The legacy of maternal SARS-CoV-2 infection on the immunology of the neonate

Nat Immunol. 2021 Dec;22(12):1490-1502. doi: 10.1038/s41590-021-01049-2. Epub 2021 Oct 6.


Despite extensive studies into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the effect of maternal infection on the neonate is unclear. To investigate this, we characterized the immunology of neonates born to mothers with confirmed SARS-CoV-2 infection during pregnancy. Here we show that maternal SARS-CoV-2 infection affects the neonatal immune system. Despite similar proportions of B cells, CD4+ T cells and CD8+ T cells, increased percentages of natural killer cells, Vδ2+ γδ T cells and regulatory T cells were detected in neonates born to mothers with recent or ongoing infection compared with those born to recovered or uninfected mothers. Increased plasma cytokine levels were also evident in neonates and mothers within the recent or ongoing infection group. Cytokine functionality was enhanced in neonates born to SARS-CoV-2-exposed mothers, compared to those born to uninfected mothers. In most neonates, this immune imprinting was nonspecific, suggesting vertical transmission of SARS-CoV-2 is limited, a finding supported by a lack of SARS-CoV-2-specific IgM in neonates despite maternal IgG transfer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / immunology
  • COVID-19 / diagnosis
  • COVID-19 / immunology*
  • COVID-19 / virology
  • Cytokines / blood
  • Cytokines / immunology
  • Cytokines / metabolism
  • Female
  • Humans
  • Immunity, Innate / immunology
  • Immunoglobulin G / immunology
  • Infant, Newborn
  • Infant, Newborn, Diseases / diagnosis
  • Infant, Newborn, Diseases / immunology*
  • Infant, Newborn, Diseases / virology
  • Infectious Disease Transmission, Vertical*
  • Killer Cells, Natural / immunology
  • Pregnancy
  • Pregnancy Complications, Infectious / immunology*
  • Pregnancy Complications, Infectious / virology
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / physiology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes, Regulatory / immunology


  • Antibodies, Viral
  • Cytokines
  • Immunoglobulin G
  • Receptors, Antigen, T-Cell, gamma-delta