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

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Bibliographical note

Funding Information: We thank the mothers and their neonates for blood collection and all the midwives (GSTT) for sample collection. We also thank S. Kamdar and other staff involved with COVID-IP (King’s College London)20 for some sample processing and T. Lechmere (King’s College London) for assistance with ELISA assays. We thank I. Zlatareva (King’s College London) for assistance with the cytokine multiplex analysis. We also acknowledge Evolve Biosystems for funding (to R.T. and D.G.) toward the NSE neonatal cord blood sample collection and the staff involved: N. Kelly, L. McMillan, S. Kheirallah and J. Mi; GSTT and King’s College London). We thank Y. Wu (King’s College London) for critical reading of the manuscript. S.G. is supported by an MRC-KCL Doctoral Training Partnership in Biomedical Sciences (MR/N013700/1); D.L.G. is supported by Action Medical Research (GN2790); M.C. is supported by the National Institute for Health Research (NIHR) BRC COVID-19 call; R.M.T. is supported by Tommy’s (charity no. 1060508) and Borne (1167073); J.S. and K.J.D. are supported by a Kings Together Rapid COVID-19 call award and a Huo Family Foundation award; and E.P. and T.T. are supported by the T1DUK Immunotherapy Consortium funded by Diabetes UK (15/0005232). The research was also supported by the NIHR Biomedical Research Centre based at GSTT and King’s College London (part of the King’s Health Partners Academic Sciences Centre) and/or the NIHR Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.

King's Authors

Abstract

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.

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