DOCSLIB.ORG

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

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read 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 The copyright holder for this preprint (which was not certified by peer review) is the author/funder.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 Center, Department of Chemical and 20 Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA. 21 fDepartment of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, 22 Baltimore, Maryland, USA 23 gDepartment of Oncology, The Johns Hopkins School of Medicine, The Sidney Kimmel 24 Comprehensive Cancer Center, Baltimore, MD, USA 25 *co-first authors 26 †To whom correspondence should be addressed: Sabra Klein, [email protected] 27 Sanjay Jain, [email protected], Andrew Pekosz, [email protected] , Joseph Mankowski, 28 [email protected] 29 ‡additional Johns Hopkins COVID-19 Hamster Study Group members: Cory F. Braytonc, Lisa 30 Pietersea, Bess Carlsonc, Selena Guerrero-Martinc, Eric K. Hutchinsonc, Andrew L. Johansonc, 31 Maggie Lowmanc, Amanda Maxwellc, Megan E. McCarronc, Kathleen R. Mulkac, Suzanne E. 32 Queenc, Erin N. Shirkc, Clarisse V. Solisc, Mitchel Stoverc, Patrick M. Tarwaterf, Rebecca T. 33 Veenhuisc, Rachel Visteinc, and Cynthia A. Zahnowg 34 Key words: animal model, COVID-19, sex differences, SARS-CoV-2 variants, receptor binding 35 domain 36 Running title: Sex differences in SARS-CoV-2 in golden Syrian hamsters 37 One Sentence Summary: Following SARS-CoV-2 infection, male hamsters experience worse 38 clinical disease and have lower antiviral antibody responses than females. 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. Dhakal and Ruiz-Bedoya et al. 2 39 Abstract: 40 In the ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the severe 41 acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more severe outcomes are reported in 42 males compared with females, including hospitalizations and deaths. Animal models can provide 43 an opportunity to mechanistically interrogate causes of sex differences in the pathogenesis of 44 SARS-CoV-2. Adult male and female golden Syrian hamsters (8-10 weeks of age) were 5 45 inoculated intranasally with 10 TCID50 of SARS-CoV-2/USA-WA1/2020 and euthanized at 46 several time points during the acute (i.e., virus actively replicating) and recovery (i.e., after the 47 infectious virus has been cleared) phases of infection. There was no mortality, but infected male 48 hamsters experienced greater morbidity, losing a greater percentage of body mass, developing 49 more extensive pneumonia as noted on chest computed tomography, and recovering more slowly 50 than females. Treatment of male hamsters with estradiol did not alter pulmonary damage. Virus 51 titers in respiratory tissues, including nasal turbinates, trachea, and lungs, and pulmonary 52 cytokine concentrations, including IFN and TNF, were comparable between the sexes. 53 However, during the recovery phase of infection, females mounted two-fold greater IgM, IgG, 54 and IgA responses against the receptor-binding domain of the spike protein (S-RBD) in both 55 plasma and respiratory tissues. Female hamsters also had significantly greater IgG antibodies 56 against whole inactivated SARS-CoV-2 and mutant S-RBDs, as well as virus neutralizing 57 antibodies in plasma. The development of an animal model to study COVID-19 sex differences 58 will allow for a greater mechanistic understanding of the SARS-CoV-2 associated sex 59 differences seen in the human population. 60 61 2 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. Dhakal and Ruiz-Bedoya et al. 3 62 Importance: 63 Men experience more severe outcomes from COVID-19 than women. Golden Syrian hamsters 64 were used to explore sex differences in the pathogenesis of a human clinical isolate of SARS- 65 CoV-2. After inoculation, male hamsters experienced greater sickness, developed more severe 66 lung pathology, and recovered more slowly than females. Sex differences in disease could not be 67 reversed by estradiol treatment in males and were not explained by either virus replication 68 kinetics or the concentrations of inflammatory cytokines in the lungs. During the recovery 69 period, antiviral antibody responses in the respiratory tract and plasma, including to newly 70 emerging SARS-CoV-2 variants, were greater in females than male hamsters. Greater lung 71 pathology during the acute phase combined with reduced antiviral antibody responses during the 72 recovery phase of infection in males than females illustrate the utility of golden Syrian hamsters 73 as a model to explore sex differences in the pathogenesis of SARS-CoV-2 and vaccine-induced 74 immunity and protection. 3 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. Dhakal and Ruiz-Bedoya et al. 4 75 Introduction 76 At the start of the coronavirus disease 2019 (COVID-19) pandemic, early publications 77 from Wuhan, China (1, 2) and European countries (3) began reporting male biases in 78 hospitalization, intensive care unit (ICU) admissions, and mortality rates. Ongoing real-time 79 surveillance (4) and meta-analyses of over 3 million cases of COVID-19 (5) continue to show 80 that while the incidence of COVID-19 cases are similar between the sexes, adult males are 81 almost 3-times more likely to be admitted into ICUs and twice as likely to die as females. 82 Differential exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is 83 likely associated with behaviors, occupations, comorbidities and societal and cultural norms (i.e., 84 gender differences) that impact the probability of exposure, access to testing, utilization of 85 healthcare, and risk of disease (6-8). This is distinct but also complementary to biological sex 86 differences (i.e., sex chromosome complement, reproductive tissues, and sex steroid hormone 87 concentrations) that can also impact susceptibility and outcomes from COVID-19 (9, 10). While 88 exposure to SARS-CoV-2 may differ based on gender, the increased mortality rate among males 89 in diverse countries and at diverse ages likely reflect biological sex. Studies have shown that in 90 males, mutations in X-linked genes (e.g., TLR7) resulting in reduced interferon signaling (11), 91 elevated proinflammatory cytokine production (e.g., IL-6 and CRP) (2, 12), reduced CD8+ T cell 92 activity (e.g., IFN-) (13), and greater antibody responses (i.e., anti-SARS-CoV-2 antigen- 93 specific IgM, IgG, and IgA, and neutralizing antibodies) (14) are associated with more severe 94 COVID-19 outcomes as compared with females. Because COVID-19 outcomes can be impacted 95 by both gender and biological sex, consideration of the intersection of these contributors is 96 necessary in human studies (15). 4 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. Dhakal and Ruiz-Bedoya et al. 5 97 Animal models can mechanistically explore sex differences in the pathogenesis of SARS- 98 CoV-2 independent of confounding gender-associated factors that impact exposure, testing, and 99 use of healthcare globally. Transgenic mice expressing human ACE2 (K18-hACE2) are 100 susceptible to SARS-CoV-2 and in this model, males experience greater morbidity than females, 101 despite having similar viral loads in respiratory tissues (e.g., nasal turbinates, trachea, and lungs) 102 (16, 17). Transcriptional analyses of lung tissue revealed that inflammatory cytokine and 103 chemokine gene expression is greater in males than females early during infection, and these 104 transcriptional patterns show a stronger correlation with disease outcomes among males than 105 females (16, 17). In addition to utilizing hACE2 mice, mouse-adapted strains of SARS-CoV-2 106 have been developed and can productively infect wild-type mice but have not yet been used to 107 evaluate sex-specific differences in the pathogenesis of disease (18-20). 108 Golden Syrian hamsters are also being used as an animal model of SARS-CoV-2 109 pathogenesis because they are susceptible to human clinical strains of viruses, without the need 110 for genetic modifications in either the host or virus.
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]
  • 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).
    [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]