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Review
. 2022 Oct 15;209(8):1465-1473.
doi: 10.4049/jimmunol.2200414.

Immune Responses to SARS-CoV-2 in Pregnancy: Implications for the Health of the Next Generation

Lydia L Shook  1   2 , Lindsay T Fourman  3 , Andrea G Edlow  4   2
Affiliations
Review

Immune Responses to SARS-CoV-2 in Pregnancy: Implications for the Health of the Next Generation

Lydia L Shook et al. J Immunol. .

Abstract

Widespread SARS-CoV-2 infection among pregnant individuals has led to a generation of fetuses exposed in utero, but the long-term impact of such exposure remains unknown. Although fetal infection is rare, children born to mothers with SARS-CoV-2 infection may be at increased risk for adverse neurodevelopmental and cardiometabolic outcomes. Fetal programming effects are likely to be mediated at least in part by maternal immune activation. In this review, we discuss recent evidence regarding the effects of prenatal SARS-CoV-2 infection on the maternal, placental, and fetal immune response, as well as the implications for the long-term health of offspring. Extrapolating from what is known about the impact of maternal immune activation in other contexts (e.g., obesity, HIV, influenza), we review the potential for neurodevelopmental and cardiometabolic morbidity in offspring. Based on available data suggesting potential increased neurodevelopmental risk, we highlight the importance of establishing large cohorts to monitor offspring born to SARS-CoV-2-positive mothers for neurodevelopmental and cardiometabolic sequelae.

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Figures

Figure.
Figure.. Maternal SARS-CoV-2 infection may drive maternal and fetoplacental immune activation, with subsequent potential for adverse offspring health outcomes.
Recent studies demonstrate maternal and fetoplacental immune activation in response to maternal SARS-CoV-2 infection. Selected impacts of SARS-CoV-2 infection on maternal and placental immune activation are detailed on the left panel. Mechanisms implicated in fetal brain and organ programming in response to infectious and non-infectious immune-activating prenatal exposures – which may parallel maternal immune activation in SARS-CoV-2 - are illustrated in the central blue box and include alterations in: placental nutrient (including fatty acid) transport, epigenetic modifications in fetal organs (e.g. brain, liver, white adipose tissue, skeletal muscle), placental serotonin/neurotransmitter production, tissue mitochondrial dysfunction, and tissue-specific macrophage reactivity (e.g., fetal brain microglia, placental macrophages, cardiac and liver macrophages, blood). Although longer-term outcomes of infants and young children born to pregnant individuals with COVID-19 infection have not yet been described, some early reports suggest immune dysregulation and increased neurodevelopmental risk. Maternal-fetoplacental immune activation in other non-SARS-CoV-2 contexts (e.g. obesity, other viral infections) has been linked to multiple other adverse health outcomes in offspring such as those depicted in the right panel. Figure created with BioRender.
See this image and copyright information in PMC

References

    1. CDC. Data on COVID-19 during Pregnancy: Severity of Maternal Illness.
    1. Rader B, Gertz A, Iuliano AD, Gilmer M, Wronski L, Astley CM, Sewalk K, Varrelman TJ, Cohen J, Parikh R, Reese HE, Reed C, and Brownstein JS. 2022. Use of At-Home COVID-19 Tests - United States, August 23, 2021-March 12, 2022. MMWR Morb. Mortal. Wkly. Rep 71: 489–494. - PMC - PubMed
    1. Clarke KEN, Jones JM, Deng Y, Nycz E, Lee A, Iachan R, Gundlapalli AV, Hall AJ, and MacNeil A. 2022. Seroprevalence of Infection-Induced SARS-CoV-2 Antibodies - United States, September 2021-February 2022. MMWR Morb. Mortal. Wkly. Rep. 71: 606–608. - PMC - PubMed
    1. Cele S, Jackson L, Khoury DS, Khan K, Moyo-Gwete T, Tegally H, San JE, Cromer D, Scheepers C, Amoako DG, Karim F, Bernstein M, Lustig G, Archary D, Smith M, Ganga Y, Jule Z, Reedoy K, Hwa S-H, Giandhari J, Blackburn JM, Gosnell BI, Abdool Karim SS, Hanekom W, Ngs SA, Team C-K, von Gottberg A, Bhiman JN, Lessells RJ, Moosa M-YS, Davenport MP, de Oliveira T, Moore PL, and Sigal A. 2021. Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization. Nature. - PMC - PubMed
    1. Planas D, Saunders N, Maes P, Guivel-Benhassine F, Planchais C, Buchrieser J, Bolland W-H, Porrot F, Staropoli I, Lemoine F, Péré H, Veyer D, Puech J, Rodary J, Baele G, Dellicour S, Raymenants J, Gorissen S, Geenen C, Vanmechelen B, Wawina-Bokalanga T, Martí-Carreras J, Cuypers L, Sève A, Hocqueloux L, Prazuck T, Rey FA, Simon-Loriere E, Bruel T, Mouquet H, André E, and Schwartz O. 2021. Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature. - PubMed

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