DOCSLIB.ORG

“Cytokine Storm” in Hospitalized COVID-19 Patients: a Retrospective Cohort Study

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
“Cytokine Storm” in Hospitalized COVID-19 Patients: a Retrospective Cohort Study Article Absence of “Cytokine Storm” in Hospitalized COVID-19 Patients: A Retrospective Cohort Study Maeghan L. Ciampa 1, Thomas A. O’Hara 1 , Constance L. Joel 1, Melinda M. Gleaton 2, Kirti K. Tiwari 3, Daniel M. Boudreaux 3 and Balakrishna M. Prasad 3,* 1 Department of General Surgery, Dwight D Eisenhower Army Medical Center, Fort Gordon, GA 30905, USA; [email protected] (M.L.C.); [email protected] (T.A.O.); [email protected] (C.L.J.) 2 Department of Pathology, Dwight D Eisenhower Army Medical Center, Fort Gordon, GA 30905, USA; [email protected] 3 Department of Clinical Investigation, Dwight D Eisenhower Army Medical Center, Fort Gordon, GA 30905, USA; [email protected] (K.K.T.); [email protected] (D.M.B.) * Correspondence: [email protected]; Tel.: +1-(706)-787-0014 Abstract: Background: A rapidly growing number of publications cite “cytokine storm” as a con- tributing factor in coronavirus disease 2019 (COVID-19) pathology. However, a few recent reports led to questioning of “cytokine storm” theory in COVID-19. This study’s primary goal is to determine if exaggerated cytokine response in the range of a “cytokine storm” develops during the initial weeks of hospitalization in COVID-19 patients. Methods: Five proinflammatory cytokines reported to be α involved in “cytokine storm” and elevated in COVID-19 (IL-6, IL-8, TNF- , MCP-1, and IP-10) were analyzed in COVID-19, influenza (with “cytokine storm”: CS), and burn injury patients. The effect of Citation: Ciampa, M.L.; O’Hara, dexamethasone use on cytokine response in COVID-19 was also analyzed. Results: None of the five T.A.; Joel, C.L.; Gleaton, M.M.; Tiwari, cytokines in COVID-19 patients reached the lower threshold (95% CI) of the influenza (CS) group K.K.; Boudreaux, D.M.; Prasad, B.M. at any point during the study period. Furthermore, mean concentrations of all five cytokines in Absence of “Cytokine Storm” in the influenza (CS) group and IL-6, IL-8, TNF-α in the burn group were significantly greater than in Hospitalized COVID-19 Patients: A COVID-19 patients (p < 0.01). Dexamethasone treatment did not significantly alter the concentrations Retrospective Cohort Study. Infect. of any of the cytokines analyzed. Conclusions: Exaggerated cytokine response similar to “cytokine Dis. Rep. 2021, 13, 377–387. https:// doi.org/10.3390/idr13020036 storm” was not observed in COVID-19 patients during two weeks of hospitalization. Academic Editor: Nicola Petrosillo Keywords: coronavirus; immunosuppressant; dexamethasone; interleukin; COVID-19; cytokine Received: 8 March 2021 Accepted: 15 April 2021 Published: 19 April 2021 1. Introduction Coronavirus disease 2019 (COVID-19), which was declared a pandemic by the World Publisher’s Note: MDPI stays neutral Health Organization, is caused by severe acute respiratory syndrome coronavirus 2 (SARS- with regard to jurisdictional claims in CoV-2). Pharmacotherapeutic choices for COVID-19 depend on the severity of symptoms, published maps and institutional affil- time after infection, patient characteristics and comorbidities [1,2]. Although no specific iations. cure is available at present, interventions commonly being used include antiviral, anticoag- ulant and immunosuppressant drugs. The therapeutic standard of care has evolved along with our understanding of the pathophysiology of COVID-19 over the past year. The rationale for using antiviral drugs is obvious, and remdesivir is the first COVID- Copyright: © 2021 by the authors. 19 treatment to be approved by the FDA in October 2020 [3]. Intracellular replication of Licensee MDPI, Basel, Switzerland. SARS-CoV-2 depends on RNA-dependent RNA polymerase, and remdesivir can decrease This article is an open access article the viral load by inhibiting this enzyme. The presence of disseminated intravascular coagu- distributed under the terms and lation and venous thromboembolism justified anticoagulant use in COVID-19 patients [4]. conditions of the Creative Commons COVID-19 patients were reported to have hyperimmune reactions based on elevated cir- Attribution (CC BY) license (https:// culating cytokine concentrations and altered lymphocyte profile. Indeed, one of the first creativecommons.org/licenses/by/ characterizations of COVID-19 clinical phenotype reported elevated concentrations of 4.0/). Infect. Dis. Rep. 2021, 13, 377–387. https://doi.org/10.3390/idr13020036 https://www.mdpi.com/journal/idr Infect. Dis. Rep. 2021, 13 378 inflammatory cytokines [5]. Furthermore, some cytokines’ plasma concentrations were associated with disease progression and severity [6–8]. These studies led to the widely publicized theory of “cytokine storm” in COVID-19 and even drew parallels with cytokine release syndrome and secondary hemophagocytic lymphohistiocytosis [9,10]. However, critical quantitative analysis of COVID-19 cytokine data than hyperinflam- matory conditions led to questioning of the “cytokine storm” theory of COVID-19 [11]. A recent study showed that plasma concentrations of three proinflammatory cytokines are not as elevated in COVID-19 as in sepsis with acute respiratory distress syndrome [12]. Almost all of the studies evaluated cytokine profiles in hospitalized COVID-19 patients within 48 h of admission. A cytokine storm, particularly in the context of an active infection, may take several days to manifest [13]. Thus, this study’s primary goal is to test the hypothesis that an exaggerated cytokine response may develop during the initial weeks of hospitalization in COVID-19 patients. In addition, we tested the effect of dexamethasone treatment on cytokine concentrations and analyzed if its use is responsible for masking the presence of a “cytokine storm”. 2. Methods All study procedures were performed in compliance with Eisenhower Army Medical Center institutional review board. Daily blood samples were collected from COVID-19 PCR-positive patients admitted to the hospital between March and October 2020. Leftover serum or plasma samples after clinical pathology tests were stored at −80 ◦C. Cytokine concentrations were measured using a 46-plex magnetic bead assay according to the manufacturer’s instructions (EMD-Millipore, Burlington, MA, USA). Samples in our tissue bank from influenza, burn or control patients (obtained before 2020) were also analyzed in the same assays. Although there is no established quantitative criterion for “cytokine storm”, several proinflammatory cytokines are increased by orders of magnitude during cytokine release syndrome with IL-6 concentrations in the range of 10 ng/mL [14]. We had previously measured IL-6 in several respiratory infections and used a cohort of influenza with pneumonia (ICD J11.0) as an appropriate positive control for “cytokine storm” in a viral infection. IL-6 concentration greater than 1 ng/mL was used to identify influenza (CS) samples. Samples from patients with greater than 40% total body surface area burns and control patients were used as additional references representing trauma-induced and normal cytokine concentrations, respectively. Relative abundance of antibodies against the receptor-binding domain (RBD) of COVID-19 spike protein was also measured using a SARS-CoV-2 multi-antigen IgG assay kit (Luminex, Austin, TX, USA). Clinical parameters, including dexamethasone use and patient characteristics, were obtained from retrospective chart reviews. Cytokine concentrations of COVID-19 patients were analyzed in samples collected on alternate days, beginning with the day of hospi- talization. Analysis was performed in samples up to 2 weeks in patients that received dexamethasone (6 mg/day for 10 days) and up to 1 week in those that did not. Sample inclusion depended on their availability and length of the patient’s hospital stay. One patient in the dexamethasone group received tocilizumab on day 4 after hospitalization. All post-tocilizumab samples in this patient were excluded from analysis because of a drug-induced increase in IL-6. Five of the 46 cytokines measured were included in the data analyses. Interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP- 1), interferon γ-induced protein-10 (IP-10) are typical proinflammatory cytokines whose concentrations were reported to be elevated in cytokine release syndrome and in COVID- 19 [5,6,14]. In addition, IL-6, IL-8 and IP-10 concentrations were correlated with COVID-19 progression and severity [6,7]. All data points for each COVID-19 patient across the moni- toring period were averaged. Geometric means of COVID-19 patients with dexamethasone treatment (DEX) and those with no-dexamethasone treatment (no-DEX) were compared to influenza (CS), burn and control groups. Log-transformed data were analyzed with ANOVA followed by Tukey’s multiple comparisons test. To further assess dexamethasone’s Infect. Dis. Rep. 2021, 13 379 effects, the data points while a patient is on dexamethasone treatment were compared to those before and after the treatment using paired t-tests. Paired t-tests on log-transformed values were used to assess changes in cytokine concentrations throughout hospitalization. Age and BMI comparisons were made with t-test, while Fisher’s exact test was used for all other patient characteristics. A p value of < 0.01 was used to define significance in all statistical comparisons. 3. Results Clinical data of hospitalized COVID-19 patients with or without dexamethasone treatment are shown in Table1. The two groups had comparable patient characteristics except hypertension
Load more

Recommended publications
  • The Management of Sepsis: What's New in 2013
    The Management of Sepsis: What’s New in 2013 Mitchell M. Levy MD, FCCM Professor of Medicine Chief, Division of Pulmonary, Sleep, and Critical Care Warren Alpert Medical School of Brown University Providence, RI Disclosures • Personal: – Financial: • None • SSC – Financial: • None • No industry support since 2006 Projected Incidence of Severe Sepsis in the US: 2001‐2050 1,800 600 Severe Sepsis Cases ) 3 US Population 1,600 500 1,400 1,200 400 Sepsis Cases (x10 1,000 800 300 Total US Population (million) US Total 2001 2025 2050 Angus DC, et al. JAMA 2000;284:2762-70. Year Angus DC, et al. Crit Care Med 2001. In Press. Pathophysiology Sepsis as Cytokine Storm • Sepsis presentation – Fever, shock, respiratory failure • Pro‐inflammatory cytokines TNFα, IL‐1, IL‐6 – All increased in sepsis • Encouraging results in animal models pre‐ treated with therapeutics that blocked pro‐ inflammatory cytokines Traditional view of sepsis and its pathophysiology Virulent pathogens (pneumococci, meningococcus, • VirulentGroup A strep, pathogens: S. aureus, Clostrida spp.) pneumococcus,Pro-inflammatory markers-cytokines, S. aureus, Groupchemokines A strep,C’ Clostridia, meningococci C, ROS RNS kinins, procoagulants • Proinflammatory mediators- Early onset septic shock, MODS cytokines, chemokines, procoagulants, kinins, ROI, RNI, C’ • Young, previously healthy patients with rapid onset septic shock - fits our animal models (Hotchkiss and Karl N Engl J Med 2003;348:138) /8 TLR’s are the major pattern recognition receptors of innate immunity PAMPs DAMPs HSP Heparan Hyaluronate Fibrinogen Microorganisms Biglycan Surfactant A HMGB-1 Heme MRP8/14 Histone 5 PRRs Immune cells NLRs TLRs CLRs CDRs RLHs ASC Caspase-1 & 5 NF-κB ASC NALP1 & 3 Pyrin Host-derived mediators Cinel and Opal CCM 2009:291 Genomic Storm Xiao et al.
    [Show full text]
  • The Mechanism Behind Influenza Virus Cytokine Storm
    viruses Review The Mechanism behind Influenza Virus Cytokine Storm Yinuo Gu, Xu Zuo, Siyu Zhang, Zhuoer Ouyang, Shengyu Jiang, Fang Wang * and Guoqiang Wang * Department of Pathogeny Biology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China; [email protected] (Y.G.); [email protected] (X.Z.); [email protected] (S.Z.); [email protected] (Z.O.); [email protected] (S.J.) * Correspondence: [email protected] (F.W.); [email protected] (G.W.); Tel.: +86-0431-8561-9486 (F.W. & G.W.) Abstract: Influenza viruses are still a serious threat to human health. Cytokines are essential for cell-to-cell communication and viral clearance in the immune system, but excessive cytokines can cause serious immune pathology. Deaths caused by severe influenza are usually related to cytokine storms. The recent literature has described the mechanism behind the cytokine–storm network and how it can exacerbate host pathological damage. Biological factors such as sex, age, and obesity may cause biological differences between different individuals, which affects cytokine storms induced by the influenza virus. In this review, we summarize the mechanism behind influenza virus cytokine storms and the differences in cytokine storms of different ages and sexes, and in obesity. Keywords: influenza virus; cytokine storm; age; sex; obesity 1. Introduction Citation: Gu, Y.; Zuo, X.; Zhang, S.; The COVID-19 pandemic showed the catastrophic impact of a new type of virus on Ouyang, Z.; Jiang, S.; Wang, F.; Wang, human health. Since the H1N1 Spanish influenza outbreak in 1918, there have been many G.
    [Show full text]
  • Consequences of Viral Toxicities and Host Immune Response
    Current Cardiology Reports (2020) 22:32 https://doi.org/10.1007/s11886-020-01292-3 HOT TOPIC Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response Han Zhu1,2,3 & June-Wha Rhee1,2,3 & Paul Cheng1,2,3 & Sarah Waliany1 & Amy Chang1,4 & Ronald M. Witteles1,3 & Holden Maecker5,6 & Mark M. Davis5,6,7 & Patricia K. Nguyen 1,2,3 & Sean M. Wu1,2,3 # Springer Science+Business Media, LLC, part of Springer Nature 2020 Abstract Purpose of Review Coronavirus disease of 2019 (COVID-19) is a cause of significant morbidity and mortality worldwide. While cardiac injury has been demonstrated in critically ill COVID-19 patients, the mechanism of injury remains unclear. Here, we review our current knowledge of the biology of SARS-CoV-2 and the potential mechanisms of myocardial injury due to viral toxicities and host immune responses. Recent Findings A number of studies have reported an epidemiological association between history of cardiac disease and worsened outcome during COVID infection. Development of new onset myocardial injury during COVID-19 also increases mortality. While limited data exist, potential mechanisms of cardiac injury include direct viral entry through the angiotensin- converting enzyme 2 (ACE2) receptor and toxicity in host cells, hypoxia-related myocyte injury, and immune-mediated cytokine release syndrome. Potential treatments for reducing viral infection and excessive immune responses are also discussed. Summary COVID patients with cardiac disease history or acquire new cardiac injury are at an increased risk for in-hospital morbidity and mortality. More studies are needed to address the mechanism of cardiotoxicity and the treatments that can minimize permanent damage to the cardiovascular system.
    [Show full text]
  • When Does the Cytokine Storm Begin in COVID-19 Patients? a Quick Score to Recognize It
    Journal of Clinical Medicine Article When Does the Cytokine Storm Begin in COVID-19 Patients? A Quick Score to Recognize It Stefano Cappanera 1,* , Michele Palumbo 1, Sherman H. Kwan 2, Giulia Priante 1, Lucia Assunta Martella 1, Lavinia Maria Saraca 1, Francesco Sicari 1, Carlo Vernelli 1, Cinzia Di Giuli 1, Paolo Andreani 3, Alessandro Mariottini 3, Marsilio Francucci 4, Emanuela Sensi 5, Monya Costantini 6, Paolo Bruzzone 7 , Vito D’Andrea 8 , Sara Gioia 9, Roberto Cirocchi 10 and Beatrice Tiri 1 1 Clinical Infectious Disease, Department of medicine, St. Maria Hospital, 05100 Terni, Italy; [email protected] (M.P.); [email protected] (G.P.); [email protected] (L.A.M.); [email protected] (L.M.S.); [email protected] (F.S.); [email protected] (C.V.); [email protected] (C.D.G.); [email protected] (B.T.) 2 Department of General Surgery, Royal Perth Hospital, Perth 6000, Australia; [email protected] 3 Hematology and Microbiology Laboratory, St. Maria Hospital, 05100 Terni, Italy; [email protected] (P.A.); [email protected] (A.M.) 4 Department of General and Oncologic Surgery, St. Maria Hospital, 05100 Terni, Italy; [email protected] 5 Department of Critical Care Medicine and Anesthesiology, St. Maria Hospital, 05100 Terni, Italy; [email protected] 6 Pharmacy Unit, St. Maria Hospital, 05100 Terni, Italy; [email protected] 7 Department of General and Specialist Surgery “Paride Stefanini”, 00185 Rome, Italy; [email protected] 8 Department of Surgical Sciences, Sapienza University of Rome, 00161 Rome, Italy; [email protected] 9 Legal Medicine, University of Perugia, 06123 Perugia, Italy; [email protected] 10 Department of General and Oncologic Surgery, University of Perugia, St.
    [Show full text]
  • FACT SHEET for HEALTHCARE PROVIDERS Coronavirus Disease Access IL-6 – Beckman Coulter, Inc
    FACT SHEET FOR HEALTHCARE PROVIDERS Coronavirus Disease Access IL-6 – Beckman Coulter, Inc. October 1, 2020 2019 This Fact Sheet informs you of the significant known and potential risks and benefits of the emergency use of the This test is to be performed only using serum or Access IL-6. plasma specimens collected from individuals The Access IL-6 is authorized for use in human serum confirmed positive for SARS-CoV-2. and plasma specimens collected from patients with confirmed Coronavirus Disease-2019 (COVID-19) to assist in identifying severe inflammatory response to aid mechanical ventilation, in conjunction with clinical in determining the risk of intubation with mechanical findings and the results of other laboratory testing. ventilation, in conjunction with clinical findings and the • The Access IL-6 is only authorized for use in results of other laboratory testing. laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, that meet requirements to perform All patients whose specimens are tested with moderate or high complexity tests. this assay will receive the Fact Sheet for Specimens should be collected with appropriate infection Patients: Access IL-6 – Beckman Coulter, Inc. control precautions. Current guidance for COVID-19 infection control precautions are available at the CDC’s website (see links provided in “Where can I go for What are the severe clinical manifestations of updates and more information” section). COVID-19 associated with IL-6? Use appropriate personal protective equipment when Many patients with confirmed COVID-19 have developed collecting and handling specimens from individuals fever and/or symptoms of severe inflammatory suspected of having COVID-19 as outlined in the CDC response, sometimes referred to as “cytokine release Interim Laboratory Biosafety Guidelines for Handling and syndrome” (CRS) or “cytokine storm”.
    [Show full text]
  • Immunological Considerations for COVID-19 Vaccine Strategies
    REVIEWS Immunological considerations for COVID-19 vaccine strategies Mangalakumari Jeyanathan1,2,3,5, Sam Afkhami1,2,3,5, Fiona Smaill2,3, Matthew S. Miller1,3,4, Brian D. Lichty 1,2 ✉ and Zhou Xing 1,2,3 ✉ Abstract | The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) is the most formidable challenge to humanity in a century. It is widely believed that prepandemic normalcy will never return until a safe and effective vaccine strategy becomes available and a global vaccination programme is implemented successfully. Here, we discuss the immunological principles that need to be taken into consideration in the development of COVID-19 vaccine strategies. On the basis of these principles, we examine the current COVID-19 vaccine candidates, their strengths and potential shortfalls, and make inferences about their chances of success. Finally, we discuss the scientific and practical challenges that will be faced in the process of developing a successful vaccine and the ways in which COVID-19 vaccine strategies may evolve over the next few years. The coronavirus disease 2019 (COVID-19) outbreak constitute a safe and immunologically effective COVID-19 was first reported in Wuhan, China, in late 2019 and, at vaccine strategy, how to define successful end points the time of writing this article, has since spread to 216 in vaccine efficacy testing and what to expect from countries and territories1. It has brought the world to a the global vaccine effort over the next few years. This standstill. The respiratory viral pathogen severe acute Review outlines the guiding immunological principles respiratory syndrome coronavirus 2 (SARS-CoV-2) has for the design of COVID-19 vaccine strategies and anal- infected at least 20.1 million individuals and killed more yses the current COVID-19 vaccine landscape and the than 737,000 people globally, and counting1.
    [Show full text]
  • Efforts at COVID-19 Vaccine Development
    Review Efforts at COVID-19 Vaccine Development: Challenges and Successes Azizul Haque 1,* and Anudeep B. Pant 2 1 One Medical Center Drive, Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA 2 New Orleans East Hospital, 5620 Read Blvd, New Orleans, LA 70127, USA; [email protected] * Correspondence: [email protected] Received: 23 November 2020; Accepted: 3 December 2020; Published: 6 December 2020 Abstract: The rapid spread of SARS-CoV-2, the new coronavirus (CoV), throughout the globe poses a daunting public health emergency. Different preventive efforts have been undertaken in response to this global health predicament; amongst them, vaccine development is at the forefront. Several sophisticated designs have been applied to create a vaccine against SARS-CoV-2, and 44 candidates have already entered clinical trials. At present, it is unclear which ones will meet the objectives of efficiency and safety, though several vaccines are gearing up to obtain emergency approval in the U.S. and Europe. This manuscript discusses the advantages and disadvantages of various vaccine platforms and evaluates the safety and efficacy of vaccines in advance stages. Once a vaccine is developed, the next challenge will be acquisition, deployment, and uptake. The present manuscript describes these challenges in detail and proposes solutions to the vast array of translational challenges. It is evident from the epidemiology of SARS-CoV-2 that the virus will remain a threat to everybody as long as the virus is still circulating in a few. We need affordable vaccines that are produced in sufficient quantity for use in every corner of the world.
    [Show full text]
  • Facts on Cytokine Storm
    FACTS ON CYTOKINE STORM Cytokine storm is an immune hyper-response. It takes place when the body’s innate immune system over responds to a threat (often an infectious agent, such as a virus or a foreign body, as What is “cytokine storm”? is the case with CAR-T) by suddenly releasing certain immune messengers known as cytokines into the bloodstream in quantities that can be out of proportion to the threat, and sometimes rapidly or long after the threat has disappeared.¹ This can lead to a potentially fatal hyperactive immune response that is often referred to as cytokine release syndrome (CRS), or cytokine storm. The exaggerated release of cytokines into the bloodstream results in an immune response that can ultimately surpass the immune threat and cause the body to attack its own healthy tissues, Why is cytokine storm a problem? including organs. The severe immune reaction brought on by a cytokine storm can damage the lungs, kidneys, heart, blood vessels, brain, nerves, liver, and lead to coagulation disorders which can result in the formation of blood clots and/or excessive bleeding. Cytokine storm can ultimately lead to multiple or individual organ failure and death.¹ Cytokine storm can ultimately lead to multiple or individual organ failure and death. Humanigen has developed a neutralizing, IgG1, monoclonal antibody against human GM-CSF, using proprietary Humaneered® technology. Cytokine Storm For more information, contact Grace Catlett: [email protected] Fact Sheet The symptoms of cytokine storm may include fever, difficulty breathing, inflammation (redness and swelling), fatigue, nausea, tremors, rash, and/or bruising. Sometimes, dangerously low What are the symptoms of blood pressure, respiratory failure, heart rhythm or neurological cytokine storm? abnormalities (like fatigue, headaches, hallucinations, or coma), and/ or kidney and liver failure can occur.² A blood test can measure a number of inflammatory markers and indicate whether a patient is progressing into cytokine storm.
    [Show full text]
  • Cytokine-Induced Liver Injury in Coronavirus
    Review Cytokine-induced liver injury in coronavirus disease-2019 (COVID-19): untangling the knots Prajna Anirvana, Sonali Narainb,c, Negin Hajizadehc,d,e, Fuad Z . Aloorc, Shivaram P. Singha,* and Sanjaya K. Satapathyf,* 01/15/2021 on BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= by https://journals.lww.com/eurojgh from Downloaded Liver dysfunction manifesting as elevated aminotransferase levels has been a common feature of coronavirus disease-2019 (COVID-19) infection. The mechanism of liver injury in COVID-19 infection is unclear. However, it has been Downloaded hypothesized to be a result of direct cytopathic effects of the virus, immune dysfunction and cytokine storm-related multiorgan damage, hypoxia-reperfusion injury and idiosyncratic drug-induced liver injury due to medications used in the management of from COVID-19. The favored hypothesis regarding the pathophysiology of liver injury in the setting of COVID-19 is cytokine storm, https://journals.lww.com/eurojgh an aberrant and unabated inflammatory response leading to hyperproduction of cytokines. In the current review, we have summarized the potential pathophysiologic mechanisms of cytokine-induced liver injury based on the reported literature. Eur J Gastroenterol Hepatol XXX: 00–00 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= Introduction Cytokines Despite being primarily a respiratory syndrome, corona- Cytokines play important roles in regulating host defense virus disease-2019 (COVID-19) has been found to cause and maintenance of homeostasis [5]. Cytokines are cellu- significant multiorgan dysfunction [1,2]. In a study involv- lar products that exert their activity on other cells through ing 5700 patients with COVID-19, more than half of the autocrine, paracrine and endocrine mechanisms [6].
    [Show full text]
  • Deficient IFN Signaling by Myeloid Cells Leads to MAVS-Dependent Virus-Induced Sepsis Amelia K
    Deficient IFN Signaling by Myeloid Cells Leads to MAVS-Dependent Virus-Induced Sepsis Amelia K. Pinto, Washington University Hilario J. Ramos, University of Washington Xiaobo Wu, Washington University Shilpa Aggarwal, University of Washington Bimmi Shrestha, Washington University Matthew Gorman, Washington University Kristin Y. Kim, Emory University Mehul Suthar, Emory University John P. Atkinson, Washington University Michael Gale Jr., University of Washington Only first 10 authors above; see publication for full author list. Journal Title: PLoS Pathogens Volume: Volume 10, Number 4 Publisher: Public Library of Science | 2014-04-01, Pages e1004086-e1004086 Type of Work: Article | Final Publisher PDF Publisher DOI: 10.1371/journal.ppat.1004086 Permanent URL: https://pid.emory.edu/ark:/25593/s5vfh Final published version: http://dx.doi.org/10.1371/journal.ppat.1004086 Copyright information: © 2014 Pinto et al This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/). Accessed September 30, 2021 6:43 PM EDT Deficient IFN Signaling by Myeloid Cells Leads to MAVS- Dependent Virus-Induced Sepsis Amelia K. Pinto1, Hilario J. Ramos2, Xiaobo Wu1, Shilpa Aggarwal2{, Bimmi Shrestha1, Matthew Gorman3, Kristin Y. Kim4, Mehul S. Suthar4, John P. Atkinson1,5, Michael Gale Jr2, Michael S. Diamond1,3,5* 1 Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America, 2 Department of Immunology, University of Washington School of Medicine, Seattle, Washington, United States of America, 3 Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America, 4 Department of Pediatrics, Emory Vaccine Center, Children’s Healthcare of Atlanta, Emory University, Atlanta, Georgia, United States of America, 5 Molecular Microbiology, Washington University School of Medicine, St.
    [Show full text]
  • Yellow Fever Vaccine - Report of the Commission on Human Medicine’S Expert Working Group on Benefit-Risk and Risk Minimisation Measures
    YELLOW FEVER VACCINE - REPORT OF THE COMMISSION ON HUMAN MEDICINE’S EXPERT WORKING GROUP ON BENEFIT-RISK AND RISK MINIMISATION MEASURES Following two fatal adverse reactions to yellow fever vaccine in the UK in 2018 and 2019, the UK Commission on Human Medicines (CHM) established an Expert Working Group to advise on measures that should be taken to optimise the balance of benefits and risks of the vaccine. The Expert Working Group’s Terms of Reference were: • To advise on the balance of benefits and risks of yellow fever vaccines • To advise on measures to minimise risks, and optimise benefit-risk balance to individual vaccinees, including any new precautions or restrictions on use • To advise on any communications to health professionals and potential vaccinees • To advise on measures to monitor impact/effectiveness of any additional risk minimisation • To report its conclusions and recommendations to the Commission on Human Medicines The Expert Working Group was chaired by Professor Sir Munir Pirmohamed, and its full membership is at Annex A. To inform its deliberations, the Group considered a review of available evidence on the safety and effectiveness of yellow fever vaccines from the Medicines and Healthcare products Regulatory Agency (MHRA), an analysis of the quality of batches of vaccine implicated in the recent fatal events, and evidence submitted by the licence holder, Sanofi Pasteur. The Group also considered contributions from the National Travel Health Network and Centre (NaTHNaC) and Health Protection Scotland (HPS) on the governance, clinical practice and training of yellow fever vaccination centres (YFVCs) across the UK, as well as ongoing work from Public Health England on a protocol for the management of severe adverse reactions to YF vaccine.
    [Show full text]
  • Cardiovascular Complications of COVID-19 and Associated Concerns: a Review
    Acta Cardiol Sin 2021;37:9-17 Review Article doi: 10.6515/ACS.202101_37(1).20200913A Cardiovascular Complications of COVID-19 and Associated Concerns: A Review Wen-Liang Yu,1,2 Han Siong Toh,1,3 Chia-Te Liao4,5 and Wei-Ting Chang3,4,6 SARS-CoV-2 is the virus that has caused the current coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 is characterized by significantly affecting the cardiovascular system of infected patients. In addition to the direct injuries caused by the virus, the subsequent cytokine storm – an overproduction of immune cells and their activating compounds – also causes damage to the heart. The development of anti-SARS-CoV-2 treatments is necessary to control the epidemic. Despite an explosive growth in research, a comprehensive review of up-to- date information is lacking. Herein, we summarize pivotal findings regarding the epidemiology, complications, and mechanisms of, and recent therapies for, COVID-19, with special focus on its cardiovascular impacts. Key Words: Cardiovascular injuries · COVID-19 · Cytokine storm · Therapies 1. EPIDEMIOLOGY OF CARDIOVASCULAR derlying cardiovascular disease or cardiac risk factors INVOLVEMENT OF COVID-19 may be more susceptible to SARS-CoV-2. In addition, pa- tients with cardiovascular disease infected by SARS-CoV- In the first study of cardiovascular involvement of 2 may have a higher risk of adverse outcomes compared COVID-19, 32% of 41 patients diagnosed with COVID-19 to those without cardiovascular disease. In a cohort of had underlying disease, including cardiovascular disease 191 patients with laboratory-confirmed COVID-19, 54 (15%), hypertension (15%), and diabetes (20%).1 In an- died and 137 survived, and those who died had higher other study which focused on 138 hospitalized patients rates of acute cardiac injury (59% vs.
    [Show full text]