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

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dc.contributor.authorTakahashi, Takehiroko
dc.contributor.authorEllingson, Mallory K.ko
dc.contributor.authorWong, Patrickko
dc.contributor.authorIsraelow, Benjaminko
dc.contributor.authorLucas, Carolinako
dc.contributor.authorKlein, Jonko
dc.contributor.authorSilva, Julioko
dc.contributor.authorMao, Tianyangko
dc.contributor.authorOh, Ji Eunko
dc.contributor.authorTokuyama, Mariako
dc.contributor.authorLu, Peiwenko
dc.contributor.authorVenkataraman, Arvindko
dc.contributor.authorPark, Annseako
dc.contributor.authorLiu, Feimeiko
dc.contributor.authorMeir, Amitko
dc.contributor.authorSun, Jonathanko
dc.contributor.authorWang, Eric Y.ko
dc.contributor.authorCasanovas-Massana, Arnauko
dc.contributor.authorWyllie, Anne L.ko
dc.contributor.authorVogels, Chantal B. F.ko
dc.contributor.authorEarnest, Rebeccako
dc.contributor.authorLapidus, Sarahko
dc.contributor.authorOtt, Isabel M.ko
dc.contributor.authorMoore, Adam J.ko
dc.contributor.authorShaw, Albertko
dc.contributor.authorFournier, John B.ko
dc.contributor.authorOdio, Camila D.ko
dc.contributor.authorFarhadian, Shelliko
dc.contributor.authorDela Cruz, Charlesko
dc.contributor.authorGrubaugh, Nathan D.ko
dc.contributor.authorSchulz, Wade L.ko
dc.contributor.authorRing, Aaron M.ko
dc.contributor.authorKo, Albert I.ko
dc.contributor.authorOmer, Saad B.ko
dc.contributor.authorIwasaki, Akikoko
dc.identifier.citationNATURE, v.588, no.7837-
dc.description.abstractMale patients with COVID-19 have higher plasma levels of innate immune cytokines and chemokines such as IL-8, IL-18 and CCL5 and more non-classical monocytes than female patients, whereas female patients mount robust T cell activation maintained even in older age. There is increasing evidence that coronavirus disease 2019 (COVID-19) produces more severe symptoms and higher mortality among men than among women(1-5). 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.-
dc.publisherNATURE RESEARCH-
dc.titleSex differences in immune responses that underlie COVID-19 disease outcomes-
dc.contributor.localauthorOh, Ji Eun-
dc.contributor.nonIdAuthorTakahashi, Takehiro-
dc.contributor.nonIdAuthorEllingson, Mallory K.-
dc.contributor.nonIdAuthorWong, Patrick-
dc.contributor.nonIdAuthorIsraelow, Benjamin-
dc.contributor.nonIdAuthorLucas, Carolina-
dc.contributor.nonIdAuthorKlein, Jon-
dc.contributor.nonIdAuthorSilva, Julio-
dc.contributor.nonIdAuthorMao, Tianyang-
dc.contributor.nonIdAuthorTokuyama, Maria-
dc.contributor.nonIdAuthorLu, Peiwen-
dc.contributor.nonIdAuthorVenkataraman, Arvind-
dc.contributor.nonIdAuthorPark, Annsea-
dc.contributor.nonIdAuthorLiu, Feimei-
dc.contributor.nonIdAuthorMeir, Amit-
dc.contributor.nonIdAuthorSun, Jonathan-
dc.contributor.nonIdAuthorWang, Eric Y.-
dc.contributor.nonIdAuthorCasanovas-Massana, Arnau-
dc.contributor.nonIdAuthorWyllie, Anne L.-
dc.contributor.nonIdAuthorVogels, Chantal B. F.-
dc.contributor.nonIdAuthorEarnest, Rebecca-
dc.contributor.nonIdAuthorLapidus, Sarah-
dc.contributor.nonIdAuthorOtt, Isabel M.-
dc.contributor.nonIdAuthorMoore, Adam J.-
dc.contributor.nonIdAuthorShaw, Albert-
dc.contributor.nonIdAuthorFournier, John B.-
dc.contributor.nonIdAuthorOdio, Camila D.-
dc.contributor.nonIdAuthorFarhadian, Shelli-
dc.contributor.nonIdAuthorDela Cruz, Charles-
dc.contributor.nonIdAuthorGrubaugh, Nathan D.-
dc.contributor.nonIdAuthorSchulz, Wade L.-
dc.contributor.nonIdAuthorRing, Aaron M.-
dc.contributor.nonIdAuthorKo, Albert I.-
dc.contributor.nonIdAuthorOmer, Saad B.-
dc.contributor.nonIdAuthorIwasaki, Akiko-
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