Foetal sex affects maternal and placental immune responses to SARS-CoV-2

Immune responses to SARS-CoV-2 show sex-specific differences, with males at higher risk of severe COVID-19. Now, Andrea G. Edlow and colleagues have examined whether foetal sex affects immune responses to SARS-CoV-2 in pregnant women. The authors examined maternal and placental immune responses in 38 women with mild or moderate COVID-19 during pregnancy, as well as a control cohort. They found reduced maternal SARS-CoV-2-specific antibody titres as well as reduced transplacental transfer of these antibodies in women carrying male foetuses. Moreover, they observed a sexually dimorphic expression of placental Fc receptors, differences in antibody fucosylation and an upregulation of interferon response genes in male placentas. These results demonstrate that foetal sex affects maternal humoral immune responses as well as placental innate and adaptive immune responses to SARS-CoV-2.