Maternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface.

Autor:	Lu-Culligan A; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA., Chavan AR; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA., Vijayakumar P; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA., Irshaid L; Department of Pathology, Yale School of Medicine, New Haven, CT, USA., Courchaine EM; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.; Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA., Milano KM; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA., Tang Z; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA., Pope SD; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA., Song E; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA., Vogels CBF; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA., Lu-Culligan WJ; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.; Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA., Campbell KH; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA., Casanovas-Massana A; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA., Bermejo S; Section of Pulmonary and Critical Care Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT, USA., Toothaker JM; Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA.; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA., Lee HJ; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA., Liu F; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA., Schulz W; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA., Fournier J; Section of Infectious Diseases, Department of Medicine, Yale School of Medicine, New Haven, CT, USA., Muenker MC; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA., Moore AJ; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA., Konnikova L; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA.; Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA., Neugebauer KM; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA., Ring A; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA., Grubaugh ND; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA., Ko AI; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA., Morotti R; Department of Pathology, Yale School of Medicine, New Haven, CT, USA., Guller S; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA., Kliman HJ; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA., Iwasaki A; Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA.; Department of Molecular, Cellular and Developmental Biology, New Haven, CT, USA.; Howard Hughes Medical Institute, Chevy Chase, MD, USA., Farhadian SF; Section of Infectious Diseases, Department of Medicine, Yale School of Medicine, New Haven, CT, USA.
Jazyk:	angličtina
Zdroj:	Med (New York, N.Y.) [Med] 2021 May 14; Vol. 2 (5), pp. 591-610.e10. Date of Electronic Publication: 2021 Apr 30.
DOI:	10.1016/j.medj.2021.04.016
Abstrakt:	Background: Pregnant women are at increased risk for severe outcomes from coronavirus disease 2019 (COVID-19), but the pathophysiology underlying this increased morbidity and its potential effect on the developing fetus is not well understood. Methods: We assessed placental histology, ACE2 expression, and viral and immune dynamics at the term placenta in pregnant women with and without respiratory severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Findings: The majority (13 of 15) of placentas analyzed had no detectable viral RNA. ACE2 was detected by immunohistochemistry in syncytiotrophoblast cells of the normal placenta during early pregnancy but was rarely seen in healthy placentas at full term, suggesting that low ACE2 expression may protect the term placenta from viral infection. Using immortalized cell lines and primary isolated placental cells, we found that cytotrophoblasts, the trophoblast stem cells and precursors to syncytiotrophoblasts, rather than syncytiotrophoblasts or Hofbauer cells, are most vulnerable to SARS-CoV-2 infection in vitro . To better understand potential immune mechanisms shielding placental cells from infection in vivo , we performed bulk and single-cell transcriptomics analyses and found that the maternal-fetal interface of SARS-CoV-2-infected women exhibited robust immune responses, including increased activation of natural killer (NK) and T cells, increased expression of interferon-related genes, as well as markers associated with pregnancy complications such as preeclampsia. Conclusions: SARS-CoV-2 infection in late pregnancy is associated with immune activation at the maternal-fetal interface even in the absence of detectable local viral invasion. Funding: NIH (T32GM007205, F30HD093350, K23MH118999, R01AI157488, U01DA040588) and Fast Grant funding support from Emergent Ventures at the Mercatus Center. Competing Interests: A.I. is a scientific advisor for 4BIO and is on the advisory board of Med. The laboratory of A.I. received sponsored research funding from Spring Discovery. (© 2021 Elsevier Inc.)
Databáze:	MEDLINE
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