Maternal SARS-CoV-2 infection elicits sexually dimorphic placental immune responses.

Journal Article (Journal Article)

There is a persistent bias toward higher prevalence and increased severity of coronavirus disease 2019 (COVID-19) in males. Underlying mechanisms accounting for this sex difference remain incompletely understood. Interferon responses have been implicated as a modulator of COVID-19 disease in adults and play a key role in the placental antiviral response. Moreover, the interferon response has been shown to alter Fc receptor expression and therefore may affect placental antibody transfer. Here, we examined the intersection of maternal-fetal antibody transfer, viral-induced placental interferon responses, and fetal sex in pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Placental Fc receptor abundance, interferon-stimulated gene (ISG) expression, and SARS-CoV-2 antibody transfer were interrogated in 68 human pregnancies. Sexually dimorphic expression of placental Fc receptors, ISGs and proteins, and interleukin-10 was observed after maternal SARS-CoV-2 infection, with up-regulation of these features in placental tissue of pregnant individuals with male fetuses. Reduced maternal SARS-CoV-2–specific antibody titers and impaired placental antibody transfer were also observed in pregnancies with a male fetus. These results demonstrate fetal sex-specific maternal and placental adaptive and innate immune responses to SARS-CoV-2.

Full Text

Duke Authors

Cited Authors

  • Bordt, EA; Shook, LL; Atyeo, C; Pullen, KM; De Guzman, RM; Meinsohn, M-C; Chauvin, M; Fischinger, S; Yockey, LJ; James, K; Lima, R; Yonker, LM; Fasano, A; Brigida, S; Bebell, LM; Roberts, DJ; Pépin, D; Huh, JR; Bilbo, SD; Li, JZ; Kaimal, A; Schust, DJ; Gray, KJ; Lauffenburger, D; Alter, G; Edlow, AG

Published Date

  • October 27, 2021

Published In

Volume / Issue

  • 13 / 617

Start / End Page

  • eabi7428 -

PubMed ID

  • 34664987

Pubmed Central ID

  • PMC8784281

Electronic International Standard Serial Number (EISSN)

  • 1946-6242

Digital Object Identifier (DOI)

  • 10.1126/scitranslmed.abi7428


  • eng

Conference Location

  • United States