Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Physician-Scientist Development
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • In-Press Preview
    • Resource and Technical Advances
    • Clinical Research and Public Health
    • Research Letters
    • Editorials
    • Perspectives
    • Physician-Scientist Development
    • Reviews
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Resource and Technical Advances
  • Clinical Research and Public Health
  • Research Letters
  • Editorials
  • Perspectives
  • Physician-Scientist Development
  • Reviews
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
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
View: Text | PDF
Research Article COVID-19 Immunology

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

  • Text
  • PDF
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

×

Figure 2

Evaluation of NAb isotypes in gestational SARS-CoV-2 infections.

Options: View larger image (or click on image) Download as PowerPoint
Evaluation of NAb isotypes in gestational SARS-CoV-2 infections.
(A) NT5...
(A) NT50 values for maternal and cord blood paired samples from SARS-CoV-2–infected (CoV-2+; n = 50 dyads) and vaccinated mothers (Vac, n = 6 dyads). (B) NT50 for CoV-2+ maternal samples segregated by gestational age of infection (n = 50). (C) Anti-RBD IgG transfer ratio in the presence (Sym) or absence (Asym) of symptoms in ongoing maternal infections (3O, n = 24). (D) Total IgG transfer ratio in the presence (Sym) or absence (Asym) of symptoms in ongoing maternal infections (3O, n = 35). (E) Correlation between maternal anti-spike IgA, IgG, and IgM and NT50 in ongoing infections (3O, n = 35). (F) Correlation between maternal anti-spike IgA, IgG, and IgM and NT50 in recovered infections (2R + 3R, n = 15). (G) Correlation between maternal anti-spike IgA, IgG, and IgM and NT50 in vaccinated participants (Vac, n = 6). (H) Ratios of NT50 values obtained from purified IgM and IgG fractions in maternal infections (n = 33). (I) Ratios of NT50 values obtained from purified IgA and IgG fractions in maternal infections (n = 33). Data represent mean ± SD for parametric tests, or median ± IQR for nonparametric tests. nd, not detectable. NS, not significant. Significance determined by parametric paired, 2-tailed t test (A), unpaired, 2-tailed t test (C), nonparametric paired Wilcoxon’s test (A), Mann-Whitney test (A, D, H, and I), Kruskal-Wallis with post hoc Dunn’s (B), Spearman’s correlation (E–G), and Pearson’s correlation (F and G). Effect sizes were determined by Cohen’s d (A and C), correlation coefficient r (A, D, H, and I), and η2 (B).

Copyright © 2026 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts