Pre-infection antiviral innate immunity contributes to sex differences in SARS-CoV-2 infection

被引：9

作者：

Sauerwald, Natalie ^{[1
]}

Zhang, Zijun ^{[1
]}

Ramos, Irene

Nair, Venugopalan D. ^{[2
]}

Soares-Schanoski, Alessandra ^{[2
]}

Ge, Yongchao

Mao, Weiguang ^{[3
]}

Alshammary, Hala ^{[4
]}

Gonzalez-Reiche, Ana S. ^{[5
]}

van de Guchte, Adriana ^{[5
]}

Goforth, Carl W. ^{[6
]}

Lizewski, Rhonda A.

Lizewski, Stephen E.

Amper, Mary Anne S. ^{[2
]}

Vasoya, Mital ^{[2
]}

Seenarine, Nitish ^{[2
]}

Guevara, Kristy ^{[2
]}

Marjanovic, Nada ^{[2
,7
]}

Miller, Clare M. ^{[2
,7
]}

Nudelman, German ^{[2
]}

Schilling, Megan A.

Sealfon, Rachel S. G. ^{[1
]}

Termini, Michael S. ^{[8
]}

Vangeti, Sindhu

Weir, Dawn L.

Zaslavsky, Elena

Chikina, Maria

Wu, Ying Nian ^{[9
]}

Bakel, Harm Van

Letizia, Andrew G.

Sealfon, Stuart C. ^{[2
]}

Troyanskaya, Olga G. ^{[1
,10
,11
]}

机构：

[1] Flatiron Inst, Ctr Computat Biol, New York, NY 10010 USA

[2] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA

[3] Univ Pittsburgh, Sch Med, Dept Computat & Syst Biol, Pittsburgh, PA 15213 USA

[4] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

[5] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA

[6] Naval Med Res Ctr, Silver Spring, MD 20910 USA

[7] Naval Med Res Unit 6, Lima 34031, Peru

[8] Navy Med Readiness & Training Command Beaufort, Beaufort, SC 29902 USA

[9] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA 90095 USA

[10] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08540 USA

[11] Princeton Univ, Dept Comp Sci, Princeton, NJ 08540 USA

来源：

CELL SYSTEMS | 2022年 / 13卷 / 11期

基金：

美国国家卫生研究院;

关键词：

GENE-EXPRESSION; CD45; COVID-19; DISEASE; CELLS;

D O I：

10.1016/j.cels.2022.10.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Male sex is a major risk factor for SARS-CoV-2 infection severity. To understand the basis for this sex differ-ence, 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 infec-tions 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 anti-viral 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 infec-tion. 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.

引用

页码：924 / +

页数：13

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