Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study
Authors: Fernandes Geraldo Magela , Sasaki Lizandra Moura Paravidine , Jardim-Santos Gabriela Profírio , Schulte Heidi Luise , Motta Felipe , da Silva Ângelo Pereira , de Carvalho Aleida Oliveira , Pereira Yacara Ribeiro , Alves Caroline de Oliveira , de Araújo Júnior David Alves , Mendonça-Silva Dayde Lane , Costa Karina Nascimento , de Castro Maria Eduarda Canellas , Lauand Lucas , Nery Rodrigo de Resende , Tristão Rosana , Kurizky Patricia Shu , Nóbrega Otávio de Toledo , Espindola Laila Salmen , de Castro Luiz Cláudio Gonçalves , Alpoim Patrícia Nessralla , Godoi Lara Carvalho , Dusse Luci Maria Sant Ana , Coelho-dos-Reis Jordana Grazziela Alves , Amaral Laurence Rodrigues do , Gomes Matheus de Souza , Bertarini Pedro Luiz Lima , Brito-de-Sousa Joaquim Pedro , Costa-Rocha Ismael Artur da , Campi-Azevedo Ana Carolina , Peruhype-Magalhães Vanessa , Teixeira-Carvalho Andrea , Zaconeta Alberto Moreno , Soares Alexandre Anderson de Sousa Munhoz , Valim Valéria , Gomes Ciro Martins , de Albuquerque Cleandro Pires , Martins-Filho Olindo Assis , da Mota Licia Maria Henrique 
Published: April 2023

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 &lt;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.