Balance between maternal antiviral response and placental transfer of protection in gestational SARS-CoV-2 infection
Juliana Gonçalves, Magda Melro, Marta Alenquer, Catarina Araújo, Júlia Castro-Neves, Daniela Amaral-Silva, Filipe Ferreira, José S. Ramalho, Nádia Charepe, Fátima Serrano, Carlos Pontinha, Maria João Amorim, Helena Soares
Juliana Gonçalves, Magda Melro, Marta Alenquer, Catarina Araújo, Júlia Castro-Neves, Daniela Amaral-Silva, Filipe Ferreira, José S. Ramalho, Nádia Charepe, Fátima Serrano, Carlos Pontinha, Maria João Amorim, Helena Soares
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Research Article COVID-19 Immunology

Balance between maternal antiviral response and placental transfer of protection in gestational SARS-CoV-2 infection

Abstract

The intricate interplay between maternal immune response to SARS-CoV-2 and the transfer of protective factors to the fetus remains unclear. By analyzing mother-neonate dyads from second and third trimester SARS-CoV-2 infections, our study shows that neutralizing antibodies (NAbs) are infrequently detected in cord blood. We uncovered that this is due to impaired IgG-NAb placental transfer in symptomatic infection and to the predominance of maternal SARS-CoV-2 NAbs of the IgA and IgM isotypes, which are prevented from crossing the placenta. Crucially, the balance between maternal antiviral response and transplacental transfer of IgG-NAbs appears to hinge on IL-6 and IL-10 produced in response to SARS-CoV-2 infection. In addition, asymptomatic maternal infection was associated with expansion of anti–SARS-CoV-2 IgM and NK cell frequency. Our findings identify a protective role for IgA/IgM-NAbs in gestational SARS-CoV-2 infection and open the possibility that the maternal immune response to SARS-CoV-2 infection might benefit the neonate in 2 ways, first by skewing maternal immune response toward immediate viral clearance, and second by endowing the neonate with protective mechanisms to curtail horizontal viral transmission in the critical postnatal period, via the priming of IgA/IgM-NAbs to be transferred by the breast milk and via NK cell expansion in the neonate.

Authors

Juliana Gonçalves, Magda Melro, Marta Alenquer, Catarina Araújo, Júlia Castro-Neves, Daniela Amaral-Silva, Filipe Ferreira, José S. Ramalho, Nádia Charepe, Fátima Serrano, Carlos Pontinha, Maria João Amorim, Helena Soares

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Figure 1

Anti–SARS-CoV-2 antibody production and transplacental transfer efficiency in gestational SARS-CoV-2 infections.

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Anti–SARS-CoV-2 antibody production and transplacental transfer efficien...
(A) Outline of participant recruitment, divided into pregnant women negative for SARS-CoV-2 (CoV-2–), recovered from infection in second (2R) or third (3R) trimesters, with ongoing infection (3O), or receiving COVID-19 vaccine (Vac). (B) Anti-spike and anti-RBD IgG endpoint titers (n = 50 dyads). (C) Anti-spike and anti-RBD IgG transfer ratios (n = 39). (D) Correlation between anti-spike and anti-RBD IgG transfer ratio and elapsed time between diagnosis and delivery (n = 39). (E) Total IgG transfer ratios (n = 50). (F) Anti-spike, anti-RBD, and total IgG transfer ratios (n = 24). (G) Correlation between total IgM and anti-RBD IgM antibody levels (n = 58). (H) Correlation between total IgG and anti-RBD IgG antibody levels (n = 58). (I) Correlation between total IgA and anti-RBD IgA antibody levels (n = 58). Data represent mean ± SD for parametric tests, or median ± IQR for nonparametric tests. NS, not significant. Significance determined by parametric paired, 2-tailed t test (B), nonparametric paired Wilcoxon’s test (B), ordinary ANOVA with post hoc Holm-Šidák (C and F), Kruskal-Wallis with post hoc Dunn’s (E), Pearson’s correlation (D), and Spearman’s correlation (G–I). Effect sizes were determined by Cohen’s d (B), correlation coefficient r (B), and η2 (C, E, and F).