Sex differences in immune responses that underlie COVID-19 disease outcomes.

Publication Type Academic Article
Authors Takahashi T, Ellingson M, Wong P, Israelow B, Lucas C, Klein J, Silva J, Mao T, Oh J, Tokuyama M, Lu P, Venkataraman A, Park A, Liu F, Meir A, Sun J, Wang E, Casanovas-Massana A, Wyllie A, Vogels C, Earnest R, Lapidus S, Ott I, Moore A, Shaw A, Fournier J, Odio C, Farhadian S, Dela Cruz C, Grubaugh N, Schulz W, Ring A, Ko A, Omer S, Iwasaki A
Journal Nature
Volume 588
Issue 7837
Pagination 315-320
Date Published 08/26/2020
ISSN 1476-4687
Keywords COVID-19, Cytokines, Immunity, Innate, SARS-CoV-2, Sex Characteristics, T-Lymphocytes
Abstract There is increasing evidence that coronavirus disease 2019 (COVID-19) produces more severe symptoms and higher mortality among men than among women1-5. However, whether immune responses against severe acute respiratory syndrome coronavirus (SARS-CoV-2) differ between sexes, and whether such differences correlate with the sex difference in the disease course of COVID-19, is currently unknown. Here we examined sex differences in viral loads, SARS-CoV-2-specific antibody titres, plasma cytokines and blood-cell phenotyping in patients with moderate COVID-19 who had not received immunomodulatory medications. Male patients had higher plasma levels of innate immune cytokines such as IL-8 and IL-18 along with more robust induction of non-classical monocytes. By contrast, female patients had more robust T cell activation than male patients during SARS-CoV-2 infection. Notably, we found that a poor T cell response negatively correlated with patients' age and was associated with worse disease outcome in male patients, but not in female patients. By contrast, higher levels of innate immune cytokines were associated with worse disease progression in female patients, but not in male patients. These findings provide a possible explanation for the observed sex biases in COVID-19, and provide an important basis for the development of a sex-based approach to the treatment and care of male and female patients with COVID-19.
DOI 10.1038/s41586-020-2700-3
PubMed ID 32846427
PubMed Central ID PMC7725931
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