Maternal-fetal immune responses in pregnant women infected with SARS-CoV-2.
Valeria Garcia-Flores, Roberto Romero, Yi Xu, Kevin R Theis, Marcia Arenas-Hernandez, Derek Miller, Azam Peyvandipour, Gaurav Bhatti, Jose Galaz, Meyer Gershater, Dustyn Levenson, Errile Pusod, Li Tao, David Kracht, Violetta Florova, Yaozhu Leng, Kenichiro Motomura, Robert Para, Megan Faucett, Chaur-Dong Hsu, Gary Zhang, Adi L Tarca, Roger Pique-Regi, Nardhy Gomez-Lopez
Author Information
Valeria Garcia-Flores: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA.
Roberto Romero: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA. prbchiefstaff@med.wayne.edu. ORCID
Yi Xu: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA.
Kevin R Theis: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA.
Marcia Arenas-Hernandez: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA. ORCID
Derek Miller: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA. ORCID
Azam Peyvandipour: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA.
Gaurav Bhatti: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA.
Jose Galaz: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA.
Meyer Gershater: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA.
Dustyn Levenson: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA.
Errile Pusod: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA.
Li Tao: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA.
David Kracht: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA.
Violetta Florova: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA.
Yaozhu Leng: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA.
Kenichiro Motomura: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA. ORCID
Robert Para: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA.
Megan Faucett: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA.
Chaur-Dong Hsu: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA.
Gary Zhang: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, 48201, USA. ORCID
Adi L Tarca: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA. ORCID
Roger Pique-Regi: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA. rpique@wayne.edu.
Nardhy Gomez-Lopez: Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892 and Detroit, MI, 48201, USA. nardhy.gomez-lopez@wayne.edu. ORCID
Pregnant women represent a high-risk population for severe/critical COVID-19 and mortality. However, the maternal-fetal immune responses initiated by SARS-CoV-2 infection, and whether this virus is detectable in the placenta, are still under investigation. Here we show that SARS-CoV-2 infection during pregnancy primarily induces unique inflammatory responses at the maternal-fetal interface, which are largely governed by maternal T cells and fetal stromal cells. SARS-CoV-2 infection during pregnancy is also associated with humoral and cellular immune responses in the maternal blood, as well as with a mild cytokine response in the neonatal circulation (i.e., umbilical cord blood), without compromising the T-cell repertoire or initiating IgM responses. Importantly, SARS-CoV-2 is not detected in the placental tissues, nor is the sterility of the placenta compromised by maternal viral infection. This study provides insight into the maternal-fetal immune responses triggered by SARS-CoV-2 and emphasizes the rarity of placental infection.
