Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggers a humoral immune response that leads to the formation of specific immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies against the virus. The aim of the study was to examine the humoral immune response after de novo SARS-CoV-2 infection in unvaccinated pregnant women by determining the profile of IgG and IgA antibodies in maternal blood at delivery and 42 days after delivery. A further aim was to assess the transplacental transfer of these antibodies to the fetus by measuring their presence in umbilical cord blood. The antibody profiles were analyzed in relation to the interval from infection to delivery, the gestational age at the time of infection, the clinical course of coronavirus disease 2019 (COVID-19), and the clinical characteristics of the pregnant women.
Methods: A prospective cohort study was conducted between September 1, 2020 and March 1, 2021 at the Department of Perinatology, Division of Gynecology and Obstetrics, University Medical Center Ljubljana, in collaboration with the Institute of Microbiology and Immunology, Faculty of Medicine,University of Ljubljana. A total of 387 pregnant women with SARS-CoV-2 infection confirmed during pregnancy by real-time reverse transcription polymerase chain reaction (RT-PCR) were included. Clinical data were recorded, including age, body mass index (BMI), smoking status, chronic diseases, gestational
age at infection and at delivery, and complications during pregnancy, delivery, and the postpartum period.
IgG and IgA antibodies were quantified using enzyme-linked immunosorbent assay (ELISA) in maternal blood samples at delivery and 42 days postpartum, and in umbilical cord blood at delivery. Associations between antibody presence and levels and gestational age at infection, the interval from infection to delivery, and clinical characteristics were analyzed using univariate and multivariate logistic and linear
regression models.
Results: The mean gestational age at the time of infection was 31 4/7 weeks. Overall, 88.1% of participants had a symptomatic course of COVID-19. IgG and IgA antibodies were detected in 45.7% and 58.9% of participants at delivery, respectively, increasing to 72.7% and 76.8% at 42 days postpartum.
The presence of IgG and IgA antibodies in maternal blood at delivery was independently associated with symptomatic COVID-19 (odds ratio [OR] 3.13; 95% confidence interval [CI] 1.47–6.69 and OR 3.62;
95% CI 1.8–7.26), but not with the interval from the positive RT-PCR test to delivery or the gestational age at the positive RT-PCR test. Antibody presence at 42 days postpartum was strongly associated with antibody presence at delivery (OR 29.97; 95% CI 10.11–88.82 for IgG and OR 13.09; 95% CI 6.37–26.9 for IgA). Higher pre-pregnancy BMI was significantly associated with the presence of IgG and IgA antibodies at both delivery and 42 days postpartum (p < 0.05), independent of maternal age and chronic diseases. Participants without chronic diseases had lower antibody levels at delivery, and those with cardiovascular diseases were less likely to have antibodies six weeks after delivery. Smoking significantly reduced the likelihood of having IgG antibodies at delivery. Other clinical parameters did not show a significant association. The presence of IgG antibodies in umbilical cord blood was significantly associated with the presence of IgG antibodies in maternal blood at delivery (p < 0.001). IgG antibodies were present in cord blood in 78.8% of participants with IgG antibodies in maternal blood at delivery.
The median ratio of IgG levels in cord blood to maternal blood was 118%. The only factor significantly associated with the cord-to-maternal IgG ratio was the time from infection to delivery (p < 0.001). The transmission ratio (TR) was greater than 1 when at least 10 days had elapsed from infection to delivery.
Conclusion: Most pregnant women in this cohort were infected with SARS-CoV-2 during the third trimester. A substantial proportion developed specific IgG and IgA antibodies during pregnancy and in the postpartum period. These humoral responses were significantly associated with a symptomatic course of COVID-19 and a higher pre-pregnancy BMI. IgG crossed the placenta in most women with detectable maternal antibodies at delivery. A significant direct correlation between maternal and umbilical cord
blood IgG levels was evident as early as 10 days after infection, suggesting a potential contribution to neonatal immunity and protection against SARS-CoV-2 infection after delivery.
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