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Pre-infection antiviral innate immunity contributes to sex differences in SARS-CoV-2 infection.
Sauerwald, Natalie; Zhang, Zijun; Ramos, Irene; Nair, Venugopalan D; Soares-Schanoski, Alessandra; Ge, Yongchao; Mao, Weiguang; Alshammary, Hala; Gonzalez-Reiche, Ana S; van de Guchte, Adriana; Goforth, Carl W; Lizewski, Rhonda A; Lizewski, Stephen E; Amper, Mary Anne S; Vasoya, Mital; Seenarine, Nitish; Guevara, Kristy; Marjanovic, Nada; Miller, Clare M; Nudelman, German; Schilling, Megan A; Sealfon, Rachel S G; Termini, Michael S; Vangeti, Sindhu; Weir, Dawn L; Zaslavsky, Elena; Chikina, Maria; Wu, Ying Nian; Van Bakel, Harm; Letizia, Andrew G; Sealfon, Stuart C; Troyanskaya, Olga G.
  • Sauerwald N; Center for Computational Biology, Flatiron Institute, New York, NY 10010, USA.
  • Zhang Z; Center for Computational Biology, Flatiron Institute, New York, NY 10010, USA.
  • Ramos I; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Nair VD; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Soares-Schanoski A; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Ge Y; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Mao W; Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • Alshammary H; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Gonzalez-Reiche AS; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • van de Guchte A; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Goforth CW; Naval Medical Research Center, Silver Spring, MD 20910, USA.
  • Lizewski RA; Naval Medical Research Unit 6, Lima 34031, Peru.
  • Lizewski SE; Naval Medical Research Unit 6, Lima 34031, Peru.
  • Amper MAS; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Vasoya M; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Seenarine N; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Guevara K; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Marjanovic N; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Miller CM; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Nudelman G; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Schilling MA; Naval Medical Research Center, Silver Spring, MD 20910, USA.
  • Sealfon RSG; Center for Computational Biology, Flatiron Institute, New York, NY 10010, USA.
  • Termini MS; Navy Medicine Readiness and Training Command Beaufort, Beaufort, SC 29902, USA.
  • Vangeti S; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Weir DL; Naval Medical Research Center, Silver Spring, MD 20910, USA.
  • Zaslavsky E; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Chikina M; Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  • Wu YN; Department of Statistics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Van Bakel H; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Letizia AG; Naval Medical Research Center, Silver Spring, MD 20910, USA.
  • Sealfon SC; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: stuart.sealfon@mssm.edu.
  • Troyanskaya OG; Center for Computational Biology, Flatiron Institute, New York, NY 10010, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08540, USA; Department of Computer Science, Princeton University, Princeton, NJ 08540, USA. Electronic address: ogt@genomics.princeton.e
Cell Syst ; 13(11): 924-931.e4, 2022 Nov 16.
Article in English | MEDLINE | ID: covidwho-2095148
ABSTRACT
Male sex is a major risk factor for SARS-CoV-2 infection severity. To understand the basis for this sex difference, we studied SARS-CoV-2 infection in a young adult cohort of United States Marine recruits. Among 2,641 male and 244 female unvaccinated and seronegative recruits studied longitudinally, SARS-CoV-2 infections occurred in 1,033 males and 137 females. We identified sex differences in symptoms, viral load, blood transcriptome, RNA splicing, and proteomic signatures. Females had higher pre-infection expression of antiviral interferon-stimulated gene (ISG) programs. Causal mediation analysis implicated ISG differences in number of symptoms, levels of ISGs, and differential splicing of CD45 lymphocyte phosphatase during infection. Our results indicate that the antiviral innate immunity set point causally contributes to sex differences in response to SARS-CoV-2 infection. A record of this paper's transparent peer review process is included in the supplemental information.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Sex Characteristics / COVID-19 / Immunity, Innate Type of study: Cohort study / Observational study / Prognostic study Limits: Adult / Female / Humans / Male / Young adult Language: English Journal: Cell Syst Year: 2022 Document Type: Article Affiliation country: J.cels.2022.10.005

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Sex Characteristics / COVID-19 / Immunity, Innate Type of study: Cohort study / Observational study / Prognostic study Limits: Adult / Female / Humans / Male / Young adult Language: English Journal: Cell Syst Year: 2022 Document Type: Article Affiliation country: J.cels.2022.10.005