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ResearchIn-Press PreviewCOVID-19Immunology Open Access | 10.1172/jci.insight.172658

Mild/asymptomatic COVID-19 in unvaccinated pregnant mothers impairs neonatal immune responses

Brianna M. Doratt,1 Suhas Sureshchandra,2 Heather True,3 Monica Rincon,4 Nicole E. Marshall,4 and Ilhem Messaoudi1

1Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, United States of America

2Department of Physiology and Biophysics, University of California Irvine, Irvine, United States of America

3Pharmaceutical Department of Pharmaceutical Sciences, University of Kentucky, Lexington, United States of America

4Maternal-Fetal Medicine, Oregon Health & Science University, Portland, United States of America

Find articles by Doratt, B. in: JCI | PubMed | Google Scholar |

1Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, United States of America

2Department of Physiology and Biophysics, University of California Irvine, Irvine, United States of America

3Pharmaceutical Department of Pharmaceutical Sciences, University of Kentucky, Lexington, United States of America

4Maternal-Fetal Medicine, Oregon Health & Science University, Portland, United States of America

Find articles by Sureshchandra, S. in: JCI | PubMed | Google Scholar |

1Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, United States of America

2Department of Physiology and Biophysics, University of California Irvine, Irvine, United States of America

3Pharmaceutical Department of Pharmaceutical Sciences, University of Kentucky, Lexington, United States of America

4Maternal-Fetal Medicine, Oregon Health & Science University, Portland, United States of America

Find articles by True, H. in: JCI | PubMed | Google Scholar |

1Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, United States of America

2Department of Physiology and Biophysics, University of California Irvine, Irvine, United States of America

3Pharmaceutical Department of Pharmaceutical Sciences, University of Kentucky, Lexington, United States of America

4Maternal-Fetal Medicine, Oregon Health & Science University, Portland, United States of America

Find articles by Rincon, M. in: JCI | PubMed | Google Scholar |

1Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, United States of America

2Department of Physiology and Biophysics, University of California Irvine, Irvine, United States of America

3Pharmaceutical Department of Pharmaceutical Sciences, University of Kentucky, Lexington, United States of America

4Maternal-Fetal Medicine, Oregon Health & Science University, Portland, United States of America

Find articles by Marshall, N. in: JCI | PubMed | Google Scholar

1Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, United States of America

2Department of Physiology and Biophysics, University of California Irvine, Irvine, United States of America

3Pharmaceutical Department of Pharmaceutical Sciences, University of Kentucky, Lexington, United States of America

4Maternal-Fetal Medicine, Oregon Health & Science University, Portland, United States of America

Find articles by Messaoudi, I. in: JCI | PubMed | Google Scholar |

Published September 12, 2023 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.172658.
Copyright © 2023, Doratt et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published September 12, 2023 - Version history
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Abstract

Maternal SARS-CoV-2 infection triggers placental inflammation and alters cord blood immune cell composition. However, most studies focus on outcomes of severe maternal infection. Therefore, we analyzed cord blood and chorionic villi from newborns of unvaccinated mothers who experienced mild/asymptomatic SARS-CoV-2 infection during pregnancy. We investigated immune cell rewiring using flow cytometry, single-cell RNA sequencing, and functional readouts using ex vivo stimulation with TLR agonists and pathogens. Maternal infection was associated with increased frequency of memory T- and B-cells, and non-classical monocytes in cord blood. Ex vivo T- and B-cell responses to stimulation were attenuated, suggesting a tolerogenic state. Maladaptive responses were also observed in cord blood monocytes, where antiviral responses were dampened but responses to bacterial TLRs were increased. Maternal infection was also associated with expansion and activation of placental Hofbauer cells, secreting elevated levels of myeloid cell recruiting chemokines. Moreover, we reported increased activation of maternal-derived monocytes/macrophages in the fetal placenta that are transcriptionally primed for antiviral responses. Our data indicate that even in the absence of vertical transmission or symptoms in the neonate, mild/asymptomatic maternal COVID-19 altered the transcriptional and functional state in fetal immune cells in circulation and in the placenta.

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  • Version 1 (September 12, 2023): In-Press Preview
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