DOCSLIB.ORG

Clinical Trials for COVID-19 Should Include Sex As a Variable

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Clinical Trials for COVID-19 Should Include Sex As a Variable VIEWPOINT The Journal of Clinical Investigation Clinical trials for COVID-19 should include sex as a variable Evelyne Bischof,1,2 Jeannette Wolfe,3 and Sabra L. Klein4,5 1Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy. 2College of Clinical Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, China. 3Department of Emergency Medicine, UMass Medical School – Baystate Campus, Springfield, Massachusetts, USA. 4W. Harry Feinstone Department of Molecular Microbiology and Immunology and 5Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. The number of COVID-19 cases appears cases revealed that 13 of 26 states disaggre- Until recently, remdesivir was regard- to be comparable between men and wom- gated data using sex as a variable. Notably, ed as promising for COVID-19, but inter- en, but the severity of disease and death is all 13 states reported that men are twice as im published results are disappointing (8). two times greater for men than for women likely to die from COVID-19 (2), with pub- The still unpublished Adaptive COVID-19 (1, 2). History, including the 1918 influen- lished data from New York City revealing Treatment Trial reported a four-day dif- za pandemic, warned us that male biases male-biased death from COVID-19 in all ference in time to recovery (11 days vs. 15 in COVID-19 could occur. In this View- adults over the age of 20 (3). days) for patients on remdesivir, suggest- point, we focus on biological explanations, Disparities between men and women ing some benefit (9). Similar outcomes with a forward look at why clinicians and in outcomes of infectious diseases, includ- have been seen for favipiravir, lopina- biomedical researchers should consider ing those caused by pathogenic coronavi- vir, and ritonavir, with the latter causing sex as a biological variable that will affect ruses, are not new. During the 2002–2003 severe side effects (10). Some studies treatment outcomes for COVID-19. There SARS outbreak and the ongoing MERS showed that hydroxychloroquine and chlo- is a long history of not analyzing or report- outbreaks, a majority of patients were roquine caused a high number of harmful ing differences between women and men men, possibly because of predominantly and lethal casualties (11). All trials to date in the prophylactic or therapeutic treat- male contact with the animal reservoirs include both men and women, but take a ment of infectious diseases. We seek to for these coronaviruses (4, 5). However, sex-blind approach to the analyses of out- reverse this trend and call on investigators for many viral respiratory tract infections, come data, with no governmental guide- developing and testing therapeutic and including but not limited to coronaviruses, lines mentioning sex-specific prophylactic prophylactic approaches for COVID-19 to the prevalence and severity of infection or therapeutic recommendations (except design studies that are inclusive of male is greater for men (6). Preclinical studies for pregnant and postpartum women). The versus female differences in drug respons- show that in mice, males are significantly lack of consideration of sex biases in drug es, immunotherapies, vaccines, and non- more susceptible to coronavirus infec- efficacy and reactivity inevitably may lead pharmacological interventions. tions, as they are less capable of controlling to increased adverse (potentially lethal) virus replication, exhibit more post-infec- reactions. A study of chloroquine treat- Disaggregating data by sex tion pulmonary damage, and have lower ment in Brazil, in which 24.7% of the sub- Initial reports from Wuhan involving immune responses than females (7). jects were female, was prematurely ceased more than 40,000 cases showed that men because of complications (especially accounted for nearly two-thirds of deaths, Drug efficacy arrhythmias and QTc prolongation, 25%) with more severe symptoms and reduced As of this writing, no antiviral agent has and lethality (17%). No sex disaggrega- recovery rates (1). This report provided the been FDA approved as a specific COVID-19 tion was provided for either outcome (12), first alarm and set a precedent for other treatment. For those drugs being tested in despite the fact that women are known countries to disaggregate their data by sex randomized clinical trials, there has been to suffer more from cardiac intricacies. (Figure 1). As reports emerged from Italy, no explicit consideration of sex biases in After the initial therapeutic and suggested Spain, France, and the United Kingdom, efficacy or adverse reactions. This occurs prophylactic use of hydroxychloroquine men have consistently been twice as likely despite studies showing clear and some- in patients with COVID-19 in March, the to die from COVID-19 as women, with the times profound differences in drug treat- FDA released a report on April 24, noting Global Health 50/50 initiative providing ment responses, including antivirals. Drug severe and lethal outcomes. It remains real-time sex-disaggregated data from most trials are typically designed and analyzed underreported whether most of these countries worldwide. Although the United without attention toward sex-specific dos- occurred in women. States has been less consistent with sex-dis- ages or differential side effects, while they Ongoing trials on hydroxychloro- aggregated reporting, a recent analysis of the should be considered in both novel and quine do not include sex-disaggregated 26 states with more than 2000 COVID-19 repositioned drugs. comparisons in their objectives. Available preliminary results of studies on remde- sivir and favipiravir also lack sex-specific Conflict of interest: The authors have declared that no conflict of interest exists. Copyright: © 2020, American Society for Clinical Investigation. data on adverse reactions or appropriate Reference information: J Clin Invest. 2020;130(7):3350–3352. https://doi.org/10.1172/JCI139306. dose adjustments. As long as drug trials 3350 jci.org Volume 130 Number 7 July 2020 The Journal of Clinical Investigation VIEWPOINT hypoxic patients by using a combination of noninvasive ventilatory support devices and patient positioning (20). As there are sex-based differences in lung physiology including airway caliber, lung volumes, diaphragmatic excursion, accessory mus- cle mechanics, and abdominal fat distribu- tion (21), sex-disaggregated outcome data on different invasive and noninvasive ven- Figure 1. Sex-disaggregated COVID-19 data. The Global Health 50/50 research initiative provides tilatory modalities are crucial, but have not real-time sex-disaggregated data from countries worldwide (accessed May 3, 2020). Based on their been included in preliminary studies. analyses of data from 69 countries, 50% of the countries are sex-disaggregating COVID-19 cases, Another rapidly evolving area of deaths, or both. For the 44 countries that have sex-disaggregated COVID-19 cases, 34% report a male bias, 45% report a female bias, and 21% report no sex bias (i.e., 50% ± 1% for each sex). For the 45 interest is the increase in thrombotic/ countries reporting sex-disaggregated COVID-19 deaths, 87% report a male bias, 2% report a female thromboembolic events in patients with bias, and 11% report no sex bias (i.e., 50% ± 1% for each sex). COVID-19 (22). Although the main driv- er of these events is currently unknown, direct viral effects, secondary hypoxia, continue to enroll both men and women Empirical evidence illustrates that liver impairment, or the amplification of but fail to sex-disaggregate outcome data, females and males differ in outcomes fol- more classical risk factors, such as severe costly mistakes will continue. Current- lowing the use of therapeutic immuno- inflammatory response and immobility, ly, there are over 1000 registered trials therapies in autoimmune diseases, infec- have been suggested (23). A recent review on COVID-19, more than half of which tious diseases, and solid tumors. Females on this topic reinforced the importance of include pharmacologic intervention or tend to experience more immunotherapy- liberal prophylaxis, suggesting therapeutic observation, and seven completed trials. related adverse reactions (17). For immu- anticoagulation of all admitted high-risk Although the latter were open to both notherapies aimed at stimulating an COVID-19 patients who lack contraindica- sexes, none reported an objective to bal- immune response, e.g., vaccines, females tions and prophylactic anticoagulation in ance participants or compared outcomes develop stronger responses and may expe- outpatients with mild disease and a history between men and women. rience greater efficacy than males. In of venous thrombosis or immobility (23). contrast, immunotherapies that repress Importantly, sex-disaggregated results Immunotherapies an immune response, e.g., cytokine or have not been reported except for a single Immunotherapies for COVID-19 are checkpoint inhibitors, are reportedly more sentence in the Helms et al. paper, noting critical for mitigation of disease and efficacious in males (18, 19). One-size-fits- that 24 of the 25 patients with pulmonary eventual long-term protection against all approaches to immunotherapies will emboli were male (22). As both under- and SARS-CoV-2. Because a vaccine is not not work, and sex/gender may contribute overanticoagulation can carry patient risk, yet available, other immunotherapies are to variable treatment success, including
Load more

Recommended publications
  • Sex and Gender Differences in COVID Testing, Hospital Admission, Presentation, and Drivers of Severe Outcomes in the DC/Maryland Region
    medRxiv preprint doi: https://doi.org/10.1101/2021.04.05.21253827; this version posted April 7, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Scully et al. 1 Sex and gender differences in COVID testing, hospital admission, presentation, and drivers of severe outcomes in the DC/Maryland region Eileen P. Scully1*, Grant Schumock2, Martina Fu2, Guido Massaccesi1, John Muschelli2, Joshua Betz2, Eili Y. Klein3, Natalie E. West4, Matthew Robinson1, Brian T. Garibaldi4, Karen Bandeen- Roche2, Scott Zeger2, Sabra L. Klein5,6*, and Amita Gupta1,7* for the JH-CROWN registry team 1Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 2Department of Biostatistics, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland USA 3Department of Emergency Medicine, Johns Hopkins University School of Medicine 4Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine 5W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland USA 6Department of Biochemistry and Molecular Biology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland USA 7Department of International Health, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
    [Show full text]
  • Inclusion of Sex and Gender Aspects in COVID-19 Clinical Studies—Acting Now Before It Is Too Late—A Joint Call for Action
    International Journal of Environmental Research and Public Health Editorial Towards Precision Medicine: Inclusion of Sex and Gender Aspects in COVID-19 Clinical Studies—Acting Now before It Is Too Late—A Joint Call for Action Evelyne Bischof 1,2,3, Sabine Oertelt-Prigione 4,5 , Rosemary Morgan 6, Sabra L. Klein 7,8,* , The Sex and Gender in COVID19 Clinical Trials Working Group (SGC) y and Gender and COVID19 Working Group z 1 Department of Advanced Biomedical Sciences, Federico II University of Naples, Via Pansini, 5, 80131 Naples, Italy; [email protected] 2 School of Clinical Medicine, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China 3 Women’s Brain Project, 8357 Guntershausen, Switzerland 4 Department of Primary and Community Care, Radboud University Medical Center, 6525 Nijmegen, The Netherlands; [email protected] 5 Institute of Legal and Forensic Medicine, Charité—Universitätsmedizin, 10117 Berlin, Germany 6 Department of International Health, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; [email protected] 7 W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA 8 Department of Biochemistry and Molecular Biology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA * Correspondence: [email protected] The Sex and Gender in COVID19 Clinical Trials Working Group members are listed in Appendix A.1 y The Gender and COVID19 Working Group members are listed in Appendix A.2 z Received: 20 May 2020; Accepted: 21 May 2020; Published: 25 May 2020 The COVID-19 global pandemic is accelerating investigations for effective vaccines and repurposable validated therapeutics.
    [Show full text]
  • 'Breakthrough Finding' Reveals Why Certain COVID Patients Die
    11/16/2020 https://www.medscape.com/viewarticle/940968_print www.medscape.com 'Breakthrough Finding' Reveals Why Certain COVID Patients Die Liz Szabo November 13, 2020 Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center. Dr. Megan Ranney has learned a lot about COVID-19 since she began treating patients with the disease in the emergency department in February. But there's one question she still can't answer: What makes some patients so much sicker than others? Advancing age and underlying medical problems explain only part of the phenomenon, said Ranney, who has seen patients of similar age, background and health status follow wildly different trajectories. "Why does one 40-year-old get really sick and another one not even need to be admitted?" asked Ranney, an associate professor of emergency medicine at Brown University. In some cases, provocative new research shows, some people — men in particular — succumb because their immune systems are hit by friendly fire. Researchers hope the finding will help them develop targeted therapies for these patients. In an international study in Science, 10% of nearly 1,000 COVID patients who developed life-threatening pneumonia had antibodies that disable key immune system proteins called interferons. These antibodies — known as autoantibodies because they attack the body itself — were not found at all in 663 people with mild or asymptomatic COVID infections. Only four of 1,227 healthy individuals had the autoantibodies. The study, published on Oct. 23, was led by the COVID Human Genetic Effort, which includes 200 research centers in 40 countries.
    [Show full text]
  • AIRBORNE TRANSMISSION of SARS-Cov-2 a VIRTUAL WORKSHOP of the ENVIRONMENTAL HEALTH MATTERS INITIATIVE AUGUST 26-27, 2020
    AIRBORNE TRANSMISSION OF SARS-CoV-2 A VIRTUAL WORKSHOP OF THE ENVIRONMENTAL HEALTH MATTERS INITIATIVE AUGUST 26-27, 2020 There is much we don’t know about the transmission of SARS-CoV-2, the virus that causes COVID-19. We know it can spread from an infected person’s sneeze or cough. But what do we know about transmission via speech and exhaled breath? How long do viruses linger in the air? How far can they travel? This workshop will delve into the rapidly evolving science on the environmental spread of the virus, as part of a larger body of COVID-19 related work at the National Academies, including the Rapid Expert Consultation on the Possibility of Bioaerosol Spread of SARS-CoV-2 for the COVID-19 Pandemic (April 1, 2020). This event will serve as a forum for interdisciplinary discussion, explanations of the basic foundational science, and clarification of terminology used differently among the relevant fields, all of which will be useful to those looking to understand the state of the science on SARS-CoV- 2. We will feature experts in aerosol science, virology, infectious disease, epidemiology, and environmental health and seek to address the most critical questions (CQ) around the transmission of the virus. Wednesday, August 26 (All times in Eastern Time, U.S. & Canada) 10:00 Welcome Gregory Symmes, the National Academies of Sciences, Engineering, and Medicine 10:10 Overview of the Environmental Health Matters Initiative Thomas Burke, Johns Hopkins Bloomberg School of Public Health 10:20 COVID-19: Public Health and Scientific Challenges
    [Show full text]
  • Aow 2021 10 COVID Kills
    1. Mark your confusion. 2. Show evidence of a close reading. 3. Write a 1+ page reflection. Why the Coronavirus Is Killing More Men than Women Men have weaker immune systems that, in some cases, may actually sabotage the body’s response to an invader. But social and cultural factors may also play a role. Source: Ben Guarino, Washington Post, October 17, 2020 Early in the coronavirus outbreak, hospital data from China revealed a startling disparity: Covid- 19, the disease caused by the virus, was killing far more men than women. That difference persisted in other Asian countries, such as South Korea, as well as in European countries, such as Italy. Then, it appeared in the United States. By mid-October, the coronavirus had killed almost 17,000 more American men than women, according to data from the Centers for Disease Control and Prevention. For every 10 women claimed by the disease in the United States, 12 men have died, found an analysis by Global Health 50/50, a U.K.- based initiative to advance gender equality in health care. That disparity was one of many alarming aspects of the new virus. It bewildered those unfamiliar with the role of gender in disease. But the specialized group of researchers who study that relationship was not surprised. It prepared an array of hypotheses. One possible culprit was male behavior. Perhaps men were more likely to be exposed to the virus due to social factors; a disproportionately male workforce, for instance, could place more men in contact with infected people. Or men’s lungs might be more vulnerable because they were more likely to smoke in the earliest countries to report the differences.
    [Show full text]
  • Friendly Fire Tablishing a School Speed Zone for the Pleasant Grove Margaret Fischer Davis Elementary School”
    2C NATION TEXARKANA GAZETTE ✯ SUNDAY, NOVEMBER 15, 2020 REAL ESTATE Judge: DHS head lacked authority to suspend DACA By David Porter order of succession as it that President Donald Trump one of the lawsuits that chal- two have been at the forefront The Associated Press was lawfully designated,” failed to follow rule-making lenged Wolf’s authority, called of administration initiatives on NEW YORK — A fed- U.S. District Judge Nicholas procedures when he tried to the ruling “another win for immigration and law enforce- eral judge in New York Garaufis wrote. “Therefore, end the program, but the jus- DACA recipients and those ment. 4158 Farm/Land for Sale ruled Saturday that Acting the actions taken by purported tices kept a window open for who have been waiting years In Garaufis’ ruling Saturday, Department of Homeland Acting Secretaries, who were him to try again. to apply for the program for the judge wrote that DHS didn’t 200 acres Miller County, AR 3/2 house, barn & shop, Security Secretary Chad Wolf not properly in their roles About 650,000 people are the first time.” follow an order of succession fenced pasture land. Joe assumed his position unlaw- according to the lawful order part of DACA, which allows In August, the Government established when then-Sec- Singletary Real Estate 870-904-4809. fully, a determination that of succession, were taken young immigrants who were Accountability Office, a bipar- retary Kirstjen Nielsen invalidated Wolf’s suspension without legal authority.” brought to the country as tisan congressional watch- resigned in April 2019. Kevin of the Deferred Action for Wolf issued a memorandum children to legally work and dog, said Wolf and his acting McAleenan, who succeeded LEGAL NOTICES Childhood Arrivals program, in July effectively suspend- shields them from deporta- deputy, Ken Cuccinelli, were Nielsen until he resigned in which shields young people ing DACA, pending review tion.
    [Show full text]
  • Paucity and Disparity of Publicly Available Sex-Disaggregated Data for the COVID-19 Epidemic Hamper Evidence-Based Decision-Making
    medRxiv preprint doi: https://doi.org/10.1101/2020.04.29.20083709; this version posted May 5, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Kristen Kocher1,2, Arthur Délot-Vilain3, D’Andre Spencer1, Jonathan LoTempio1,2, and Emmanuèle C. Délot1,2,4* 1 Children’s National Research Institute, Center for Genetic Medicine Research 2 George Washington University Dept of Genomics & Precision Medicine 3 Georgetown Day School, Washington, D.C. 4 Children’s National Research Institute, Center for Translational Research * Corresponding author [email protected]; [email protected] Children’s National Hospital 111 Michigan avenue NW, Washington, D.C., USA Paucity and disparity of publicly available sex-disaggregated data for the COVID-19 epidemic hamper evidence-based decision-making Keywords: Sexual dimorphism, COVID-19, Sars-CoV-2, sex differences, sex ratio, data accessibility, standardization FIGURES: Table 1: Available sex-disaggregated data with source URLs & dates accessed Table 2: Variability of reported sex ratios for COVID-19 infection - decrease with time Table 3: Available cases and deaths by sex data (20 countries, 2nd capture) Table 4: Sex ratio among hospitalizations and ICU Figure 1: Visualization of sex ratios for infection cases by pie charts show data disparity by country and longitudinal evolution (screen captures) Figure
    [Show full text]
  • Inclusion of Sex and Gender Aspects in COVID-19 Clinical Studies—Acting Now Before It Is Too Late—A Joint Call for Action
    International Journal of Environmental Research and Public Health Editorial Towards Precision Medicine: Inclusion of Sex and Gender Aspects in COVID-19 Clinical Studies—Acting Now before It Is Too Late—A Joint Call for Action Evelyne Bischof 1,2,3, Sabine Oertelt-Prigione 4,5 , Rosemary Morgan 6, Sabra L. Klein 7,8,* , The Sex and Gender in COVID19 Clinical Trials Working Group (SGC) y and Gender and COVID19 Working Group z 1 Department of Advanced Biomedical Sciences, Federico II University of Naples, Via Pansini, 5, 80131 Naples, Italy; [email protected] 2 School of Clinical Medicine, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China 3 Women’s Brain Project, 8357 Guntershausen, Switzerland 4 Department of Primary and Community Care, Radboud University Medical Center, 6525 Nijmegen, The Netherlands; [email protected] 5 Institute of Legal and Forensic Medicine, Charité—Universitätsmedizin, 10117 Berlin, Germany 6 Department of International Health, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; [email protected] 7 W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA 8 Department of Biochemistry and Molecular Biology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA * Correspondence: [email protected] The Sex and Gender in COVID19 Clinical Trials Working Group members are listed in Appendix A.1 y The Gender and COVID19 Working Group members are listed in Appendix A.2 z Received: 20 May 2020; Accepted: 21 May 2020; Published: 25 May 2020 The COVID-19 global pandemic is accelerating investigations for effective vaccines and repurposable validated therapeutics.
    [Show full text]
  • Women's Health in Focus at NIH, Vol. 3, Issue 3
    WOMEN’S HEALTH In Focus AT NIH A QUARTERLY PUBLICATION OF THE NIH OFFICE OF RESEARCH ON WOMEN’S HEALTH National Institutes of Health • Office of the Director | Volume 3, Issue 3, 2020 The NIH Sex as a Biological Variable Policy 3 Transforming How Science Is Done IN THIS 8 Animal Models Illuminate Sex Differences ISSUE 12 Coronavirus & Workplace Gender Equity Visit the subscription page to sign up to receive future issues of Women’s Health in Focus at NIH. TABLE OF CONTENTS 2 DIRECTOR’S CORNER Director’s Corner Janine Austin Clayton, M.D. 3 FEATURE STORY Director, NIH Office of Research on Transforming How Science Is Done: Women’s Health Biomedical Research and the NIH Sex as a NIH Associate Director for Research on Biological Variable Policy Women’s Health 8 SEX AS A BIOLOGICAL VARIABLE Animal Models Illuminate Sex Differences in Human Physiology and Disease: An Interview with Researcher I write this in the midst of the coronavirus lockdown, and the associated news Arthur P. Arnold coverage provides daily reminders of the importance of the NIH Policy on Sex as 10 IN THE JOURNALS a Biological Variable (SABV). Early observations of COVID-19 indicate that more Researchers and ORWH Address the Need men are dying from the disease but that women, who are more often on the front for Sex- and Gender-Based Biomedical lines of caregiving, risk greater exposure. Training Curricula The SABV policy articulates the expectation that NIH-supported research will Neurologists Evaluate Their Consideration of Sex as a Biological Variable account for sex as a biological variable in experimental designs, analyses, and Religiosity May Mitigate Psychosocial reporting of vertebrate animal and human studies.
    [Show full text]
  • Sex Differences in Lung Imaging and SARS-Cov-2 Antibody Responses in a COVID-19 3 Golden Syrian Hamster Model 4 5 Santosh Dhakala,*, Camilo A
    bioRxiv preprint doi: https://doi.org/10.1101/2021.04.02.438292; this version posted April 4, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Submitted to mBio on: 31 March 2021 2 Sex differences in lung imaging and SARS-CoV-2 antibody responses in a COVID-19 3 golden Syrian hamster model 4 5 Santosh Dhakala,*, Camilo A. Ruiz-Bedoyab,*, Ruifeng Zhoua, Patrick S. Creishera, Jason S. 6 Villanoc, Kirsten Littlefielda, Jennie Ruelas Castillod, Paula Marinhoa, Anne Jedlickaa, Alvaro A. 7 Ordonezb, Natalia Majewskie, Michael J. Betenbaughe, Kelly Flavahanb, Alice L. Muellera, 8 Monika M. Looneyd, Darla Quijadad, Filipa Motab, Sarah E. Beckc, Jacqueline Brockhurstc, 9 Alicia Braxtonc, Natalie Castellc, Franco R. D’Alessiod, Kelly A. Metcalf Patec, Petros C. 10 Karakousisd, Joseph L. Mankowskic,† ,Andrew Pekosza,†, Sanjay K. Jainb,†, and Sabra L. Kleina,† 11 for the Johns Hopkins COVID-19 Hamster Study Group‡ 12 aW. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns 13 Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA 14 bDepartment of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, 15 Maryland, USA 16 cDepartment of Molecular and Comparative Pathobiology, The Johns Hopkins School of 17 Medicine, Baltimore, Maryland, USA 18 dDepartment of Medicine, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA 19 eAdvanced Mammalian Biomanufacturing Innovation
    [Show full text]