Sexually dimorphic placental responses to maternal SARS-CoV-2 infection

Author:

Bordt Evan A,Shook Lydia L,Atyeo Caroline,Pullen Krista M,De Guzman Rose M,Meinsohn Marie-Charlotte,Chauvin Maeva,Fischinger Stephanie,Yockey Laura J.,James Kaitlyn,Lima Rosiane,Yonker Lael M,Fasano Alessio,Brigida Sara,Bebell Lisa M,Roberts Drucilla J,Pépin David,Huh Jun R,Bilbo Staci D,Li Jonathan Z,Kaimal Anjali,Schust Danny,Gray Kathryn J,Lauffenburger Douglas,Alter Galit,Edlow Andrea G

Abstract

ABSTRACTThere is a persistent male bias in the prevalence and severity of COVID-19 disease. Underlying mechanisms accounting for this sex difference remain incompletely understood. Interferon responses have been implicated as a modulator of disease in adults, and play a key role in the placental anti-viral response. Moreover, the interferon response has been shown to alter Fc-receptor expression, and therefore may impact placental antibody transfer. Here we examined the intersection of viral-induced placental interferon responses, maternal-fetal antibody transfer, and fetal sex. Placental interferon stimulated genes (ISGs), Fc-receptor expression, and SARS-CoV-2 antibody transfer were interrogated in 68 pregnancies. Sexually dimorphic placental expression of ISGs, interleukin-10, and Fc receptors was observed following maternal SARS-CoV-2 infection, with upregulation in males. Reduced maternal SARS-CoV-2-specific antibody titers and impaired placental antibody transfer were noted in pregnancies with a male fetus. These results demonstrate fetal sex-specific maternal and placental adaptive and innate immune responses to SARS-CoV-2.

Publisher

Cold Spring Harbor Laboratory

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