Transplacental transfer of anti-SARS-CoV-2 neutralizing antibodies in comparison to other pathogens total antibodies

Abstract

Backgrounds: Due to immaturity of their immune system, passive maternal immunization is essential for newborns during their first months of life. Therefore, in the current context of intense circulation of SARS-CoV-2, identifying factors influencing the transfer ratio (TR) of neutralizing antibodies against SARS-CoV-2 (NAb) appears important.

Methods: Our study nested in the COVIPREG cohort (NCT04355234), included mothers who had a SARS-CoV-2 PCR positive during their pregnancy and their newborns. Maternal and neonatal NAb levels were measured with the automated iFlash system.

Results: For the 173 mother-infant pairs included in our study, the median gestational age (GA) at delivery was 39.4 weeks of gestation (WG), and 29.7 WG at maternal SARS-CoV-2 infection. Using a multivariate logistic model, having a NAb TR above 1 was positively associated with a longer delay from maternal positive SARS-CoV-2 PCR to delivery (aOR 1.09, 95% CI: 1.03 - 1.17) and with a later GA at delivery (aOR = 1.58, 95% CI: 1.09 - 2.52). It was negatively associated with being a male newborn (aOR 0.21, 95% CI: 0.07 - 0.59). In 3rd trimester SARS-CoV-2 infected mothers, NAb TR was inferior to VZV, toxoplasmosis, CMV, measle and rubella's TR. However, in 1st or 2nd trimester infected mothers, only measle TR was different from NAb TR.

Conclusion: Male newborn of mothers infected by SARS-CoV-2 during their pregnancy appear to have less protection against SARS-CoV-2 in their first months of life than female newborns. Measle TR was superior to NAb TR even in case of 1st or 2nd trimester maternal SARS-CoV-2 infection. Future studies are needed to investigate possible differences in transmission of NAb following infection vs vaccination and its impact on TR.

Keywords: Neutralizing antibodies; Newborn; Pregnancy; SARS-CoV-2; Transplacental transmission.

Fig. 1

Scatter plot of maternal and cord blood NAb with Spearman's correlation between NAb titer (AU/mL) in cord blood and mothers’ sera according to the trimester at SARS-CoV-2 infection. In 1st or 2nd trimester SARS-CoV-2 infection: N = 46, rho = 0.67, p < 0.001. In 3rd trimester SARS-CoV-2 infection: N = 40, rho = 0.41, p < 0.01. the empty dots represent the observed data for 1st and 2nd trimester at SARS-CoV-2 infection and the filled dots represent the 3rd trimester.

Fig. 2

Scatter plot of NAb TR and delay from infection to delivery with the Spearman correlation: N = 86, rho coefficient = 0.58, p < 0.001.

Fig. 3

Boxplot of NAb TR according to pregnancies’ trimester at SARS-CoV-2 infection. Wilcoxon Rank Sum tests, adjusted p-value by Holm, NS: non-significant test (lower hinge = 25% quantile, upper hinge = 75% quantile, lower whisker = smallest observation greater than or equal to lower hinge - 1.5 * IQR, upper whisker = largest observation less than or equal to upper hinge + 1.5 * IQR). the gray dots represent the observed data.

Fig. 4

Boxplot between TR and pathogens other than SARS-CoV or SARS-CoV-2 NAb according to patients' trimester at SARS-CoV-2 infection with the comparison using Wilcoxon Rank Sum test, adjusted p-value by Bonferroni (number of tests = 10). NS: non-significant test. Lower hinge = 25% quantile, upper hinge = 75% quantile, lower whisker = smallest observation greater than or equal to lower hinge - 1.5 * IQR, upper whisker = largest observation less than or equal to upper hinge + 1.5 * IQR. the empty dots represent the observed data for 1st and 2nd trimester at SARS-CoV-2 infection and the filled dots represent the 3rd trimester.