The Legacy of Maternal SARS-CoV-2 Infection on the Immunology of the Neonate

Overview

Journal Nat Immunol

Date 2021 Oct 7

PMID 34616036

Citations 59

Authors

Sarah Gee

Manju Chandiramani

Jeffrey Seow

Emily Pollock

Carlotta Modestini

Abhishek Das

Timothy Tree

Katie J Doores

Rachel M Tribe

Deena L Gibbons

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Sutton D, Fuchs K, DAlton M, Goffman D . Universal Screening for SARS-CoV-2 in Women Admitted for Delivery. N Engl J Med. 2020; 382(22):2163-2164. PMC: 7175422. DOI: 10.1056/NEJMc2009316. View

Allotey J, Stallings E, Bonet M, Yap M, Chatterjee S, Kew T . Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ. 2020; 370:m3320. PMC: 7459193. DOI: 10.1136/bmj.m3320. View

Kadiwar S, Smith J, Ledot S, Johnson M, Bianchi P, Singh N . Were pregnant women more affected by COVID-19 in the second wave of the pandemic?. Lancet. 2021; 397(10284):1539-1540. PMC: 8046416. DOI: 10.1016/S0140-6736(21)00716-9. View

Martinez-Perez O, Prats Rodriguez P, Muner Hernandez M, Pardilla M, Perez Perez N, Hernandez M . The association between SARS-CoV-2 infection and preterm delivery: a prospective study with a multivariable analysis. BMC Pregnancy Childbirth. 2021; 21(1):273. PMC: 8016158. DOI: 10.1186/s12884-021-03742-4. View

Gale C, Quigley M, Placzek A, Knight M, Ladhani S, Draper E . Characteristics and outcomes of neonatal SARS-CoV-2 infection in the UK: a prospective national cohort study using active surveillance. Lancet Child Adolesc Health. 2020; 5(2):113-121. PMC: 7818530. DOI: 10.1016/S2352-4642(20)30342-4. View

Salvatore C, Han J, Acker K, Tiwari P, Jin J, Brandler M . Neonatal management and outcomes during the COVID-19 pandemic: an observation cohort study. Lancet Child Adolesc Health. 2020; 4(10):721-727. PMC: 7377726. DOI: 10.1016/S2352-4642(20)30235-2. View

Vivanti A, Vauloup-Fellous C, Prevot S, Zupan V, Suffee C, Do Cao J . Transplacental transmission of SARS-CoV-2 infection. Nat Commun. 2020; 11(1):3572. PMC: 7360599. DOI: 10.1038/s41467-020-17436-6. View

Fenizia C, Biasin M, Cetin I, Vergani P, Mileto D, Spinillo A . Analysis of SARS-CoV-2 vertical transmission during pregnancy. Nat Commun. 2020; 11(1):5128. PMC: 7552412. DOI: 10.1038/s41467-020-18933-4. View

Dong L, Tian J, He S, Zhu C, Wang J, Liu C . Possible Vertical Transmission of SARS-CoV-2 From an Infected Mother to Her Newborn. JAMA. 2020; 323(18):1846-1848. PMC: 7099527. DOI: 10.1001/jama.2020.4621. View

10.

Chen G, Liao Q, Ai J, Yang B, Bai H, Chen J . Immune Response to COVID-19 During Pregnancy. Front Immunol. 2021; 12:675476. PMC: 8126657. DOI: 10.3389/fimmu.2021.675476. View

11.

Kamdar S, Hutchinson R, Laing A, Stacey F, Ansbro K, Millar M . Perinatal inflammation influences but does not arrest rapid immune development in preterm babies. Nat Commun. 2020; 11(1):1284. PMC: 7062833. DOI: 10.1038/s41467-020-14923-8. View

12.

Gabriel B, Medin C, Alves J, Nduati R, Bosire R, Wamalwa D . Analysis of the TCR Repertoire in HIV-Exposed but Uninfected Infants. Sci Rep. 2019; 9(1):11954. PMC: 6697688. DOI: 10.1038/s41598-019-48434-4. View

13.

Babik J, Cohan D, Monto A, Hartigan-OConnor D, McCune J . The human fetal immune response to hepatitis C virus exposure in utero. J Infect Dis. 2011; 203(2):196-206. PMC: 3071071. DOI: 10.1093/infdis/jiq044. View

14.

Gomez de Aguero M, Ganal-Vonarburg S, Fuhrer T, Rupp S, Uchimura Y, Li H . The maternal microbiota drives early postnatal innate immune development. Science. 2016; 351(6279):1296-302. DOI: 10.1126/science.aad2571. View

15.

Torow N, Hornef M . The Neonatal Window of Opportunity: Setting the Stage for Life-Long Host-Microbial Interaction and Immune Homeostasis. J Immunol. 2017; 198(2):557-563. DOI: 10.4049/jimmunol.1601253. View

16.

Liu P, Zheng J, Yang P, Wang X, Wei C, Zhang S . The immunologic status of newborns born to SARS-CoV-2-infected mothers in Wuhan, China. J Allergy Clin Immunol. 2020; 146(1):101-109.e1. PMC: 7211641. DOI: 10.1016/j.jaci.2020.04.038. View

17.

Pickering S, Betancor G, Galao R, Merrick B, Signell A, Wilson H . Comparative assessment of multiple COVID-19 serological technologies supports continued evaluation of point-of-care lateral flow assays in hospital and community healthcare settings. PLoS Pathog. 2020; 16(9):e1008817. PMC: 7514033. DOI: 10.1371/journal.ppat.1008817. View

18.

Laing A, Lorenc A, Del Molino Del Barrio I, Das A, Fish M, Monin L . A dynamic COVID-19 immune signature includes associations with poor prognosis. Nat Med. 2020; 26(10):1623-1635. DOI: 10.1038/s41591-020-1038-6. View

19.

Arunachalam P, Wimmers F, Mok C, Perera R, Scott M, Hagan T . Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans. Science. 2020; 369(6508):1210-1220. PMC: 7665312. DOI: 10.1126/science.abc6261. View

20.

Tornblom S, Maul H, Klimaviciute A, Garfield R, Bystrom B, Malmstrom A . mRNA expression and localization of bNOS, eNOS and iNOS in human cervix at preterm and term labour. Reprod Biol Endocrinol. 2005; 3:33. PMC: 1188074. DOI: 10.1186/1477-7827-3-33. View