, the World Health Organization's Emergency Committee declared the rapid, worldwide spread of COVID-19 a global health emergency. Since then, tireless efforts have been made to mitigate the spread of the disease and its impact, and these efforts have mostly relied on nonpharmaceutical interventions. By December 2020, the safety and efficacy of the first COVID-19 vaccines were demonstrated. The large social media platform Twitter has been used by medical researchers for the analysis of important public health topics, such as the public's perception on antibiotic use and misuse and human papillomavirus vaccination. The analysis of Twitter-generated data can be further facilitated by using Twitter's built-in, anonymous polling tool to gain insight into public health issues and obtain rapid feedback on an international scale. During the fast-paced course of the COVID-19 pandemic, the Twitter polling system has provided a viable method for gaining rapid, large-scale, international public health insights on highly relevant and timely SARS-CoV-2-related topics. OBJECTIVE: The purpose of this study was to understand the public's perception on the safety and acceptance of COVID-19 vaccines in real time by using Twitter polls. METHODS: We developed 2 Twitter polls to explore the public's views on available COVID-19 vaccines. The surveys were pinned to the Digital Health and Patient Safety Platform Twitter timeline for 1 week in mid-February 2021, and Twitter users and influencers were asked to participate in and retweet the polls to reach the largest possible audience. RESULTS: The adequacy of COVID-19 vaccine safety (ie, the safety of currently available vaccines; poll 1) was agreed upon by 1579 out of 3439 (45.9%) Twitter users. In contrast, almost as many Twitter users (1434/3439, 41.7%) were unsure about the safety of COVID-19 vaccines. Only 5.2% (179/3439) of Twitter users rated the available COVID-19 vaccines as generally unsafe. Poll 2, which addressed the question of whether users would undergo vaccination, was answered affirmatively by 82.8% (2862/3457) of Twitter users, and only 8% (277/3457) categorically rejected vaccination at the time of polling. CONCLUSIONS: In contrast to the perceived high level of uncertainty about the safety of the available COVID-19 vaccines, we observed an elevated willingness to undergo vaccination among our study sample. Since people's perceptions and views are strongly influenced by social media, the snapshots provided by these media platforms represent a static image of a moving target. Thus, the results of this study need to be followed up by long-term surveys to maintain their validity. This is especially relevant due to the circumstances of the fast-paced pandemic and the need to not miss sudden rises in the incidence of vaccine hesitancy, which may have detrimental effects on the pandemic's course. URL: https://www.ncbi.nlm.nih.gov/pubmed/33872185 DOI: 10.2196/28973
Evidence Search Report: INF031801v4 ESR 26 50. Elalamy I, Gerotziafas G, Alamowitch S, et al. SARS-CoV-2 vaccine and thrombosis: Expert opinions. Thromb Haemost. 2021;04:04. DOI: 10.1055/a-1499-0119 ABSTRACT: Historically, the vaccination strategies developed in the second half of the 20th century have permitted to eradicate infectious diseases. From the onset of COVID-19 pandemic to March 2021, more than 141 million cases and 3 million deaths were documented worldwide with disruption of the economic and social activity, devastating material, physical and psychological consequences. Reports of unusual and severe thrombotic events, including cerebral and splanchnic venous thrombosis and other autoimmune adverse reactions such as immune thrombocytopenia or thrombotic microangiopathies (TMA) in connection with some of the SARS-CoV-2 vaccine have caused a great deal of concern within the population and the medical community. This report is intended to provide practical answers following an overview of our knowledge on these thrombotic events that are extremely rare but have serious consequences. Vaccine hesitancy threatens to reverse the progress made in controlling vaccine- preventable diseases. These adverse events must be put into perspective with an objective analysis of the facts and the issues of the vaccination strategy during this SARS-Cov-2 pandemic. Healthcare professionals remain the most pertinent advisors and influencers regarding vaccination decisions; they have to be supported in order to provide reliable and credible information on vaccines. We need to inform, reassure and support our patients when the prescription is made. Facing these challenges and these observations, a panel of experts express their insights and propose a tracking algorithm for vaccinated patients based on a10-point guideline for decision-making on what to do and not to do. URL: https://www.ncbi.nlm.nih.gov/pubmed/33946120 DOI: 10.1055/a-1499-0119
51. El-Nakeep S. To vaccinate or not to vaccinate; that is the question! (New insights on COVID-19 Vaccination). Curr Mol Med. 2021;11:11. DOI: 10.2174/1566524021666210512012315 ABSTRACT: AIM: This is a mini-review of the literature; to discuss the obstacles and benefits of vaccination in the era of current pandemic, either the COVID-19 vaccines, which are on their way to be released or the influenza vaccines. There is much debate concerning their effectiveness on ameliorating the severity of the COVID-19 pandemic. METHODOLOGY: Searching the literature till November 2020 in the PubMed database. RESULTS: Pathophysiology behind the COVID-19 vaccination obstacles is discussed in detail with future hopes. Influenza vaccination during the debate of the pandemic is also discussed with the most recent guidelines. CONCLUSIONS: During the COVID-19 pandemic, influenza vaccination is mandatory for all individuals provided no contraindications. Three SARS-CoV-2 vaccines are being released , while FDA approval for monoclonal antibodies for the treatment of at-risk outpatients to lower hospitalization rates is ongoing. URL: https://www.ncbi.nlm.nih.gov/pubmed/33982651 DOI: 10.2174/1566524021666210512012315
52. Emanuel EJ, Boyle CW. Assessment of Length and Readability of Informed Consent Documents for COVID-19 Vaccine Trials. JAMA Netw Open. 2021;4(4):e2110843. DOI: 10.1001/jamanetworkopen.2021.10843 ABSTRACT: Importance: Informed consent is a fundamental element of research ethics. The COVID-19 vaccine trials are high profile trials that have enrolled more than 100000 participants. Consent documents must be succinct and understandable to ensure informed voluntary participation. Objective: To assess how well informed consent documents of the COVID-19 vaccine trials achieve the ideal of being succinct and understandable, and to create a shorter, more readable document. Design, Setting, and Participants: This quality improvement study collected and analyzed the informed consent documents used in 4 COVID-19 vaccine phase III randomized clinical trials to quantitatively assess readability and length and, based on this analysis, created a measurably more accessible informed
Evidence Search Report: INF031801v4 ESR 27 consent document. Analysis was conducted from October 2020 to January 2021. Main Outcomes and Measures: The main outcomes were number of words (measured as word count), time-to-read (measured at reading speeds of 175-300 words per minute), language complexity (measured using Flesch-Kincaid Grade Level assessment), and readability (measured using Flesch Reading Ease Score). Secondary outcomes included clarity of how the placebo group could access the vaccine if it is proven safe and effective. The study also examined the length and readability of an improved consent document. Results: The 4 informed consent documents were a mean (range) of 8333 (7821 to 9340) words long, with a mean (range) 35 (32.6 to 38.9) minutes to read at 240 words per minute. All documents exceeded grade 9 language complexity and scored lower than 60 in the formal reading ease metric, which constitutes difficult. Only 1 document specified that participants in the placebo group might receive vaccine. It was possible to write a document in fewer than 3000 words with a grade 7 to 8 reading level and a formal readability score that was not difficult. Conclusions and Relevance: These findings suggest that existing COVID-19 vaccine informed consent documents were too long, difficult to read, and exceeded grade 9 in language complexity. It was possible to create a shorter, more readable informed consent document for these trials. URL: https://www.ncbi.nlm.nih.gov/pubmed/33909052 DOI: 10.1001/jamanetworkopen.2021.10843
53. Erdeljic Turk V. Anaphylaxis associated with the mRNA COVID-19 vaccines: Approach to allergy investigation. Clin Immunol. 2021;227:108748. DOI: 10.1016/j.clim.2021.108748 ABSTRACT: Reports about cases of anaphylaxis to mRNA vaccines have created anxiety in the community and could increase vaccine hesitancy in the population. There are no standardized protocols for allergy testing to mRNA vaccines. PEG is currently the only excipient in both vaccines with recognized allergenic potential. Allergy to PEG has been reported with increasing frequency over recent years, often in patients who had repeated systemic allergic reactions/anaphylaxis to several classes of drugs before diagnosis. Proposed protocols are based on current knowledge about potential mechanisms of anaphylaxis associated with the mRNA vaccines, and the assumption that polyethylene glycol (PEG) is the most likely culprit. Allergy testing to PEGs and mRNA vaccines is complex and carries the risk of anaphylaxis and should be conducted in a specialist drug allergy center. Appropriate PEG-free emergency medical treatment and supervision should be readily available. URL: https://www.ncbi.nlm.nih.gov/pubmed/33932618 DOI: 10.1016/j.clim.2021.108748
54. Evans WD, French J. Demand Creation for COVID-19 Vaccination: Overcoming Vaccine Hesitancy through Social Marketing. Vaccines (Basel). 2021;9(4):01. DOI: 10.3390/vaccines9040319 ABSTRACT: The COVID-19 pandemic has led to millions of deaths and tested the capabilities of the medical and public health systems worldwide. Over the next two years as more approved vaccines are made available and supply meets or exceeds demand, medical and public health professionals will increasingly be faced with the challenge of vaccine hesitancy. There is an urgent need to create demand in groups that are either uninformed, vaccine hesitant, or actively resistant to COVID-19 vaccination. This study reviews theory, evidence, and practice recommendations to develop a vaccine demand creation strategy that has wide applicability. Specifically, we focus on key elements including supply side confidence, vaccine brand promotion strategy, service marketing as it relates to vaccine distribution, and competition strategy. We present evidence that these strategies can make a significant contribution to overcoming COVID-19 hesitancy in a high supply scenario. The paper also makes recommendations about factors that need to be considered in relation to vaccine delivery services and systems that, if done badly, may reduce uptake or result in the creation of more vaccine hesitancy. In summary, there is
Evidence Search Report: INF031801v4 ESR 28 a need for well researched and tested demand creation strategies that integrate with brand strategy, supply side, and service delivery. URL: https://www.ncbi.nlm.nih.gov/pubmed/33915695 DOI: 10.3390/vaccines9040319
55. Farthing TS, Lanzas C. When can we stop wearing masks? Agent-based modeling to identify when vaccine coverage makes nonpharmaceutical interventions for reducing SARS-CoV-2 infections redundant in indoor gatherings. medRxiv. 2021;27:27. DOI: 10.1101/2021.04.19.21255737 ABSTRACT: As vaccination efforts to combat the COVID-19 pandemic are ramping up worldwide, there are rising concerns that individuals will begin to eschew nonpharmaceutical interventions for preventing SARS-CoV-2 transmission and attempt to return to pre-pandemic normalcy before vaccine coverage levels effectively mitigate transmission risk. In the U.S.A., some governing bodies have already weakened or repealed guidelines for nonpharmaceutical intervention use, despite a recent spike in national COVID-19 cases and majority population of unvaccinated individuals. Recent modeling suggests that repealing nonpharmaceutical intervention guidelines too early into vaccine rollouts will lead to localized increases in COVID-19 cases, but the magnitude of nonpharmaceutical intervention effects on individual-level SARS-CoV-2 infection risk in fully- and partially-vaccinated populations is unclear. We use a previously-published agent-based model to simulate SARS-CoV-2 transmission in indoor gatherings of varying durations, population densities, and vaccination coverage levels. By simulating nonpharmaceutical interventions in some gatherings but not others, we were able to quantify the difference in SARS-CoV-2 infection risk when nonpharmaceutical interventions were used, relative to scenarios with no nonpharmaceutical interventions. We found that nonpharmaceutical interventions will often reduce secondary attack rates, especially during brief interactions, and therefore there is no definitive vaccination coverage level that makes nonpharmaceutical interventions completely redundant. However, the reduction effect on absolute SARS-CoV-2 infection risk conferred by nonpharmaceutical interventions is likely proportional to COVID-19 prevalence. Therefore, if COVID-19 prevalence decreases in the future, nonpharmaceutical interventions will likely still confer protective effects but potential benefits may be small enough to remain within "effectively negligible" risk thresholds. URL: https://www.ncbi.nlm.nih.gov/pubmed/33948613 DOI: 10.1101/2021.04.19.21255737
56. Fernandez-Prada M, Garcia-Gonzalez P, Garcia-Moran A, et al. Personal and vaccination history as factors associated with SARS-CoV-2 infection. Med Clin (Barc). 2021;19:19. DOI: 10.1016/j.medcli.2021.02.011 ABSTRACT: BACKGROUND AND OBJECTIVE: SARS-CoV-2 has been and is a major global Public Health challenge. Since the beginning of the pandemic, different comorbidities have been postulated and associated with spectra of increased severity and mortality. The objectives of this research are: 1) to analyse the factors associated with SARS-CoV-2 infection (COVID-19) in a health area in northern Spain; 2) to understand the possible role of influenza vaccination and pneumococcal vaccination in the development of COVID-19. MATERIALS AND METHOD: A test-negative case-control study was conducted. Variables related to personal and vaccination history were considered. Although the epidemiological definition of the case varied over time, the reference definition was that corresponding to 31/01/2020 in Spain. A bivariate and multivariate analysis was performed. RESULTS: The sample included 188 patients, of which 63 were cases and 125 controls. The results show that obesity increases the risk 2.4-fold of suffering this infection (IC 95% 1,301-4,521) and ARA-2 increases it 2.2-fold (95% CI 1,256-6,982). On the other hand, anti-pneumococcal vaccination of 13 serotypes showed results close to statistical significance (OR = 0.4; 95% CI 0.170-1,006). CONCLUSION: Obesity and the use of ARA-2
Evidence Search Report: INF031801v4 ESR 29 increases the risk of COVID-19. Scientific knowledge about factors associated with COVID-19 should be expanded. The authors consider that the present research raises the need further investigate the role of vaccines in this infection and their possible heterologous properties. URL: https://www.ncbi.nlm.nih.gov/pubmed/33966881 DOI: 10.1016/j.medcli.2021.02.011
57. Ferorelli D, Spagnolo L, Marrone M, et al. Off-Label Use of COVID-19 Vaccines from Ethical Issues to Medico-Legal Aspects: An Italian Perspective. Vaccines (Basel). 2021;9(5):23. DOI: 10.3390/vaccines9050423 ABSTRACT: During the COVID-19 outbreak, the lack of official recommendations on the treatment has led healthcare workers to use multiple drugs not specifically tested and approved for the new insidious disease. After the availability of the first COVID-19 vaccines (Comirnaty Pfizer-BioNTech and Moderna COVID19 vaccine), an authorization was issued by national and international Drug Regulatory Agencies in order to speed up their introduction on the market and their administration on a large scale. Despite the authorization, the off-label use of these vaccines may still be possible especially to answer specific concerns as the lack of vaccine doses, the delay in the delivery of planned doses or the pressure from public opinion and political influence also in relation to the evolution of the pandemic. This paper aims to assess the possible off-label use of COVID-19 vaccines and the ethical and medico-legal implications of this eventuality. The scope of this paper is to point out the possible consequences of off-label use of COVID-19 vaccines and possible mitigation and preventive measures to be taken by healthcare workers involved in vaccination procedures. URL: https://www.ncbi.nlm.nih.gov/pubmed/33922415 DOI: 10.3390/vaccines9050423
58. Ferranna M, Cadarette D, Bloom DE. COVID-19 Vaccine Allocation: Modeling Health Outcomes and Equity Implications of Alternative Strategies. Engineering (Beijing). 2021;03:03. DOI: 10.1016/j.eng.2021.03.014 ABSTRACT: Given the scarcity of safe and effective COVID-19 vaccines, a chief policy question is how to allocate them among different sociodemographic groups. This paper evaluates COVID-19 vaccine prioritization strategies proposed to date, focusing on their stated goals; the mechanisms through which the selected allocations affect the course and burden of the pandemic; and the main epidemiological, economic, logistical, and political issues that arise when setting the prioritization strategy. The paper uses a simple, age-stratified susceptible-exposed-infectious-recovered model to quantitatively assess the performance of alternative prioritization strategies with respect to avoided deaths, avoided infections, and life-years gained. We demonstrate that prioritizing essential workers is a viable strategy for reducing the number of cases and years of life lost, while the largest reduction in deaths is achieved by prioritizing older adults in most scenarios, even if the vaccine is effective at blocking viral transmission. Uncertainty regarding this property and potential delays in dose delivery reinforce the call for prioritizing older adults. Additionally, we investigate the strength of the equity motive that would support an allocation strategy attaching absolute priority to essential workers for a vaccine that reduces infection-fatality risk. URL: https://www.ncbi.nlm.nih.gov/pubmed/33968462 DOI: 10.1016/j.eng.2021.03.014
59. Ferretti F, Cannatelli R, Benucci M, et al. How to Manage COVID-19 Vaccination in Immune- Mediated Inflammatory Diseases: An Expert Opinion by IMIDs Study Group. Front Immunol. 2021;12:656362. DOI: 10.3389/fimmu.2021.656362
Evidence Search Report: INF031801v4 ESR 30 ABSTRACT: Since March 2020, the outbreak of Sars-CoV-2 pandemic has changed medical practice and daily routine around the world. Huge efforts from pharmacological industries have led to the development of COVID-19 vaccines. In particular two mRNA vaccines, namely the BNT162b2 (Pfizer- BioNTech) and the mRNA-1273 (Moderna), and a viral-vectored vaccine, i.e. ChAdOx1 nCoV-19 (AstraZeneca), have recently been approved in Europe. Clinical trials on these vaccines have been published on the general population showing a high efficacy with minor adverse events. However, specific data about the efficacy and safety of these vaccines in patients with immune-mediated inflammatory diseases (IMIDs) are still lacking. Moreover, the limited availability of these vaccines requires prioritizing some vulnerable categories of patients compared to others. In this position paper, we propose the point of view about the management of COVID-19 vaccination from Italian experts on IMIDs and the identification of high-risk groups according to the different diseases and their chronic therapy. URL: https://www.ncbi.nlm.nih.gov/pubmed/33936084 DOI: 10.3389/fimmu.2021.656362
60. Ficarra V, Novara G, Giannarini G, et al. Urology practice during the COVID-19 vaccination campaign. Urologia. 2021:3915603211016321. DOI: 10.1177/03915603211016321 ABSTRACT: INTRODUCTION: The current scenario of the COVID-19 pandemic is significantly different from that of the first, emergency phase. Several countries in the world are experiencing a second, or even a third, wave of contagion, while awaiting the effects of mass vaccination campaigns. The aim of this report was to provide an update of previously released recommendations on prioritization and restructuring of urological activities. METHODS: A large group of Italian urologists directly involved in the reorganization of their urological wards during the first and second phase of the pandemic agreed on a set of updated recommendations for current urology practice. RESULTS: The updated recommendations included strategies for the prioritization of both surgical and outpatient activities, implementation of perioperative pathways for patients scheduled for elective surgery, management of urological conditions in infected patients. Future scenarios with possible implementation of telehealth and reshaping of clinical practice following the effects of vaccination are also discussed. CONCLUSION: The present update may be a valid tool to be used in the clinical practice, may provide useful recommendations for national and international urological societies, and may be a cornerstone for further discussion on the topic, also considering further evolution of the pandemic after the recently initiated mass vaccination campaigns. URL: https://www.ncbi.nlm.nih.gov/pubmed/33983086 DOI: 10.1177/03915603211016321
61. Fintzi J, Follmann D. Assessing vaccine durability in randomized trials following placebo crossover. Stat Med. 2021;29:29. DOI: 10.1002/sim.9001 ABSTRACT: Randomized vaccine trials are used to assess vaccine efficacy (VE) and to characterize the durability of vaccine-induced protection. If efficacy is demonstrated, the treatment of placebo volunteers becomes an issue. For COVID-19 vaccine trials, there is broad consensus that placebo volunteers should be offered a vaccine once efficacy has been established. This will likely lead to most placebo volunteers crossing over to the vaccine arm, thus complicating the assessment of long term durability. We show how to analyze durability following placebo crossover and demonstrate that the VE profile that would be observed in a placebo controlled trial is recoverable in a trial with placebo crossover. This result holds no matter when the crossover occurs and with no assumptions about the form of the efficacy profile. We only require that the VE profile applies to the newly vaccinated irrespective of the timing of vaccination. We develop different methods to estimate efficacy within the context of a proportional hazards regression model and explore via simulation the implications of
Evidence Search Report: INF031801v4 ESR 31 placebo crossover for estimation of VE under different efficacy dynamics and study designs. We apply our methods to simulated COVID-19 vaccine trials with durable and waning VE and a total follow-up of 2 years. URL: https://www.ncbi.nlm.nih.gov/pubmed/33928660 DOI: 10.1002/sim.9001
62. Fouad SH, Allam MF, Ibrahim S, et al. ICU admission of COVID-19 patients: Identification of risk factors. Egyptian Journal of Anaesthesia. 2021;37(1):202-7. DOI: 10.1080/11101849.2021.1919433 ABSTRACT: Background: The WHO has declared COVID-19 as a global pandemic with a rapidly increasing number of patients at a rate exceeding the limits of health-care resources. Some people seem to be at higher risk of worse prognosis and increased mortality. Identifying these vulnerable groups is a necessity. Aim of study: To identify the risk factors associated with ICU admission in COVID-19 patients. Methodology: We present a retrospective study where the clinical data of patients with laboratory- confirmed COVID-19 infection were collected from Ain-Shams University Isolation-Hospital records on admission from 10 April 2020 to 30 July 2020 to identify risk factors in patients requiring ICU admission during hospital stay. Result(s): Of 323 subjects diagnosed by the RT-PCR as positive COVID-19, 62 (19.2%) of which were admitted at the ICU. The mean age of the subjects was 46.6 +/- 16 years. Significant morbidities were associated with higher age groups (p value 0.000), smokers (p value 0.004), Cairo-residents (p value 0.009), being a health-care provider (p value 0.001) and hypertensive patients (p value 0.000). Conclusion(s): Elderly, smokers, diabetic and hypertensive need further attention during disease course. Our results call for further investigations of risk factors for COVID-19 severity; preferably on large prospective cohorts, to increase their validity.Copyright © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. URL: https://www.tandfonline.com/loi/teja20 http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emedx&NEWS=N&AN=2011287621 DOI: 10.1080/11101849.2021.1919433
63. Foulkes S, Saei A, Wellington E, et al. COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study. The Lancet. 2021;397(10286):1725-35. DOI: http://dx.doi.org/10.1016/S0140- 6736%2821%2900790-X ABSTRACT: Background: BNT162b2 mRNA and ChAdOx1 nCOV-19 adenoviral vector vaccines have been rapidly rolled out in the UK from December, 2020. We aimed to determine the factors associated with vaccine coverage for both vaccines and documented the vaccine effectiveness of the BNT162b2 mRNA vaccine in a cohort of health-care workers undergoing regular asymptomatic testing. Method(s): The SIREN study is a prospective cohort study among staff (aged >=18 years) working in publicly-funded hospitals in the UK. Participants were assigned into either the positive cohort (antibody positive or history of infection [indicated by previous positivity of antibody or PCR tests]) or the negative cohort (antibody negative with no previous positive test) at the beginning of the follow-up period. Baseline risk factors were collected at enrolment, symptom status was collected every 2 weeks, and vaccination status was collected through linkage to the National Immunisations Management System and questionnaires. Participants had fortnightly asymptomatic SARS-CoV-2 PCR testing and monthly antibody testing, and all tests (including symptomatic testing) outside SIREN were captured. Data cutoff for this analysis was Feb 5, 2021. The follow-up period was Dec 7, 2020, to Feb 5, 2021. The primary outcomes were vaccinated participants (binary ever vacinated variable; indicated by at least one vaccine dose recorded by at least one of the two vaccination data sources) for the vaccine coverage analysis and SARS-CoV-2 infection confirmed by a PCR test for the vaccine effectiveness analysis. We did a mixed- effect logistic regression analysis to identify factors associated with vaccine coverage. We used a
Evidence Search Report: INF031801v4 ESR 32 piecewise exponential hazard mixed-effects model (shared frailty-type model) using a Poisson distribution to calculate hazard ratios to compare time-to-infection in unvaccinated and vaccinated participants and estimate the impact of the BNT162b2 vaccine on all PCR-positive infections (asymptomatic and symptomatic). This study is registered with ISRCTN, number ISRCTN11041050, and is ongoing. Finding(s): 23 324 participants from 104 sites (all in England) met the inclusion criteria for this analysis and were enrolled. Included participants had a median age of 46.1 years (IQR 36.0-54.1) and 19 692 (84%) were female; 8203 (35%) were assigned to the positive cohort at the start of the analysis period, and 15 121 (65%) assigned to the negative cohort. Total follow-up time was 2 calendar months and 1 106 905 person-days (396 318 vaccinated and 710 587 unvaccinated). Vaccine coverage was 89% on Feb 5, 2021, 94% of whom had BNT162b2 vaccine. Significantly lower coverage was associated with previous infection, gender, age, ethnicity, job role, and Index of Multiple Deprivation score. During follow-up, there were 977 new infections in the unvaccinated cohort, an incidence density of 14 infections per 10 000 person-days; the vaccinated cohort had 71 new infections 21 days or more after their first dose (incidence density of eight infections per 10 000 person-days) and nine infections 7 days after the second dose (incidence density four infections per 10 000 person-days). In the unvaccinated cohort, 543 (56%) participants had typical COVID-19 symptoms and 140 (14%) were asymptomatic on or 14 days before their PCR positive test date, compared with 29 (36%) with typical COVID-19 symptoms and 15 (19%) asymptomatic in the vaccinated cohort. A single dose of BNT162b2 vaccine showed vaccine effectiveness of 70% (95% CI 55-85) 21 days after first dose and 85% (74-96) 7 days after two doses in the study population. Interpretation(s): Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort was vaccinated when the dominant variant in circulation was B1.1.7 and shows effectiveness against this variant. Funding(s): Public Health England, UK Department of Health and Social Care, and the National Institute for Health Research.Copyright © 2021 URL: http://www.journals.elsevier.com/the-lancet/ http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emedx&NEWS=N&AN=2011943377 DOI: http://dx.doi.org/10.1016/S0140-6736%2821%2900790-X
64. Frisch MF, Scott KW, Binagwaho A. An Implementation Research Approach to Re-orient Health Supply Chains Toward an Equity Agenda in the COVID-19 Era. Ann Glob Health. 2021;87(1):42. DOI: 10.5334/aogh.3209 ABSTRACT: The Covid-19 pandemic has exposed critical inequities in global healthcare supply chains and the need for these systems to be analyzed and reoriented with an equity lens. Implementation research methodology can guide the use of evidence-based interventions to re-orient health supply chains towards equity and optimize health outcomes. Using this approach, private and public sector entities can adapt their strategies to focus not just on efficiency and cost savings but ensuring that vulnerable populations have access to essential medications, vaccines, and supplies. Findings can inform regulations that address supply chain inequities at the global level, strengthen existing systems to fill structural gaps at the national level, and address contextual challenges at the subnational level. This methodology can help account for historical practices from prior health initiatives, identify contemporary barriers and facilitators for positive change, and have applicability to the Covid-19 pandemic and ongoing vaccine distribution efforts. An implementation research approach is critical in equipping health supply chains with a path for more resilient and equitable distribution of necessary supplies, vaccines, and delivery of care. URL: https://www.ncbi.nlm.nih.gov/pubmed/33977085 DOI: 10.5334/aogh.3209
Evidence Search Report: INF031801v4 ESR 33 65. Frohman EM, Villemarette-Pittman NR, Rodriguez A, et al. Application of an evidence-based, out- patient treatment strategy for COVID-19: Multidisciplinary medical practice principles to prevent severe disease. J Neurol Sci. 2021;426:117463. DOI: 10.1016/j.jns.2021.117463 ABSTRACT: The COVID-19 pandemic has devastated individuals, families, and institutions throughout the world. Despite the breakneck speed of vaccine development, the human population remains at risk of further devastation. The decision to not become vaccinated, the protracted rollout of available vaccine, vaccine failure, mutational forms of the SARS virus, which may exhibit mounting resistance to our molecular strike at only one form of the viral family, and the rapid ability of the virus(es) to hitch a ride on our global transportation systems, means that we are will likely continue to confront an invisible, yet devastating foe. The enemy targets one of our human physiology's most important and vulnerable life-preserving body tissues, our broncho-alveolar gas exchange apparatus. Notwithstanding the fear and the fury of this microbe's potential to raise existential questions across the entire spectrum of human endeavor, the application of an early treatment intervention initiative may represent a crucial tool in our defensive strategy. This strategy is driven by evidence-based medical practice principles, those not likely to become antiquated, given the molecular diversity and mutational evolution of this very clever "world traveler". URL: https://www.ncbi.nlm.nih.gov/pubmed/33971376 DOI: 10.1016/j.jns.2021.117463
66. Gabarda A, Butterworth SW. Using Best Practices to Address COVID-19 Vaccine Hesitancy: The Case for the Motivational Interviewing Approach. Health Promot Pract. 2021:15248399211016463. DOI: 10.1177/15248399211016463 ABSTRACT: Future control of the coronavirus disease 2019 (COVID-19) pandemic is dependent on the uptake of the COVID-19 vaccine. Many factors have swayed the public's perception of this coronavirus and the new vaccinations, including misinformation, heightened emotions, and the divisive and tumultuous partisan climate. As such, vaccine hesitancy may be more prevalent for the COVID-19 vaccine than others. Healthcare workers are trusted sources of information and have the opportunity to influence an individual's choice to take the vaccine. For those who initially present as unwilling to be vaccinated, trying to persuade them with facts and scare tactics may cause more resistance. By using the communication approach of motivational interviewing, practitioners can support autonomy to reduce defensiveness, use a guiding style to elicit ambivalence and provide information, address personal agency to ensure that their patients understand that their efforts can reduce risk, and evoke a person's own argument for vaccination to decrease vaccine hesitancy. URL: https://www.ncbi.nlm.nih.gov/pubmed/33966471 DOI: 10.1177/15248399211016463
67. Gallagher KME, Leick MB, Larson RC, et al. SARS -CoV-2 T-cell immunity to variants of concern following vaccination. bioRxiv. 2021;03:03. DOI: 10.1101/2021.05.03.442455 ABSTRACT: Recently, two mRNA vaccines to severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) have become available, but there is also an emergence of SARS-CoV-2 variants with increased transmissibility and virulence (1-6) . A major concern is whether the available vaccines will be equally effective against these variants. The vaccines are designed to induce an immune response against the SARS-CoV-2 spike protein (7, 8) , which is required for viral entry to host cells (9) . Immunity to SARS- CoV-2 is often evaluated by antibody production, while less is known about the T-cell response. Here we developed, characterized, and implemented two standardized, functional assays to measure T-cell immunity to SARS-CoV-2 in uninfected, convalescent, and vaccinated individuals. We found that vaccinated individuals had robust T-cell responses to the wild type spike and nucleocapsid proteins, even more so than convalescent patients. We also found detectable but diminished T-cell responses to
Evidence Search Report: INF031801v4 ESR 34 spike variants (B.1.1.7, B.1.351, and B.1.1.248) among vaccinated but otherwise healthy donors. Since decreases in antibody neutralization have also been observed with some variants (10-12) , investigation into the T-cell response to these variants as an alternative means of viral control is imperative. Standardized measurements of T-cell responses to SARS-CoV-2 are feasible and can be easily adjusted to determine changes in response to variants. URL: https://www.ncbi.nlm.nih.gov/pubmed/33972942 DOI: 10.1101/2021.05.03.442455
68. Garcia P, Montez-Rath ME, Moore H, et al. SARS-CoV-2 Vaccine Acceptability in Patients on Hemodialysis: A Nationwide Survey. J Am Soc Nephrol. 2021;29:29. DOI: 10.1681/ASN.2021010104 ABSTRACT: BACKGROUND: Patients on dialysis are at increased risk for COVID-19-related complications. However, a substantial fraction of patients on dialysis belong to groups more likely to be hesitant about vaccination. METHODS: With the goal of identifying strategies to increase COVID-19 vaccine uptake among patients on hemodialysis, we conducted a nationwide vaccine acceptability survey, partnering with a dialysis network to distribute an anonymized English and Spanish language online survey in 150 randomly selected facilities in the United States. We used logistic regression to evaluate characteristics of vaccine-hesitant persons. RESULTS: A total of 1515 (14% of eligible) patients responded; 20% of all responders, 29% of patients aged 18-44 years, and 29% of Black responders reported being hesitant to seek the COVID-19 vaccine, even if the vaccine was considered safe for the general population. Odds of vaccine hesitancy were higher among patients aged 18-44 years versus those 45-64 years (odds ratio [OR], 1.5; 95% confidence interval [95% CI], 1.0 to 2.3), Black patients versus non-Hispanic White patients (OR, 1.9; 95% CI, 1.3 to 2.7), Native Americans or Pacific Islanders versus non-Hispanic White patients (OR, 2.0; 95% CI, 1.1 to 3.7), and women versus men (OR, 1.6; 95% CI, 1.2 to 2.0). About half (53%) of patients who were vaccine hesitant expressed concerns about side effects. Responders' main information sources about COVID-19 vaccines were television news and dialysis staff (68% and 38%, respectively). CONCLUSIONS: A substantial proportion of patients receiving in-center hemodialysis in the United States are hesitant about seeking COVID-19 vaccination. Facilitating uptake requires outreach to younger patients, women, and Black, Native American, or Pacific Islander patients, and addressing concerns about side effects. URL: https://www.ncbi.nlm.nih.gov/pubmed/33927004 DOI: 10.1681/ASN.2021010104
69. Garvey MI, McMurray C, Casey AL, et al. Observations of SARS-CoV-2 variant of concern B.1.1.7 at the UK's largest hospital Trust. J Infect. 2021. DOI: 10.1016/j.jinf.2021.04.026 URL: https://www.ncbi.nlm.nih.gov/pubmed/33932449 DOI: 10.1016/j.jinf.2021.04.026
70. Goncu Ayhan S, Oluklu D, Atalay A, et al. COVID-19 vaccine acceptance in pregnant women. Int J Gynaecol Obstet. 2021. DOI: 10.1002/ijgo.13713 ABSTRACT: OBJECTIVE: To determine vaccine acceptance and hesitancy attitudes toward coronavirus disease 2019 (COVID-19) vaccines in pregnant women. METHODS: Three hundred pregnant women were surveyed face to face with 40 questions. Sociodemographic characteristics, vaccination history, perception of risk for the COVID-19 pandemic, the impact of the COVID-19 pandemic, and acceptance of and attitude toward future COVID-19 vaccination were prospectively evaluated. RESULTS: Among all participants, 111 (37%) stated their intent to receive the vaccine if it were recommended for pregnant women. Most common refusal reasons were lack of data about COVID-19 vaccine safety in pregnant populations and possibility of harm to the fetus. There was a weak positive correlation between COVID- 19 vaccine acceptancy and number of school-age children. Pregnant women in the first trimester
Evidence Search Report: INF031801v4 ESR 35 expressed higher acceptance of COVID-19 vaccination than those in the second and third trimesters. CONCLUSION: The present study reported low acceptance of COVID-19 vaccination in a sample of pregnant women. Concern about vaccine safety was the major reason for hesitancy. Identifying attitudes among priority groups will be useful for creating vaccination strategies that increase uptake during the current pandemic. URL: https://www.ncbi.nlm.nih.gov/pubmed/33872386 DOI: 10.1002/ijgo.13713
71. Gregory N. Pharmacy leadership, expertise imperative for successful COVID-19 vaccine rollout. Am J Health Syst Pharm. 2021;06:06. DOI: 10.1093/ajhp/zxab187 URL: https://www.ncbi.nlm.nih.gov/pubmed/33955454 DOI: 10.1093/ajhp/zxab187
72. Haas EJ, Angulo FJ, McLaughlin JM, et al. Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data. Lancet. 2021;05:05. DOI: 10.1016/S0140-6736(21)00947-8 ABSTRACT: BACKGROUND: Following the emergency use authorisation of the Pfizer-BioNTech mRNA COVID-19 vaccine BNT162b2 (international non-proprietary name tozinameran) in Israel, the Ministry of Health (MoH) launched a campaign to immunise the 6.5 million residents of Israel aged 16 years and older. We estimated the real-world effectiveness of two doses of BNT162b2 against a range of SARS- CoV-2 outcomes and to evaluate the nationwide public-health impact following the widespread introduction of the vaccine. METHODS: We used national surveillance data from the first 4 months of the nationwide vaccination campaign to ascertain incident cases of laboratory-confirmed SARS-CoV-2 infections and outcomes, as well as vaccine uptake in residents of Israel aged 16 years and older. Vaccine effectiveness against SARS-CoV-2 outcomes (asymptomatic infection, symptomatic infection, and COVID-19-related hospitalisation, severe or critical hospitalisation, and death) was calculated on the basis of incidence rates in fully vaccinated individuals (defined as those for whom 7 days had passed since receiving the second dose of vaccine) compared with rates in unvaccinated individuals (who had not received any doses of the vaccine), with use of a negative binomial regression model adjusted for age group (16-24, 25-34, 35-44, 45-54, 55-64, 65-74, 75-84, and >/=85 years), sex, and calendar week. The proportion of spike gene target failures on PCR test among a nationwide convenience-sample of SARS-CoV-2-positive specimens was used to estimate the prevelance of the B.1.1.7 variant. FINDINGS: During the analysis period (Jan 24 to April 3, 2021), there were 232 268 SARS-CoV-2 infections, 7694 COVID-19 hospitalisations, 4481 severe or critical COVID-19 hospitalisations, and 1113 COVID-19 deaths in people aged 16 years or older. By April 3, 2021, 4 714 932 (72.1%) of 6 538 911 people aged 16 years and older were fully vaccinated with two doses of BNT162b2. Adjusted estimates of vaccine effectiveness at 7 days or longer after the second dose were 95.3% (95% CI 94.9-95.7; incidence rate 91.5 per 100 000 person-days in unvaccinated vs 3.1 per 100 000 person-days in fully vaccinated individuals) against SARS-CoV-2 infection, 91.5% (90.7-92.2; 40.9 vs 1.8 per 100 000 person-days) against asymptomatic SARS-CoV-2 infection, 97.0% (96.7-97.2; 32.5 vs 0.8 per 100 000 person-days) against symptomatic COVID-19, 97.2% (96.8-97.5; 4.6 vs 0.3 per 100 000 person-days) against COVID-19-related hospitalisation, 97.5% (97.1-97.8; 2.7 vs 0.2 per 100 000 person-days) against severe or critical COVID- 19-related hospitalisation, and 96.7% (96.0-97.3; 0.6 vs 0.1 per 100 000 person-days) against COVID-19- related death. In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined. 8006 of 8472 samples tested showed a spike gene target failure, giving an estimated prevalence of the B.1.1.7 variant of 94.5% among SARS-CoV-2 infections. INTERPRETATION: Two doses of BNT162b2 are highly effective across all age groups (>/=16 years, including older adults aged >/=85
Evidence Search Report: INF031801v4 ESR 36 years) in preventing symptomatic and asymptomatic SARS-CoV-2 infections and COVID-19-related hospitalisations, severe disease, and death, including those caused by the B.1.1.7 SARS-CoV-2 variant. There were marked and sustained declines in SARS-CoV-2 incidence corresponding to increasing vaccine coverage. These findings suggest that COVID-19 vaccination can help to control the pandemic. FUNDING: None. URL: https://www.ncbi.nlm.nih.gov/pubmed/33964222 DOI: 10.1016/S0140-6736(21)00947-8
73. Hadjiargyrou M. What Do COVID-19 Vaccines Tell Us About Nucleic Acid Delivery In Vivo? Nucleic Acid Ther. 2021;06:06. DOI: 10.1089/nat.2021.0013 ABSTRACT: The utilization of the RNA-based Pfizer-BioNTech and Moderna coronavirus disease 2019 (COVID-19) vaccines represents the culmination of many years of nonviral nucleic acid delivery, but more importantly, they signify a massive clinical "experiment." Scientists working in the area of nucleic acid delivery using lipid nanoparticles will undoubtedly be energized by the success of these vaccines and begin to collect much needed data in the realm of nonviral-based RNA delivery, specifically, the use of lipid nanoparticles, the immune response, safety, and efficacy. It is easily conceivable that in the future we can utilize these data to streamline our approach for the delivery of genes or microRNA mimics or antigomers for gene therapy and therapeutic and regenerative medicine (ie, wound repair) applications, respectively. URL: https://www.ncbi.nlm.nih.gov/pubmed/33960839 DOI: 10.1089/nat.2021.0013
74. Haghpanah F, Lin G, Levin SA, et al. Analysis of the potential impact of durability, timing, and transmission blocking of COVID-19 vaccine on morbidity and mortality. EClinicalMedicine. 2021;35:100863. DOI: 10.1016/j.eclinm.2021.100863 ABSTRACT: Background: COVID-19 vaccines have been approved and made available. While questions of vaccine allocation strategies have received significant attention, important questions remain regarding the potential impact of the vaccine given uncertainties regarding efficacy against transmission, availability, timing, and durability. Methods: We adapted a susceptible-exposed-infectious-recovered (SEIR) model to examine the potential impact on hospitalization and mortality assuming increasing rates of vaccine efficacy, coverage, and administration. We also evaluated the uncertainty of the vaccine to prevent infectiousness as well as the impact on outcomes based on the timing of distribution and the potential effects of waning immunity. Findings: Increased vaccine efficacy against disease reduces hospitalizations and deaths from COVID-19; however, the relative benefit of transmission blocking varied depending on the timing of vaccine distribution. Early in an outbreak, a vaccine that reduces transmission will be relatively more effective than one introduced later in the outbreak. In addition, earlier and accelerated implementation of a less effective vaccine is more impactful than later implementation of a more effective vaccine. These findings are magnified when considering the durability of the vaccine. Vaccination in the spring will be less impactful when immunity is less durable. Interpretation: Policy choices regarding non-pharmaceutical interventions, such as social distancing and face mask use, will need to remain in place longer if the vaccine is less effective at reducing transmission or distributed slower. In addition, the stage of the local outbreak greatly impacts the overall effectiveness of the vaccine in a region and should be considered when allocating vaccines. Funding: Centers for Disease Control and Prevention (CDC) MInD-Healthcare Program (U01CK000589, 1U01CK000536), James S. McDonnell Foundation 21st Century Science Initiative Collaborative Award in Understanding Dynamic and Multiscale Systems, National Science Foundation (CNS-2027908), National Science Foundation Expeditions (CCF1917819), C3.ai Digital Transformation Institute (AWD1006615), and Google, LLC.
Evidence Search Report: INF031801v4 ESR 37 URL: https://www.ncbi.nlm.nih.gov/pubmed/33937734 DOI: 10.1016/j.eclinm.2021.100863
75. Hakalehto E. Chicken IgY Antibodies Provide Mucosal Barrier against SARS-CoV-2 Virus and Other Pathogens. Isr Med Assoc J. 2021;23(4):208-11. ABSTRACT: BACKGROUND: This mini review includes two case descriptions. It introduces the use of chicken egg yolk antibody (IgY) solutions in the prevention and cure of viral and bacterial infections. Application for the protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), rotavirus, and influenza viruses, as well as for the eradication of Pseudomonas aeruginosa, caries, various enteric bacteria and other pathogens, and toxins have been developed. This approach is a fast, reliable, safe, and tested method for producing molecular shield and protection against emerging pathogens and epidemics. In the current pandemic situation caused by coronavirus disease-2019 (COVID-19), this method of passive immunization could be applied for rapid protection against modifiable agents. The specific IgY antibodies start to accumulate into egg yolks about 3 weeks after the immunization of the chicken. The product can be collected safely, as the antigen is not found in the eggs. This method for microbial safety uses natural means and commonly used food substances, which have been tested and could be produced for both blocking epidemics and applying personalized medicine. URL: https://www.ncbi.nlm.nih.gov/pubmed/33899350
76. Han PKJ, Scharnetzki E, Scherer AM, et al. Communicating Scientific Uncertainty About the COVID- 19 Pandemic: Online Experimental Study of an Uncertainty-Normalizing Strategy. J Med Internet Res. 2021;23(4):e27832. DOI: 10.2196/27832 ABSTRACT: BACKGROUND: Communicating scientific uncertainty about public health threats such as COVID-19 is an ethically desirable task endorsed by expert guidelines on crisis communication. However, the communication of scientific uncertainty is challenging because of its potential to promote ambiguity aversion-a well-described syndrome of negative psychological responses consisting of heightened risk perceptions, emotional distress, and decision avoidance. Communication strategies that can inform the public about scientific uncertainty while mitigating ambiguity aversion are a critical unmet need. OBJECTIVE: This study aimed to evaluate whether an "uncertainty-normalizing" communication strategy-aimed at reinforcing the expected nature of scientific uncertainty about the COVID-19 pandemic-can reduce ambiguity aversion, and to compare its effectiveness to conventional public communication strategies aimed at promoting hope and prosocial values. METHODS: In an online factorial experiment conducted from May to June 2020, a national sample of 1497 US adults read one of five versions of an informational message describing the nature, transmission, prevention, and treatment of COVID-19; the versions varied in level of expressed scientific uncertainty and supplemental focus (ie, uncertainty-normalizing, hope-promoting, and prosocial). Participants then completed measures of cognitive, emotional, and behavioral manifestations of ambiguity aversion (ie, perceived likelihood of getting COVID-19, COVID-19 worry, and intentions for COVID-19 risk-reducing behaviors and vaccination). Analyses assessed (1) the extent to which communicating uncertainty produced ambiguity-averse psychological responses; (2) the comparative effectiveness of uncertainty-normalizing, hope-promoting, and prosocial communication strategies in reducing ambiguity-averse responses; and (3) potential moderators of the effects of alternative uncertainty communication strategies. RESULTS: The communication of scientific uncertainty about the COVID-19 pandemic increased perceived likelihood of getting COVID-19 and worry about COVID-19, consistent with ambiguity aversion. However, it did not affect intentions for risk-reducing behaviors or vaccination. The uncertainty-normalizing strategy reduced these aversive effects of communicating scientific uncertainty, resulting in levels of both perceived likelihood of getting COVID-19 and worry about COVID-19 that did not differ from the
Evidence Search Report: INF031801v4 ESR 38 control message that did not communicate uncertainty. In contrast, the hope-promoting and prosocial strategies did not decrease ambiguity-averse responses to scientific uncertainty. Age and political affiliation, respectively, moderated the effects of uncertainty communication strategies on intentions for COVID-19 risk-reducing behaviors and worry about COVID-19. CONCLUSIONS: Communicating scientific uncertainty about the COVID-19 pandemic produces ambiguity-averse cognitive and emotional, but not behavioral, responses among the general public, and an uncertainty-normalizing communication strategy reduces these responses. Normalizing uncertainty may be an effective strategy for mitigating ambiguity aversion in crisis communication efforts. More research is needed to test uncertainty-normalizing communication strategies and to elucidate the factors that moderate their effectiveness. URL: https://www.ncbi.nlm.nih.gov/pubmed/33769947 DOI: 10.2196/27832
77. Harbour JC, Lyski ZL, Schell JB, et al. Cellular and Humoral Immune Responses in Mice Immunized with Vaccinia Virus Expressing the SARS-CoV-2 Spike Protein. J Immunol. 2021;10:10. DOI: 10.4049/jimmunol.2100054 ABSTRACT: The COVID-19 pandemic is a global health emergency, and the development of a successful vaccine will ultimately be required to prevent the continued spread and seasonal recurrence of this disease within the human population. However, very little is known about either the quality of the adaptive immune response or the viral Ag targets that will be necessary to prevent the spread of the infection. In this study, we generated recombinant Vaccinia virus expressing the full-length spike protein from SARS-CoV-2 (VacV-S) to evaluate the cellular and humoral immune response mounted against this viral Ag in mice. Both CD8(+) and CD4(+) T cells specific to the SARS-CoV-2 spike protein underwent robust expansion, contraction, and persisted for at least 40 d following a single immunization with VacV- S. Vaccination also caused the rapid emergence of spike-specific IgG-neutralizing Abs. Interestingly, both the cellular and humoral immune responses strongly targeted the S1 domain of spike following VacV-S immunization. Notably, immunization with VacV-expressing spike conjugated to the MHC class II invariant chain, a strategy previously reported by us and others to enhance the immunogenicity of antigenic peptides, did not promote stronger spike-specific T cell or Ab responses in vivo. Overall, these findings demonstrate that an immunization approach using VacV or attenuated versions of VacV expressing the native, full-length SARS-CoV-2 spike protein could be used for further vaccine development to prevent the spread of COVID-19. URL: https://www.ncbi.nlm.nih.gov/pubmed/33972374 DOI: 10.4049/jimmunol.2100054
78. Hasan T, Beardsley J, Marais BJ, et al. The Implementation of Mass-Vaccination against SARS-CoV- 2: A Systematic Review of Existing Strategies and Guidelines. Vaccines (Basel). 2021;9(4):01. DOI: 10.3390/vaccines9040326 ABSTRACT: The global drive to vaccinate against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) began in December 2020 with countries in Europe, Middle East, and North America leading the roll out of a mass-vaccination program. This systematic review synthesised all available English-language guidelines and research regarding mass-vaccination for COVID-19 until 1 March 2021- the first three months of the global mass-vaccination effort. Data were extracted from national websites, PubMed, Embase, Medline and medRxiv, including peer and non-peer review research findings. A total of 15 national policy documents were included. Policies were summarised according to the World Health Organisation (WHO) framework for mass vaccination. All included policies prioritised front-line health care workers and the elderly. Limited information was available regarding staffing, cold chain, communication strategies and infrastructure requirements for effective vaccine delivery. A total
Evidence Search Report: INF031801v4 ESR 39 of 26 research studies were identified, reporting roll-out strategies, vaccine uptake and reasons for refusal, adverse effects, and real-life estimates of efficacy. Early data showed a reduction in SARS-CoV-2 cases, hospitalisation and deaths in settings with good coverage. Very low rates of vaccine-related serious adverse events were observed. These findings provide an overview of current practice and early outcomes of COVID-19 mass-vaccination, guiding countries where roll-out is yet to commence. URL: https://www.ncbi.nlm.nih.gov/pubmed/33915829 DOI: 10.3390/vaccines9040326
79. Hofman K, Shenoy GN, Chak V, et al. Pharmaceutical Aspects and Clinical Evaluation of COVID-19 Vaccines. Immunol Invest. 2021:1-37. DOI: 10.1080/08820139.2021.1904977 ABSTRACT: COVID-19, the disease caused by the novel severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2), was first detected in December 2019 and has since morphed into a global pandemic claiming over 2.4 million human lives and severely impacting global economy. The race for a safe and efficacious vaccine was thus initiated with government agencies as well as major pharmaceutical companies as frontrunners. An ideal vaccine would activate multiple arms of the adaptive immune system to generate cytotoxic T cell responses as well as neutralizing antibody responses, while avoiding pathological or deleterious immune responses that result in tissue damage or exacerbation of the disease. Developing an effective vaccine requires an inter-disciplinary effort involving virology, protein biology, biotechnology, immunology and pharmaceutical sciences. In this review, we provide a brief overview of the pathology and immune responses to SARS-CoV-2, which are fundamental to vaccine development. We then summarize the rationale for developing COVID-19 vaccines and provide novel insights into vaccine development from a pharmaceutical science perspective, such as selection of different antigens, adjuvants, delivery platforms and formulations. Finally, we review multiple clinical trial outcomes of novel vaccines in terms of safety and efficacy. URL: https://www.ncbi.nlm.nih.gov/pubmed/33929280 DOI: 10.1080/08820139.2021.1904977
80. Hogan AB, Winskill P, Watson OJ, et al. Within-country age-based prioritisation, global allocation, and public health impact of a vaccine against SARS-CoV-2: A mathematical modelling analysis. Vaccine. 2021;08:08. DOI: 10.1016/j.vaccine.2021.04.002 ABSTRACT: The worldwide endeavour to develop safe and effective COVID-19 vaccines has been extraordinary, and vaccination is now underway in many countries. However, the doses available in 2021 are likely to be limited. We extend a mathematical model of SARS-CoV-2 transmission across different country settings to evaluate the public health impact of potential vaccines using WHO- developed target product profiles. We identify optimal vaccine allocation strategies within- and between-countries to maximise averted deaths under constraints on dose supply. We find that the health impact of SARS-CoV-2 vaccination depends on the cumulative population-level infection incidence when vaccination begins, the duration of natural immunity, the trajectory of the epidemic prior to vaccination, and the level of healthcare available to effectively treat those with disease. Within a country we find that for a limited supply (doses for < 20% of the population) the optimal strategy is to target the elderly. However, with a larger supply, if vaccination can occur while other interventions are maintained, the optimal strategy switches to targeting key transmitters to indirectly protect the vulnerable. As supply increases, vaccines that reduce or block infection have a greater impact than those that prevent disease alone due to the indirect protection provided to high-risk groups. Given a 2 billion global dose supply in 2021, we find that a strategy in which doses are allocated to countries proportional to population size is close to optimal in averting deaths and aligns with the ethical principles agreed in pandemic preparedness planning. URL: https://www.ncbi.nlm.nih.gov/pubmed/33933313
Evidence Search Report: INF031801v4 ESR 40 DOI: 10.1016/j.vaccine.2021.04.002
81. Hosseini SA, Zahedipour F, Mirzaei H, et al. Potential SARS-CoV-2 vaccines: Concept, progress, and challenges. Int Immunopharmacol. 2021;97:107622. DOI: 10.1016/j.intimp.2021.107622 ABSTRACT: Since September 2020, the world has had more than 28 million cases of coronavirus disease 2019 (COVID-19). Many countries are facing a second wave of the COVID-19 outbreak. A pressing need is evident for the development of a potent vaccine to control the SARS-CoV-2. Institutions and companies in many countries have announced their vaccine research programs and progress against the COVID-19. While most vaccines go through the designation and preparation stages, some of them are under evaluation for efficacy among animal models and clinical trials, and three approved vaccine candidates have been introduced for limited exploitation in Russia and China. An effective vaccine must induce a protective response of both cell-mediated and humoral immunity and should meet the safety and efficacy criteria. Although the emergence of new technologies has accelerated the development of vaccines, there are several challenges on the way, such as limited knowledge about the pathophysiology of the virus, inducing humoral or cellular immunity, immune enhancement with animal coronavirus vaccines, and lack of an appropriate animal model. In this review, we firstly discuss the immune responses against SARS-CoV-2 disease, subsequently, give an overview of several vaccine platforms for SARS-CoV-2 under clinical trials and challenges in vaccine development against this virus. URL: https://www.ncbi.nlm.nih.gov/pubmed/33895475 DOI: 10.1016/j.intimp.2021.107622
82. Hutchison AL, Pillai A. The effect of COVID-19 on liver transplantation: impact, practice patterns, therapeutics, and next steps. Curr Opin Organ Transplant. 2021;26(3):339-45. DOI: 10.1097/MOT.0000000000000883 ABSTRACT: PURPOSE OF REVIEW: To assess the impact of coronavirus disease 2019 (COVID-19) and the pandemic on liver transplant candidates, recipients, and donors, and review guidelines and recommendations for integrating COVID-19 therapies into current practice. RECENT FINDINGS: COVID- 19 has high morbidity and mortality for transplant candidates; interestingly, posttransplant comorbidities play a larger role than immunosuppression status. COVID-19 therapies and vaccinations are well tolerated in pre and postliver transplant patients with few exceptions, although further research is needed regarding effectiveness in this patient population. Provider practice patterns should evolve to minimize contagion during the current pandemic and prepare for an increase in liver disease due to after-shocks of missed diagnosis and progression of liver disease. SUMMARY: COVID-19 has spurred new research and technologies to ensure the safety of liver transplant candidates, recipients, and donors, and most COVID-19 therapies are safe in this patient population. Further work needs to be done regarding the use of COVID-19 positive organs and the efficacy of vaccines in the transplant population. URL: https://www.ncbi.nlm.nih.gov/pubmed/33938470 DOI: 10.1097/MOT.0000000000000883
83. Iddins BO, Buck B, Cato T, et al. mRNA SARS-CoV-2 Immunization Confers Robust Antibody Response in Occupational Healthcare Workers and Fosters Workplace Safety. J Occup Environ Med. 2021;63(5):e314-e7. DOI: 10.1097/JOM.0000000000002187 URL: https://www.ncbi.nlm.nih.gov/pubmed/33928943 DOI: 10.1097/JOM.0000000000002187
84. Ikiisik H, Sezerol MA, Tasci Y, et al. COVID-19 Vaccine Hesitancy: A Community-Based Research in Turkey. Int J Clin Pract. 2021:e14336. DOI: 10.1111/ijcp.14336
Evidence Search Report: INF031801v4 ESR 41 ABSTRACT: AIM: The frequency of vaccine refusal and hesitation, which is associated with many factors, is increasing worldwide. The purpose of this study is to estimate the frequency of vaccine refusal against COVID-19 vaccines and to identify the underlying factors for refusal or hesitation. MATERIALS AND METHODS: This is a cross-sectional study carried out in a district of Istanbul between 25-30 December 2020. A sample of people between the ages of 20-85 in the district was selected, and a total of 384 people were enrolled. A questionnaire about the COVID-19 vaccine was administered to the participants by phone. The questionnaire consisted of questions about the sociodemographic characteristics of participants and their thoughts about possible COVID-19 vaccines. RESULTS: 45.3% of the participants were hesitant about getting the COVID-19 vaccine, which was declared appropriate by the Ministry of Health. The rate of those who think that the COVID-19 vaccine will be effective in preventing and controlling the disease was 51.6%. 89.6% of the participants were hesitant about getting their children vaccinated. Those who do not consider COVID-19 disease as a risk to their health were 22.9%, and 32.8% thought that they would be protected from the disease by natural and traditional ways. The median score of the participants' risk perception was 7 (IQR: 6-8; Mean: 6.8; SD: 1.7). The median value of risk perception score of those who accept the vaccine was 6 (IQR: 4-6), while the median value for those who did not accept the vaccine was 4 (IQR: 4-6) (p <0.01). Factors affecting vaccine acceptance were determined as the perception of risk (OR: 1.26% 95CI 1.03-1.55) and age (OR: 0.94% 95CI: 0.91-0.98) in logistic regression analysis. CONCLUSION: Half of the participants were hesitant about the COVID-19 vaccines. The success of COVID-19 vaccination programs largely depends on the public willingness to accept the vaccine. URL: https://www.ncbi.nlm.nih.gov/pubmed/33973322 DOI: 10.1111/ijcp.14336
85. Inchingolo AD, Inchingolo AM, Bordea IR, et al. SARS-CoV-2 Disease through Viral Genomic and Receptor Implications: An Overview of Diagnostic and Immunology Breakthroughs. Microorganisms. 2021;9(4):10. DOI: 10.3390/microorganisms9040793 ABSTRACT: The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which is believed to have originated in China towards the end of November 2019, has now spread across the globe, causing a pandemic in 192 countries. The World Health Organization has called it the SARS-CoV-2 pandemic. Rapid dissemination of the virus occurs mainly through the saliva (Flugge's droplets) and aerosol, together with nasal and lachrymal passages. The literature associated with the recent advancement in terms of rapid diagnostics and SARS-CoV-2 vaccines has thoroughly studied the role of ACE2 receptors and Furin, as well as viral agent access into the host cell and its significant persistence at the level of the oral mucosa, which represents the main access to the virus. The purpose of this review was to underline the processes of SARS-CoV-2 infection mechanisms and novel breakthroughs in diagnostics and vaccines. Different technologies, such as the RT-PCR molecular test and the antigenic test, have been developed to identify subjects affected by the SARS-CoV-2 in order to improve the tracking of infection geographical diffusion. Novel rapid and highly sensitive diagnostic tests has been proposed for the detection of SARS-CoV-2 to improve the screening capability of suspected contagions. The strengthening of the vaccination campaign represents the most effective means to combat the SARS-CoV-2 infection and prevent severe manifestations of the virus-different classes of vaccines have been developed for this purpose. Further attention on the novel SARS-CoV-2 variant is necessary in order to verify the protection efficacy and virulence reduction of the infective agent in the recent vaccine campaign. URL: https://www.ncbi.nlm.nih.gov/pubmed/33920179 DOI: 10.3390/microorganisms9040793
Evidence Search Report: INF031801v4 ESR 42 86. Indolfi C, Barilla F, Basso C, et al. [Position paper of the Italian Society of Cardiology (SIC) on COVID-19 vaccine priority in patients with cardiovascular diseases]. G Ital Cardiol (Rome). 2021;22(5):363-75. DOI: 10.1714/3592.35745 ABSTRACT: In over a year, the COVID-19 pandemic caused 2.69 million deaths and 122 million infections. Social isolation and distancing measures have been the only prevention available for months. Scientific research has done a great deal of work, developing in a few months safe and effective vaccines against COVID-19. In the European Union, nowadays, four vaccines have been authorized for use: Pfizer- BioNTech, Moderna, ChAdOx1 (AstraZeneca/Oxford), Janssen (Johnson & Johnson), and three others are currently under rolling review.Vaccine allocation policy is crucial to optimize the advantage of treatment preferring people with the highest risk of contagion. These days the priority in the vaccination program is of particular importance since it has become clear that the number of vaccines is not sufficient for the entire Italian population in the short term. Cardiovascular diseases are frequently associated with severe COVID-19 infections, leading to the worst prognosis. The elderly population suffering from cardiovascular diseases is, therefore, to be considered a particularly vulnerable population. However, age cannot be considered the only discriminating factor because in the young-adult population suffering from severe forms of heart disease, the prognosis, if affected by COVID-19, is particularly ominous and these patients should have priority access to the vaccination program. The aim of this position paper is to establish a consensus on a priority in the vaccination of COVID-19 among subjects suffering from different cardiovascular diseases. URL: https://www.ncbi.nlm.nih.gov/pubmed/33960979 DOI: 10.1714/3592.35745
87. Islam MS, Kamal AM, Kabir A, et al. COVID-19 vaccine rumors and conspiracy theories: The need for cognitive inoculation against misinformation to improve vaccine adherence. PLoS ONE. 2021;16(5):e0251605. DOI: 10.1371/journal.pone.0251605 ABSTRACT: INTRODUCTION: Rumors and conspiracy theories, can contribute to vaccine hesitancy. Monitoring online data related to COVID-19 vaccine candidates can track vaccine misinformation in real- time and assist in negating its impact. This study aimed to examine COVID-19 vaccine rumors and conspiracy theories circulating on online platforms, understand their context, and then review interventions to manage this misinformation and increase vaccine acceptance. METHOD: In June 2020, a multi-disciplinary team was formed to review and collect online rumors and conspiracy theories between 31 December 2019-30 November 2020. Sources included Google, Google Fact Check, Facebook, YouTube, Twitter, fact-checking agency websites, and television and newspaper websites. Quantitative data were extracted, entered in an Excel spreadsheet, and analyzed descriptively using the statistical package R version 4.0.3. We conducted a content analysis of the qualitative information from news articles, online reports and blogs and compared with findings from quantitative data. Based on the fact-checking agency ratings, information was categorized as true, false, misleading, or exaggerated. RESULTS: We identified 637 COVID-19 vaccine-related items: 91% were rumors and 9% were conspiracy theories from 52 countries. Of the 578 rumors, 36% were related to vaccine development, availability, and access, 20% related to morbidity and mortality, 8% to safety, efficacy, and acceptance, and the rest were other categories. Of the 637 items, 5% (30/) were true, 83% (528/637) were false, 10% (66/637) were misleading, and 2% (13/637) were exaggerated. CONCLUSIONS: Rumors and conspiracy theories may lead to mistrust contributing to vaccine hesitancy. Tracking COVID-19 vaccine misinformation in real-time and engaging with social media to disseminate correct information could help safeguard the public against misinformation. URL: https://www.ncbi.nlm.nih.gov/pubmed/33979412 DOI: 10.1371/journal.pone.0251605
Evidence Search Report: INF031801v4 ESR 43 88. Jahn B, Sroczynski G, Bicher M, et al. Targeted COVID-19 Vaccination (TAV-COVID) Considering Limited Vaccination Capacities-An Agent-Based Modeling Evaluation. Vaccines (Basel). 2021;9(5):27. DOI: 10.3390/vaccines9050434 ABSTRACT: (1) Background: The Austrian supply of COVID-19 vaccine is limited for now. We aim to provide evidence-based guidance to the authorities in order to minimize COVID-19-related hospitalizations and deaths in Austria. (2) Methods: We used a dynamic agent-based population model to compare different vaccination strategies targeted to the elderly (65 >/= years), middle aged (45-64 years), younger (15-44 years), vulnerable (risk of severe disease due to comorbidities), and healthcare workers (HCW). First, outcomes were optimized for an initially available vaccine batch for 200,000 individuals. Second, stepwise optimization was performed deriving a prioritization sequence for 2.45 million individuals, maximizing the reduction in total hospitalizations and deaths compared to no vaccination. We considered sterilizing and non-sterilizing immunity, assuming a 70% effectiveness. (3) Results: Maximum reduction of hospitalizations and deaths was achieved by starting vaccination with the elderly and vulnerable followed by middle-aged, HCW, and younger individuals. Optimizations for vaccinating 2.45 million individuals yielded the same prioritization and avoided approximately one third of deaths and hospitalizations. Starting vaccination with HCW leads to slightly smaller reductions but maximizes occupational safety. (4) Conclusion: To minimize COVID-19-related hospitalizations and deaths, our study shows that elderly and vulnerable persons should be prioritized for vaccination until further vaccines are available. URL: https://www.ncbi.nlm.nih.gov/pubmed/33925650 DOI: 10.3390/vaccines9050434
89. Jahn M, Korth J, Dorsch O, et al. Humoral Response to SARS-CoV-2-Vaccination with BNT162b2 (Pfizer-BioNTech) in Patients on Hemodialysis. Vaccines (Basel). 2021;9(4):08. DOI: 10.3390/vaccines9040360 ABSTRACT: mRNA-based SARS-CoV-2 vaccines offer a preventive strategy against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections that is of interest in the care of patients on hemodialysis (HDP). We measured humoral immune responses in 72 HDP after standard vaccination with two doses of the mRNA-based SARS-CoV-2 vaccine BNT162b2 (Pfizer-BioNTech). Antibody responses were evaluated with an anti-SARS-CoV-2 IgG ChemiLuminescent ImmunoAssay (CLIA) two weeks after the second dose. In addition, SARS-CoV-2 IgG was determined in a control of 16 healthy healthcare workers (HCW). The control group of HCW has shown a strong antibody response with a median (MD (Q1; Q3)) antibody titer of 800.0 AU/mL (520.5; 800.0). In comparison to HCW, HDP under 60 years of age responded equally (597.0 AU/mL (410.5; 800.0), p = 0.051). However, the antibody responses of the HDP negatively correlated with age (r(2) = 0.2954 p < 0.0001), leading to significantly lower antibody titers in HDP over 60 years (280.0 AU/mL (45.7; 477.0), p < 0.0001). To thoroughly understand the immunogenicity of the new mRNA-based vaccines in HDP, longitudinal data on the effectiveness and durability of antibody responses are needed. Modifications of immunization schedules should be considered in HDP with low or without antibody responsiveness after standard vaccination to boost immune reactivity and prolong protective effects in these vulnerable patients. URL: https://www.ncbi.nlm.nih.gov/pubmed/33918085 DOI: 10.3390/vaccines9040360
90. Jecker N, Atuire C. Out of Africa: A Solidarity-Based Approach to Vaccine Allocation. Hastings Cent Rep. 2021;03:03. DOI: 10.1002/hast.1250 ABSTRACT: This article sets forth a solidaristic approach to global distribution of vaccines against the SARS-CoV-2 virus. Our approach draws inspiration from African ethics and from the characterization of the Covid-19 crisis as a syndemic, a convergence of biosocial forces that interact with one another to
Evidence Search Report: INF031801v4 ESR 44 produce and exacerbate clinical disease and prognosis. The first section elaborates the twin ideas of syndemic and solidarity. The second section argues that these ideas lend support to global health alliances to distribute vaccines beyond national borders. The third section introduces ethical criteria to guide global distribution, emphasizing priority to low- and middle-income countries, which have the least ability to obtain vaccines on their own. It also justifies giving priority to people at high risk of infection and high risk of severe disease and death. URL: https://www.ncbi.nlm.nih.gov/pubmed/33939182 DOI: 10.1002/hast.1250
91. Johansen K, Nohynek H. No country or continent is on its own in the ongoing COVID-19 pandemic. Euro Surveill. 2021;26(17):04. DOI: 10.2807/1560-7917.ES.2021.26.17.2100430 URL: https://www.ncbi.nlm.nih.gov/pubmed/33928901 DOI: 10.2807/1560-7917.ES.2021.26.17.2100430
92. Kadali RAK, Janagama R, Peruru S, et al. Side effects of BNT162b2 mRNA COVID-19 vaccine: A randomized, cross-sectional study with detailed self-reported symptoms from healthcare workers. Int J Infect Dis. 2021;106:376-81. DOI: 10.1016/j.ijid.2021.04.047 ABSTRACT: INTRODUCTION: Concerns are prevailing about the safety and side effects of the BNT162b2 mRNA vaccine for coronavirus disease 2019 (COVID-19). METHODS: A randomized, cross-sectional study was performed to investigate the side effects of the BNT162b2 vaccine using an independent online questionnaire gathering responses from healthcare workers (HCWs) with detailed review of organ systems. RESULTS: Of all HCWs, 87.98% (1245/1415) completed the survey. Of them, 64.5% (803/1245) received the BNT162b2 mRNA vaccine and reported at least one or more symptoms (classified based on organ systems and occurrence rate) post vaccination. Of these, 640/803 (79.7%) were able to continue activities of daily living (ADL), 103/803 (12.83%) had trouble temporarily to perform ADL, 99/803 (12.33%) took time off work temporarily, 20/803 (2.49%) required help from an outpatient provider, 5/803 (0.62%) required help from an emergency department and 2/803 (0.25%) required hospitalization. Despite this, 97.61% intended to have the second dose and 92.9% had already received it. CONCLUSIONS: Commonly reported symptoms (occurrence in descending order) were soreness, fatigue, myalgia, headache, chills, fever, joint pain, nausea, muscle spasm, sweating, dizziness, flushing, feelings of relief, brain fogging, anorexia, localized swelling, decreased sleep quality, itching, tingling, diarrhoea, nasal stuffiness and palpitations. Despite this, remarkable acceptance for the second dose of the BNT162b2 vaccine was found among HCWs. URL: https://www.ncbi.nlm.nih.gov/pubmed/33866000 DOI: 10.1016/j.ijid.2021.04.047
93. Kang HM, Choi EH, Kim Y-J. Updates on Coronavirus Disease-2019 Vaccine and Consideration in Children. Pediatric Infection & Vaccine. 2021;28(1):7-20. DOI: 10.14776/piv.2021.28.e6 ABSTRACT: As of March 2021, humanity has been suffering from the global severe acute respiratory syndrome coronavirus 2 pandemic that began late 2019. In 2020, new vaccine platforms- including mRNA vaccines and viral vector-based DNA vaccines-have been given emergency use authorization (EUA), leading to rolling out the vaccines for global mass vaccinations. The purpose of this article is to review the currently most widely used coronavirus disease 2019 vaccines: their action mechanisms and efficacy and safety data from clinical trials that have been published to date. In addition, the current status of clinical trials in the pediatric population was summarized, and further consideration for them was discussed.Copyright © 2021 The Korean Society of Pediatric Infectious Diseases. URL: http://www.piv.or.kr/ http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emedx&NEWS=N&AN=2007092484
Evidence Search Report: INF031801v4 ESR 45 DOI: 10.14776/piv.2021.28.e6
94. Kaur H, Kaur M, Bhattacharyya A, et al. Indian contribution toward biomedical research and development in COVID-19: A systematic review. Indian J Pharmacol. 2021;53(1):63-72. DOI: 10.4103/ijp.ijp_168_21 ABSTRACT: COVID-19 pandemic led to an unprecedented collaborative effort among industry, academia, regulatory bodies, and governments with huge financial investments. Scientists and researchers from India also left no stone unturned to find therapeutic and preventive measures against COVID-19. Indian pharmaceutical companies are one of the leading manufacturers of vaccine in the world, are utilizing its capacity to its maximum, and are one among the forerunners in vaccine research against COVID-19 across the globe. In this systematic review, the information regarding contribution of Indian scientists toward COVID-19 research has been gathered from various news articles across Google platform apart from searching PubMed, WHO site, COVID-19 vaccine tracker, CTRI, clinicaltrials.gov, and websites of pharmaceutical companies. The article summarizes and highlights the various therapeutic and vaccine candidates, diagnostic kits, treatment agents, and technology being developed and tested by Indian researcher community against COVID-19. URL: https://www.ncbi.nlm.nih.gov/pubmed/33976001 DOI: 10.4103/ijp.ijp_168_21
95. Kennedy NA, Lin S, Goodhand JR, et al. Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD. Gut. 2021:324789. DOI: 10.1136/gutjnl-2021-324789 ABSTRACT: OBJECTIVE: Delayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single dose of a SARS-CoV-2 vaccine. DESIGN: Antibody responses and seroconversion rates in infliximab- treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut- selective anti-integrin alpha4beta7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) antibody assay 3-10 weeks after vaccination, in patients without evidence of prior infection. Secondary outcomes were seroconversion rates (defined by a cut-off of 15 U/mL), and antibody responses following past infection or a second dose of the BNT162b2 vaccine. RESULTS: Geometric mean (SD) anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs 28.8 U/mL (5.4) p<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL (4.9)) vs 13.8 U/mL (5.9) p<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab- treated compared with vedolizumab-treated patients who received the BNT162b2 (fold change (FC) 0.29 (95% CI 0.21 to 0.40), p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 (95% CI 0.30 to 0.51), p<0.0001) vaccines. In both models, age >/=60 years, immunomodulator use, Crohn's disease and smoking were associated with lower, while non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine. CONCLUSION: Infliximab is associated with attenuated immunogenicity to a single dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab. TRIAL REGISTRATION NUMBER: ISRCTN45176516. URL: https://www.ncbi.nlm.nih.gov/pubmed/33903149 DOI: 10.1136/gutjnl-2021-324789
Evidence Search Report: INF031801v4 ESR 46 96. Kerr JR, Freeman ALJ, Marteau TM, et al. Effect of Information about COVID-19 Vaccine Effectiveness and Side Effects on Behavioural Intentions: Two Online Experiments. Vaccines (Basel). 2021;9(4):13. DOI: 10.3390/vaccines9040379 ABSTRACT: The success of mass COVID-19 vaccination campaigns rests on widespread uptake. However, although vaccinations provide good protection, they do not offer full immunity and while they likely reduce transmission of the virus to others, the extent of this remains uncertain. This produces a dilemma for communicators who wish to be transparent about benefits and harms and encourage continued caution in vaccinated individuals but not undermine confidence in an important public health measure. In two large pre-registered experimental studies on quota-sampled UK public participants we investigate the effects of providing transparent communication-including uncertainty-about vaccination effectiveness on decision-making. In Study 1 (n = 2097) we report that detailed information about COVID-19 vaccines, including results of clinical trials, does not have a significant impact on beliefs about the efficacy of such vaccines, concerns over side effects, or intentions to receive a vaccine. Study 2 (n = 2217) addressed concerns that highlighting the need to maintain protective behaviours (e.g., social distancing) post-vaccination may lower perceptions of vaccine efficacy and willingness to receive a vaccine. We do not find evidence of this: transparent messages did not significantly reduce perceptions of vaccine efficacy, and in some cases increased perceptions of efficacy. We again report no main effect of messages on intentions to receive a vaccine. The results of both studies suggest that transparently informing people of the limitations of vaccinations does not reduce intentions to be vaccinated but neither does it increase intentions to engage in protective behaviours post-vaccination. URL: https://www.ncbi.nlm.nih.gov/pubmed/33924542 DOI: 10.3390/vaccines9040379
97. Khan A, Khan S, Saleem S, et al. Immunogenomics guided design of immunomodulatory multi- epitope subunit vaccine against the SARS-CoV-2 new variants, and its validation through in silico cloning and immune simulation. Comput Biol Med. 2021;133:104420. DOI: 10.1016/j.compbiomed.2021.104420 ABSTRACT: Reports of the novel and more contagious strains of SARS-CoV-2 originating in different countries have further aggravated the pandemic situation. The recent substitutions in spike protein may be critical for the virus to evade the host's immune system and therapeutics that have already been developed. Thus, this study has employed an immunoinformatics pipeline to target the spike protein of this novel strain to construct an immunogenic epitope (CTL, HTL, and B cell) vaccine against the new variant. Our investigation revealed that 12 different epitopes imparted a critical role in immune response induction. This was validated by an exploration of physiochemical properties and experimental feasibility. In silico and host immune simulation confirmed the expression and induction of both primary and secondary immune factors such as IL, cytokines, and antibodies. The current study warrants further lab experiments to demonstrate its efficacy and safety. URL: https://www.ncbi.nlm.nih.gov/pubmed/33930764 DOI: 10.1016/j.compbiomed.2021.104420
98. Klimek L, Pfaar O, Hamelmann E, et al. COVID-19 Vaccination of Allergic Patients in Conjunction with allergen immunotherapy (AIT) - A position paper of the Association of German Allergists (AeDA) and the German Society for Allergology and Clinical Immunology (DGAKI). Allergologie. 2021;44(5):339-48. DOI: http://dx.doi.org/10.5414/ALX02245 ABSTRACT: Background: Vaccinations against Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are intended to induce an immune response in the sense of protection against infection/disease. Allergen-specific immunotherapy (AIT) is also thought to induce a (different) immune response in the sense of tolerance to allergens. There is uncertainty among patients and physicians
Evidence Search Report: INF031801v4 ESR 47 regarding the use of vaccination and AIT in temporal relation, which this position paper aims to clarify. The four vaccines currently approved in Germany for vaccination against SARS-CoV-2 are described and possible immunological interactions with AIT are highlighted, as well as practical recommendations for action. Method(s): Based on the current internationally published literature, this position paper provides specific recommendations for action regarding the use of AIT in temporal relation to a SARS-CoV-2 vaccination. Result(s): The present recommendations for action relate to the following conditions for which AIT is used i) allergic rhinitis, ii) allergic bronchial asthma, iii) insect venom allergy, iiii) food allergy (peanut). Conclusion(s): If vaccination is imminent, initiation of subcutaneous (SCIT), sublingual (SLIT), or oral (OIT) AIT should be delayed until 1 week after the 2nd vaccination date. Thus, there should generally be an interval of approximately 1 week between SCIT and COVID-19 vaccination. For the continuation of an ongoing AIT, we recommend an interval of 1 week before and after vaccination for SCIT. For SLIT and OIT, we recommend taking them up to the day before vaccination and taking a break from SLIT and OIT for 2 - 7 days after vaccination.Copyright © 2021 Dustri-Verlag Dr. Karl Feistle. All rights reserved. URL: https://www.dustri.com/nc/de/deutschsprachige-zeitschriften/mag/allergologie/vol/jahrgang-44- 2021/issue/mai-49.html http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emedx&NEWS=N&AN=2011924732 DOI: http://dx.doi.org/10.5414/ALX02245
99. Kmietowicz Z. Covid-19: Caution urged while lockdown eases in England because of vaccine success. Bmj. 2021;373:n1203. DOI: 10.1136/bmj.n1203 URL: https://www.ncbi.nlm.nih.gov/pubmed/33975884 DOI: 10.1136/bmj.n1203
100. Koch T, Fathi A, Addo MM. The COVID-19 Vaccine Landscape. Adv Exp Med Biol. 2021;1318:549- 73. DOI: 10.1007/978-3-030-63761-3_31 ABSTRACT: The history of vaccine development spans centuries. At first, whole pathogens were used as vaccine agents, either inactivated or attenuated, to reduce virulence in humans. Safety and tolerability were increased by including only specific proteins as antigens and using cell culture methods, while novel vaccine strategies, like nucleic acid- or vector-based vaccines, hold high promise for the future. Vaccines have generally not been employed as the primary tools in outbreak response, but this might change since advances in medical technology in the last decades have made the concept of developing vaccines against novel pathogens a realistic strategy. Wandering the uncharted territory of a novel pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we can learn from other human Betacoronaviridae that emerged in the last decades, SARS-CoV-1 and MERS-CoV. We can identify the most likely target structures of immunity, establish animal models that emulate human disease and immunity as closely as possible, and learn about complex mechanisms of immune interaction such as cross-reactivity or antibody-dependent enhancement (ADE). However, significant knowledge gaps remain. What are the correlates of protection? How do we best induce immunity in vulnerable populations like the elderly? Will the immunity induced by vaccination (or by natural infection) wane over time? To date, at least 149 vaccine candidates against SARS-CoV-2 are under development. At the time of writing, at least 17 candidates have already progressed past preclinical studies (in vitro models and in vivo animal experiments) into clinical development. This chapter will provide an overview of this rapidly developing field. URL: https://www.ncbi.nlm.nih.gov/pubmed/33973199 DOI: 10.1007/978-3-030-63761-3_31
Evidence Search Report: INF031801v4 ESR 48 101. Kreps SE, Kriner DL. Factors influencing Covid-19 vaccine acceptance across subgroups in the United States: Evidence from a conjoint experiment. Vaccine. 2021;24:24. DOI: 10.1016/j.vaccine.2021.04.044 ABSTRACT: Public health officials warn that the greatest barrier to widespread vaccination against Covid-19 will not be scientific or technical, but the considerable public hesitancy to take a novel vaccine. Understanding the factors that influence vaccine acceptance is critical to informing public health campaigns aiming to combat public fears and ensure broad uptake. Employing a conjoint experiment embedded on an online survey of almost 2,000 adult Americans, we show that the effects of seven vaccine attributes on subjects' willingness to vaccinate vary significantly across subgroups. Vaccine efficacy was significantly more influential on vaccine acceptance among whites than among Blacks, while bringing a vaccine to market under a Food and Drug Administration Emergency Use Authorization had a stronger adverse effect on willingness to vaccinate among older Americans and women. Democrats were more sensitive to vaccine efficacy than Republicans, and both groups responded differently to various endorsements of the vaccine. We also explored whether past flu vaccination history, attitudes toward general vaccine safety, and personal contact with severe cases of Covid-19 can explain variation in group vaccination hesitancy. Many subgroups that exhibit the greatest Covid-19 vaccine hesitancy did not report significantly lower frequencies of flu vaccination. Several groups that exhibited greater Covid-19 vaccine hesitancy also reported greater concerns about vaccine safety generally, but others did not. Finally, subgroup variation in reported personal contact with severe cases of Covid-19 did not strongly match subgroup variation in vaccine acceptance. URL: https://www.ncbi.nlm.nih.gov/pubmed/33966909 DOI: 10.1016/j.vaccine.2021.04.044
102. Kumari A, Ranjan P, Chopra S, et al. Knowledge, barriers and facilitators regarding COVID-19 vaccine and vaccination programme among the general population: A cross-sectional survey from one thousand two hundred and forty-nine participants. Diabetes Metab Syndr. 2021;15(3):987-92. DOI: 10.1016/j.dsx.2021.04.015 ABSTRACT: BACKGROUND AND AIMS: The success of the COVID-19 vaccination program is dependent on people's knowledge and attitude regarding the vaccination program. Higher vaccine acceptance can be ensured by strengthening the facilitators and limiting the barriers being observed among the general population. MATERIAL AND METHODS: Indexed study is a cross-sectional web-based survey using a pre- validated questionnaire to assess knowledge, barriers and facilitators of COVID-19 vaccine and vaccination programme administered on adults across India using a Google online survey platform. RESULTS: A total of 1294 responses (age: 38.02 +/- 13.34 years) were collected. Most of the participants had limited knowledge regarding the eligibility of vaccines in vulnerable population groups such as people with allergies (57.89%) and immune-compromised patients (62.98%), pregnant and lactating women (41.89%) and patients with chronic illness (34.78%). Older participants (>45 years) were more willing to take the COVID-19 vaccine (p < 0.001) as they believed the vaccine is not harmful and considered it as societal responsibility. Younger participants (<45 years) and those residing in urban settings raised concerns on the availability of the vaccine and authenticity of the vaccine (p < 0.001). CONCLUSION: There is a scope for improvement in people's knowledge regarding COVID-19 vaccine and the vaccination programme by addressing the barriers and facilitators which can improve the participants' turnover at vaccination centres. URL: https://www.ncbi.nlm.nih.gov/pubmed/33984818 DOI: 10.1016/j.dsx.2021.04.015
Evidence Search Report: INF031801v4 ESR 49 103. Kumari A, Ranjan P, Chopra S, et al. Development and validation of a questionnaire to assess knowledge, attitude, practices, and concerns regarding COVID-19 vaccination among the general population. Diabetes Metab Syndr. 2021;15(3):919-25. DOI: 10.1016/j.dsx.2021.04.004 ABSTRACT: BACKGROUND AND AIMS: There seems to be hesitation in the general population in accepting COVID 19 vaccine because of associated myths and/or misinformation. This study is dedicated to develop and validate a tool to interpret vaccine acceptance and/or hesitancy by assessing the knowledge, attitude, practices, and concerns regarding the COVID vaccine. MATERIAL AND METHODS: Mixed methods study design was used. In phase 1, the questionnaire was developed through literature review, focus group discussion, expert evaluation, and pre-testing. In phase 2, the validity of the questionnaire was obtained by conducting a cross-sectional survey on 201 participants. The construct validity was established via principal component analysis. Cronbach's alpha value was used to assess the reliability of the questionnaire. RESULTS: The 39-item questionnaire to assess the knowledge, attitude, practices, and concerns regarding the COVID-19 vaccine was developed. The Cronbach's alpha value of the questionnaire was 0.86 suggesting a good internal consistency. CONCLUSION: The developed tool is valid to assess the knowledge, attitude, practices and concerns regarding the COVID-19 vaccine acceptance and/or hesitancy. It has the potential utility for healthcare workers and government authorities to further build vaccine literacy. URL: https://www.ncbi.nlm.nih.gov/pubmed/33930855 DOI: 10.1016/j.dsx.2021.04.004
104. Kute V, Agarwal S, Prakash J, et al. Notto covid-19 vaccine guidelines for transplant recipients. Indian Journal of Nephrology. 2021;31(2):89-91. DOI: http://dx.doi.org/10.4103/ijn.IJN-64-21 ABSTRACT: In December 2019, novel coronavirus (SARS-CoV-2) infection started in Wuhan and resulted in a pandemic within a few weeks' time. Organ transplant recipients being at a risk for more severe COVID-19 if they get SARS CoV-2 viral infection, COVID-19 vaccine has a significant role in these patients. The vaccine is a safer way to help build protection and would either prevent COVID-19 infection or at least diminish the severity of the disease. It would also reduce the risk of the continuing transmission and enhance herd immunity. Immuno-compromised patients should not receive live vaccines as they can cause vaccine-related disease and hence the guidelines suggest that all transplant recipients should receive age-appropriate 'inactivated vaccine' as recommended for general population. Though trials have not been undertaken on transplant recipients, efficacy and safety of COVID-19 vaccine have been scientifically documented for few vaccines among the general population.Copyright © 2021 Indian Journal of Nephrology. URL: http://www.indianjnephrol.org http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emedx&NEWS=N&AN=634933545 DOI: http://dx.doi.org/10.4103/ijn.IJN-64-21
105. Lee K, Eyal N. COVID-19 controlled human infection studies: worries about local community impact and demands for local engagement. J Med Ethics. 2021;12:12. DOI: 10.1136/medethics-2021- 107229 ABSTRACT: In spring, summer and autumn 2020, one abiding argument against controlled human infection (CHI) studies of SARS-CoV-2 vaccines has been their impact on local communities. Leading scientists and bioethicists expressed concern about undue usage of local residents' direly needed scarce resources at a time of great need and even about their unintended infection. They recommended either avoiding CHI trials or engaging local communities before conducting any CHIs. Similar recommendations were not made for the alternative-standard phase III field trials of these same vaccines. We argue that the health effects of CHI studies on local residents not participating in the study tend to be smaller and more positive than those of field trials. That is all the more so now that tested vaccines are being rolled
Evidence Search Report: INF031801v4 ESR 50 out. Whether or not local community engagement is necessary for urgent vaccine studies in the pandemic, the case for its engagement is stronger prior to field trials than prior to CHI studies. URL: https://www.ncbi.nlm.nih.gov/pubmed/33980657 DOI: 10.1136/medethics-2021-107229
106. Leong DP, Banerjee A, Yusuf S. COVID-19 Vaccination Prioritization Based on Cardiovascular Risk Factors and Number-Needed-to-Vaccinate to Prevent Death. Can J Cardiol. 2021;29:29. DOI: 10.1016/j.cjca.2021.04.012 ABSTRACT: The supply limitations of COVID-19 vaccines have led to the need to prioritize vaccine distribution. Obesity, diabetes and hypertension have been associated with an increased risk of severe COVID-19 infection. Approximately half as many individuals with a cardiovascular risk factor need to be vaccinated against COVID-19 to prevent related death as compared with individuals without a risk factor. Adults with body-mass index >/=30kg/m(2), diabetes or hypertension should be of a similar priority for COVID-19 vaccination to adults 10 years older with a body-mass index 20 to <30kg/m(2), no diabetes and no hypertension. URL: https://www.ncbi.nlm.nih.gov/pubmed/33933606 DOI: 10.1016/j.cjca.2021.04.012
107. Li H, Guo L, Zheng H, et al. Self-Assembling Nanoparticle Vaccines Displaying the Receptor Binding Domain of SARS-CoV-2 Elicit Robust Protective Immune Responses in Rhesus Monkeys. Bioconjug Chem. 2021;05:05. DOI: 10.1021/acs.bioconjchem.1c00208 ABSTRACT: SARS-CoV-2 caused the COVID-19 pandemic that lasted for more than a year. Globally, there is an urgent need to use safe and effective vaccines for immunization to achieve comprehensive protection against SARS-CoV-2 infection. Focusing on developing a rapid vaccine platform with significant immunogenicity as well as broad and high protection efficiency, we designed a SARS-CoV-2 spike protein receptor-binding domain (RBD) displayed on self-assembled ferritin nanoparticles. In a 293i cells eukaryotic expression system, this candidate vaccine was prepared and purified. After rhesus monkeys are immunized with 20 mug of RBD-ferritin nanoparticles three times, the vaccine can elicit specific humoral immunity and T cell immune response, and the neutralizing antibodies can cross- neutralize four SARS-CoV-2 strains from different sources. In the challenge protection test, after nasal infection with 2 x 10(5) CCID50 SARS-CoV-2 virus, compared with unimmunized control animals, virus replication in the vaccine-immunized rhesus monkeys was significantly inhibited, and respiratory pathology observations also showed only slight pathological damage. These analyses will benefit the immunization program of the RBD-ferritin nanoparticle vaccine in the clinical trial design and the platform construction to present a specific antigen domain in the self-assembling nanoparticle in a short time to harvest stable, safe, and effective vaccine candidates for new SARS-CoV-2 isolates. URL: https://www.ncbi.nlm.nih.gov/pubmed/33951913 DOI: 10.1021/acs.bioconjchem.1c00208
108. Li J, Hui A, Zhang X, et al. Safety and immunogenicity of the SARS-CoV-2 BNT162b1 mRNA vaccine in younger and older Chinese adults: a randomized, placebo-controlled, double-blind phase 1 study. Nat Med. 2021. DOI: 10.1038/s41591-021-01330-9 ABSTRACT: An effective vaccine is needed to end the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Here, we assess the preliminary safety, tolerability and immunogenicity data from an ongoing single-center (in Jiangsu province, China), parallel-group, double-blind phase 1 trial of the vaccine candidate BNT162b1 in 144 healthy SARS-CoV-2-naive Chinese participants. These participants are randomized 1:1:1 to receive prime and boost vaccinations of 10 microg or 30 microg BNT162b1 or placebo, given 21 d apart, with equal allocation of younger (aged 18-55 years) and older
Evidence Search Report: INF031801v4 ESR 51 adults (aged 65-85 years) to each treatment group (ChiCTR2000034825). BNT162b1 encodes the SARS- CoV-2 spike glycoprotein receptor-binding domain (RBD) and is one of several messenger RNA-based vaccine candidates under clinical investigation. Local reactions and systemic events were generally dose dependent, transient and mild to moderate. Fever was the only grade 3 adverse event. BNT162b1 induced robust interferon-gamma T cell responses to a peptide pool including the RBD in both younger and older Chinese adults, and geometric mean neutralizing titers reached 2.1-fold (for younger participants) and 1.3-fold (for the older participants) that of a panel of COVID-19 convalescent human sera obtained at least 14 d after positive SARS-CoV-2 polymerase chain reaction test. In summary, BNT162b1 has an acceptable safety profile and produces high levels of humoral and T cell responses in an Asian population. URL: https://www.ncbi.nlm.nih.gov/pubmed/33888900 DOI: 10.1038/s41591-021-01330-9
109. Lio CF, Cheong HH, Lei CI, et al. Effectiveness of personal protective health behaviour against COVID-19. BMC Public Health. 2021;21(1):827. DOI: 10.1186/s12889-021-10680-5 ABSTRACT: BACKGROUND: Novel coronavirus disease 2019 (COVID-19) has become a pandemic, and over 80 million cases and over 1.8 million deaths were reported in 2020. This highly contagious virus is spread primarily via respiratory droplets from face-to-face contact and contaminated surfaces as well as potential aerosol spread. Over half of transmissions occur from presymptomatic and asymptomatic carriers. Although several vaccines are currently available for emergency use, there are uncertainties regarding the duration of protection and the efficacy of preventing asymptomatic spread. Thus, personal protective health behaviour and measures against COVID-19 are still widely recommended after immunization. This study aimed to clarify the efficacy of these measures, and the results may provide valuable guidance to policymakers to educate the general public about how to reduce the individual- level risk of COVID-19 infection. METHODS: This case-control study enrolled 24 laboratory-confirmed COVID-19 patients from Centro Hospitalar Conde de Sao Januario (C.H.C.S.J.), which was the only hospital designated to manage COVID-19 patients in Macao SAR, China, and 1113 control participants who completed a 14-day mandatory quarantine in 12 designated hotels due to returning from high-risk countries between 17 March and 15 April 2020. A questionnaire was developed to extract demographic information, contact history, and personal health behaviour. RESULTS: Participants primarily came from the United Kingdom (33.2%), followed by the United States (10.5%) and Portugal (10.2%). Independent factors for COVID-19 infection were having physical contact with confirmed/suspected COVID-19 patients (adjusted OR, 12.108 [95% CI, 3.380-43.376], P < 0.005), participating in high-risk gathering activities (adjusted OR, 1.129 [95% CI, 1.048-1.216], P < 0.005), handwashing after outdoor activity (adjusted OR, 0.021 [95% CI, 0.003-0.134], P < 0.005), handwashing before touching the mouth and nose area (adjusted OR, 0.303 [95% CI, 0.114-0.808], P < 0.05), and wearing a mask whenever outdoors (adjusted OR, 0.307 [95% CI, 0.109-0.867], P < 0.05). The daily count of handwashing remained similar between groups. Only 31.6% of participants had a sufficient 20-s handwashing duration. CONCLUSIONS: Participating in high-risk gatherings, wearing a mask whenever outdoors, and practising hand hygiene at key times should be advocated to the public to mitigate COVID-19 infection. URL: https://www.ncbi.nlm.nih.gov/pubmed/33926406 DOI: 10.1186/s12889-021-10680-5
110. MacIntyre R. Vaccination for COVID-19 control and considerations for Australia. Microbiology Australia. 2021;42(1):30-4. DOI: 10.1071/ma21009 ABSTRACT: Vaccines remain the main prospect for an exit strategy from the COVID-19 pandemic, and may, depending on efficacy, duration of protection and uptake, make herd immunity feasible. If herd immunity is not achievable, SARS-COV-2 will circulate long-term. There are many vaccine candidates in
Evidence Search Report: INF031801v4 ESR 52 development and choices between vaccines that will vary in efficacy and safety. The efficacy of available vaccines is compared and ranges from 62-95% against symptomatic infection with the G614 variant. Efficacy is reduced against new variants of concern and is uncertain against asymptomatic infection. Some vaccines show a better protective immune response than natural infection. The principles of herd immunity and prerequisites for achieving it, such as vaccine efficacy, duration of protection and coverage, are discussed. The alternative vaccine strategies including mass vaccination, targeted risk or age-based vaccination and ring vaccination, as well as speed of vaccination are reviewed. Finally, the impact of variants of concern on vaccine programs and the logistics of mass vaccination are discussed.Copyright © 2021 Journal Compilation URL: http://microbiology.publish.csiro.au/nid/206.htm http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emedx&NEWS=N&AN=634932402 DOI: 10.1071/ma21009
111. Mahallawi WH, Aljeraisi TM. In vitro cell culture model of human nasal-associated lymphoid tissue (NALT) to evaluate the humoral immune response to SARS-CoV-2 spike proteins. Saudi J Biol Sci. 2021;24:24. DOI: 10.1016/j.sjbs.2021.04.051 ABSTRACT: To date, coronavirus disease 2019 (COVID-19) continues to be considered a pandemic worldwide, with a mild to severe disease presentation that is sometimes associated with serious complications that are concerning to global health authorities. Scientists are working hard to understand the pathogenicity of this novel virus, and a great deal of attention and effort has been focused on identifying therapeutics and vaccines to control this pandemic. Methods: This study used tonsils removed from twelve patients who underwent an elective tonsillectomy in the ear, nose, and throat (ENT) department at Saudi Germany Hospital, Madinah, Saudi Arabia. Tonsillar mononuclear cells (MNCs) were separated and co-cultured in RPMI complete medium in the presence and absence of viral spike (S) proteins (the full-length S, S1 subunit, and S2 subunit proteins). Enzyme-linked immunosorbent assay (ELISA) was used to measure secreted antibody concentrations following stimulation. Results: The in vitro human nasal-associated lymphoid tissue (NALT) cell culture model was successfully used to evaluate the humoral immune response against SARS-CoV-2- S protein. Significant (p < 0.0001, n = 12) levels of specific, anti-S IgG, IgM, and IgA antibody responses were detected in cells culture supernatanat folloeing stimulation with the full-length S protein compared with unstimulated cells. In contrast, S1 and S2 subunit proteins alone failed to induce a mucosal humoral immune response following tonsillar MNC stimulation. Conclusion: We demonstrated a successful human NALT in vitro cell culture model that was used to study the mucosal humoral immune response to the SARS-CoV-2 S protein. This model could be advantageous for the in-depth study of cellular immune responses to the S protein and other viral antigens, such as nucleocapsid and matrix antigen. The S protein appears to be the important viral protein that may be able to mimic the natural infection process intranasally and should be studied as a component of a candidate vaccine. URL: https://www.ncbi.nlm.nih.gov/pubmed/33942008 DOI: 10.1016/j.sjbs.2021.04.051
112. Majeed A, Papaluca M, Molokhia M. Assessing the long-term safety and efficacy of COVID-19 vaccines. J R Soc Med. 2021:1410768211013437. DOI: 10.1177/01410768211013437 URL: https://www.ncbi.nlm.nih.gov/pubmed/33945346 DOI: 10.1177/01410768211013437
113. Marks SM, Clara A, Fiebelkorn AP, et al. Influenza Vaccination in Health Centers during the COVID-19 Pandemic-United States, November 7-27, 2020. Clin Infect Dis. 2021;12:12. DOI: 10.1093/cid/ciab318
Evidence Search Report: INF031801v4 ESR 53 ABSTRACT: BACKGROUND: Influenza vaccination is the most effective way to prevent influenza and influenza-associated complications including those leading to hospitalization. Resources otherwise used for influenza could support caring for patients with Coronavirus Disease 2019 (COVID-19). The Health Resources and Services Administration (HRSA) Health Center Program serves 30 million people annually by providing comprehensive primary health care, including influenza vaccination, to demographically diverse and historically underserved communities. As racial and ethnic minority groups have been disproportionately impacted by COVID-19, the objective of this analysis was to assess disparities in influenza vaccination at HRSA-funded health centers during the COVID-19 pandemic. METHODS: The Centers for Disease Control and Prevention (CDC) and HRSA analyzed cross-sectional data on influenza vaccinations from a weekly, voluntary Health Center COVID-19 survey after addition of an influenza- related question covering November 7-27, 2020. RESULTS: During the three-week period, 1,126 (81%) of 1385 health centers responded to the survey. Most of the 811,738 influenza vaccinations took place in urban areas and in the Western US Region. There were disproportionately more health center influenza vaccinations among racial and ethnic minorities in comparison with county demographics, except among Non-Hispanic Blacks and American Indian/Alaska Natives. CONCLUSIONS: HRSA-funded health centers were able to quickly vaccinate large numbers of mostly racial or ethnic minority populations, disproportionately more than county demographics. However, additional efforts might be needed to reach specific racial populations and persons in rural areas. Success in influenza vaccination efforts can support success in SARS-CoV-2 vaccination efforts. URL: https://www.ncbi.nlm.nih.gov/pubmed/33977297 DOI: 10.1093/cid/ciab318
114. McAlister FA, Bushnik T, Leung AA, et al. Informing COVID-19 vaccination priorities based on the prevalence of risk factors among adults in Canada. Cmaj. 2021;193(17):E617-E21. DOI: 10.1503/cmaj.210529 URL: https://www.ncbi.nlm.nih.gov/pubmed/33837040 DOI: 10.1503/cmaj.210529
115. Menni C, Klaser K, May A, et al. Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study. Lancet Infect Dis. 2021;27:27. DOI: 10.1016/S1473-3099(21)00224-3 ABSTRACT: BACKGROUND: The Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in phase 3 trials. We aimed to investigate the safety and effectiveness of these vaccines in a UK community setting. METHODS: In this prospective observational study, we examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine. We also compared infection rates in a subset of vaccinated individuals subsequently tested for SARS- CoV-2 with PCR or lateral flow tests with infection rates in unvaccinated controls. All analyses were adjusted by age (55 years), sex, health-care worker status (binary variable), obesity (BMI <30 kg/m(2)vs >/=30 kg/m(2)), and comorbidities (binary variable, with or without comorbidities). FINDINGS: Between Dec 8, and March 10, 2021, 627 383 individuals reported being vaccinated with 655 590 doses: 282 103 received one dose of BNT162b2, of whom 28 207 received a second dose, and 345 280 received one dose of ChAdOx1 nCoV-19. Systemic side-effects were reported by 13.5% (38 155 of 282 103) of individuals after the first dose of BNT162b2, by 22.0% (6216 of 28 207) after the second dose of BNT162b2, and by 33.7% (116 473 of 345 280) after the first dose of ChAdOx1 nCoV-19. Local side-effects were reported by 71.9% (150 023 of 208 767) of individuals after the first dose of BNT162b2, by 68.5% (9025 of 13 179) after the second dose of BNT162b2, and by 58.7% (104 282 of 177
Evidence Search Report: INF031801v4 ESR 54 655) after the first dose of ChAdOx1 nCoV-19. Systemic side-effects were more common (1.6 times after the first dose of ChAdOx1 nCoV-19 and 2.9 times after the first dose of BNT162b2) among individuals with previous SARS-CoV-2 infection than among those without known past infection. Local effects were similarly higher in individuals previously infected than in those without known past infection (1.4 times after the first dose of ChAdOx1 nCoV-19 and 1.2 times after the first dose of BNT162b2). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. Significant reductions in infection risk were seen starting at 12 days after the first dose, reaching 60% (95% CI 49-68) for ChAdOx1 nCoV-19 and 69% (66-72) for BNT162b2 at 21-44 days and 72% (63-79) for BNT162b2 after 45-59 days. INTERPRETATION: Systemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials. Both vaccines decrease the risk of SARS-CoV-2 infection after 12 days. FUNDING: ZOE Global, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, UK Medical Research Council, Wellcome Trust, UK Research and Innovation, American Gastroenterological Association. URL: https://www.ncbi.nlm.nih.gov/pubmed/33930320 DOI: 10.1016/S1473-3099(21)00224-3
116. Min L, Sun Q. Antibodies and Vaccines Target RBD of SARS-CoV-2. Front Mol Biosci. 2021;8:671633. DOI: 10.3389/fmolb.2021.671633 ABSTRACT: The novel human coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV- 2), which gives rise to the coronavirus disease 2019 (COVID-19), has caused a serious threat to global public health. On March 11, 2020, the WHO had officially announced COVID-19 as a pandemic. Therefore, it is vital to find effective and safe neutralizing antibodies and vaccines for COVID-19. The critical neutralizing domain (CND) that is contained in the receptor-binding domain (RBD) of the spike protein (S protein) could lead to a highly potent neutralizing antibody response as well as the cross- protection of other strains of SARS. By using RBD as an antigen, many neutralizing antibodies are isolated that are essential to the therapeutics of COVID-19. Furthermore, a subunit vaccine, which is based on the RBD, is expected to be safer than others, thus the RBD in the S protein is a more important target for vaccine development. In this review, we focus on neutralizing antibodies that are targeting RBD as well as the vaccine based on RBD under current development. URL: https://www.ncbi.nlm.nih.gov/pubmed/33968996 DOI: 10.3389/fmolb.2021.671633
117. Mohan S, Reagu S, Lindow S, et al. COVID-19 vaccine hesitancy in perinatal women: a cross sectional survey. J Perinat Med. 2021. DOI: 10.1515/jpm-2021-0069 ABSTRACT: OBJECTIVES: To explore attitudes to COVID-19 vaccination among perinatal women. METHODS: A nationwide online, cross-sectional survey was conducted in Qatar from 15th October 2020 to 15th November 2020 with voluntary participation open to all adult residents. Of the respondents, the population group for this study comprised the 341 pregnant and breastfeeding participants. The survey utilized a composite questionnaire incorporating a validated instrument to measure vaccine attitudes. The responses were recorded and analysed with statistical analysis being performed with SPSS software. Outcome measures included intentions towards vaccination and potential factors influencing vaccine hesitancy (contextual factors, vaccine specific concerns and group/individual influences). RESULTS: Perinatal women exhibited a vaccine hesitancy rate of 25% towards COVID-19 immunisation. The main concerns of the group were of infection risks and main factor determining vaccine hesitancy was of vaccine specific safety concerns. Previous vaccine "acceptors" showed vaccine hesitancy to COVID-19 immunisation. A third of the group cited non availability of the vaccine as a concern. CONCLUSIONS: COVID-19 vaccine trials amongst pregnant and lactating women have lagged behind those for general
Evidence Search Report: INF031801v4 ESR 55 populations and this has compounded concerns around safety in this special group. Perinatal women constitute a vulnerable group and play an important role in vaccination of wider family members. This study highlights the need for trials and data for COVID-19 vaccine in this group to be able to achieve appreciable numbers needed for herd immunity and ultimately control of the pandemic. URL: https://www.ncbi.nlm.nih.gov/pubmed/33905622 DOI: 10.1515/jpm-2021-0069
118. Monin L, Laing AG, Munoz-Ruiz M, et al. Safety and immunogenicity of one versus two doses of the COVID-19 vaccine BNT162b2 for patients with cancer: interim analysis of a prospective observational study. Lancet Oncol. 2021;27:27. DOI: 10.1016/S1470-2045(21)00213-8 ABSTRACT: BACKGROUND: The efficacy and safety profiles of vaccines against SARS-CoV-2 in patients with cancer is unknown. We aimed to assess the safety and immunogenicity of the BNT162b2 (Pfizer- BioNTech) vaccine in patients with cancer. METHODS: For this prospective observational study, we recruited patients with cancer and healthy controls (mostly health-care workers) from three London hospitals between Dec 8, 2020, and Feb 18, 2021. Participants who were vaccinated between Dec 8 and Dec 29, 2020, received two 30 mug doses of BNT162b2 administered intramuscularly 21 days apart; patients vaccinated after this date received only one 30 mug dose with a planned follow-up boost at 12 weeks. Blood samples were taken before vaccination and at 3 weeks and 5 weeks after the first vaccination. Where possible, serial nasopharyngeal real-time RT-PCR (rRT-PCR) swab tests were done every 10 days or in cases of symptomatic COVID-19. The coprimary endpoints were seroconversion to SARS-CoV-2 spike (S) protein in patients with cancer following the first vaccination with the BNT162b2 vaccine and the effect of vaccine boosting after 21 days on seroconversion. All participants with available data were included in the safety and immunogenicity analyses. Ongoing follow-up is underway for further blood sampling after the delayed (12-week) vaccine boost. This study is registered with the NHS Health Research Authority and Health and Care Research Wales (REC ID 20/HRA/2031). FINDINGS: 151 patients with cancer (95 patients with solid cancer and 56 patients with haematological cancer) and 54 healthy controls were enrolled. For this interim data analysis of the safety and immunogenicity of vaccinated patients with cancer, samples and data obtained up to March 19, 2021, were analysed. After exclusion of 17 patients who had been exposed to SARS-CoV-2 (detected by either antibody seroconversion or a positive rRT-PCR COVID-19 swab test) from the immunogenicity analysis, the proportion of positive anti-S IgG titres at approximately 21 days following a single vaccine inoculum across the three cohorts were 32 (94%; 95% CI 81-98) of 34 healthy controls; 21 (38%; 26-51) of 56 patients with solid cancer, and eight (18%; 10-32) of 44 patients with haematological cancer. 16 healthy controls, 25 patients with solid cancer, and six patients with haematological cancer received a second dose on day 21. Of the patients with available blood samples 2 weeks following a 21-day vaccine boost, and excluding 17 participants with evidence of previous natural SARS-CoV-2 exposure, 18 (95%; 95% CI 75-99) of 19 patients with solid cancer, 12 (100%; 76-100) of 12 healthy controls, and three (60%; 23-88) of five patients with haematological cancers were seropositive, compared with ten (30%; 17-47) of 33, 18 (86%; 65-95) of 21, and four (11%; 4-25) of 36, respectively, who did not receive a boost. The vaccine was well tolerated; no toxicities were reported in 75 (54%) of 140 patients with cancer following the first dose of BNT162b2, and in 22 (71%) of 31 patients with cancer following the second dose. Similarly, no toxicities were reported in 15 (38%) of 40 healthy controls after the first dose and in five (31%) of 16 after the second dose. Injection-site pain within 7 days following the first dose was the most commonly reported local reaction (23 [35%] of 65 patients with cancer; 12 [48%] of 25 healthy controls). No vaccine-related deaths were reported. INTERPRETATION: In patients with cancer, one dose of the BNT162b2 vaccine yields poor efficacy. Immunogenicity increased significantly in patients with solid cancer within 2 weeks of a vaccine boost at day 21 after the first dose. These data support prioritisation
Evidence Search Report: INF031801v4 ESR 56 of patients with cancer for an early (day 21) second dose of the BNT162b2 vaccine. FUNDING: King's College London, Cancer Research UK, Wellcome Trust, Rosetrees Trust, and Francis Crick Institute. URL: https://www.ncbi.nlm.nih.gov/pubmed/33930323 DOI: 10.1016/S1470-2045(21)00213-8
119. Moons P, Fieuws S, Vandermeulen C, et al. Influenza vaccination in congenital heart disease in the pre-COVID19 era: Coverage rate, patient characteristics and outcome. Can J Cardiol. 2021;04:04. DOI: 10.1016/j.cjca.2021.04.010 ABSTRACT: BACKGROUND: Influenza vaccination is the most commonly recommended immune prevention strategy. However, data on influenza vaccination in patients with congenital heart disease (CHD) is scarce. In this study, our goals were to (i) measure vaccination coverage rates (VCR) for influenza in a large cohort of children, adolescents and adults with CHD, (ii) identity patient characteristics as predictors for vaccination, and (iii) investigate the impact of influenza vaccination on hospitalization. METHODS: A nationwide cohort study in Belgium included 16,778 patients, representing 134,782 vaccination years, from the BELgian COngenital heart disease Database combining Administrative and Clinical data (BELCODAC). Data over 9 vaccination years (2006-2015) were used, and patients were stratified into five age cohorts: 6 months-4 years; 5-17 years; 18-49 years; 50-64 years; and >/=65 years. RESULTS: In the respective age cohorts, the VCR was estimated to be 6.6%, 8.0%, 23.9%, 46.6%, and 72.8%. There was a steep increase in VCR as of the age of 40 years. Multivariable logistic regression showed that higher anatomical complexity of CHD, older age, presence of genetic syndromes, and prior cardiac interventions were associated with significantly higher VCRs. Among adults, men had lower and pregnant women had higher VCRs. The association between influenza vaccination and all-cause hospitalization was not significant in this study. CONCLUSION: The influenza VCR in people with CHD is low, especially in children and adolescents. Older patients, particularly those with complex CHD, are well covered. Our findings should inform vaccination promotion strategies in populations with CHD. URL: https://www.ncbi.nlm.nih.gov/pubmed/33961983 DOI: 10.1016/j.cjca.2021.04.010
120. Moyad MA. Adult preventive vaccines with other synergistic lifestyle options: is it time to add these ancillary benefits to the overall AS management checklist? World J Urol. 2021;07:07. DOI: 10.1007/s00345-021-03709-2 ABSTRACT: PURPOSE: To review the potential ancillary cardiovascular and other health impacts of compliance with general adult vaccination series in the prostate cancer active surveillance (AS) population. No previous review has been published in regard to this specific topic. METHODS: Literature review of PubMed data up to December 2020 RESULTS: Compliance rates for adult vaccination are in the approximate anemic range of 25-50% with occasional higher rates of specific vaccines in the elderly population including annual influenza and pneumococcal prevention. Herpes zoster (HZ) and numerous other vaccine preventive illnesses are associated with an increased risk of cardiovascular events. Preliminary evidence suggests vaccine compliance could reduce overall morbidity and mortality, and adherence to heart healthy lifestyle changes and parameters could further improve vaccine efficacy and overall wellness. COVID-19 vaccine utilization and research should also continue to reinforce the direct and ancillary benefits of this entire preventive intervention category. CONCLUSIONS: Multiple ancillary lifestyle change recommendations could be included in the AS criteria to potentially reduce morbidity and mortality in this population, and perhaps the most unsung intervention is to improve the inadequate rates of general adult vaccination compliance and other heart healthy behavioral changes that impact their efficacy. Heart health, prostate health, and immune system health are closely interlinked.
Evidence Search Report: INF031801v4 ESR 57 URL: https://www.ncbi.nlm.nih.gov/pubmed/33963444 DOI: 10.1007/s00345-021-03709-2
121. Murshidi MM, Ihmeidan MK, Murshidi MM, et al. Risk of Covid-19 infection after resection of high grade transitional cell carcinoma with renal impairment. Int J Surg Case Rep. 2021;82:105924. DOI: 10.1016/j.ijscr.2021.105924 ABSTRACT: Introduction and importance: Covid-19 pandemic has had huge impact on health care system and put the health care system under strain, so efforts made to minimize the elective surgeries however some surgeries especially those for high risk malignant tumors cannot be postponed.The aim of this case report is to highlight the importance of screening cancer patients and those with co- morbidities such as renal impairment for Covid-19 and encouraging them to get vaccinated before undergoing elective surgeries. Case presentation: We report a case of an 80 year old male patient with renal impairment who developed Covid-19 infection after transurethral resection of high grade transitional cell carcinoma of urinary bladder. Clinical discussion: Although intra-hospital contagion of Covid-19 is not rare, increased risk of acquiring Covid-19 among cancer patient particularly if they have co-morbidities like renal impairment should be kept in mind and strict protective measures for Covid-19 for those patients should be done before, during and after the procedure. Conclusion: We theorized that patients with high grade transitional cell carcinoma of urinary bladder should be screened for Covid-19 and get vaccinated before the procedure. URL: https://www.ncbi.nlm.nih.gov/pubmed/33936935 DOI: 10.1016/j.ijscr.2021.105924
122. Murtada R, Carbonnel M, Revaux A, et al. Managing a Department of Obstetrics and Gynecology in Times of COVID-19 Outbreak: The Foch Hospital Experience. Front Surg. 2021;8:564145. DOI: 10.3389/fsurg.2021.564145 ABSTRACT: Departments of Gynecology and Obstetrics, as other departments, were faced with a major challenge at the outbreak of the COVID-19 pandemic. Fast restructuring was necessary in order to provide the means for COVID-related care. In this article we share our 1-year experience in reshaping our activities, managing healthcare workers and securing a pathway for pregnant patients, including potential, and confirmed COVID-19 cases. Priorities were set on ensuring patients' and healthcare workers' safety. Key containment measures included facemasks, systematic screening, dedicated spaces for COVID-19 cases with reinforced measures and vaccination campaign. URL: https://www.ncbi.nlm.nih.gov/pubmed/33928113 DOI: 10.3389/fsurg.2021.564145
123. Mysore V, Cullere X, Settles ML, et al. Protective heterologous T cell immunity in COVID-19 induced by MMR and Tdap vaccine antigens. bioRxiv. 2021;04:04. DOI: 10.1101/2021.05.03.441323 ABSTRACT: T cells are critical for control of viral infection and effective vaccination. We investigated whether prior Measles-Mumps-Rubella (MMR) or Tetanus-Diphtheria-pertussis (Tdap) vaccination elicit cross-reactive T cells that mitigate COVID-19. Using co-cultures of antigen presenting cells (APC) loaded with antigens and autologous T cells, we found a high correlation between responses to SARS-CoV-2 (Spike-S1 and Nucleocapsid) and MMR and Tdap vaccine proteins in both SARS-CoV-2 infected individuals and individuals immunized with mRNA-based SARS-CoV-2 vaccines. The overlapping T cell population contained effector memory T cells (TEMRA) previously implicated in anti-viral immunity and their activation required APC-derived IL-15. TCR- and scRNA-sequencing detected cross-reactive clones with TEMRA features among the cells recognizing SARS-CoV-2, MMR and Tdap epitopes. A propensity- weighted analysis of 73,582 COVID-19 patients revealed that severe disease outcomes (hospitalization and transfer to intensive care unit or death) were reduced in MMR or Tdap vaccinated individuals by 38-
Evidence Search Report: INF031801v4 ESR 58 32% and 23-20% respectively. In summary, SARS-CoV-2 re-activates memory T cells generated by Tdap and MMR vaccines, which may reduce disease severity. URL: https://www.ncbi.nlm.nih.gov/pubmed/33972940 DOI: 10.1101/2021.05.03.441323
124. Nagy A, Alhatlani B. An overview of current COVID-19 vaccine platforms. Comput Struct Biotechnol J. 2021;19:2508-17. DOI: 10.1016/j.csbj.2021.04.061 ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic that emerged in December 2019 in Wuhan city, China. An effective vaccine is urgently needed to protect humans and to mitigate the economic and societal impacts of the pandemic. Despite standard vaccine development usually requiring an extensive process and taking several years to complete all clinical phases, there are currently 184 vaccine candidates in pre-clinical testing and another 88 vaccine candidates in clinical phases based on different vaccine platforms as of April 13, 2021. Moreover, three vaccine candidates have recently been granted an Emergency Use Authorization by the United States Food and Drug Administration (for Pfizer/BioNtech, Moderna mRNA vaccines, and Johnson and Johnson viral vector vaccine) and by the UK government (for University of Oxford/AstraZeneca viral vector vaccine). Here we aim to briefly address the current advances in reverse genetics system of SARS-CoV-2 and the use of this in development of SARS-CoV-2 vaccines. Additionally, we cover the essential points concerning the different platforms of current SARS- CoV-2 vaccine candidates and the advantages and drawbacks of these platforms. We also assess recommendations for controlling the COVID-19 pandemic and future pandemics using the benefits of genetic engineering technology to design effective vaccines against emerging and re-emerging viral diseases with zoonotic and/or pandemic potential. URL: https://www.ncbi.nlm.nih.gov/pubmed/33936564 DOI: 10.1016/j.csbj.2021.04.061
125. Ogbebor O, Seth H, Min Z, et al. Guillain-Barre syndrome following the first dose of SARS-CoV-2 vaccine: A temporal occurrence, not a causal association. IDCases. 2021;24:e01143. DOI: 10.1016/j.idcr.2021.e01143 ABSTRACT: Safety monitoring is of paramount importance for vaccines authorized for emergent use (EUA) by the US Food and Drug Administration (FDA) against SARS-CoV-2. Mass immunization is an essential tool to end the current pandemic, but vaccine surveillance is necessary to identify any potentially associated harms. At the same time, probability of temporal bias should be borne in mind before making conclusions about causality between the vaccine and an attributable undesired effect. We report a case of Guillain-Barre syndrome after the first dose of SARS-CoV-2 vaccine and believe this is a temporal, rather than causal association. URL: https://www.ncbi.nlm.nih.gov/pubmed/33968610 DOI: 10.1016/j.idcr.2021.e01143
126. Oldenburg J, Klamroth R, Langer F, et al. Erratum: Diagnosis and Management of Vaccine-Related Thrombosis following AstraZeneca COVID-19 Vaccination: Guidance Statement from the GTH. Hamostaseologie. 2021;12:12. DOI: 10.1055/s-0041-1729135 URL: https://www.ncbi.nlm.nih.gov/pubmed/33979842 DOI: 10.1055/s-0041-1729135
127. Orskov S, Frost Nielsen B, Fons S, et al. The COVID-19 pandemic: Key considerations for the epidemic and its control. APMIS. 2021;01:01. DOI: 10.1111/apm.13141
Evidence Search Report: INF031801v4 ESR 59 ABSTRACT: The response to the ongoing COVID-19 pandemic has been characterized by draconian measures and far too many important unknowns, such as the true mortality risk, the role of children as transmitters and the development and duration of immunity in the population. More than a year into the pandemic much has been learned and insights into this novel type of pandemic and options for control are shaping up. Using a historical lens, we review what we know and still do not know about the ongoing COVID-19 pandemic. A pandemic caused by a member of the coronavirus family is a new situation following more than a century of influenza A pandemics. However, recent pandemic threats such as outbreaks of the related and novel deadly coronavirus SARS in 2003 and of MERS since 2012 had put coronaviruses on WHOs blueprint list of priority diseases. Like pandemic influenza, SARS-CoV-2 is highly transmissible (R0 ~2.5). Furthermore, it can fly under the radar due to a broad clinical spectrum where asymptomatic and pre-symptomatic infected persons also transmit the virus - including children. COVID-19 is far more deadly than seasonal influenza; initial data from China suggested a case fatality rate of 2.3% - which would have been on par with the deadly 1918 Spanish influenza. But, while the Spanish influenza killed young, otherwise healthy adults, it is the elderly who are at extreme risk of dying of COVID-19. We review available seroepidemiological evidence of infection rates and compute infection fatality rates (IFR) for Denmark (0.5%), Spain (0.85%) and Iceland (0.3%). We also deduce that population age structure is key. SARS-CoV-2 is characterized by superspreading, so that ~10% of infected individuals yield 80% of new infections. This phenomenon turns out to be an Achilles heel of the virus that may explain our ability to effectively mitigate outbreaks so far. How will this pandemic come to an end? Herd immunity has not been achieved in Europe due to intense mitigation by non-pharmaceutical interventions; for example, only ~8% of Danes were infected across the 1(st) and 2(nd) wave. Luckily, we now have several safe and effective vaccines. Global vaccine control of the pandemic depends in great measure on our ability to keep up with current and future immune escape variants of the virus. We should thus be prepared for a race between vaccine updates and mutations of the virus. A permanent reopening of society highly depends on winning that race. URL: https://www.ncbi.nlm.nih.gov/pubmed/33932317 DOI: 10.1111/apm.13141
128. Pan HX, Liu JK, Huang BY, et al. Immunogenicity and safety of a SARS-CoV-2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials. Chin Med J (Engl). 2021;28:28. DOI: 10.1097/CM9.0000000000001573 ABSTRACT: BACKGROUND: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults. METHODS: Phase 1 and phase 2 randomized, double-blind, and placebo- controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18-59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 mug/dose or 10 mug/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 mug/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose. RESULTS: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-mug vaccine (n = 24), 10-mug vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-mug vaccine (n = 100 for 0/14 or 0/28 regimens), 10-mug vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and 7 (58%) participants reported at least
Evidence Search Report: INF031801v4 ESR 60 one adverse event (AE) after receiving 5-mug vaccine, 10-mug vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and 9 (18%) 0/14-regimen participants reported at least one AE after receiving 5-mug vaccine, 10-mug vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses. CONCLUSIONS: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-mug vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353). URL: https://www.ncbi.nlm.nih.gov/pubmed/33928916 DOI: 10.1097/CM9.0000000000001573
129. Paoletti G, Racca F, Piona A, et al. Successful SARS-CoV-2 vaccine allergy risk-management: The experience of a large Italian University Hospital. World Allergy Organ J. 2021;14(5):100541. DOI: 10.1016/j.waojou.2021.100541 ABSTRACT: Background: Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines have been approved recently, and public concern regarding the risk of anaphylactic reactions arose after a few cases during the first days of mass vaccination. Polyethylene glycol (PEG) has been suggested as the most probable culprit agent for allergic reactions. Objective: We describe the allergy work-up protocol implemented for the vaccination campaign in our Center, aiming to allow the greatest number of people to be vaccinated safely. Methods: The protocol included the self-report of a history of suspected drug or vaccine allergies, and subsequent teleconsultation and allergometric tests for PEG and Polysorbate 80 (PS80). A desensitizing protocol of vaccine administration was applied to patients sensitized only to PS80, and to those with a suspect allergic reaction after the first vaccine dose. Results: 10.2% (414 out of 4042) of the entire vaccine population have been screened: only one patient resulted allergic to PEG and therefore excluded from the vaccination. Another patient was sensitized to PS80 only and safely vaccinated applying the desensitizing protocol. Seven subjects without a previous history of allergic disease experienced suspect hypersensitivity reactions to the first administered dose: one of them resulted allergic to PEG and was excluded from the second dose, while the others safely completed the vaccination with the desensitizing protocol. Conclusion: A careful allergological risk- assessment protocol significantly reduces the number of patients who would have avoided SARS-CoV-2 vaccination for their allergies and to effectively identify and manage those rare patients with sensitization to PEGs and/or PS80. URL: https://www.ncbi.nlm.nih.gov/pubmed/33850601 DOI: 10.1016/j.waojou.2021.100541
130. Pascual-Ferra P, Alperstein N, Barnett DJ. A Multi-platform Approach to Monitoring Negative Dominance for COVID-19 Vaccine-Related Information Online. Disaster Med Public Health Prep. 2021:1-24. DOI: 10.1017/dmp.2021.136 ABSTRACT: OBJECTIVE: The aim of this study was to test the appearance of negative dominance in COVID-19 vaccine-related information and activity online. We hypothesized that if negative dominance appeared, it would be a reflection of peaks in adverse events related to the vaccine, that negative content would attract more engagement on social media than other vaccine-related posts, and posts referencing adverse events related to COVID-19 vaccination would have a higher average toxicity score. METHODS: We collected data using Google Trends for search behavior, CrowdTangle for social media
Evidence Search Report: INF031801v4 ESR 61 data, and Media Cloud for media stories, and compared them against the dates of key adverse events related to COVID-19. We used Communalytic to analyze the toxicity of social media posts by platform and topic. RESULTS: While our first hypothesis was partially supported, with peaks in search behavior for image and YouTube videos driven by adverse events, we did not find negative dominance in other types of searches or patterns of attention by news media or on social media. CONCLUSION: We did not find evidence in our data to prove the negative dominance of adverse events related to COVID-19 vaccination on social media. Future studies should corroborate these findings and, if consistent, focus on explaining why this may be the case. URL: https://www.ncbi.nlm.nih.gov/pubmed/33938423 DOI: 10.1017/dmp.2021.136
131. Paul E, Steptoe A, Fancourt D. Attitudes towards vaccines and intention to vaccinate against COVID-19: Implications for public health communications. Lancet Reg Health Eur. 2021;1:100012. DOI: 10.1016/j.lanepe.2020.100012 ABSTRACT: Background: Negative attitudes towards vaccines and an uncertainty or unwillingness to receive vaccinations are major barriers to managing the COVID-19 pandemic in the long-term. We estimate predictors of four domains of negative attitudes towards vaccines and identify groups most at risk of uncertainty and unwillingness to receive a COVID-19 vaccine in a large sample of UK adults. Methods: Data were cross-sectional and from 32,361 adults in the UCL COVID-19 Social Study. Ordinary least squares regression analyses examined the impact of socio-demographic and COVID-19 related factors on four types of negative vaccine attitudes: mistrust of vaccine benefit, worries about unforeseen effects, concerns about commercial profiteering, and preference for natural immunity. Multinomial regression examined the impact of socio-demographic and COVID-19 related factors, negative vaccine attitudes, and prior vaccine behaviour on uncertainty and unwillingness to be vaccinated for COVID-19. Findings: 16% of respondents displayed high levels of mistrust about vaccines across one or more domains. Distrustful attitudes towards vaccination were higher amongst individuals from ethnic minority backgrounds, with lower levels of education, lower annual income, poor knowledge of COVID-19, and poor compliance with government COVID-19 guidelines. Overall, 14% of respondents reported unwillingness to receive a vaccine for COVID-19, whilst 23% were unsure. The largest predictors of both COVID-19 vaccine uncertainty and refusal were low-income groups (< pound16,000, a year), having not received a flu vaccine last year, poor adherence to COVID-19 government guidelines, female gender, and living with children. Amongst vaccine attitudes, intermediate to high levels of mistrust of vaccine benefit and concerns about future unforeseen side effects were the most important determinants of both uncertainty and unwillingness to vaccinate against COVID-19. Interpretation: Negative attitudes towards vaccines are a major public health concern in the UK. General mistrust in vaccines and concerns about future side effects in particular will be barriers to achieving population immunity to COVID-19 through vaccination. Public health messaging should be tailored to address these concerns and specifically to women, ethnic minorities, and people with lower levels of education and incomes. Funding: The Nuffield Foundation [WEL/FR-000022583], the MARCH Mental Health Network funded by the Cross-Disciplinary Mental Health Network Plus initiative supported by UK Research and Innovation [ES/S002588/1], and the Wellcome Trust [221400/Z/20/Z and 205407/Z/16/Z]. URL: https://www.ncbi.nlm.nih.gov/pubmed/33954296 DOI: 10.1016/j.lanepe.2020.100012
132. Pedote PD, Termite S, Gigliobianco A, et al. Influenza Vaccination and Health Outcomes in COVID- 19 Patients: A Retrospective Cohort Study. Vaccines (Basel). 2021;9(4):08. DOI: 10.3390/vaccines9040358
Evidence Search Report: INF031801v4 ESR 62 ABSTRACT: COVID-19 is an infectious disease caused by the novel coronavirus SARS-CoV-2. Several measures aimed at containing the spread of this virus have been recommended by international and nation public health institutions, but whether the influenza vaccine, while not protective against COVID- 19, nonetheless reduces disease severity is unclear. This study evaluated the potential role of influenza vaccine in reducing the rate of hospitalization and death in COVID-19 patients. COVID-19 cases recorded in the province of Brindisi (Apulia, Southern Italy) during the first pandemic wave (February-May 2020) and occurring in patients vaccinated with the influenza vaccine during the 2019-2020 influenza season were considered. From February 2020 to May 2020, 3872 inhabitants of the province of Brindisi underwent SARS-CoV-2 PCR testing and 664 (8.7%) tested positive. A multivariate analysis showed that among COVID-19 patients neither hospitalization nor death was significantly associated with influenza vaccination (p > 0.05), whereas within this group male sex, older age, and chronic diseases were identified as risk factors for morbidity and mortality. Our study did not show an association between the influenza vaccine and complications of COVID-19. Nonetheless, influenza vaccination must be promoted as a central public health measure, because by reducing the burden on hospitals it can greatly benefit the management of COVID-19 patients. URL: https://www.ncbi.nlm.nih.gov/pubmed/33917898 DOI: 10.3390/vaccines9040358
133. Peter J. COVID-19 vaccination: Recommendations for management of patients with allergy or immune-based diseases. S Afr Med J. 2021;111(4):291-4. DOI: 10.7196/SAMJ.2021.v111i4.15576 ABSTRACT: As South Africa continues to battle the second wave of SARS-CoV-2 infections, the imminent arrival of vaccines against COVID-19 offers hope. Vaccine roll-out has been accompanied by heightened media coverage that has created both excitement and anxiety, reporting on the shortened timeline of vaccine trials and approvals, as well as the recent series of anaphylaxis cases associated with the two approved mRNA COVID-19 vaccines. Patients with allergic and other immune-based diseases are subgroups especially concerned about vaccine safety and efficacy. This practice guideline offers broad recommendations for COVID-19 vaccination in various subgroups of allergic and immunebased disease, highlighting risk/benefit evaluation, and where and how routine vaccination should be altered. URL: https://www.ncbi.nlm.nih.gov/pubmed/33944757 DOI: 10.7196/SAMJ.2021.v111i4.15576
134. Phanhdone T, Drummond P, Meisel T, et al. Barriers to Vaccination Among People with Parkinson's Disease and Implications for COVID-19. J Parkinsons Dis. 2021;30:30. DOI: 10.3233/JPD- 202497 ABSTRACT: BACKGROUND: Patients with Parkinson's disease (PD) are at higher risk of vaccine- preventable respiratory infections. However, advanced, homebound individuals may have less access to vaccinations. In light of COVID-19, understanding barriers to vaccination in PD may inform strategies to increase vaccine uptake. OBJECTIVE: To identify influenza and pneumococcal vaccination rates, including barriers and facilitators to vaccination, among homebound and ambulatory individuals with PD and related disorders. METHODS: Cross-sectional US-based study among individuals with PD, aged > 65 years, stratified as homebound or ambulatory. Participants completed semi-structured interviews on vaccination rates and barriers, and healthcare utilization. RESULTS: Among 143 participants, 9.8% had missed all influenza vaccinations in the past 5 years, and 32.2% lacked any pneumococcal vaccination, with no between-group differences. Homebound participants (n = 41) reported difficulty traveling to clinic (p < 0.01) as a vaccination barrier, and despite similar outpatient visit frequencies, had more frequent emergency department visits (31.7% vs. 9.8%, p < 0.01) and hospitalizations (14.6% vs. 2.9%, p = 0.03). Vaccine hesitancy was reported in 35% of participants, vaccine refusal in 19%, and 13.3% reported unvaccinated household members, with no between-group differences. Nearly 13% thought
Evidence Search Report: INF031801v4 ESR 63 providers recommended against vaccines for PD patients, and 31.5% were unsure of vaccine recommendations in PD. CONCLUSION: Among a sample of homebound and ambulatory people with PD, many lack age-appropriate immunizations despite ample healthcare utilization. Many participants were unsure whether healthcare providers recommend vaccinations for people with PD. In light of COVID-19, neurologist reinforcement that vaccinations are indicated, safe, and recommended may be beneficial. URL: https://www.ncbi.nlm.nih.gov/pubmed/33935103 DOI: 10.3233/JPD-202497
135. Pinnawala NU, Thrastardottir TO, Constantinou C. Keeping a Balance During the Pandemic: a Narrative Review on the Important Role of Micronutrients in Preventing Infection and Reducing Complications of COVID-19. Curr Nutr Rep. 2021;05:05. DOI: 10.1007/s13668-021-00356-2 ABSTRACT: PURPOSE OF REVIEW: The SARS-CoV-2 (COVID-19) outbreak has manifested into a major public health concern across the globe, affecting particularly the most vulnerable population groups. Currently, there are various clinical trials being conducted to develop effective treatments. It is estimated that it could take one or more years before these drugs pass all safety tests and concrete results with regard to their effectiveness become available. In addition, despite the recent development of vaccines (licensed for use under conditional licenses) and the commencement of COVID-19 vaccination programs in several countries, there is still a need for safe and novel strategies that may reduce the symptomatology and/or prevent the severe complications associated with COVID-19. Natural compounds previously shown to have antiviral potential should be thoroughly considered and investigated for use in prophylactic treatment of COVID-19 due to their availability and safety. RECENT FINDINGS: The current narrative review investigates whether there is evidence in the literature that supplementation with dietary minerals and vitamins may have a role in preventing infection with SARS- CoV-2 or in reducing COVID-19 symptomatology and disease progression. The current evidence from the literature supports that zinc and vitamin C have a potential in reducing the inflammatory response associated with SARS-CoV-2 while folate and vitamin D may have a role in antagonizing the entry of SARs-CoV-2 virus in host calls. Thus, further research should be conducted that could lead to the development of nutritional supplements involving natural and widely available compounds such as zinc, folate, vitamin C, and vitamin D. The latter could be an effective, safe, and inexpensive way to either prevent infection with SARS-CoV-2 and/or lessen the burden of COVID-19 disease. URL: https://www.ncbi.nlm.nih.gov/pubmed/33948913 DOI: 10.1007/s13668-021-00356-2
136. Puteikis K, Mameniskiene R. Factors Associated with COVID-19 Vaccine Hesitancy among People with Epilepsy in Lithuania. Int J Environ Res Public Health. 2021;18(8):20. DOI: 10.3390/ijerph18084374 ABSTRACT: The purpose of our study was to determine the willingness to be vaccinated against COVID- 19 and factors associated with vaccine hesitancy among people with epilepsy (PWE). In December 2020, we performed an online cross-sectional survey of PWE and their caregivers in Lithuania before the rollout of COVID-19 vaccines to the public. The study sample consisted of 111 respondents (44 (39.6%) male, median age 25 years (range 1 to 70)). From 58 PWE who personally responded to the survey, 27 (46.6%) would be willing to be vaccinated against COVID-19. Among the 53 caregivers, 18 (34.0%) would accept the person they care for to be vaccinated. Willingness to be vaccinated was associated with receiving an influenza shot in 2020 (odds ratio (OR) = 9.17, 95% confidence interval (CI = 1.15-73.47), the beliefs that vaccines are generally safe (OR = 7.90, 95% CI = 2.43-25.74) and that they are the only convenient way to gain immunity (OR = 3.91, 95% CI = 1.02-15.05). Respondents were hesitant to accept the COVID-19 vaccine if they thought it could cause the infection (OR = 0.14, 95% CI = 0.04-0.49). COVID-
Evidence Search Report: INF031801v4 ESR 64 19 vaccine hesitancy is frequent among PWE and their caregivers. It is probably related to erroneous beliefs about their safety and mechanism of action. URL: https://www.ncbi.nlm.nih.gov/pubmed/33924140 DOI: 10.3390/ijerph18084374
137. Ragan IK, Hartson LM, Dutt TS, et al. A Whole Virion Vaccine for COVID-19 Produced via a Novel Inactivation Method and Preliminary Demonstration of Efficacy in an Animal Challenge Model. Vaccines (Basel). 2021;9(4):01. DOI: 10.3390/vaccines9040340 ABSTRACT: The COVID-19 pandemic has generated intense interest in the rapid development and evaluation of vaccine candidates for this disease and other emerging diseases. Several novel methods for preparing vaccine candidates are currently undergoing clinical evaluation in response to the urgent need to prevent the spread of COVID-19. In many cases, these methods rely on new approaches for vaccine production and immune stimulation. We report on the use of a novel method (SolaVAX) for production of an inactivated vaccine candidate and the testing of that candidate in a hamster animal model for its ability to prevent infection upon challenge with SARS-CoV-2 virus. The studies employed in this work included an evaluation of the levels of neutralizing antibody produced post-vaccination, levels of specific antibody sub-types to RBD and spike protein that were generated, evaluation of viral shedding post-challenge, flow cytometric and single cell sequencing data on cellular fractions and histopathological evaluation of tissues post-challenge. The results from this preliminary evaluation provide insight into the immunological responses occurring as a result of vaccination with the proposed vaccine candidate and the impact that adjuvant formulations, specifically developed to promote Th1 type immune responses, have on vaccine efficacy and protection against infection following challenge with live SARS-CoV-2. This data may have utility in the development of effective vaccine candidates broadly. Furthermore, the results of this preliminary evaluation suggest that preparation of a whole virion vaccine for COVID-19 using this specific photochemical method may have potential utility in the preparation of one such vaccine candidate. URL: https://www.ncbi.nlm.nih.gov/pubmed/33916180 DOI: 10.3390/vaccines9040340
138. Ramaswamy M, Satterwhite CL, Lipnicky A, et al. Recommendations for Delivering COVID-19 Vaccine in Jails: Evidence from Kansas, Iowa, Nebraska, and Missouri. Am J Public Health. 2021;111(6):1035-9. DOI: 10.2105/AJPH.2021.306218 ABSTRACT: We report on data we collected from a 2018 survey examining jails' human papillomavirus virus vaccine delivery capacity and on a secondary analysis we conducted to describe factors similarly associated with delivery planning for the COVID-19 vaccine. We provide recommendations for delivering the COVID-19 vaccine in jails, based on evidence from Kansas, Iowa, Nebraska, and Missouri. Our key finding is that jails have limited staff to implement vaccination and will require collaboration between jail administrators, jail medical staff, and local health departments. URL: https://www.ncbi.nlm.nih.gov/pubmed/33950714 DOI: 10.2105/AJPH.2021.306218
139. Rammensee HG, Gouttefangeas C, Heidu S, et al. Designing a SARS-CoV-2 T-Cell-Inducing Vaccine for High-Risk Patient Groups. Vaccines (Basel). 2021;9(5):24. DOI: 10.3390/vaccines9050428 ABSTRACT: We describe the results of two vaccinations of a self-experimenting healthy volunteer with SARS-CoV-2-derived peptides performed in March and April 2020, respectively. The first set of peptides contained eight peptides predicted to bind to the individual's HLA molecules. The second set consisted of ten peptides predicted to bind promiscuously to several HLA-DR allotypes. The vaccine formulation contained the new TLR 1/2 agonist XS15 and was administered as an emulsion in Montanide as a single
Evidence Search Report: INF031801v4 ESR 65 subcutaneous injection. Peripheral blood mononuclear cells isolated from blood drawn before and after vaccinations were assessed using Interferon-gamma ELISpot assays and intracellular cytokine staining. We detected vaccine-induced CD4 T cell responses against six out of 11 peptides predicted to bind to HLA-DR after 19 days, following vaccination, for one peptide already at day 12. We used these results to support the design of a T-cell-inducing vaccine for application in high-risk patients, with weakened lymphocyte performance. Meanwhile, an according vaccine, incorporating T cell epitopes predominant in convalescents, is undergoing clinical trial testing. URL: https://www.ncbi.nlm.nih.gov/pubmed/33923363 DOI: 10.3390/vaccines9050428
140. Rao IJ, Brandeau ML. Optimal allocation of limited vaccine to control an infectious disease: Simple analytical conditions. Math Biosci. 2021;337:108621. DOI: 10.1016/j.mbs.2021.108621 ABSTRACT: When allocating limited vaccines to control an infectious disease, policy makers frequently have goals relating to individual health benefits (e.g., reduced morbidity and mortality) as well as population-level health benefits (e.g., reduced transmission and possible disease eradication). We consider the optimal allocation of a limited supply of a preventive vaccine to control an infectious disease, and four different allocation objectives: minimize new infections, deaths, life years lost, or quality-adjusted life years (QALYs) lost due to death. We consider an SIR model with n interacting populations, and a single allocation of vaccine at time 0. We approximate the model dynamics to develop simple analytical conditions characterizing the optimal vaccine allocation for each objective. We instantiate the model for an epidemic similar to COVID-19 and consider n=2 population groups: one group (individuals under age 65) with high transmission but low mortality and the other group (individuals age 65 or older) with low transmission but high mortality. We find that it is optimal to vaccinate younger individuals to minimize new infections, whereas it is optimal to vaccinate older individuals to minimize deaths, life years lost, or QALYs lost due to death. Numerical simulations show that the allocations resulting from our conditions match those found using much more computationally expensive algorithms such as exhaustive search. Sensitivity analysis on key parameters indicates that the optimal allocation is robust to changes in parameter values. The simple conditions we develop provide a useful means of informing vaccine allocation decisions for communicable diseases. URL: https://www.ncbi.nlm.nih.gov/pubmed/33915160 DOI: 10.1016/j.mbs.2021.108621
141. Raturi M, Kusum A, Kala M, et al. Locally harvested Covid-19 convalescent plasma could probably help combat the geographically determined SARS-CoV-2 viral variants. Transfus Clin Biol. 2021;07:07. DOI: 10.1016/j.tracli.2021.05.003 ABSTRACT: The only effective way to provide individuals with herd immunity against the novel coronavirus [SARS-CoV-2] is to administer an effective vaccine that will help check the current pandemic status. In India, the central drugs standard control organization (CDSCO) has granted the emergency-use authorization [EUA] to three vaccines namely, Covishield (live vaccine, Oxford AstraZeneca, United Kingdom being manufactured by the Serum Institute of India), Covaxin (inactivated vaccine, Bharat Biotech, India) and Sputnik V (live vaccine, Gamaleya, Russia). However, there is a rising need for the efficacy of the vaccines to be proven against the "SARS-CoV-2 viral variants." Also, human plasma is polyclonal in nature with an inherent propensity to identify multiple epitopes of either an antigen or pathogen. With this context in mind, the researchers hypothesize that using COVID-19 convalescent plasma [CCP] harvested from the locally recovered individuals [i.e. potential CCP donors] may be particularly beneficial in combating not only the founder SARS-CoV-2 virus but also the geographically confined SARS-CoV-2 variants among the regionally affected COVID-19 patients. URL: https://www.ncbi.nlm.nih.gov/pubmed/33971318
Evidence Search Report: INF031801v4 ESR 66 DOI: 10.1016/j.tracli.2021.05.003
142. Reno C, Maietti E, Fantini MP, et al. Enhancing COVID-19 Vaccines Acceptance: Results from a Survey on Vaccine Hesitancy in Northern Italy. Vaccines (Basel). 2021;9(4):13. DOI: 10.3390/vaccines9040378 ABSTRACT: In March 2021, the coronavirus disease 2019 (COVID-19) pandemic still poses a threat to the global population, and is a public health challenge that needs to be overcome. Now more than ever, action is needed to tackle vaccine hesitancy, especially in light of the availability of effective and safe vaccines. A cross-sectional online survey was carried out on a representative random sample of 1011 citizens from the Emilia-Romagna region, in Italy, in January 2021. The questionnaire collected information on socio-demographics, comorbidities, past vaccination refusal, COVID-19-related experiences, risk perception of infection, and likelihood to accept COVID-19 vaccination. Multiple logistic regression analyses and classification tree analyses were performed to identify significant predictors of vaccine hesitancy and to distinguish groups with different levels of hesitancy. Overall, 31.1% of the sample reported hesitancy. Past vaccination refusal was the key discriminating variable followed by perceived risk of infection. Other significant predictors of hesitancy were: ages between 35 and 54 years, female gender, low educational level, low income, and absence of comorbidities. The most common concerns about the COVID-19 vaccine involved safety (54%) and efficacy (27%). Studying the main determinants of vaccine hesitancy can help with targeting vaccination strategies, in order to gain widespread acceptance-a key path to ensure a rapid way out of the current pandemic emergency. URL: https://www.ncbi.nlm.nih.gov/pubmed/33924534 DOI: 10.3390/vaccines9040378
143. Riad A, Pokorna A, Attia S, et al. Prevalence of COVID-19 Vaccine Side Effects among Healthcare Workers in the Czech Republic. J Clin Med. 2021;10(7):01. DOI: 10.3390/jcm10071428 ABSTRACT: BACKGROUND: COVID-19 vaccine side effects have a fundamental role in public confidence in the vaccine and its uptake process. Thus far, the evidence on vaccine safety has exclusively been obtained from the manufacturer-sponsored studies; therefore, this study was designed to provide independent evidence on Pfizer-BioNTech COVID-19 vaccine side effects. METHODS: A cross-sectional survey-based study was carried out between January and February 2021 to collect data on the side effects following the COVID-19 vaccine among healthcare workers in the Czech Republic. The study used a validated questionnaire with twenty-eight multiple-choice items covering the participants' demographic data, medical anamneses, COVID-19-related anamneses, general, oral, and skin-related side effects. RESULTS: Injection site pain (89.8%), fatigue (62.2%), headache (45.6%), muscle pain (37.1%), and chills (33.9%) were the most commonly reported side effects. All the general side effects were more prevalent among the
144. Ricco M, De Nard F, Peruzzi S. Mosaic vaccination schedule: An unexpected card to play against SARS-CoV-2? Infect Dis Now. 2021;51(4):402-5. DOI: 10.1016/j.idnow.2021.03.001
Evidence Search Report: INF031801v4 ESR 67 URL: https://www.ncbi.nlm.nih.gov/pubmed/33748805 DOI: 10.1016/j.idnow.2021.03.001
145. Ring J, Beyer K, Biedermann T, et al. Guideline (S2k) on acute therapy and management of anaphylaxis: 2021 update: S2k-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Medical Association of German Allergologists (AeDA), the Society of Pediatric Allergology and Environmental Medicine (GPA), the German Academy of Allergology and Environmental Medicine (DAAU), the German Professional Association of Pediatricians (BVKJ), the Society for Neonatology and Pediatric Intensive Care (GNPI), the German Society of Dermatology (DDG), the Austrian Society for Allergology and Immunology (OGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Anaesthesiology and Intensive Care Medicine (DGAI), the German Society of Pharmacology (DGP), the German Respiratory Society (DGP), the patient organization German Allergy and Asthma Association (DAAB), the German Working Group of Anaphylaxis Training and Education (AGATE). Allergo J Int. 2021;30(1):1-25. DOI: 10.1007/s40629-020- 00158-y URL: https://www.ncbi.nlm.nih.gov/pubmed/33527068 DOI: 10.1007/s40629-020-00158-y
146. Ripari N, Sartori AA, da Silva Honorio M, et al. Propolis antiviral and immunomodulatory activity: a review and perspectives for COVID-19 treatment. J Pharm Pharmacol. 2021;73(3):281-99. DOI: 10.1093/jpp/rgaa067 ABSTRACT: OBJECTIVES: Viral outbreaks are a frequent concern for humans. A great variety of drugs has been used to treat viral diseases, which are not always safe and effective and may induce adverse effects, indicating the need for new antiviral drugs extracted from natural sources. Propolis is a bee- made product exhibiting many biological properties. An overview of viruses, antiviral immunity, propolis safety and its immunomodulatory and antiviral action is reported, as well as perspectives for coronavirus disease 2019 (COVID-19) treatment. PubMed platform was used for data collection, searching for the keywords "propolis", "virus", "antiviral", "antimicrobial" and "coronavirus". KEY FINDINGS: Propolis is safe and exerts antiviral and immunomodulatory activity; however, clinical trials should investigate its effects on individuals with viral diseases, in combination or not with antiviral drugs or vaccines. SUMMARY: Regarding COVID-19, the effects of propolis should be investigated directly on the virus in vitro or on infected individuals alone or in combination with antiviral drugs, due to its immunomodulatory and anti-inflammatory action. Propolis administration simultaneously with vaccines should be analyzed, due to its adjuvant properties, to enhance the individuals' immune response. The search for therapeutic targets may be useful to find out how propolis can help to control COVID-19. URL: https://www.ncbi.nlm.nih.gov/pubmed/33793885 DOI: 10.1093/jpp/rgaa067
147. Romer D, Jamieson KH. Patterns of Media Use, Strength of Belief in COVID-19 Conspiracy Theories, and the Prevention of COVID-19 From March to July 2020 in the United States: Survey Study. J Med Internet Res. 2021;23(4):e25215. DOI: 10.2196/25215 ABSTRACT: BACKGROUND: Holding conspiracy beliefs regarding the COVID-19 pandemic in the United States has been associated with reductions in both actions to prevent the spread of the infection (eg, mask wearing) and intentions to accept a vaccine when one becomes available. Patterns of media use have also been associated with acceptance of COVID-19 conspiracy beliefs. Here we ask whether the type of media on which a person relies increased, decreased, or had no additional effect on that person's COVID-19 conspiracy beliefs over a 4-month period. OBJECTIVE: We used panel data to explore whether use of conservative and social media in the United States, which were previously found to be
Evidence Search Report: INF031801v4 ESR 68 positively related to holding conspiracy beliefs about the origins and prevention of COVID-19, were associated with a net increase in the strength of those beliefs from March to July of 2020. We also asked whether mainstream news sources, which were previously found to be negatively related to belief in pandemic-related conspiracies, were associated with a net decrease in the strength of such beliefs over the study period. Additionally, we asked whether subsequent changes in pandemic conspiracy beliefs related to the use of media were also related to subsequent mask wearing and vaccination intentions. METHODS: A survey that we conducted with a national US probability sample in March of 2020 and again in July with the same 840 respondents assessed belief in pandemic-related conspiracies, use of various types of media information sources, actions taken to prevent the spread of the disease and intentions to vaccinate, and various demographic characteristics. Change across the two waves was analyzed using path analytic techniques. RESULTS: We found that conservative media use predicted an increase in conspiracy beliefs (beta=.17, 99% CI .10-.25) and that reliance on mainstream print predicted a decrease in their belief (beta=-.08, 99% CI -.14 to -.02). Although many social media platforms reported downgrading or removing false or misleading content, ongoing use of such platforms by respondents predicted growth in conspiracy beliefs as well (beta=.072, 99% CI .018-.123). Importantly, conspiracy belief changes related to media use between the two waves of the study were associated with the uptake of mask wearing and changes in vaccination intentions in July. Unlike other media, use of mainstream broadcast television predicted greater mask wearing (beta=.17, 99% CI .09-.26) and vaccination intention (beta=.08, 95% CI .02-.14), independent of conspiracy beliefs. CONCLUSIONS: The findings point to the need for greater efforts on the part of commentators, reporters, and guests on conservative media to report verifiable information about the pandemic. The results also suggest that social media platforms need to be more aggressive in downgrading, blocking, and counteracting claims about COVID-19 vaccines, claims about mask wearing, and conspiracy beliefs that have been judged problematic by public health authorities. URL: https://www.ncbi.nlm.nih.gov/pubmed/33857008 DOI: 10.2196/25215
148. Romero-Brufau S, Chopra A, Ryu AJ, et al. Public health impact of delaying second dose of BNT162b2 or mRNA-1273 covid-19 vaccine: simulation agent based modeling study. Bmj. 2021;373:n1087. DOI: 10.1136/bmj.n1087 ABSTRACT: OBJECTIVE: To estimate population health outcomes with delayed second dose versus standard schedule of SARS-CoV-2 mRNA vaccination. DESIGN: Simulation agent based modeling study. SETTING: Simulated population based on real world US county. PARTICIPANTS: The simulation included 100 000 agents, with a representative distribution of demographics and occupations. Networks of contacts were established to simulate potentially infectious interactions though occupation, household, and random interactions. INTERVENTIONS: Simulation of standard covid-19 vaccination versus delayed second dose vaccination prioritizing the first dose. The simulation runs were replicated 10 times. Sensitivity analyses included first dose vaccine efficacy of 50%, 60%, 70%, 80%, and 90% after day 12 post-vaccination; vaccination rate of 0.1%, 0.3%, and 1% of population per day; assuming the vaccine prevents only symptoms but not asymptomatic spread (that is, non-sterilizing vaccine); and an alternative vaccination strategy that implements delayed second dose for people under 65 years of age, but not until all those above this age have been vaccinated. MAIN OUTCOME MEASURES: Cumulative covid-19 mortality, cumulative SARS-CoV-2 infections, and cumulative hospital admissions due to covid- 19 over 180 days. RESULTS: Over all simulation replications, the median cumulative mortality per 100 000 for standard dosing versus delayed second dose was 226 v 179, 233 v 207, and 235 v 236 for 90%, 80%, and 70% first dose efficacy, respectively. The delayed second dose strategy was optimal for vaccine efficacies at or above 80% and vaccination rates at or below 0.3% of the population per day, under both sterilizing and non-sterilizing vaccine assumptions, resulting in absolute cumulative mortality reductions
Evidence Search Report: INF031801v4 ESR 69 between 26 and 47 per 100 000. The delayed second dose strategy for people under 65 performed consistently well under all vaccination rates tested. CONCLUSIONS: A delayed second dose vaccination strategy, at least for people aged under 65, could result in reduced cumulative mortality under certain conditions. URL: https://www.ncbi.nlm.nih.gov/pubmed/33980718 DOI: 10.1136/bmj.n1087
149. Rosenkranz GK. Replicability of studies following a dual-criterion design. Stat Med. 2021;29:29. DOI: 10.1002/sim.9014 ABSTRACT: Replicability of results is regarded as the corner stone of science. Recent research seems to raise doubts about whether this requirement is generally fulfilled. Often, replicability of results is defined as repeating a statistically significant result. However, since significance may not imply scientific relevance, dual-criterion study designs that take both aspects into account have been proposed and investigated during the last decade. Originally developed for proof-of-concept trials, the design could be appropriate for phase III trials as well. In fact, a dual-criterion design has been requested for COVID-19 vaccine applications by major health authorities. In this article, replicability of dual-criterion designs is investigated. It turns out that the probability to replicate a significant and relevant result can become as low as 0.5. The replication probability increases if the effect estimator exceeds the minimum relevant effect in the original study by an extra amount. URL: https://www.ncbi.nlm.nih.gov/pubmed/33928668 DOI: 10.1002/sim.9014
150. Rudolph JL, Hartronft S, McConeghy K, et al. Proportion of SARS-CoV-2 positive tests and vaccination in Veterans Affairs Community Living Centers. J Am Geriatr Soc. 2021. DOI: 10.1111/jgs.17180 ABSTRACT: BACKGROUND/OBJECTIVES: COVID-19 has caused significant morbidity and mortality in nursing homes. Vaccination against SARS-COV-2 holds promise for reduction in COVID-19. This operational analysis describes the proportion of SARS-COV-2 positive tests before, during, and after vaccination. DESIGN: Retrospective longitudinal cohort analysis from October 1, 2020 until February 14, 2021. SETTING: A total of 130 Department of Veterans Affairs (VA) Community Living Centers (CLC), analogous to nursing homes. INTERVENTION: Vaccination for SARS-CoV-2. MEASUREMENTS: The primary measure is the proportion of SARS-CoV-2 positive tests among CLC residents. In a pooled analysis of weekly testing and vaccine data, the proportion of positive tests was compared for the unvaccinated, first dose, and second dose. For each CLC, we identified the week in which 50% of CLC residents were vaccinated (index week). The analysis aligned the index week for CLCs and examined the proportion of SARS-CoV-2 positive tests at the CLC level before and after. As a reference, we plotted the proportion of positive tests in nursing homes in the same county as the CLC using publicly reported data. RESULTS: Within the pooled VA CLCs, the first SARS-CoV-2 vaccine dose was delivered to 50% of CLC residents within 1 week of availability and second dose within 5 weeks. Relative to the index week, the risk ratio of SARS-CoV-2 positive tests in the vaccinated relative to unvaccinated was significantly lower in Week 4 (relative risk 0.37, 95% confidence interval 0.20-0.68). Throughout the study period, the proportion of SARS-CoV-2 positive tests in community nursing homes was higher compared to VA CLC and also declined after vaccine availability. CONCLUSION: The proportion of SARS-CoV-2 positive tests significantly declined in VA CLCs 4 weeks after vaccine delivery and continued to decline in vaccinated and unvaccinated residents. The results describe the importance of SARS-CoV-2 surveillance and vaccination in VA nursing home residents. URL: https://www.ncbi.nlm.nih.gov/pubmed/33861871 DOI: 10.1111/jgs.17180
Evidence Search Report: INF031801v4 ESR 70
151. Rusk DS, Strachan CC, Hunter BR. Lack of immune response after mRNA vaccination to SARS -CoV- 2 in a solid organ transplant patient. J Med Virol. 2021. DOI: 10.1002/jmv.27044 ABSTRACT: The recent approval and distribution of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been a major development in the fight against the current coronavirus disease 2019 (COVID-19) pandemic. The first two vaccines approved in the United States, mRNA-1273, and BNT162b2, are both messenger RNA (mRNA) based and highly effective in immunocompetent persons, but efficacy in patients on immunosuppressants has not been established. Additionally, data suggests these patients are less likely than immunocompetent people to develop neutralizing antibodies after COVID-19 infection. Given the high risk of poor outcomes in organ transplant and immunosuppressed patients, effective vaccination is paramount in this group. We present the first reported case of a solid organ transplant patient who failed to achieve seroconversion after two doses of mRNA vaccine. This case has significant implications about how immunosuppressed patients should be counseled about SARS-CoV-2 vaccination and the protection provided. Physicians should remain clinically suspicious for infection with SARS-CoV-2 despite vaccination status in solid organ transplant patients. URL: https://www.ncbi.nlm.nih.gov/pubmed/33913552 DOI: 10.1002/jmv.27044
152. Ryzhikov AB, Ryzhikov ЕА, Bogryantseva MP, et al. A single blind, placebo-controlled randomized study of the safety, reactogenicity and immunogenicity of the “EpiVacCorona” Vaccine for the prevention of COVID-19, in volunteers aged 18–60 years (phase I–II). Russian Journal of Infection and Immunity. 2021;11(2):283-96. DOI: 10.15789/2220-7619-asb-1699 ABSTRACT: Vaccination of the population is one of the most effective countermeasures in responding to the pandemic caused by novel coronavirus infection. Therefore, scientists all over the world have been working to develop effective and safe vaccines. We have developed a synthetic peptide vaccine, EpiVacCorona, against novel SARS-CoV-2 coronavirus, which is a suspension for intramuscular administration containing a composition of chemically synthesized peptide immunogens of the S protein of SARS-CoV-2 coronavirus conjugated to a carrier protein and adsorbed on aluminum hydroxide. Phase I-II clinical trials of the vaccine have started that consist of two stages: Stage 1 is an open study of the safety, reactogenicity, and immunological activity of the vaccine with the involvement of 14 volunteers aged 18-30 years; Stage 2 is a single blind, comparative, randomized placebo-controlled study with the involvement of 86 volunteers. The study involved volunteers aged 18-60 years; the vaccine was injected intramuscularly twice, spaced 21 days apart between injections. All local reactions in response to vaccine administration were mild, such as a short-term pain at the injection site. There were no signs of development of local or systemic adverse reactions. The two-dose vaccination scheme induced the production of antibodies, specific to the antigens that make up the vaccine, in 100% of the volunteers. Seroconversion with a neutralizing antibody titer >= 1:20 was reported in 100% of the volunteers 21 days following the second immunization dose. No seroconversion was reported in the groups of volunteers vaccinated with a placebo. The peptide-based EpiVacCorona Vaccine has low reactogenicity and is a safe, immunogenic product. Clinical Trials Identifier: NCT04527575.Copyright © Ryzhikov A.B. et al., 2021 URL: https://www.iimmun.ru/iimm/article/view/1699 http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emedx&NEWS=N&AN=2011856887 DOI: 10.15789/2220-7619-asb-1699
Evidence Search Report: INF031801v4 ESR 71 153. Rzymski P, Zeyland J, Poniedzialek B, et al. The Perception and Attitudes toward COVID-19 Vaccines: A Cross-Sectional Study in Poland. Vaccines (Basel). 2021;9(4):14. DOI: 10.3390/vaccines9040382 ABSTRACT: Vaccine hesitancy is a major threat to the success of COVID-19 vaccination programs. The present cross-sectional online survey of adult Poles (n = 1020) expressing a willingness to receive the COVID-19 vaccine was conducted between February and March 2021 and aimed to assess (i) the general trust in different types of vaccines, (ii) the level of acceptance of the COVID-19 vaccines already in use in Poland (BNT162b2 by BioNTech/Pfizer, mRNA-1273 by Moderna and AZD1222 by Oxford/AstraZeneca) as well as eight vaccines approved outside European Union (EU) or in advanced stages of clinical trials, (iii) level of fear of vaccination against COVID-19, and (iv) main sources of information on COVID-19 vaccination. Among all major vaccine technology, the highest level of trust was observed for the mRNA platform, with a considerable number of surveyed (>20%) not aware of the existence of vaccines produced using the traditional approach (inactivated and live attenuated vaccines). The age of participants was the main factor differentiating the level of trust in a particular vaccine type. Both BNT162b and mRNA-1273 received a high level of acceptance, contrary to AZD1222. From eight vaccines unauthorized in the EU at the moment of study, the CVnCoV (mRNA; CureVac) was met with the highest level of trust, followed by Ad26.COV2.S (vector; Janssen/Johnson&Johnson) and NVX-CoV2373 (protein; Novavax). Sputnik V (vector; Gamaleya Research Institute) was decidedly the least trusted vaccine. The median level of fear (measured by the 10-point Likert-type scale) in the studied group was 4.0, mostly related to the risk of serious allergic reactions, other severe adverse events and unknown long-term effects of vaccination. Female, individuals with a lower level of education and those not seeking any information on the COVID-19 vaccines revealed a higher fear of vaccination. Experts' materials were the major source of information on COVID-19 vaccines in the studied group. The study shows the level of trust in COVID-19 vaccines can vary much across the producers while the mRNA vaccines are received with a high level of acceptance. It also emphasizes the need for effective and continuous science communication when fighting the pandemic as it may be an ideal time to increase the general awareness of vaccines. URL: https://www.ncbi.nlm.nih.gov/pubmed/33919672 DOI: 10.3390/vaccines9040382
154. Saadoun D, Vieira M, Vautier M, et al. SARS-CoV-2 outbreak in immune-mediated inflammatory diseases: the Euro-COVIMID multicentre cross-sectional study. Lancet Rheumatol. 2021;28:28. DOI: 10.1016/S2665-9913(21)00112-0 ABSTRACT: Background: The COVID-19 pandemic has raised numerous questions among patients with immune-mediated inflammatory diseases regarding potential reciprocal effects of COVID-19 and their underlying disease, and potential effects of immunomodulatory therapy on outcomes related to COVID- 19. The seroprevalence of SARS-CoV-2 and factors associated with symptomatic COVID-19 in patients with immune-mediated inflammatory diseases are still unclear. The Euro-COVIMID study aimed to determine the serological and clinical prevalence of COVID-19 among patients with immune-mediated inflammatory diseases, as well as factors associated with COVID-19 occurrence and the impact of the pandemic in its management. Methods: In this multicentre cross-sectional study, patients aged 18 years or older with a clinical diagnosis of rheumatoid arthritis, axial spondyloarthritis, systemic lupus erythematosus, Sjogren's syndrome, or giant cell arteritis were recruited from six tertiary referral centres in France, Germany, Italy, Portugal, Spain, and the UK. Demographics, comorbidities, treatments, and recent disease flares, as well as information on COVID-19 symptoms, were collected through a questionnaire completed by participants. SARS-CoV-2 serology was systematically tested. The main outcome was the serological and clinical prevalence of COVID-19. Factors associated with symptomatic COVID-19 were assessed by multivariable logistic regression, and incidence of recent
Evidence Search Report: INF031801v4 ESR 72 disease flares, changes in treatments for underlying disease, and the reasons for treatment changes were also assessed. This study is registered with ClinicalTrials.gov, NCT04397237. Findings: Between June 7 and Dec 8, 2020, 3136 patients with an immune-mediated inflammatory disease answered the questionnaire. 3028 patients (median age 58 years [IQR 46-67]; 2239 [73.9%] women and 789 [26.1%] men) with symptomatic COVID-19, serological data, or both were included in analyses. SARS-CoV-2 antibodies were detected in 166 (5.5% [95% CI 4.7-6.4]) of 3018 patients who had serology tests. Symptomatic COVID-19 occurred in 122 (4.0% [95% CI 3.4-4.8]) of 3028 patients, of whom 24 (19.7%) were admitted to hospital and four (3.3%) died. Factors associated with symptomatic COVID-19 were higher concentrations of C-reactive protein (odds ratio 1.18, 95% CI 1.05-1.33; p=0.0063), and higher numbers of recent disease flares (1.27, 1.02-1.58; p=0.030), whereas use of biological therapy was associated with reduced risk (0.51, 0.32-0.82; p=0.0057). At least one disease flare occurred in 654 (21.6%) of 3028 patients. Over the study period, 519 (20.6%) of 2514 patients had treatment changes, of which 125 (24.1%) were due to the pandemic. Interpretation: This study provides key insights into the epidemiology and risk factors of COVID-19 among patients with immune-mediated inflammatory diseases. Overall, immunosuppressants do not seem to be deleterious in this scenario, and the control of inflammatory activity seems to be key when facing the pandemic. Funding: Pfizer, Sanofi, Amgen, Galapagos, and Lilly. URL: https://www.ncbi.nlm.nih.gov/pubmed/33942031 DOI: 10.1016/S2665-9913(21)00112-0
155. Sah P, Vilches TN, Moghadas SM, et al. Accelerated vaccine rollout is imperative to mitigate highly transmissible COVID-19 variants. EClinicalMedicine. 2021;35:100865. DOI: 10.1016/j.eclinm.2021.100865 ABSTRACT: Background: More contagious variants of SARS-CoV-2 have emerged around the world, sparking concerns about impending surge in cases and severe outcomes. Despite the development of effective vaccines, rollout has been slow. We evaluated the impact of accelerated vaccine distribution on curbing the disease burden of novel SARS-CoV-2 variants. Methods: We used an agent-based model of SARS-CoV-2 transmission and vaccination to simulate the spread of novel variants with S-Gene Target Failure (SGTF) in addition to the original strain. We incorporated age-specific risk and contact patterns and implemented a two-dose vaccination campaign in accord with CDC-recommended prioritization. As a base case, we projected hospitalizations and deaths at a daily vaccination rate of 1 million doses in the United States (US) and compared with accelerated campaigns in which daily doses were expanded to 1.5, 2, 2.5, or 3 million. Findings: We found that at a vaccination rate of 1 million doses per day, an emergent SGTF variant that is 20-70% more transmissible than the original variant would become dominant within 2 to 9 weeks, accounting for as much as 99% of cases at the outbreak peak. Our results show that accelerating vaccine delivery would substantially reduce severe health outcomes. For a SGTF with 30% higher transmissibility, increasing vaccine doses from 1 to 3 million per day would avert 152,048 (95% CrI: 134,772-168,696) hospitalizations and 48,448 (95% CrI: 42,042-54,285) deaths over 300 days. Accelerated vaccination would also prevent additional COVID-19 waves that would otherwise be fuelled by waning adherence to non-pharmaceutical interventions (NPIs). Interpretation: We found that the current pace of vaccine rollout is insufficient to prevent the exacerbation of the pandemic that will be attributable to the novel, more contagious SARS-CoV-2 variants. Accelerating the vaccination rate should be a public health priority for averting the expected surge in COVID-19 hospitalizations and deaths that would be associated with widespread dissemination of the SGTF variants. Our results underscore the need to bolster the production and distribution of COVID-19 vaccines, to rapidly expand vaccination priority groups and distribution sites. URL: https://www.ncbi.nlm.nih.gov/pubmed/33937735 DOI: 10.1016/j.eclinm.2021.100865
Evidence Search Report: INF031801v4 ESR 73
156. Saha S, Kadam S. Convalescent plasma therapy - a silver lining for COVID-19 management? Hematol Transfus Cell Ther. 2021. DOI: 10.1016/j.htct.2021.03.004 ABSTRACT: Introduction: The COVID-19 pandemic has pushed the world towards social, economic, and medical challenges. Scientific research in medicine is the only means to overcome novel and complex diseases like COVID-19. To sum up the therapeutic wild-goose chase, many available antivirals and repurposed drugs have failed to show successful clinical evidence in patient recovery, several vaccine candidates are still waiting in the trial pipelines and a few have become available to the common public for administration in record time. Objective and Method: However, with upcoming evidence of coronavirus mutations, available vaccines may thrive on the spirit of doubt about efficacy and effectiveness towards these new strains of Severe Acute Respiratory Syndrome Coronavirus (SARS- CoV2). In all these collective uncertainties, plasma therapy has shown a ray of hope for critically ill patients. Results: To date, with very few published case studies of convalescent plasma in COVID-19, there are two school of thought process in the scientific community regarding plasma therapy efficiency and this leads to confusion due to the lack of optimal randomized and controlled studies. Conclusion: Without undertaking any robust scientific studies, evidence or caution, accepting any therapy unanimously may cause more harm than good, but with a clearer understanding of SARS-CoV2 immunopathology and drug response, plasma therapy might be the silver lining against COVID-19 for the global community. URL: https://www.ncbi.nlm.nih.gov/pubmed/33903854 DOI: 10.1016/j.htct.2021.03.004
157. Salma U. Relationship of COVID-19 with pregnancy. Taiwan J Obstet Gynecol. 2021;60(3):405-11. DOI: 10.1016/j.tjog.2021.03.005 ABSTRACT: COVID-19 a pandemic disease caused by the SARS-CoV2 virus, which has been emerged in Wuhan city China from early December 2019 which subsequently spreading globally. As a consequence of the physiological adaptive changes and immunosuppressive condition during pregnancy are more susceptible to respiratory tract infection and pneumonia that perhaps makes them more at risk to COVID-19. There is scarce information available on COVID-19 pregnancy and no reliable evidence for vertical transmission. It is a concern that newborns are risk from postpartum contamination. Meanwhile, there was no vaccine and specific therapeutic drugs for COVID19. The Multidisciplinary team will manage by close supervision, isolated negative pressure room, and routinely fetal monitoring. The timing and mode of delivery depend on the critical condition of the mother and fetal. The newborns need a14 days period of precautionary isolation. In the present study, addressed the most recent data on 149 pregnant women and 96 newborns with typical symptoms and planning of management which response to COVID-19 that will help for frontline doctor to the management of COVID-19 associated pregnancy and newborns baby. Repeated testing, contact tracing and self-isolation will assist to control the spread of SARS-CoV2 infection and COVID-19 disease until specific vaccine and pharmaceuticals drugs of COVID-19 are available. URL: https://www.ncbi.nlm.nih.gov/pubmed/33966721 DOI: 10.1016/j.tjog.2021.03.005
158. Sami S, Tenforde MW, Talbot HK, et al. Adults Hospitalized with COVID-19 -United States, March- June and October-December 2020: Implications for the Potential Effects of COVID-19 Tier-1 Vaccination on Future Hospitalizations and Outcomes. Clin Infect Dis. 2021;12:12. DOI: 10.1093/cid/ciab319 ABSTRACT: BACKGROUND: Because of the increased risk for severe coronavirus disease 2019 (COVID- 19), the Advisory Committee on Immunization Practices (ACIP) initially prioritized COVID-19 vaccination
Evidence Search Report: INF031801v4 ESR 74 for persons in long-term care facilities (LTCF), persons aged >/=65 years, and persons aged 16-64 years with high-risk medical conditions when there is limited vaccine supply. We compared characteristics and severe outcomes of hospitalized patients with COVID-19 in the United States between early and later in the pandemic categorized by groups at higher risk of severe COVID-19. METHODS: Observational study of sampled patients aged >/=18 years who tested positive for SARS-CoV-2 and admitted to one of 14 academic hospitals in the United States during March-June and October-December 2020. Demographic and clinical information were gathered from electronic health record data. RESULTS: Among 647 patients, 91% met >/=1 of the following risk factors for severe COVID-19 [91% March-June (n=434); 90% October-December (n=213)]; 19% were LTCF residents, 45% were aged >/=65-years, and 84% had >/=1 high-risk condition. The proportion of patients who resided in a LTCF declined significantly (25% vs. 6%) from early to later pandemic periods. Compared with patients at lower risk for severe COVID-19, in- hospital mortality was higher among patients at high risk for severe COVID-19 (20% vs. 7%); these differences were consistently observed between March-June and October-December. CONCLUSIONS: Most adults hospitalized with COVID-19 were those recommended to be prioritized for vaccination based on risk for developing severe COVID-19. These findings highlight the urgency to vaccinate patients at high risk for severe COVID-19 and monitor vaccination impact on hospitalizations and outcomes. URL: https://www.ncbi.nlm.nih.gov/pubmed/33977301 DOI: 10.1093/cid/ciab319
159. Santosa A, Xu C, Arkachaisri T, et al. Recommendations for COVID-19 vaccination in people with rheumatic disease: Developed by the Singapore Chapter of Rheumatologists. Int J Rheum Dis. 2021;10:10. DOI: 10.1111/1756-185X.14107 ABSTRACT: AIM: People with rheumatic diseases (PRD) remain vulnerable in the era of the COVID-19 pandemic. We formulated recommendations to meet the urgent need for a consensus for vaccination against SARS-CoV-2 in PRD. METHODS: Systematic literature reviews were performed to evaluate: (a) outcomes in PRD with COVID-19; (b) efficacy, immunogenicity and safety of COVID-19 vaccination; and (c) published guidelines/recommendations for non-live, non-COVID-19 vaccinations in PRD. Recommendations were formulated based on the evidence and expert opinion according to the Grading of Recommendations Assessment, Development and Evaluation methodology. RESULTS: The consensus comprises 2 overarching principles and 7 recommendations. Vaccination against SARS-CoV-2 in PRD should be aligned with prevailing national policy and should be individualized through shared decision between the healthcare provider and patient. We strongly recommend that eligible PRD and household contacts be vaccinated against SARS-CoV-2. We conditionally recommended that the COVID-19 vaccine be administered during quiescent disease if possible. Immunomodulatory drugs, other than rituximab, can be continued alongside vaccination. We conditionally recommend that the COVID-19 vaccine be administered prior to commencing rituximab if possible. For patients on rituximab, the vaccine should be administered a minimum of 6 months after the last dose and/or 4 weeks prior to the next dose of rituximab. Post-vaccination antibody titers against SARS-CoV-2 need not be measured. Any of the approved COVID-19 vaccines may be used, with no particular preference. CONCLUSION: These recommendations provide guidance for COVID-19 vaccination in PRD. Most recommendations in this consensus are conditional, reflecting a lack of evidence or low-level evidence. URL: https://www.ncbi.nlm.nih.gov/pubmed/33973379 DOI: 10.1111/1756-185X.14107
160. Scarpato S, Sebastiani M, Quartuccio L, et al. Provisional recommendations for SARS-CoV-2 vaccination in patients with cryoglobulinaemic vasculitis. Clin Exp Rheumatol. 2021;30:30. ABSTRACT: People with cryoglobulinaemic vasculitis (CV) have an increased risk of infections, attributed to different causes: impairment of the immune system due to the disease itself, comorbidities, and
Evidence Search Report: INF031801v4 ESR 75 immunosuppressive therapy. Therefore, these patients may be at high risk for a more severe course of COVID-19, including hospitalisation and death. Concerns about efficacy, immunogenicity and safety of vaccines, as well as doubts, not yet fully clarified in patients with systemic autoimmune diseases, represent other important factors for a low vaccination rate in people with (CV). Indeed, providing an expert position on the issues related to SARS-CoV-2 vaccination in patients suffering from CV is of critical relevance in order to help both patients and clinicians who are treating them in making the best choice in each case. A multidisciplinary task force of the Italian Group for the Study of Cryoglobulinaemia (GISC) was convened, and through a Delphi technique produced provisional recommendations regarding SARS- CoV-2 vaccination in cryoglobulinaemic patients. URL: https://www.ncbi.nlm.nih.gov/pubmed/33938790
161. Schernhammer E, Weitzer J, Laubichler MD, et al. Correlates of COVID-19 vaccine hesitancy in Austria: trust and the government. J Public Health (Oxf). 2021;05:05. DOI: 10.1093/pubmed/fdab122 ABSTRACT: BACKGROUND: With the coronavirus disease 2019 (COVID-19) pandemic surging and new mutations evolving, trust in vaccines is essential. METHODS: We explored correlates of vaccine hesitancy, considering political believes and psychosocial concepts, conducting a non-probability quota- sampled online survey with 1007 Austrians. RESULTS: We identified several important correlates of vaccine hesitancy, ranging from demographics to complex factors such as voting behavior or trust in the government. Among those with hesitancy towards a COVID-19 vaccine, having voted for opposition parties (opp) or not voted (novote) were (95% Confidence Intervall (CI)opp, 1.44-2.95) to 2.25-times (95%CInovote, 1.53-3.30) that of having voted for governing parties. Only 46.2% trusted the Austrian government to provide safe vaccines, and 80.7% requested independent scientific evaluations regarding vaccine safety to increase willingness to vaccine. CONCLUSIONS: Contrary to expected, psychosocial dimensions were only weakly correlated with vaccine hesitancy. However, the strong correlation between distrust in the vaccine and distrust in authorities suggests a common cause of disengagement from public discourse. URL: https://www.ncbi.nlm.nih.gov/pubmed/33948665 DOI: 10.1093/pubmed/fdab122
162. Selby L, Hewlett A, Cawcutt K, et al. Effect of SARS-CoV-2 mRNA Vaccination in Healthcare Workers with High Risk COVID-19 Exposure. Infect Control Hosp Epidemiol. 2021:1-7. DOI: 10.1017/ice.2021.193 ABSTRACT: Appropriate precautions for fully vaccinated healthcare providers following high risk household SARS CoV-2 exposure remains unknown. Herein, we report initial results from our employee health protocol for such situations. URL: https://www.ncbi.nlm.nih.gov/pubmed/33934742 DOI: 10.1017/ice.2021.193
163. Sharma A, Ahmed S, Kaur J, et al. Exploring status of emergency drugs and vaccine development in Covid-19 pandemic: an update. Virusdisease. 2021:1-13. DOI: 10.1007/s13337-021-00684-5 ABSTRACT: COVID-19 outburst initiated from the city of Wuhan in China in December 2019 and has been declared as a public health emergency of international concern. This pandemic portrays a spectrum of clinical complications, primarily affecting the respiratory system reported to be caused by a pathogen SARS-CoV-2 belonging to the family of beta coronavirus. Currently, the main objective of the government authorities of all affected countries and research organizations is to find a potential solution in the form of a pharmacological intervention or a vaccination to eradicate the disease and to have a long-term solution to deal with the pandemic. A multitude of anti-viral regimens is proposed based on the repurposing of currently available drugs for other issues or the compassionate use of drugs to
Evidence Search Report: INF031801v4 ESR 76 immediately control and optimize the healthcare facilities. Meanwhile, a number of agencies are proposing new drug candidates to recreate the possibility of treating the disease. Similarly, a lot of research work is going on worldwide for the development of vaccination. Currently, a good number of candidates has finally reached the borders of Clinical Trials and are expected to be launched as soon as possible. However, the regulatory framework and authorization of these candidates is the most significant aspect of the whole scenario, which needs a specific set of time for validation purposes. The present work is widely focused on the general aspects of COVID-19 and the regulatory landscape for the emergency authorization of repurposed drug candidates, compassionate use of drugs, investigational entities, and vaccine development worldwide. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-021-00684-5. URL: https://www.ncbi.nlm.nih.gov/pubmed/33969152 DOI: 10.1007/s13337-021-00684-5
164. Shaw RH, Stuart A, Greenland M, et al. Heterologous prime-boost COVID-19 vaccination: initial reactogenicity data. The Lancet. 2021. DOI: 10.1016/s0140-6736(21)01115-6 URL: https://doi.org/10.1016/S0140-6736(21)01115-6 DOI: 10.1016/s0140-6736(21)01115-6
165. Shay DK, Gee J, Su JR, et al. Safety Monitoring of the Janssen (Johnson & Johnson) COVID-19 Vaccine - United States, March-April 2021. MMWR Morb Mortal Wkly Rep. 2021;70(18):680-4. DOI: 10.15585/mmwr.mm7018e2 ABSTRACT: On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for Janssen (Ad.26.COV2.S) COVID-19 vaccine (Janssen Biotech, Inc., a Janssen Pharmaceutical company, Johnson & Johnson) (1). The Janssen COVID-19 vaccine, the third COVID-19 vaccine authorized for use in the United States, uses a replication-incompetent human adenoviral type 26 vector platform* (2) and is administered as a single intramuscular dose, whereas the first two authorized vaccines use an mRNA platform and require 2 doses. On February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for use of Janssen COVID- 19 vaccine among persons aged >/=18 years (3). During April 13-23, CDC and FDA recommended a pause in use of Janssen vaccine after reports of six cases of cerebral venous sinus thrombosis (CVST) with thrombocytopenia (platelet count <150,000/muL of blood) among Janssen vaccine recipients (4). Similar thrombotic events, primarily among women aged <60 years, have been described in Europe after receipt of the AstraZeneca COVID-19 vaccine, which uses a replication-incompetent chimpanzee adenoviral vector (5-7). The U.S. CVST cases that prompted the pause in Janssen vaccination, as well as subsequently detected CVST cases, are described elsewhere (8). This report summarizes adverse events among Janssen vaccine recipients, including non-CVST cases of thrombosis with thrombocytopenia syndrome (TTS), reported to the Vaccine Adverse Events Reporting System (VAERS), a passive surveillance system, and through v-safe, an active monitoring system. As of April 21, 2021, 7.98 million doses of the Janssen COVID-19 vaccine had been administered. Among 13,725 VAERS reports reviewed, 97% were classified as nonserious and 3% as serious,(dagger) including three reports among women of cases of thrombosis in large arteries or veins accompanied by thrombocytopenia during the second week after vaccination. These three cases and the previously detected CVST cases are consistent with 17 cases of TTS,( section sign) a newly defined condition. Approximately 338,700 Janssen COVID-19 vaccine recipients completed at least one v-safe survey during the week after vaccination; 76% reported a systemic reaction, 61% reported a local reaction, and 34% reported a health impact.( paragraph sign) Fatigue and pain were commonly reported symptoms in both VAERS and v-safe. The overall safety profile is consistent with preauthorization clinical trials data. Prompt review of U.S. vaccine safety data detected three additional cases of non-CVST TTS, in addition to the previously recognized CVST cases
Evidence Search Report: INF031801v4 ESR 77 that initiated the pause in use of the Janssen COVID-19 vaccine. Ongoing monitoring of adverse events after COVID-19 vaccination, including vaccination with the Janssen single-dose vaccine, is essential for evaluating the risks and benefits of each vaccine. URL: https://www.ncbi.nlm.nih.gov/pubmed/33956784 DOI: 10.15585/mmwr.mm7018e2
166. She R, Chen X, Li L, et al. Factors associated with behavioral intention of free and self-paid COVID- 19 vaccination based on the social cognitive theory among nurses and doctors in China. Infect Control Hosp Epidemiol. 2021:1-25. DOI: 10.1017/ice.2021.201 ABSTRACT: OBJECTIVE: To examine the associations between factors based on the Social Cognitive Theory (SCT) and behavioral intention of free and self-paid (600 RMB or 91 USD) COVID-19 vaccination of 80% effectiveness and rare mild side effects among doctors and nurses in China. DESIGN: Cross- sectional study. SETTING: Public hospitals. PARTICIPANTS: 362 doctors and 1702 nurses in major departments of five hospitals of three Chinese provinces. METHODS: An anonymous online survey was conducted from October to November 2020, facilitated by hospital administrators through online WeChat/QQ working groups. Data on outcome expectations, self-efficacy, norms, and COVID-19-related work experiences were collected. Multivariate logistic regression models were used for data analysis. RESULTS: The logistic regression analysis showed that physical (e.g., protective effect of vaccination) and self-evaluative outcome expectations (e.g., anticipated regret), self-efficacy, norms (e.g., descriptive norm, subjective norm, professional norm, and moral norm), and job satisfaction were significantly and positively associated with the free and self-paid COVID-19 vaccination intention outcomes among doctors and nurses, adjusted for background variables. Doctors who had engaged in COVID-19-related work reported higher self-paid vaccination intention. CONCLUSIONS: Health promotion is needed to improve the uptake of COVID-19 vaccination among healthcare workers. Such interventions may consider modifying the identified factors of vaccination intention, including strengthening perceived efficacy, positive feelings about vaccination, the need to avoid future regret, self-efficacy, and social norms. Future studies should examine the actual behavior patterns of COVID-19 vaccination and testing the efficacy of promotion intervention through randomized controlled studies. URL: https://www.ncbi.nlm.nih.gov/pubmed/33938413 DOI: 10.1017/ice.2021.201
167. Shinde V, Bhikha S, Hoosain Z, et al. Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant. The New England journal of medicine. 2021;05:05. DOI: 10.1056/NEJMoa2103055 ABSTRACT: BACKGROUND: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) variants threatens progress toward control of the coronavirus disease 2019 (Covid-19) pandemic. In a phase 1-2 trial involving healthy adults, the NVX-CoV2373 nanoparticle vaccine had an acceptable safety profile and was associated with strong neutralizing-antibody and antigen-specific polyfunctional CD4+ T-cell responses. Evaluation of vaccine efficacy was needed in a setting of ongoing SARS-CoV-2 transmission. METHODS: In this phase 2a-b trial in South Africa, we randomly assigned human immunodeficiency virus (HIV)-negative adults between the ages of 18 and 84 years or medically stable HIV-positive participants between the ages of 18 and 64 years in a 1:1 ratio to receive two doses of either the NVX-CoV2373 vaccine (5 mug of recombinant spike protein with 50 mug of Matrix-M1 adjuvant) or placebo. The primary end points were safety and vaccine efficacy against laboratory- confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants without previous SARS-CoV-2 infection. RESULTS: Of 6324 participants who underwent screening, 4387 received at least one injection of vaccine or placebo. Approximately 30% of the participants were seropositive for SARS-CoV-2 at baseline. Among 2684 baseline seronegative participants (94% HIV-negative and 6% HIV- positive), predominantly mild-to-moderate Covid-19 developed in 15 participants in the vaccine group
Evidence Search Report: INF031801v4 ESR 78 and in 29 in the placebo group (vaccine efficacy, 49.4%; 95% confidence interval [CI], 6.1 to 72.8). Vaccine efficacy among HIV-negative participants was 60.1% (95% CI, 19.9 to 80.1). Of 41 sequenced isolates, 38 (92.7%) were the B.1.351 variant. Post hoc vaccine efficacy against B.1.351 was 51.0% (95% CI, -0.6 to 76.2) among the HIV-negative participants. Preliminary local and systemic reactogenicity events were more common in the vaccine group; serious adverse events were rare in both groups. CONCLUSIONS: The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, with higher vaccine efficacy observed among HIV-negative participants. Most infections were caused by the B.1.351 variant. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT04533399.). URL: https://www.ncbi.nlm.nih.gov/pubmed/33951374 DOI: 10.1056/NEJMoa2103055
168. Simonetti O, Rizzetto G, Molinelli E, et al. Safety and Efficacy of Vaccines during COVID-19 Pandemic in Patients Treated with Biological Drugs in a Dermatological Setting. Healthcare (Basel). 2021;9(4):01. DOI: 10.3390/healthcare9040401 ABSTRACT: The BNT162b2 and mRNA-1273 vaccines, consisting of mRNA, have recently become available. The absolute novelty of these vaccines introduces questions about their safety and efficacy, especially in patients who are treated with biological drugs in dermatology. The aim of our review was to provide a broad overview of the current use of all available vaccinations in concomitance with biological therapy and to suggest indications for the new mRNA Covid-19 vaccines. We conducted a narrative review of the literature regarding the indications and safety of the various types of vaccines currently available in dermatological patients treated with biological therapy. The safety and efficacy of administering inactivated vaccines in patients undergoing biological therapy with inhibitors of TNF- alpha, IL-17, IL-12/23, and IL-4/13 was confirmed. Inactivated vaccines can be administered during therapy with inhibitors of IL-23 and IgE, taking into account that the level of evidence is lower due to the lack of specific studies. Live attenuated vaccines were contraindicated in concomitance with all biological therapies considered, except omalizumab. According to this evidence, we assume that there are currently no contraindications to the administration of the new Covid-19 BNT162b2 and mRNA-1273 vaccines during biological therapy with inhibitors of TNF-alpha, IL-17, IL-12/23, IL-23, and IL-4/13, since these vaccines are comparable to inactivated ones. For patients with chronic urticaria or allergic asthma treated with omalizumab, we currently recommend caution in using the mRNA Covid-19 vaccines (30 min observation). The only contraindications were a previous history of hypersensitivity to the Covid-19 vaccines themself or to their excipients. In conclusion, further randomized clinical trials are needed to evaluate the efficacy of the antibody response in these patients. URL: https://www.ncbi.nlm.nih.gov/pubmed/33916122 DOI: 10.3390/healthcare9040401
169. Singh JA, Kochhar S, Wolff J, et al. Author Correction: Placebo use and unblinding in COVID-19 vaccine trials: recommendations of a WHO Expert Working Group. Nat Med. 2021;04:04. DOI: 10.1038/s41591-021-01360-3 URL: https://www.ncbi.nlm.nih.gov/pubmed/33948020 DOI: 10.1038/s41591-021-01360-3
170. Stevens J. The PANDEMIC framework for encouraging COVID-19 vaccinations. Am J Manag Care. 2021;27(5). DOI: 10.37765/ajmc.2021.88605 ABSTRACT: After sufficient doses are manufactured and logistical barriers are reduced, convincing an overwhelming majority of people to receive a COVID-19 vaccination may be the next major challenge during this pandemic. A group of experts recently proposed strategies that have compelling rationales
Evidence Search Report: INF031801v4 ESR 79 and are well grounded in behavioral science. However, their approaches may sometimes be unacceptable, impractical, and/or unsuccessful. Therefore, other strategies will be greatly needed to address vaccine hesitancy. The present commentary offers 8 additional promising approaches forming a framework known as PANDEMIC. This acronym stands for the following strategies: presumptive language, asking for advice, norms on an anonymous level, description of favorable attributes, emphasizing clinicians' own experiences, mandated choice, images, and communication of risk. Each of the strategies is discussed in turn. Many of the proposed strategies have empirical support for achieving desired outcomes in other domains. However, the PANDEMIC framework is untested in regard to increasing the uptake of COVID-19 vaccinations. Therefore, the strategies should be carefully evaluated before they are widely disseminated through public health announcements, email distribution lists, electronic health record messages, and other outlets. URL: https://www.ncbi.nlm.nih.gov/pubmed/33733721 DOI: 10.37765/ajmc.2021.88605
171. Stingeni L, Bianchi L, Zalaudek I, et al. Adverse cutaneous and mucous reactions from anti SARS - CoV-2 vaccines: recommendations from the Italian Society of Dermatology (SIDeMaST). Ital J Dermatol Venerol. 2021;156(2):115-7. DOI: 10.23736/S2784-8671.21.06992-3 URL: https://www.ncbi.nlm.nih.gov/pubmed/33960747 DOI: 10.23736/S2784-8671.21.06992-3
172. Stoddard M, Van Egeren D, Johnson KE, et al. Individually optimal choices can be collectively disastrous in COVID-19 disease control. BMC Public Health. 2021;21(1):832. DOI: 10.1186/s12889-021- 10829-2 ABSTRACT: BACKGROUND: The word 'pandemic' conjures dystopian images of bodies stacked in the streets and societies on the brink of collapse. Despite this frightening picture, denialism and noncompliance with public health measures are common in the historical record, for example during the 1918 Influenza pandemic or the 2015 Ebola epidemic. The unique characteristics of SARS-CoV-2-its high basic reproduction number (R0), time-limited natural immunity and considerable potential for asymptomatic spread-exacerbate the public health repercussions of noncompliance with interventions (such as vaccines and masks) to limit disease transmission. Our work explores the rationality and impact of noncompliance with measures aimed at limiting the spread of SARS-CoV-2. METHODS: In this work, we used game theory to explore when noncompliance confers a perceived benefit to individuals. We then used epidemiological modeling to predict the impact of noncompliance on control of SARS-CoV-2, demonstrating that the presence of a noncompliant subpopulation prevents suppression of disease spread. RESULTS: Our modeling demonstrates that noncompliance is a Nash equilibrium under a broad set of conditions and that the existence of a noncompliant population can result in extensive endemic disease in the long-term after a return to pre-pandemic social and economic activity. Endemic disease poses a threat for both compliant and noncompliant individuals; all community members are protected if complete suppression is achieved, which is only possible with a high degree of compliance. For interventions that are highly effective at preventing disease spread, however, the consequences of noncompliance are borne disproportionately by noncompliant individuals. CONCLUSIONS: In sum, our work demonstrates the limits of free-market approaches to compliance with disease control measures during a pandemic. The act of noncompliance with disease intervention measures creates a negative externality, rendering suppression of SARS-CoV-2 spread ineffective. Our work underscores the importance of developing effective strategies for prophylaxis through public health measures aimed at complete suppression and the need to focus on compliance at a population level. URL: https://www.ncbi.nlm.nih.gov/pubmed/33931055 DOI: 10.1186/s12889-021-10829-2
Evidence Search Report: INF031801v4 ESR 80
173. Strully KW, Harrison TM, Pardo TA, et al. Strategies to Address COVID-19 Vaccine Hesitancy and Mitigate Health Disparities in Minority Populations. Front Public Health. 2021;9:645268. DOI: 10.3389/fpubh.2021.645268 ABSTRACT: Beyond the complex logistical task of prioritizing, distributing and safely storing millions of doses of COVID-19 vaccines, state and local governments must simultaneously devise and carry out transparent plans that center equity and overcome the barriers to vaccination facing minority communities. Using insights gleaned from four focus groups conducted with health care and social service professionals serving minority communities in New York State as well as from existing research on vaccination, our results emphasize that vaccine hesitancy and access barriers-particularly within minority communities-pose significant hurdles to achieving widespread uptake of COVID-19 vaccines. Overcoming barriers requires community-engaged campaigns that acknowledge and address the historical injustices and on-going inequities that drive distrust within communities of color, emphasize understandable and culturally appropriate messages that directly address people's concerns about vaccine safety and access, and tap existing community infrastructure to make full use of trusted voices to deliver timely and accurate information about vaccines. Given emerging data and changing conditions, campaigns must also be self-reflective and adaptive, assessing progress and outcomes and reevaluating strategies as needed. However, above all, primary goals should remain focused on transparency, equity and building trust. URL: https://www.ncbi.nlm.nih.gov/pubmed/33968884 DOI: 10.3389/fpubh.2021.645268
174. Tam LS, Tanaka Y, Handa R, et al. Updated APLAR consensus statements on care for patients with rheumatic diseases during the COVID-19 pandemic. Int J Rheum Dis. 2021;04:04. DOI: 10.1111/1756- 185X.14124 ABSTRACT: AIM: To update previous guidance of the Asia Pacific League of Associations for Rheumatology (APLAR) on the management of patients with rheumatic and musculoskeletal diseases (RMD) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Research questions were formulated focusing on diagnosis and treatment of adult patients with RMD within the context of the pandemic, including the management of RMD in patients who developed COVID-19. MEDLINE was searched for eligible studies to address the questions, and the APLAR COVID-19 task force convened 2 meetings through video conferencing to discuss its findings and integrate best available evidence with expert opinion. Consensus statements were finalized using the modified Delphi process. RESULTS: Agreement was obtained around key aspects of screening for or diagnosis of COVID-19; management of patients with RMD without confirmed COVID-19; and management of patients with RMD with confirmed COVID-19. The task force achieved consensus on 25 statements covering the potential risk of acquiring COVID-19 in RMD patients, advice on RMD medication adjustment and continuation, the roles of telemedicine and vaccination, and the impact of the pandemic on quality of life and on treatment adherence. CONCLUSIONS: Available evidence primarily from descriptive research supported new recommendations for aspects of RMD care not covered in the previous document, particularly with regard to risk factors for complicated COVID-19 in RMD patients, modifications to RMD treatment regimens in the context of the pandemic, and COVID-19 vaccination in patients with RMD. URL: https://www.ncbi.nlm.nih.gov/pubmed/33945214 DOI: 10.1111/1756-185X.14124
175. Tenforde MW, Olson SM, Self WH, et al. Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Among Hospitalized Adults Aged >/=65 Years - United States, January-March 2021. MMWR Morb Mortal Wkly Rep. 2021;70(18):674-9. DOI: 10.15585/mmwr.mm7018e1
Evidence Search Report: INF031801v4 ESR 81 ABSTRACT: Adults aged >/=65 years are at increased risk for severe outcomes from COVID-19 and were identified as a priority group to receive the first COVID-19 vaccines approved for use under an Emergency Use Authorization (EUA) in the United States (1-3). In an evaluation at 24 hospitals in 14 states,* the effectiveness of partial or full vaccination(dagger) with Pfizer-BioNTech or Moderna vaccines against COVID-19-associated hospitalization was assessed among adults aged >/=65 years. Among 417 hospitalized adults aged >/=65 years (including 187 case-patients and 230 controls), the median age was 73 years, 48% were female, 73% were non-Hispanic White, 17% were non-Hispanic Black, 6% were Hispanic, and 4% lived in a long-term care facility. Adjusted vaccine effectiveness (VE) against COVID-19-associated hospitalization among adults aged >/=65 years was estimated to be 94% (95% confidence interval [CI] = 49%-99%) for full vaccination and 64% (95% CI = 28%-82%) for partial vaccination. These findings are consistent with efficacy determined from clinical trials in the subgroup of adults aged >/=65 years (4,5). This multisite U.S. evaluation under real-world conditions suggests that vaccination provided protection against COVID-19-associated hospitalization among adults aged >/=65 years. Vaccination is a critical tool for reducing severe COVID-19 in groups at high risk. URL: https://www.ncbi.nlm.nih.gov/pubmed/33956782 DOI: 10.15585/mmwr.mm7018e1
176. Thi TTH, Suys EJA, Lee JS, et al. Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines. Vaccines (Basel). 2021;9(4):08. DOI: 10.3390/vaccines9040359 ABSTRACT: COVID-19 vaccines have been developed with unprecedented speed which would not have been possible without decades of fundamental research on delivery nanotechnology. Lipid-based nanoparticles have played a pivotal role in the successes of COVID-19 vaccines and many other nanomedicines, such as Doxil((R)) and Onpattro((R)), and have therefore been considered as the frontrunner in nanoscale drug delivery systems. In this review, we aim to highlight the progress in the development of these lipid nanoparticles for various applications, ranging from cancer nanomedicines to COVID-19 vaccines. The lipid-based nanoparticles discussed in this review are liposomes, niosomes, transfersomes, solid lipid nanoparticles, and nanostructured lipid carriers. We particularly focus on the innovations that have obtained regulatory approval or that are in clinical trials. We also discuss the physicochemical properties required for specific applications, highlight the differences in requirements for the delivery of different cargos, and introduce current challenges that need further development. This review serves as a useful guideline for designing new lipid nanoparticles for both preventative and therapeutic vaccines including immunotherapies. URL: https://www.ncbi.nlm.nih.gov/pubmed/33918072 DOI: 10.3390/vaccines9040359
177. Thiele T, Beider S, Kuhl H, et al. [Care of rheumatology patients during the lockdown in early 2020 : Telemedicine, delegation, patient satisfaction and vaccination behavior]. Z Rheumatol. 2021;11:11. DOI: 10.1007/s00393-021-01005-3 ABSTRACT: BACKGROUND: Telemedicine was implemented in outpatient care during the lockdown between March and May 2020. The aim of the study was to assess patients from a private practice and the university outpatient department with respect to patient satisfaction with telemedicine, COVID-19 worries and vaccination behavior and to compare the teleconsultation by a medical assistant for rheumatology (RFA) and a physician. METHODS: Patients with rheumatoid arthritis, psoriatric arthropathy or spondylarthritis without treatment modifications since the previous presentation were offered a telemedical replacement appointment within the framework of this study in the case of appointment cancellation by the treating center. Participants were randomized to a telemedicine appointment by a physician or an RFA (RFA university only). The patient history was carried out by
Evidence Search Report: INF031801v4 ESR 82 telephone and standardized using a questionnaire. The disease activity was determined using the modified clinical disease activity score (CDAI) and the BASDAI. Subsequently, all patients received a pseudonymized evaluation questionnaire. RESULTS: In total 112/116 (96%) patients participated. Of these 88/112 (79%) returned the questionnaire. The RFAs conducted 19/112 (17%) of the telephone calls. The treatment was modified in 19/112 (17%) patients. Concerns about contracting COVID-19 correlated with high disease activity (p= 0.031) including the presence of painful joints (p= 0.001) and high pain levels (VAS >/=7, p= 0.009). These patients would have also cancelled their appointment themselves (p= 0.015). Patient satisfaction with the consultation was good (mean 4.3/5.0 modified FAPI) independent of the institution, the duration of the consultation and the consultation partner. Patients with a high pain intensity were the least satisfied (p= 0.036). Only 42/100 (38.2%) of the patients had been vaccinated against pneumococci and 59/100 (53.6%) against influenza. CONCLUSION: Telemedical care within the framework of a telephone consultation is well-suited for selected patients. With respect to patient satisfaction the delegation of a telemedical consultation to an RFA is possible. There is a need for improvement with respect to the vaccination behavior. URL: https://www.ncbi.nlm.nih.gov/pubmed/33974131 DOI: 10.1007/s00393-021-01005-3
178. Thompson KM, Kalkowska DA, Badizadegan K. Hypothetical emergence of poliovirus in 2020: part 2. exploration of the potential role of vaccines in control and eradication. Expert Rev Vaccines. 2021:1- 12. DOI: 10.1080/14760584.2021.1891889 ABSTRACT: OBJECTIVES: The emergence of human pathogens with pandemic potential motivates rapid vaccine development. We explore the role of vaccines in control and eradication of a novel emerging pathogen. METHODS: We hypothetically simulate emergence of a novel wild poliovirus (nWPV) in 2020 assuming an immunologically naive population. Assuming different nonpharmaceutical interventions (NPIs), we explore the impacts of vaccines resembling serotype-specific oral poliovirus vaccine (OPV), novel OPV (nOPV), or inactivated poliovirus vaccine (IPV). RESULTS: Vaccines most effectively change the trajectory of an emerging disease when disseminated early, rapidly, and widely in the background of ongoing strict NPIs, unless the NPIs successfully eradicate the emerging pathogen before it establishes endemic transmission. Without strict NPIs, vaccines primarily reduce the burden of disease in the remaining susceptible individuals and in new birth cohorts. Live virus vaccines that effectively compete with the nWPVs can reduce disease burdens more than other vaccines. When relaxation of existing NPIs occurs at the time of vaccine introduction, nWPV transmission can counterintuitively increase in the short term. CONCLUSIONS: Vaccines can increase the probability of disease eradication in the context of strict NPIs. However, successful eradication will depend on specific immunization strategies used and a global commitment to eradication. URL: https://www.ncbi.nlm.nih.gov/pubmed/33599178 DOI: 10.1080/14760584.2021.1891889
179. Tobaiqy M, Elkout H, MacLure K. Analysis of Thrombotic Adverse Reactions of COVID-19 AstraZeneca Vaccine Reported to EudraVigilance Database. Vaccines (Basel). 2021;9(4):16. DOI: 10.3390/vaccines9040393 ABSTRACT: The development of safe, effective, affordable vaccines against COVID-19 remains the cornerstone to mitigating this pandemic. Early in December 2020, multiple research groups had designed potential vaccines. From 11 March 2021, several European countries temporarily suspended the use of the Oxford-AstraZeneca vaccine amid reports of blood clot events and the death of a vaccinated person, despite the European Medicines Agency (EMA) and the World Health Organization's assurance that there was no indication that vaccination was linked. This study aimed to identify and analyse the thrombotic adverse reactions associated with the Oxford-AstraZeneca vaccine. This was a
Evidence Search Report: INF031801v4 ESR 83 retrospective descriptive study using spontaneous reports submitted to the EudraVigilance database in the period from 17 February to 12 March 2021. There were 54,571 adverse reaction reports, of which 28 were associated with thrombotic adverse reactions. Three fatalities were related to pulmonary embolism; one fatality to thrombosis. With 17 million people having had the AstraZeneca vaccine, these are extremely rare events The EMA's Pharmacovigilance Risk Assessment Committee (18 March 2021) concluded that the vaccine was safe, effective and the benefits outweighed the risks. Conducting further analyses based on more detailed thrombotic adverse event reports, including patients' characteristics and comorbidities, may enable assessment of the causality with higher specificity. URL: https://www.ncbi.nlm.nih.gov/pubmed/33923530 DOI: 10.3390/vaccines9040393
180. Tougeron D, Hentzien M, Seitz-Polski B, et al. Severe acute respiratory syndrome coronavirus 2 vaccination for patients with solid cancer: Review and point of view of a French oncology intergroup (GCO, TNCD, UNICANCER). Eur J Cancer. 2021;150:232-9. DOI: 10.1016/j.ejca.2021.03.030 ABSTRACT: The impacts of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on cancer care are multiple, entailing a high risk of death from coronavirus disease 2019 (COVID-19) in patients with cancer treated by chemotherapy. SARS-CoV-2 vaccines represent an opportunity to decrease the rate of severe COVID-19 cases in patients with cancer and also to restore normal cancer care. Patients with cancer to be targeted for vaccination are difficult to define owing to the limited contribution of these patients in the phase III trials testing the different vaccines. It seems appropriate to vaccinate not only patients with cancer with ongoing treatment or with a treatment having been completed less than 3 years ago but also household and close contacts. High-risk patients with cancer who are candidates for priority access to vaccination are those treated by chemotherapy. The very high- priority population includes patients with curative treatment and palliative first- or second-line chemotherapy, as well as patients requiring surgery or radiotherapy involving a large volume of lung, lymph node and/or haematopoietic tissue. When possible, vaccination should be carried out before cancer treatment begins. SARS-CoV-2 vaccination can be performed during chemotherapy while avoiding periods of neutropenia and lymphopenia. For organisational reasons, vaccination should be performed in cancer care centres with messenger RNA vaccines (or non-replicating adenoviral vaccines in non-immunocompromised patients). Considering the current state of knowledge, the benefit-risk ratio strongly favours SARS-CoV-2 vaccination of all patients with cancer. To obtain more data concerning the safety and effectiveness of vaccines, it is necessary to implement cohorts of vaccinated patients with cancer. URL: https://www.ncbi.nlm.nih.gov/pubmed/33934060 DOI: 10.1016/j.ejca.2021.03.030
181. Tran VD, Pak TV, Gribkova EI, et al. Determinants of COVID-19 vaccine acceptance in a high infection-rate country: a cross-sectional study in Russia. Pharm Pract (Granada). 2021;19(1):2276. DOI: 10.18549/PharmPract.2021.1.2276 ABSTRACT: Background: COVID-19 vaccine development is proceeding at an unprecedented pace. Once COVID-19 vaccines become widely available, it will be necessary to maximize public vaccine acceptance and coverage. Objective: This research aimed to analyze the predictors of COVID-19 vaccine acceptance in Russia. Methods: A cross-sectional online survey was conducted among Russian adults from September 26(th) to November 9(th), 2020. Predictors of the intent to take up COVID-19 vaccination were explored using logistic regression. Results: Out of 876 participants, 365 (41.7%) would be willing to receive the vaccine if it became available. Acceptance increased for a vaccine with verified safety and effectiveness (63.2%). Intention to receive the COVID-19 vaccine was relatively higher among males (aOR=2.37, 95% CI 1.41-4.00), people with lower monthly income (aOR=2.94, 95%CI 1.32-6.57), and with
Evidence Search Report: INF031801v4 ESR 84 positive trust in the healthcare system (aOR=2.73, 95% CI 1.76-4.24). The Russian people were more likely to accept the COVID-19 vaccine if they believed that the vaccine reduces the risk of virus infection (aOR=8.80, 95%CI 5.21-14.87) or relieves the complications of the disease (aOR=10.46, 95%CI 6.09- 17.96). Other barriers such as being unconcerned about side-effects (aOR=1.65, 95%CI 1.03-2.65) and the effectiveness and safety of the vaccination (aOR=2.55, 95%CI 1.60-4.08), also affected acceptance. Conclusions: The study showed the usefulness of the health belief model constructs in understanding the COVID-19 vaccination acceptance rate in the Russian population. This rate was influenced by sociodemographic and health-related characteristics, and health beliefs. These findings might help guide future efforts for policymakers and stakeholders to improve vaccination rates by enhancing trust in the healthcare system. URL: https://www.ncbi.nlm.nih.gov/pubmed/33828622 DOI: 10.18549/PharmPract.2021.1.2276
182. Traynor K. Children's hospital celebrates successful COVID-19 vaccine rollout. Am J Health Syst Pharm. 2021;78(10):838-9. DOI: 10.1093/ajhp/zxab107 URL: https://www.ncbi.nlm.nih.gov/pubmed/33954418 DOI: 10.1093/ajhp/zxab107
183. Troiano G, Nardi A. Vaccine hesitancy in the era of COVID-19. Public Health. 2021;194:245-51. DOI: 10.1016/j.puhe.2021.02.025 ABSTRACT: OBJECTIVES: In 2019, a new coronavirus has been identified and many efforts have been directed toward the development of effective vaccines. However, the willingness for vaccination is deeply influenced by several factors. So the aim of our review was to analyze the theme of vaccine hesitancy during COVID-19 pandemic, with a particular focus on vaccine hesitancy toward COVID-19 vaccine. STUDY DESIGN: Narrative review. METHODS: In November 2020, we performed a search for original peer-reviewed articles in the electronic database PubMed (MEDLINE). The key search terms were "Vaccine hesitancy AND COVID-19". We searched for studies published during COVID-19 pandemic and reporting information about the phenomenon of vaccine hesitancy. RESULTS: Fifteen studies were included in the review. The percentage of COVID-19 vaccine acceptance was not so high (up to 86.1% students or 77.6% general population); for influenza vaccine, the maximum percentage was 69%. Several factors influenced the acceptance or refusal (ethnicity, working status, religiosity, politics, gender, age, education, income, etc.). The most given reasons to refuse vaccine were as follows: being against vaccines in general, concerns about safety/thinking that a vaccine produced in a rush is too dangerous, considering the vaccine useless because of the harmless nature of COVID-19, general lack of trust, doubts about the efficiency of the vaccine, belief to be already immunized, doubt about the provenience of vaccine. CONCLUSIONS: The high vaccine hesitancy, also during COVID-19 pandemic, represents an important problem, and further efforts should be done to support people and give them correct information about vaccines. URL: https://www.ncbi.nlm.nih.gov/pubmed/33965796 DOI: 10.1016/j.puhe.2021.02.025
184. Tsiambas E, Chrysovergis A, Papanikolaou V, et al. Impact of Ribosome Activity on SARS-CoV-2 LNP - Based mRNA Vaccines. Front Mol Biosci. 2021;8:654866. DOI: 10.3389/fmolb.2021.654866 ABSTRACT: Coronavirus-related Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) initially was detected in Wuhan, Hubei, China. Since early 2021, World Health Organization (WHO) has declared Coronavirus Disease 2019 (COVID-19) a pandemic due to rapidly transformed to a globally massive catastrophic viral infection. In order to confront this emergency situation, many pharmaceutical companies focused on the design and development of efficient vaccines that are considered necessary
Evidence Search Report: INF031801v4 ESR 85 for providing a level of normalization in totally affected human social-economical activity worldwide. A variety of vaccine types are under development, validation or even some of them have already completed these stages, initially approved as conditional marketing authorisation by Food and Drug Administration (FDA), European Medicines Agency (EMA), and other national health authorities for commercial purposes (in vivo use in general population), accelerating their production and distribution process. Innovative nucleoside-modified viral messenger RNA (v-mRNA)-based vaccines encapsulated within nanoparticles-specifically lipid ones (LNPs)-are now well recognized. Although this is a promising genetic engineering topic in the field of nanopharmacogenomics or targeted nucleic vaccines, there are limited but continuously enriched in vivo data in depth of time regarding their safety, efficacy, and immune response. In the current paper we expand the limited published data in the field of ribosome machinery and SARS-CoV-2 mRNA fragment vaccines interaction by describing their functional specialization and modifications. Additionally, alterations in post-transcriptional/translational molecules and mechanisms that could potentially affect the interaction between target cells and vaccines are also presented. Understanding these mechanisms is a crucial step for the next generation v-mRNA vaccines development. URL: https://www.ncbi.nlm.nih.gov/pubmed/33959636 DOI: 10.3389/fmolb.2021.654866
185. Vandeputte J, Saville M, Cavaleri M, et al. IABS/CEPI platform technology webinar: Is it possible to reduce the vaccine development time? Biologicals. 2021;06:06. DOI: 10.1016/j.biologicals.2021.04.005 ABSTRACT: The International Alliance for Biological Standardization and the Coalition for Epidemic Preparedness Innovations organized a joint webinar on the use of platform technologies for vaccine development. To tackle new emerging infectious diseases, including SARS-CoV-2, rapid response platforms, using the same basic components as a backbone, yet adaptable for use against different pathogens by inserting new genetic or protein sequences, are essential. Furthermore, it is evident that development of platform technologies needs to continue, due to the emerging variants of SARS-CoV-2. The objective of the meeting was to discuss techniques for platform manufacturing that have been used for COVID-19 vaccine development, with input from regulatory authorities on their experiences with, and expectations of, the platforms. Industry and regulators have been very successful in cooperating, having completed the whole process from development to licensing at an unprecedented speed. However, we should learn from the experiences, to be able to be even faster when a next pandemic of disease X occurs. URL: https://www.ncbi.nlm.nih.gov/pubmed/33966960 DOI: 10.1016/j.biologicals.2021.04.005
186. Vicari AS, Olson D, Vilajeliu A, et al. Seasonal Influenza Prevention and Control Progress in Latin America and the Caribbean in the Context of the Global Influenza Strategy and the COVID-19 Pandemic. Am J Trop Med Hyg. 2021;10:10. DOI: 10.4269/ajtmh.21-0339 ABSTRACT: Each year in Latin America and the Caribbean, seasonal influenza is associated with an estimated 36,500 respiratory deaths and 400,000 hospitalizations. Since the 2009 influenza A(H1N1) pandemic, the Region has made significant advances in the prevention and control of seasonal influenza, including improved surveillance systems, burden estimates, and vaccination of at-risk groups. The Global Influenza Strategy 2019-2030 provides a framework to strengthen these advances. Against the backdrop of this new framework, the University of Colorado convened in October 2020 its Immunization Advisory Group of Experts to review and discuss current surveillance, prevention, and control strategies for seasonal influenza in Latin America and the Caribbean, also in the context of the COVID-19 pandemic. This review identified five areas for action and made recommendations specific to each area. The Region
Evidence Search Report: INF031801v4 ESR 86 should continue its efforts to strengthen surveillance and impact evaluations. Existing data on disease burden, seasonality patterns, and vaccination effectiveness should be used to inform decision-making at the country level as well as advocacy efforts for programmatic resources. Regional and country strategic plans should be prepared and include specific targets for 2030. Existing investments in influenza prevention and control, including for immunization programs, should be optimized. Finally, regional partnerships, such as the regional networks for syndromic surveillance and vaccine effectiveness evaluation (SARInet and REVELAC-i), should continue to play a critical role in continuous learning and standardization by sharing experiences and best practices among countries. URL: https://www.ncbi.nlm.nih.gov/pubmed/33970888 DOI: 10.4269/ajtmh.21-0339
187. Vikse J, Nelson V, O'Doherty K. COVID-19, vaccination, and trust: An interview study. BMJ Open. 2021;11(SUPPL 1):A12-A3. DOI: http://dx.doi.org/10.1136/bmjopen-2021-QHRN.34 ABSTRACT: In addition to direct health threats of the COVID-19 pandemic, societies are experiencing significant harms and burdens associated with measures to mitigate the effects of the virus. In this context, a possible vaccine is perhaps the most highly regarded prospect to combat the novel coronavirus and enable societies to lift COVID related restrictions. Governments and other institutions around the world have invested large amounts of resources into the development, testing, and production capacity for several different vaccines. When vaccines become available, public health authorities will need information about the concerns and decision-making considerations of constituents. We outline here the key findings from interviews with residents of Ontario, Canada, (n=40) in July and August of 2020 regarding their views, concerns, and intentions with respect to a prospective COVID-19 vaccine. In particular, participants expressed concern about the safety and efficacy of any prospective vaccine that is developed in a short timeframe, despite eagerness to eventually take it. Additionally, participants expressed considerations that, while not directly related to vaccines, nevertheless factored into their attitudes about accepting a possible COVID vaccination. These included how successful governments have managed COVID- 19 so far, existing relationships with healthcare providers, and how they have assessed their risk of contracting or becoming very ill from COVID-19. Trust in science, regulators, and governments will play a critical role in the successful deployment of a COVID-19 vaccine. Governments and public health institutions can take actions to earn trust. Implementing monitoring programs for long-term adverse effects would measure and potentially mitigate risk of unforeseen effects. Supports that provide financial and social stability during the wait for rigorously tested vaccines may increase trust in governments to act in the best interest of their constituents. URL: http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emedx&NEWS=N&AN=634934770 DOI: http://dx.doi.org/10.1136/bmjopen-2021-QHRN.34
188. Vitiello A, Ferrara F. Brief review of the mRNA vaccines COVID-19. Inflammopharmacology. 2021;01:01. DOI: 10.1007/s10787-021-00811-0 ABSTRACT: The global COVID-19 pandemic continues to claim victims worldwide, representing a health and socioeconomic challenge with few precedents in human history. The therapeutic agents used to treat COVID-19 infection are mostly aimed at avoiding the most serious complications and organ damage that in a percentage of cases can be fatal. Recently, the first COVID-19 vaccines have been authorised, starting a massive vaccination campaign worldwide. The COVID-19 vaccines authorized or under testing use different methods of action such as mRNA, DNA vaccine, viral vector, protein subunit, and virus inactivated immunization strategies. The mRNA vaccines are the first authorised vaccines with this new method of action, initiating a new era of preventive medicine. To date, data indicate that they may be effective against the newly identified SARS-CoV-2 variants. Short-term studies indicated an
Evidence Search Report: INF031801v4 ESR 87 acceptable safety profile but long-term immunity as well as safety is not yet available. In this article, we briefly describe mRNA vaccines and highlight some aspects yet to be fully defined. URL: https://www.ncbi.nlm.nih.gov/pubmed/33932192 DOI: 10.1007/s10787-021-00811-0
189. Volk GF, Kuttenreich AM, Geitner M, et al. [Acute facial paresis as a possible complication of vaccination against SARS-CoV-2]. Laryngorhinootologie. 2021;11:11. DOI: 10.1055/a-1501-0470 ABSTRACT: Although acute facial nerve palsy (Bell's palsy) is explicitly mentioned in the information sheets for vaccines as a possible complication of vaccination against SARS-CoV-2, from our point of view the benefits of the vaccination clearly outweigh the possible risks. At most, if at all, a slightly increased risk can be derived from the previous case reports. In general, the risk of acute facial palsy is described in association with many vaccinations. The risk, if any, does not appear to be a specific risk of SARS-CoV- 2 vaccines. On the other hand, cases of acute facial palsy as symptom of a COVID-19 disease have also been described, so that the theoretical question arises as to the extent to which the vaccination may prevent rather than promote the occurrence of facial palsy. Ultimately, if acted quickly, acute facial paralysis can be treated well and its severity and sequelae cannot be compared with the severity of a COVID-19 disease and its possible long-COVID sequelae. URL: https://www.ncbi.nlm.nih.gov/pubmed/33975372 DOI: 10.1055/a-1501-0470
190. Wang H, Le Z. Expert recommendations based on link prediction during the COVID-19 outbreak. Scientometrics. 2021:1-20. DOI: 10.1007/s11192-021-03893-3 ABSTRACT: Since the emergence of COVID-19, the number of infections has significantly increased. As of April 7, 8:00 am, the total number of global infections has already reached 1,338,415, with the number of deaths being 74,556. Medical experts from various countries have conducted relevant researches in their own fields and countries, and the development of an effective vaccine has been expected soon. Although some progress has been made in the development of therapeutic drugs and vaccines, interdisciplinary and cooperative studies are scarce. However, it is easy to form information islands and conduct repeated scientific research. To date, no therapeutic drug or vaccine for COVID-19 has been officially approved yet for marketing. In this article, the features of experts in cooperation networks, such as graph structure, context attribute, sequential co-occurrence probability, weight features and auxiliary features, are comprehensively analyzed. Based on this, a novel graph neural network + long short-term memory + generative adversarial network (GNN + LSTM + GAN) expert recommendation model based on link prediction is constructed to encourage cooperation among relevant experts in research social networks. Finding experts in related fields, establishing cooperative relations with them and achieving multinational and cross-field expert cooperation are significant to promote the development of therapeutic drugs and vaccines. URL: https://www.ncbi.nlm.nih.gov/pubmed/33935334 DOI: 10.1007/s11192-021-03893-3
191. Watad A, De Marco G, Mahajna H, et al. Immune-Mediated Disease Flares or New-Onset Disease in 27 Subjects Following mRNA/DNA SARS-CoV-2 Vaccination. Vaccines (Basel). 2021;9(5):29. DOI: 10.3390/vaccines9050435 ABSTRACT: BACKGROUND: Infectious diseases and vaccines can occasionally cause new-onset or flare of immune-mediated diseases (IMDs). The adjuvanticity of the available SARS-CoV-2 vaccines is based on either TLR-7/8 or TLR-9 agonism, which is distinct from previous vaccines and is a common pathogenic mechanism in IMDs. METHODS: We evaluated IMD flares or new disease onset within 28-days of SARS- CoV-2 vaccination at five large tertiary centres in countries with early vaccination adoption, three in
Evidence Search Report: INF031801v4 ESR 88 Israel, one in UK, and one in USA. We assessed the pattern of disease expression in terms of autoimmune, autoinflammatory, or mixed disease phenotype and organ system affected. We also evaluated outcomes. FINDINGS: 27 cases included 17 flares and 10 new onset IMDs. 23/27 received the BNT - 162b2 vaccine, 2/27 the mRNA-1273 and 2/27 the ChAdOx1 vaccines. The mean age was 54.4 +/- 19.2 years and 55% of cases were female. Among the 27 cases, 21 (78%) had at least one underlying autoimmune/rheumatic disease prior the vaccination. Among those patients with a flare or activation, four episodes occurred after receiving the second-dose and in one patient they occurred both after the first and the second-dose. In those patients with a new onset disease, two occurred after the second- dose and in one patient occurred both after the first (new onset) and second-dose (flare). For either dose, IMDs occurred on average 4 days later. Of the cases, 20/27 (75%) were mild to moderate in severity. Over 80% of cases had excellent resolution of inflammatory features, mostly with the use of corticosteroid therapy. Other immune-mediated conditions included idiopathic pericarditis (n = 2), neurosarcoidosis with small fiber neuropathy (n = 1), demyelination (n = 1), and myasthenia gravis (n = 2). In 22 cases (81.5%), the insurgence of Adverse event following immunization (AEFI)/IMD could not be explained based on the drug received by the patient. In 23 cases (85.2%), AEFI development could not be explained based on the underlying disease/co-morbidities. Only in one case (3.7%), the timing window of the insurgence of the side effect was considered not compatible with the time from vaccine to flare. INTERPRETATION: Despite the high population exposure in the regions served by these centers, IMDs flares or onset temporally-associated with SARS-CoV-2 vaccination appear rare. Most are moderate in severity and responsive to therapy although some severe flares occurred. FUNDING: none. URL: https://www.ncbi.nlm.nih.gov/pubmed/33946748 DOI: 10.3390/vaccines9050435
192. Werfel T, Raulf M. From anaphylaxis - To occupational dermatology, COVID-19 vaccination and micronutrition to guideline work - The whole variety of current allergological topics in this issue. Allergologie. 2021;44(5):333-4. DOI: http://dx.doi.org/10.5414/ALX02248 URL: https://www.dustri.com/nc/de/deutschsprachige-zeitschriften/mag/allergologie/vol/jahrgang-44- 2021/issue/mai-49.html http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emedx&NEWS=N&AN=2011924730 DOI: http://dx.doi.org/10.5414/ALX02248
193. Williams SR, Driscoll AJ, LeBuhn HM, et al. National routine adult immunisation programmes among World Health Organization Member States: an assessment of health systems to deploy COVID- 19 vaccines. Euro Surveill. 2021;26(17):04. DOI: 10.2807/1560-7917.ES.2021.26.17.2001195 ABSTRACT: IntroductionAs SARS-CoV-2 disproportionately affects adults, the COVID-19 pandemic vaccine response will rely on adult immunisation infrastructures.AimTo assess adult immunisation programmes in World Health Organization (WHO) Member States.MethodsWe evaluated country reports from 2018 on adult immunisation programmes sent to WHO and UNICEF. We described existing programmes and used multivariable regression to identify independent factors associated with having them.ResultsOf 194 WHO Member States, 120 (62%) reported having at least one adult immunisation programme. The Americas and Europe had the highest proportions of adult immunisation programmes, most commonly for hepatitis B and influenza vaccines (> 47% and > 91% of countries, respectively), while Africa and South-East Asia had the lowest proportions, with < 11% of countries reporting adult immunisation programmes for hepatitis B or influenza vaccines, and none for pneumococcal vaccines. In bivariate analyses, high or upper-middle country income, introduction of new or underused vaccines, having achieved paediatric immunisation coverage goals and meeting National Immunisation Technical Advisory Groups basic functional indicators were significantly associated (p < 0.001) with having an adult immunisation programme. In multivariable analyses, the most strongly associated factor was country
Evidence Search Report: INF031801v4 ESR 89 income, with high- or upper-middle-income countries significantly more likely to report having an adult immunisation programme (adjusted odds ratio: 19.3; 95% confidence interval: 6.5- 57.7).DiscussionWorldwide, 38% of countries lack adult immunisation programmes. COVID-19 vaccine deployment will require national systems for vaccine storage and handling, delivery and waste management to target adult risk groups. There is a need to strengthen immunisation systems to reach adults with COVID-19 vaccines. URL: https://www.ncbi.nlm.nih.gov/pubmed/33928899 DOI: 10.2807/1560-7917.ES.2021.26.17.2001195
194. Wu K, Choi A, Koch M, et al. Preliminary Analysis of Safety and Immunogenicity of a SARS-CoV-2 Variant Vaccine Booster. medRxiv. 2021:2021.05.05.21256716. DOI: 10.1101/2021.05.05.21256716 ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic of coronavirus disease 2019 (COVID-19) that has led to more than 3 million deaths worldwide. Safe and effective vaccines are now available, including the mRNA-1273 prototype vaccine, which encodes for the Wuhan SARS-CoV-2 spike (S) protein stabilized in the prefusion conformation by 2 proline substitutions. This vaccine showed 94% efficacy in prevention of symptomatic COVID-19 disease in a phase 3 clinical study. Recently, SARS-CoV-2 variants have emerged, some of which have shown decreased susceptibility to neutralization by vaccine-induced antibody, most notably the B.1.351 variant, although the overall impact on vaccine efficacy remains to be determined. In addition, recent evidence of waning antibody levels after infection or vaccination point to the need for periodic boosting of immunity. Here we present the preliminary evaluation of a clinical study on the use of the prototype mRNA-1273 or modified COVID-19 mRNA vaccines, designed to target emerging SARS-CoV-2 variants as booster vaccines in participants previously vaccinated approximately 6 months earlier with two doses of the prototype vaccine, mRNA-1273. The modified vaccines include a monovalent mRNA-1273.351 encoding for the S protein found in the B.1.351 variant and multivalent mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. As single 50 µg booster vaccinations, both mRNA-1273 and mRNA-1273.351 had acceptable safety profiles and were immunogenic. Antibody neutralization titers against B.1.351 and P.1 variants measured by SARS-CoV-2 pseudovirus neutralization (PsVN) assays before the booster vaccinations, approximately 6 to 8 months after the primary series, were low or below the assay limit of quantification, although geometric mean titers versus the wild-type strain remained above levels likely to be protective. Two weeks after the booster vaccinations, titers against the wild-type original strain, B.1.351, and P.1 variants increased to levels similar to or higher than peak titers after the primary series vaccinations. Although both mRNA-1273 and mRNA-1273.351 boosted neutralization of the wild-type original strain, and B.1.351 and P.1 variants, mRNA-1273.351 appeared to be more effective at increasing neutralization of the B.1.351 virus versus a boost with mRNA-1273. The vaccine trial is ongoing and boosting of clinical trial participants with the multivalent mRNA-1273.211 is currently being evaluated.Competing Interest StatementK.W., A.C., M.K., L.M., L.M., A.H, N.N., W.H., J.O., H.B., H.L., Y.P., B.N., B.D., R.P., A.C., J.M., B.L., R.M., and D.E. are employees of Moderna, Inc., and may hold stock/stock options in the company.Clinical TrialNCT04405076Funding StatementThis work was supported in whole or in part with Federal funds from the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under Contract No. 75A50120C00034, and Moderna, Inc.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The trial was conducted in accordance with the International Council for Technical Requirements for Registration of Pharmaceuticals for Human Use, Good Clinical Practice Guidance, and applicable government regulations. The central Institutional Review Board approved the protocol and consent forms. All participants provided written informed consent before enrollment. The
Evidence Search Report: INF031801v4 ESR 90 Central IRB for the P201 study was Advarra IRB, 6100 Merriweather Dr., Suite 600, Columbia, MD 21044, Phone: 410.884.2900All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as C inicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData sharing statement: Moderna is committed to sharing data supporting the findings of eligible studies. The results of this study are preliminary and the study is ongoing. Access to patient-level data and supporting clinical documents with qualified external researchers may be available upon request once the trial is complete. URL: http://medrxiv.org/content/early/2021/05/06/2021.05.05.21256716.abstract DOI: 10.1101/2021.05.05.21256716
195. Wu X, Li N, Wang G, et al. Tolerability, Safety, Pharmacokinetics, and Immunogenicity of a Novel SARS-CoV-2 Neutralizing Antibody, Etesevimab in Chinese Healthy Adults: A Randomized, Double- Blind, Placebo-Controlled, First-In-Human Phase 1 Study. Antimicrob Agents Chemother. 2021;10:10. DOI: 10.1128/AAC.00350-21 ABSTRACT: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread rapidly worldwide. This study is the first to report the tolerability, safety, pharmacokinetics (PK), and immunogenicity of a recombinant human anti-SARS-CoV-2 monoclonal antibody, etesevimab (CB6, JS016, LY3832479 or LY-CoV016), in healthy adults. This paper involves a randomized, double-blind, placebo-controlled, phase 1 study. A total of 40 participants were enrolled to receive a single intravenous dose of either etesevimab or a placebo in one of four sequential ascending intravenous dose cohorts. All 40 participants completed the study. Seventeen (42.5%) participants experienced 22 treatment emergent adverse events (TEAEs) that were drug-related, and the rates of these TEAEs among different dose cohorts were numerically comparable. No difference was observed between the combined etesevimab group and the placebo group. The exposure after etesevimab infusion increased in an approximately proportional manner as the dose (increased from 2.5 to 50 mg/kg. The) elimination half-life ((t1/2) value did not differ among different dose) cohorts and was estimated to be around 4 weeks. Etesevimab was well tolerated after administration of a single dose at a range of 2.5 mg/kg to 50 mg/kg in healthy Chinese adults. The PK profiles of etesevimab in healthy volunteers showed typical monoclonal antibody distribution and elimination characteristics. (This study has been registered at ClinicalTrials.gov under identifier NCT04441918.). URL: https://www.ncbi.nlm.nih.gov/pubmed/33972256 DOI: 10.1128/AAC.00350-21
196. Yamoah MA, Thai PN, Zhang XD. Transgene Delivery to Human Induced Pluripotent Stem Cells Using Nanoparticles. Pharmaceuticals (Basel). 2021;14(4):06. DOI: 10.3390/ph14040334 ABSTRACT: Human induced pluripotent stem cells (hiPSCs) and hiPSCs-derived cells have the potential to revolutionize regenerative and precision medicine. Genetically reprograming somatic cells to generate hiPSCs and genetic modification of hiPSCs are considered the key procedures for the study and application of hiPSCs. However, there are significant technical challenges for transgene delivery into somatic cells and hiPSCs since these cells are known to be difficult to transfect. The existing methods, such as viral transduction and chemical transfection, may introduce significant alternations to hiPSC culture which affect the potency, purity, consistency, safety, and functional capacity of hiPSCs.
Evidence Search Report: INF031801v4 ESR 91 Therefore, generation and genetic modification of hiPSCs through non-viral approaches are necessary and desirable. Nanotechnology has revolutionized fields from astrophysics to biology over the past two decades. Increasingly, nanoparticles have been used in biomedicine as powerful tools for transgene and drug delivery, imaging, diagnostics, and therapeutics. The most successful example is the recent development of SARS-CoV-2 vaccines at warp speed to combat the 2019 coronavirus disease (COVID- 19), which brought nanoparticles to the center stage of biomedicine and demonstrated the efficient nanoparticle-mediated transgene delivery into human body. Nanoparticles have the potential to facilitate the transgene delivery into the hiPSCs and offer a simple and robust approach. Nanoparticle- mediated transgene delivery has significant advantages over other methods, such as high efficiency, low cytotoxicity, biodegradability, low cost, directional and distal controllability, efficient in vivo applications, and lack of immune responses. Our recent study using magnetic nanoparticles for transfection of hiPSCs provided an example of the successful applications, supporting the potential roles of nanoparticles in hiPSC biology. This review discusses the principle, applications, and significance of nanoparticles in the transgene delivery to hiPSCs and their successful application in the development of COVID-19 vaccines. URL: https://www.ncbi.nlm.nih.gov/pubmed/33917388 DOI: 10.3390/ph14040334
197. Yan ZP, Yang M, Lai CL. COVID-19 Vaccines: A Review of the Safety and Efficacy of Current Clinical Trials. Pharmaceuticals (Basel). 2021;14(5):25. DOI: 10.3390/ph14050406 ABSTRACT: Various strategies have been designed to contain the COVID-19 pandemic. Among them, vaccine development is high on the agenda in spite of the unknown duration of the protection time. Various vaccines have been under clinical trials with promising results in different countries. The protective efficacy and the short-term and long-term side effects of the vaccines are of major concern. Therefore, comparing the protective efficacy and risks of vaccination is essential for the global control of COVID-19 through herd immunity. This study reviews the most recent data of 12 vaccines to evaluate their efficacy, safety profile and usage in various populations. URL: https://www.ncbi.nlm.nih.gov/pubmed/33923054 DOI: 10.3390/ph14050406
198. Young B, Kotzur M, Gatting L, et al. The impact of theory-based messages on COVID-19 vaccination intentions: a structured summary of a study protocol for a randomised controlled trial. Trials. 2021;22(1):311. DOI: 10.1186/s13063-021-05277-7 ABSTRACT: OBJECTIVES: Uptake of vaccination against COVID-19 is key to controlling the pandemic. However, a significant proportion of people report that they do not intend to have a vaccine, often because of concerns they have about vaccine side effects or safety. This study will assess the impact of theory-based messages on COVID-19 vaccination intention, drawing on the Necessity-Concerns framework to address previously reported beliefs and concerns about COVID-19 vaccination, and assess whether hypothesised variables (illness coherence, perceived necessity and concerns) mediate change in vaccination intention. TRIAL DESIGN: Prospective, parallel two-arm, individually randomised (1:1) trial. PARTICIPANTS: Adults aged over 18 years, living in Scotland and not vaccinated for COVID-19. A quota sampling approach will be used with the aim of achieving a nationally representative sample on gender, region and ethnic group, with oversampling of individuals with no educational qualifications or with only school-level qualifications. INTERVENTION AND COMPARATOR: Intervention: Brief exposure to online text and image-based messages addressing necessity beliefs and concerns about COVID-19 vaccination. Comparator: Brief exposure to online text and image-based messages containing general information about COVID-19 and COVID-19 vaccination. MAIN OUTCOMES: Primary outcome: Self-reported intention to receive a vaccine for COVID-19 if invited, immediately post-intervention. SECONDARY
Evidence Search Report: INF031801v4 ESR 92 OUTCOMES: Self-reported COVID-19 illness coherence, perceived necessity of a COVID-19 vaccine and concerns about a COVID-19 vaccine, immediately post-intervention. RANDOMISATION: Quasi- randomisation performed automatically by online survey software, by creating a variable derived from the number of seconds in the minute that the participant initiates the survey. Participants starting the survey at 0-14 or 30-44 seconds in the minute are allocated to the intervention and 15-29 or 45-59 seconds to the comparator. BLINDING (MASKING): Participants will not be blinded to group assignment but will not be informed of the purpose of the study until they have completed the follow-up survey. Investigators will be blinded to allocation as all procedures will be undertaken digitally and remotely without any investigator contact with participants. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 1,094 will be randomised 1:1 into two groups with 547 individuals in each. TRIAL STATUS: Protocol version number 1.0, 26(th) February 2021. Recruitment status: Not yet recruiting, set to start April 2021 and end April 2021. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04813770 , 24(th) March 2021. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. URL: https://www.ncbi.nlm.nih.gov/pubmed/33926540 DOI: 10.1186/s13063-021-05277-7
199. Yutuc AV, Olazo DB, Sarmiento PJD. Business sectors' initiatives on health and safety protocols and vaccination program among employees during the COVID-19 pandemic. J Public Health (Oxf). 2021;04:04. DOI: 10.1093/pubmed/fdab139 ABSTRACT: In a recent correspondence, the author discussed the issues of 'no-jab, no job' policy, which is planned to be implemented by governments and companies in many countries. This paper highlights the business sectors' initiatives in ensuring the implementation of health and safety protocols and vaccination program among employees during the COVID-19 pandemic. URL: https://www.ncbi.nlm.nih.gov/pubmed/33942855 DOI: 10.1093/pubmed/fdab139
200. Zhang MX, Zhang TT, Shi GF, et al. Safety of an inactivated SARS-CoV-2 vaccine among healthcare workers in China. Expert Rev Vaccines. 2021:1-8. DOI: 10.1080/14760584.2021.1925112 ABSTRACT: Background: Although the inactivated SARS-CoV-2 vaccine (CoronaVac) has undergone preclinical tests and clinical trials evaluating its efficacy and safety, few data have been reported in the post-licensure real-world setting. We aimed to assess the safety of the vaccine among healthcare workers.Methods: A self-administered online survey on monitoring adverse reactions post vaccination was conducted among the staff who worked at and were vaccinated in a tertiary hospital in Taizhou, China, from February 24 to 7 March 2021. A total of 1526 subjects responded to the questionnaire when they received an e-mail or an e-poster on WeChat.Results: The incidences of overall adverse reactions after the first and second injections were 15.6% (238/1526) and 14.6% (204/1397), respectively. The most common adverse reaction was localized pain at the injection site, with an incidence of 9.6% and 10.7% after each dose, accounting for 61.8% and 73.0% of adverse reactions, respectively. Fatigue, muscle pain, and headache were the most common systemic adverse reactions.Conclusions: These findings implied that the inactivated CoronaVac vaccine has an acceptable safety profile among healthcare workers due to the low incidence of self-reported adverse reactions. This may boost public confidence in nationwide mass vaccination campaigns. URL: https://www.ncbi.nlm.nih.gov/pubmed/33929930 DOI: 10.1080/14760584.2021.1925112
Evidence Search Report: INF031801v4 ESR 93 201. Zhao X, Chen H, Wang H. Glycans of SARS-CoV-2 Spike Protein in Virus Infection and Antibody Production. Front Mol Biosci. 2021;8:629873. DOI: 10.3389/fmolb.2021.629873 ABSTRACT: Viral protein glycosylation represents a successful strategy employed by the parasite to take advantage of host-cell machinery for modification of its own proteins. The resulting glycans have unneglectable roles in viral infection and immune response. The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which presents on the surface of matured virion and mediates viral entry into the host, also undergoes extensive glycosylation to shield it from the human defense system. It is believed that the ongoing COVID-19 pandemic with more than 90,000,000 infections and 1,900,000 deaths is partly due to its successful glycosylation strategy. On the other hand, while glycan patches on S protein have been reported to shield the host immune response by masking "nonself" viral peptides with "self-glycans," the epitopes are also important in eliciting neutralizing antibodies. In this review, we will summarize the roles of S protein glycans in mediating virus-receptor interactions, and in antibody production, as well as indications for vaccine development. URL: https://www.ncbi.nlm.nih.gov/pubmed/33928117 DOI: 10.3389/fmolb.2021.629873
202. Zhu W, Shyr ZA, Lo DC, et al. Viral Proteases as Targets for COVID-19 Drug Development. J Pharmacol Exp Ther. 2021;10:10. DOI: 10.1124/jpet.121.000688 ABSTRACT: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a global threat since its emergence. Although several COVID-19 vaccines have become available, the prospective timeframe for achieving effective levels of vaccination across global populations remains uncertain. Moreover, the emergence of SARS-CoV-2 variants presents continuing potential challenges for future vaccination planning. Therefore, development of effective antiviral therapies continues to be an urgent unmet need for COVID-19. Successful antiviral regimens for the treatment of human immunodeficiency virus and hepatitis C virus infections have established viral proteases as validated targets for antiviral drug development. In this context, we review here protease targets in drug development, currently available antiviral protease inhibitors, and therapeutic development efforts on SARS-CoV-2 main protease and papain-like protease. Significance Statement Coronavirus disease 2019 (COVID-19) continues to be a global threat since its emergence. The development of effective antiviral therapeutics for COVID-19 remains an urgent and long-term need. Because viral proteases are validated drug targets, specific SARS-CoV-2 protease inhibitors are critical therapeutics to be developed for treatment of COVID-19. URL: https://www.ncbi.nlm.nih.gov/pubmed/33972366 DOI: 10.1124/jpet.121.000688
203. Graham F. Daily briefing: How desperate measures might shorten the coronavirus vaccine timeline - and at what risk. Nature. 2020;01:01. DOI: 10.1038/d41586-020-01333-5 URL: https://www.ncbi.nlm.nih.gov/pubmed/33931774 DOI: 10.1038/d41586-020-01333-5
204. Perosa F, Favoino E, Prete M. Why Do We Still Lack a COVID-19 Vaccine? Searching for the Missing Pieces. Endocr Metab Immune Disord Drug Targets. 2020;21(4):567-8. DOI: 10.2174/1871530320666201207234914 URL: https://www.ncbi.nlm.nih.gov/pubmed/33290205 DOI: 10.2174/1871530320666201207234914
Evidence Search Report: INF031801v4 ESR 94
Appendix 1: Evidence Search Details
Filters, Limits English only & Exclusions: April 30, 2021 – May 14, 2021
Sources Agency for Clinical Innovation McMaster Plus Searched: (ACI) and the New South Wales Medline Government MedRXiv CanCOVID National Collaborating Centre for CBC Methods and Tools CDC Newfoundland & Laborador Centre Centre for Effective Practice for Applied Health Research Center for Infectious Disease NHS Research and Policy (CIDRAP) NHS Library and Knowledge Centre for Evidence-Based Services Medicine, Oxford University Prevent Epidemics COVID-19 Immunity Task Force Public Health England Embase Public Health Ontario European Centre for Disease Science Table (Ontario) Prevention and Control (ECDC) Strategy for Patient Oriented Evidence Synthesis Network Research (SPOR) Evidence Alliance EvidenceAid Usher Institute for COVid-19 Google Evidence Reviews (UNCOVER), Google Scholar University of Edinburgh McMaster Health Forum WHO
Librarian(s): Lukas Miller, Clinical Librarian, Saskatchewan Health Authority Brianna Howell-Spooner, Clinical Librarian, Saskatchewan Health Authority
Appendix 2: Search Strategies
Ovid MEDLINE(R) ALL <1946 to May 13, 2021> # Searches Results
1 (nCoV* or 2019nCoV or 19nCoV or COVID19* or COVID or SARS-COV-2 or 133514 SARSCOV-2 or SARSCOV2 or Severe Acute Respiratory Syndrome Coronavirus 2 or Severe Acute Respiratory Syndrome Corona Virus 2 or coronavirus*).ti,kf,nm,ox,rx,px. 2 ((new or novel or "19" or "2019" or Wuhan or Hubei or China or Chinese) adj3 13732 (coronavirus* or corona virus* or betacoronavirus* or CoV or HCoV)).ti,kf. 3 ((coronavirus* or corona virus* or betacoronavirus*) adj3 (pandemic* or 2481 epidemic* or outbreak* or crisis)).ti,kf.
Evidence Search Report: INF031801v4 ESR 95 4 or/1-3 133615
5 (vaccinat* or vaccine? or inoculat* or immunization? or immunize? or 341339 immunogenicity).ti,kf. or (vaccinat* or vaccine? or inoculat* or immunization? or immunize? or immunogenicity).ab. /freq=2 6 4 and 5 7037
7 (moderna? or mrna-1273 or mrna1273).mp. 1209
8 (pfizer* or biontech* or tozinameran or BNT162b2).mp. 3410
9 (astrazeneca or astra zeneca or "ChAdOx1-S" or ChAdOx1* or COVISHIELD or 1448 (oxford adj3 astrazeneca)).mp. 10 (janssen? or "ad26.cov2.s" or ad26cov2s or ad26cov2* or (johnson adj2 16306 johnson)).mp. 11 or/7-10 21932
12 4 and 11 615
13 (safe* or risk? or harm* or unsafe* or effect* of efficacy or viability or viable or 1729234 success* or valid* or evidence-based? or outcome? or guidance or best practice? or guideline? or recommendation? or advisor* or standard*).ti,kf. 14 (safe* or risk? or harm* or unsafe* or effect* of efficacy or viability or viable or 3349803 success* or valid* or evidence-based? or outcome? or guidance or best practice? or guideline? or recommendation? or advisor* or standard*).ab. /freq=2 15 (random* or placebo or clinical trial? or control* trial? or trial?).ti,kf. 434779
16 (random* or placebo or clinical trial? or control* trial?).ab. /freq=2 587404
17 ((prevent* or control* or reduce?) adj2 (infect* or re-infect* or reinfect* or 28290 spread* or outbreak* or epidemic or pandemic or illness* or critical or hospitaliz* or intubat* or death* or fatal* or morbid* or severe* or severity)).ti,kf. 18 ((prevent* or control* or reduce?) adj2 (infect* or re-infect* or reinfect* or 19963 spread* or outbreak* or epidemic or pandemic or illness* or critical or hospitaliz* or intubat* or death* or fatal* or morbid* or severe* or severity)).ab. /freq=2 19 or/13-18 4566504
20 (6 or 12) and 19 1943
21 limit 20 to dt=20210430-20210514 158
Embase <1974 to 2021 May 13> # Searches Results 1 (nCoV* or 2019nCoV or 19nCoV or COVID19* or COVID or SARS-COV-2 or 127778
Evidence Search Report: INF031801v4 ESR 96 SARSCOV-2 or SARSCOV2 or Severe Acute Respiratory Syndrome Coronavirus 2 or Severe Acute Respiratory Syndrome Corona Virus 2 or coronavirus*).ti,kw. 2 ((new or novel or "19" or "2019" or Wuhan or Hubei or China or Chinese) 13196 adj3 (coronavirus* or corona virus* or betacoronavirus* or CoV or HCoV)).ti,kw. 3 ((coronavirus* or corona virus* or betacoronavirus*) adj3 (pandemic* or 2428 epidemic* or outbreak* or crisis)).ti,kw. 4 or/1-3 127898 5 (vaccinat* or vaccine? or inoculat* or immunization? or immunize? or 381982 immunogenicity).ti,kw. or (vaccinat* or vaccine? or inoculat* or immunization? or immunize? or immunogenicity).ab. /freq=2 6 4 and 5 5997 7 (moderna? or mrna-1273 or mrna1273).mp. 962 8 (pfizer* or biontech* or tozinameran or BNT162b2).mp. 53174 9 (astrazeneca or astra zeneca or "ChAdOx1-S" or ChAdOx1* or COVISHIELD or 22696 (oxford adj3 astrazeneca)).mp. 10 (janssen? or "ad26.cov2.s" or ad26cov2s or ad26cov2* or (johnson adj2 58387 johnson)).mp. 11 or/7-10 123171 12 4 and 11 821 13 (safe* or risk? or harm* or unsafe* or effect* of efficacy or viability or viable 2491255 or success* or valid* or evidence-based? or outcome? or guidance or best practice? or guideline? or recommendation? or advisor* or standard*).ti,kw. 14 (safe* or risk? or harm* or unsafe* or effect* of efficacy or viability or viable 5011580 or success* or valid* or evidence-based? or outcome? or guidance or best practice? or guideline? or recommendation? or advisor* or standard*).ab. /freq=2 15 (random* or placebo or clinical trial? or control* trial? or trial?).ti,kw. 606667 16 (random* or placebo or clinical trial? or control* trial?).ab. /freq=2 838909 17 ((prevent* or control* or reduce?) adj2 (infect* or re-infect* or reinfect* or 32490 spread* or outbreak* or epidemic or pandemic or illness* or critical or hospitaliz* or intubat* or death* or fatal* or morbid* or severe* or severity)).ti,kw. 18 ((prevent* or control* or reduce?) adj2 (infect* or re-infect* or reinfect* or 27478 spread* or outbreak* or epidemic or pandemic or illness* or critical or hospitaliz* or intubat* or death* or fatal* or morbid* or severe* or severity)).ab. /freq=2 19 or/13-18 6604826 20 (6 or 12) and 19 1754 21 limit 20 to dd=20210430-20210514 147 22 limit 21 to medline 84 23 21 not 22 63
Other Sources Vaccin*
Evidence Search Report: INF031801v4 ESR 97
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Evidence Search Report: INF031801v4 ESR 98