Maternal and neonatal immune response to SARS-CoV-2, IgG transplacental transfer and cytokine profile

Rubio, Rocío; Aguilar, Ruth; Bustamante Pineda, Mariona; Muñoz, Erica; Vázquez-Santiago, Miquel; Santano, Rebeca; Vidal, Marta; Rodrigo Melero, Natalia; Parras, Daniel; Serra, Pau; Santamaria, Pere; Carolis, Carlo; Izquierdo, Luis; Gómez-Roig, María Dolores; Dobaño, Carlota; Moncunill, Gemma; Mazarico, Edurne

doi:http://dx.doi.org/10.3389/fimmu.2022.999136

Maternal and neonatal immune response to SARS-CoV-2, IgG transplacental transfer and cytokine profile

Citation

Rubio R, Aguilar R, Bustamante M, Muñoz E, Vázquez-Santiago M, Santano R, Vidal M, Melero NR, Parras D, Serra P, Santamaria P, Carolis C, Izquierdo L, Gómez-Roig MD, Dobaño C, Moncunill G, Mazarico E. Maternal and neonatal immune response to SARS-CoV-2, IgG transplacental transfer and cytokine profile. Front Immunol. 2022 Sep 27;13:999136. DOI: 10.3389/fimmu.2022.999136

Abstract

SARS-CoV-2 infected pregnant women are at increased risk of severe COVID-19 than non-pregnant women and have a higher risk of adverse pregnancy outcomes like intrauterine/fetal distress and preterm birth. However, little is known about the impact of SARS-CoV-2 infection on maternal and neonatal immunological profiles. In this study, we investigated the inflammatory and humoral responses to SARS-CoV-2 in maternal and cord blood paired samples. Thirty-six pregnant women were recruited at delivery at Hospital Sant Joan de Déu, Barcelona, Spain, between April-August 2020, before having COVID-19 available vaccines. Maternal and pregnancy variables, as well as perinatal outcomes, were recorded in questionnaires. Nasopharyngeal swabs and maternal and cord blood samples were collected for SARS-CoV-2 detection by rRT-PCR and serology, respectively. We measured IgM, IgG and IgA levels to 6 SARS-CoV-2 antigens (spike [S], S1, S2, receptor-binding domain [RBD], nucleocapsid [N] full-length and C-terminus), IgG to N from 4 human coronaviruses (OC43, HKU1, 229E and NL63), and the concentrations of 30 cytokines, chemokines and growth factors by Luminex. Mothers were classified as infected or non-infected based on the rRT-PCR and serology results. Sixty-four % of pregnant women were infected with SARS-CoV-2 (positive by rRT-PCR during the third trimester and/or serology just after delivery). None of the newborns tested positive for rRT-PCR. SARS-CoV-2 infected mothers had increased levels of virus-specific antibodies and several cytokines. Those with symptoms had higher cytokine levels. IFN-α was increased in cord blood from infected mothers, and in cord blood of symptomatic mothers, EGF, FGF, IL-17 and IL-15 were increased, whereas RANTES was decreased. Maternal IgG and cytokine levels showed positive correlations with their counterparts in cord blood. rRT-PCR positive mothers showed lower transfer of SARS-CoV-2-specific IgGs, with a stronger effect when infection was closer to delivery. SARS-CoV-2 infected mothers carrying a male fetus had higher antibody levels and higher EGF, IL-15 and IL-7 concentrations. Our results show that SARS-CoV-2 infection during the third trimester of pregnancy induces a robust antibody and cytokine response at delivery and causes a significant reduction of the SARS-CoV-2-specific IgGs transplacental transfer, with a stronger negative effect when the infection is closer to delivery.