TY - JOUR
T1 - Pre-infection antiviral innate immunity contributes to sex differences in SARS-CoV-2 infection
AU - Sauerwald, Natalie
AU - Zhang, Zijun
AU - Ramos, Irene
AU - Nair, Venugopalan D.
AU - Soares-Schanoski, Alessandra
AU - Ge, Yongchao
AU - Mao, Weiguang
AU - Alshammary, Hala
AU - Gonzalez-Reiche, Ana S.
AU - van de Guchte, Adriana
AU - Goforth, Carl W.
AU - Lizewski, Rhonda A.
AU - Lizewski, Stephen E.
AU - Amper, Mary Anne S.
AU - Vasoya, Mital
AU - Seenarine, Nitish
AU - Guevara, Kristy
AU - Marjanovic, Nada
AU - Miller, Clare M.
AU - Nudelman, German
AU - Schilling, Megan A.
AU - Sealfon, Rachel S.G.
AU - Termini, Michael S.
AU - Vangeti, Sindhu
AU - Weir, Dawn L.
AU - Zaslavsky, Elena
AU - Chikina, Maria
AU - Wu, Ying Nian
AU - Van Bakel, Harm
AU - Letizia, Andrew G.
AU - Sealfon, Stuart C.
AU - Troyanskaya, Olga G.
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022/11/16
Y1 - 2022/11/16
N2 - 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.
AB - 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.
KW - COVID-19
KW - SARS-CoV-2
KW - alternative splicing
KW - causal mediation
KW - differential expression
KW - interferon-stimulated genes
KW - sex differences
KW - viral infection
UR - http://www.scopus.com/inward/record.url?scp=85141230812&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85141230812&partnerID=8YFLogxK
U2 - 10.1016/j.cels.2022.10.005
DO - 10.1016/j.cels.2022.10.005
M3 - Article
C2 - 36323307
AN - SCOPUS:85141230812
SN - 2405-4712
VL - 13
SP - 924-931.e4
JO - Cell Systems
JF - Cell Systems
IS - 11
ER -