Frontiers in Immunology (Apr 2023)

Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study

  • Geraldo Magela Fernandes,
  • Lizandra Moura Paravidine Sasaki,
  • Lizandra Moura Paravidine Sasaki,
  • Gabriela Profírio Jardim-Santos,
  • Heidi Luise Schulte,
  • Felipe Motta,
  • Ângelo Pereira da Silva,
  • Aleida Oliveira de Carvalho,
  • Yacara Ribeiro Pereira,
  • Caroline de Oliveira Alves,
  • David Alves de Araújo Júnior,
  • Dayde Lane Mendonça-Silva,
  • Karina Nascimento Costa,
  • Maria Eduarda Canellas de Castro,
  • Maria Eduarda Canellas de Castro,
  • Lucas Lauand,
  • Rodrigo de Resende Nery,
  • Rosana Tristão,
  • Patricia Shu Kurizky,
  • Patricia Shu Kurizky,
  • Otávio de Toledo Nóbrega,
  • Laila Salmen Espindola,
  • Luiz Cláudio Gonçalves de Castro,
  • Luiz Cláudio Gonçalves de Castro,
  • Patrícia Nessralla Alpoim,
  • Lara Carvalho Godoi,
  • Luci Maria Sant Ana Dusse,
  • Jordana Grazziela Alves Coelho-dos-Reis,
  • Laurence Rodrigues do Amaral,
  • Matheus de Souza Gomes,
  • Pedro Luiz Lima Bertarini,
  • Joaquim Pedro Brito-de-Sousa,
  • Ismael Artur da Costa-Rocha,
  • Ana Carolina Campi-Azevedo,
  • Vanessa Peruhype-Magalhães,
  • Andrea Teixeira-Carvalho,
  • Alberto Moreno Zaconeta,
  • Alexandre Anderson de Sousa Munhoz Soares,
  • Alexandre Anderson de Sousa Munhoz Soares,
  • Valéria Valim,
  • Valéria Valim,
  • Ciro Martins Gomes,
  • Ciro Martins Gomes,
  • Ciro Martins Gomes,
  • Cleandro Pires de Albuquerque,
  • Cleandro Pires de Albuquerque,
  • Olindo Assis Martins-Filho,
  • Licia Maria Henrique da Mota,
  • Licia Maria Henrique da Mota,
  • Licia Maria Henrique da Mota

DOI
https://doi.org/10.3389/fimmu.2023.1176898
Journal volume & issue
Vol. 14

Abstract

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IntroductionSARS-CoV-2 infection during pregnancy can induce changes in the maternal immune response, with effects on pregnancy outcome and offspring. This is a cross-sectional observational study designed to characterize the immunological status of pregnant women with convalescent COVID-19 at distinct pregnancy trimesters. The study focused on providing a clear snapshot of the interplay among serum soluble mediators.MethodsA sample of 141 pregnant women from all prenatal periods (1st, 2nd and 3rd trimesters) comprised patients with convalescent SARS-CoV-2 infection at 3-20 weeks after symptoms onset (COVID, n=89) and a control group of pre-pandemic non-infected pregnant women (HC, n=52). Chemokine, pro-inflammatory/regulatory cytokine and growth factor levels were quantified by a high-throughput microbeads array.ResultsIn the HC group, most serum soluble mediators progressively decreased towards the 2nd and 3rd trimesters of pregnancy, while higher chemokine, cytokine and growth factor levels were observed in the COVID patient group. Serum soluble mediator signatures and heatmap analysis pointed out that the major increase observed in the COVID group related to pro-inflammatory cytokines (IL-6, TNF-α, IL-12, IFN-γ and IL-17). A larger set of biomarkers displayed an increased COVID/HC ratio towards the 2nd (3x increase) and the 3rd (3x to 15x increase) trimesters. Integrative network analysis demonstrated that HC pregnancy evolves with decreasing connectivity between pairs of serum soluble mediators towards the 3rd trimester. Although the COVID group exhibited a similar profile, the number of connections was remarkably lower throughout the pregnancy. Meanwhile, IL-1Ra, IL-10 and GM-CSF presented a preserved number of correlations (≥5 strong correlations in HC and COVID), IL-17, FGF-basic and VEGF lost connectivity throughout the pregnancy. IL-6 and CXCL8 were included in a set of acquired attributes, named COVID-selective (≥5 strong correlations in COVID and <5 in HC) observed at the 3rd pregnancy trimester.Discussion and conclusionFrom an overall perspective, a pronounced increase in serum levels of soluble mediators with decreased network interplay between them demonstrated an imbalanced immune response in convalescent COVID-19 infection during pregnancy that may contribute to the management of, or indeed recovery from, late complications in the post-symptomatic phase of the SARS-CoV-2 infection in pregnant women.

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