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

Bordt, E. A.; Shook, L. L.; Atyeo, C.; Pullen, K. M.; De Guzman, R. M.; Meinsohn, M.-C.; Chauvin, M.; Fischinger, S.; Yockey, L. J.; James, K.; Lima, R.; Yonker, L. M.; Fasano, A.; Brigida, S.; Bebell, L. M.; Roberts, D. J.; Pepin, D.; Huh, J. R.; Bilbo, S. D.; Li, J. Z.; Kaimal, A.; Schust, D.; Gray, K. J.; Lauffenburger, D.; Alter, G.; Edlow, A. G.

doi:10.1101/2021.03.29.437516

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bioRxiv · 10.1101/2021.03.29.437516

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

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Abstract

There 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.

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Bordt, E. A., Shook, L. L., Atyeo, C., Pullen, K. M., De Guzman, R. M., Meinsohn, M.-C., Chauvin, M., Fischinger, S., Yockey, L. J., James, K., Lima, R., Yonker, L. M., Fasano, A., Brigida, S., Bebell, L. M., Roberts, D. J., Pepin, D., Huh, J. R., Bilbo, S. D., Li, J. Z., Kaimal, A., Schust, D., Gray, K. J., Lauffenburger, D., Alter, G., Edlow, A. G.. 2021-03-29. Sexually dimorphic placental responses to maternal SARS-CoV-2 infection. https://doi.org/10.1101/2021.03.29.437516

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