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Pre-infection antiviral innate immunity contributes to sex differences in SARS-CoV-2 infection
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,...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
The Author(s). Published by Elsevier Inc.
2022
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9623453/ https://www.ncbi.nlm.nih.gov/pubmed/36323307 http://dx.doi.org/10.1016/j.cels.2022.10.005 |
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| author | 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. |
| author_facet | 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. |
| author_sort | Sauerwald, Natalie |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-9623453 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | The Author(s). Published by Elsevier Inc. |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-96234532022-11-01 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. Cell Syst Report 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. The Author(s). Published by Elsevier Inc. 2022-11-16 2022-11-01 /pmc/articles/PMC9623453/ /pubmed/36323307 http://dx.doi.org/10.1016/j.cels.2022.10.005 Text en © 2022 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
| spellingShingle | Report 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. Pre-infection antiviral innate immunity contributes to sex differences in SARS-CoV-2 infection |
| title | Pre-infection antiviral innate immunity contributes to sex differences in SARS-CoV-2 infection |
| title_full | Pre-infection antiviral innate immunity contributes to sex differences in SARS-CoV-2 infection |
| title_fullStr | Pre-infection antiviral innate immunity contributes to sex differences in SARS-CoV-2 infection |
| title_full_unstemmed | Pre-infection antiviral innate immunity contributes to sex differences in SARS-CoV-2 infection |
| title_short | Pre-infection antiviral innate immunity contributes to sex differences in SARS-CoV-2 infection |
| title_sort | pre-infection antiviral innate immunity contributes to sex differences in sars-cov-2 infection |
| topic | Report |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9623453/ https://www.ncbi.nlm.nih.gov/pubmed/36323307 http://dx.doi.org/10.1016/j.cels.2022.10.005 |
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