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

• Published in: Pediatric research Vol. 91; no. 5; pp. 1090 - 1098
• Main Authors: Matute, Juan D., Finander, Benjamin, Pepin, David, Ai, Xingbin, Smith, Neal P., Li, Jonathan Z., Edlow, Andrea G., Villani, Alexandra-Chloe, Lerou, Paul H., Kalish, Brian T.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-04-2022; Nature Publishing Group
• Subjects: Basic Science; Basic Science Article; Child; Coronaviruses; COVID-19; Female; Fetus; Gene expression; Humans; Immune system; Immunity; Immunophenotyping; Infant, Newborn; Infections; Infectious Disease Transmission, Vertical; Medicine; Medicine & Public Health; Pandemics; Pediatric Surgery; Pediatrics; Pregnancy; Pregnancy Complications, Infectious - epidemiology; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; T cell receptors
• ISSN: 0031-3998; 1530-0447; 1530-0447
• DOI: 10.1038/s41390-021-01793-z

Background
During the COVID-19 pandemic, thousands of pregnant women have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The implications of maternal SARS-CoV-2 infection on fetal and childhood well-being need to be characterized. We aimed to characterize the fetal immune response to maternal SARS-CoV-2 infection.
Methods
We performed single-cell RNA-sequencing and T cell receptor sequencing on cord blood mononuclear cells (CBMCs) from newborns of mothers infected with SARS-CoV-2 in the third trimester (cases) or without SARS-CoV-2 infection (controls).
Results
We identified widespread gene expression changes in CBMCs 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 natural killer cells. Lastly, we observed fetal T cell clonal expansion in cases compared to controls.
Conclusions
As none of the infants were infected with SARS-CoV-2, our results suggest that maternal SARS-CoV-2 infection might modulate the fetal immune system in the absence of vertical transmission.
Impact
The implications of maternal SARS-CoV-2 infection in the absence of vertical transmission on fetal and childhood well-being are poorly understood.
Maternal SARS-CoV-2 infection might modulate the fetal immune system in the absence of vertical transmission.
This study raises important questions about the untoward effects of maternal SARS-CoV-2 on the fetus, even in the absence of vertical transmission.