Thread by @VirusesImmunity

Men are at higher risk of developing severe #COVID19 disease. We investigated whether this difference might be due to the immune response.

Fantastic team work by @taka_takehiro et al found that women develop more robust T cell response than men. (1/n)

medrxiv.org/content/10.110…

Study design: to examine baseline immune parameters in patients who are not on immunomodulating drugs (steroids or tocilizumab), which alter the nature of immune responses. Then we look overtime to observe how their initial immune responses correlate with disease course. (2/n)

There was no significant difference in nasal or saliva viral RNA load, although women had lower mean viral load than men. Amazing work of the @awyllie13 & @NathanGrubaugh team, @VogelsChantal @IsabelOtt Rebecca Earnest, Sarah Lapidus, Adam Moore 💪🏽
(3/n)

Similarly, we did not find significant differences in baseline antibody responses between men and women. Carried out by the @aaronmring team, @FeimeiL, Amit Meir, Jonathan Sun, Eric Wang. (4/n)

Men produced more proinflammatory cytokines and chemokines than women at baseline. Moreover, chemokine (CCL5) levels in men correlated with monocyte increase but not in women. (5/n)

Women had more activated T cells than men at baseline. (6/n)

In #COVID19 patients, men developed more proinflammatory cytokine responses, whereas women had more activated T cell response. Men's ability to activate T cells declined with age, where women's immune T cell response did not decline with age. (7/n)

Men who developed poor T cell activation at baseline went on to develop worse disease, while women who developed proinflammatory cytokines/chemokines at baseline went onto develop more severe disease. Sex matters in how we should think about #COVID19 therapy and prevention. (8/n)

This work is a fantastic collaboration with so many: @taka_takehiro, Patrick Wong, Mallory Ellingson, @carolilucas @sneakyvirus1 as co-first authors. Super clinical team @ShelFarFar @DelaCruzYaleMed, amazing @arnaucasanovas. Numerous inspiring discussions with @SaadOmer3 🙏🏽 (9/n)

It all began by the support of @WHRYale through its fearless director, Dr. Carolyn Mazure. Thank you Dr. Mazure for inspiring us to carry out this research on sex differences in immune response during #COVID19. Finally, this entire work was enabled by the Yale IMPACT team (end)