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Mar 16, 2021;

Single-cell immunophenotyping of the fetal immune response to maternal SARS-CoV-2 infection in late gestation.

Juan Matute, Benjamin Finander, David Pepin, Xinbin Ai, Neal Smith, Jonathan Li, Andrea Edlow, Alexandra Villani, Paul Lerou, Brian Kalish
Author Information
  1. Juan Matute: Massachusetts General Hospital and Harvard Medical School. ORCID
  2. Benjamin Finander: Boston Children's Hospital and Harvard Medical School.
  3. David Pepin: Massachusetts General Hospital.
  4. Xinbin Ai: Massachusetts General Hospital and Harvard Medical School.
  5. Neal Smith: Massachusetts General Hospital and Harvard Medical School.
  6. Jonathan Li: Harvard Medical School. ORCID
  7. Andrea Edlow: Massachusetts General Hospital and Harvard Medical School.
  8. Alexandra Villani: Harvard University.
  9. Paul Lerou: Massachusetts General Hospital and Harvard Medical School.
  10. Brian Kalish: The Hospital for Sick Children and University of Toronto.
PMID: 33758834 DOI: 10.21203/rs.3.rs-311000/v1

Abstract

During the COVID-19 pandemic, thousands of pregnant women have been infected with SARS-CoV-2. The implications of maternal SARS-CoV-2 infection on fetal and childhood well-being are unknown. We aimed to characterize the fetal immune response to maternal SARS-CoV-2 infection. We performed single-cell RNA sequencing and T-cell receptor (TCR) sequencing on cord blood mononuclear cells (CBMC) from newborns of mothers infected with SARS-CoV-2 in the third-trimester (cases) or without SARS-CoV-2 infection. We identified widespread gene expression changes in CBMC from cases, including upregulation of interferon-stimulated genes and Major Histocompatibility Complex genes in CD14���+���monocytes; transcriptional changes suggestive of activation of plasmacytoid dendritic cells, and activation and exhaustion of NK cells and CD8���+���T-cells. Lastly, we observed fetal TCR repertoire expansion in cases. As none of the infants were infected with SARS-CoV-2, our results suggest that SARS-CoV-2 maternal infection might modulate the fetal immune system in the absence of vertical transmission.

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Grants

  1. K08 NS112338/NINDS NIH HHS
  2. R01 HD102014/NICHD NIH HHS
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