Transplacental transfer of SARS-CoV-2 antibodies in recovered and BNT162b2-vaccinated patients.

Objective

Neonates have been found to be more susceptible to severe SARS-CoV-2 infection. Data regarding the transfer of anti-SARS-CoV-2 antibodies to the neonate of vaccinated women is limited, including only 3 studies concerning late third-trimester vaccination.2, 3, 4 The objective of this study was to assess the transplacental transfer of anti-SARS-CoV-2 antibodies in women vaccinated with the BNT162b2 vaccine during the second and third trimester.

Study Design

A total of 40 parturients with singleton term pregnancies were recruited. Samples were collected from maternal and cord blood. Both maternal and neonatal samples were analyzed for anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies. The study was approved by the local institutional review board (number 0055-21-AAA) and written informed consent was obtained from all participants.

Results

Of the 40 women recruited, 28 were vaccinated with 2 doses of the BNT162b2 vaccine and 12 were COVID-19-convalescents (Supplemental Table 1). Median interval between COVID-19 diagnosis and delivery in the recovered group was 20.6 weeks (interquartile range [IQR], 17.6–36.9), whereas the median interval between second vaccine and delivery in the vaccinated group was 11.1 weeks (IQR, 9.3–15). Two women in the vaccinated group were anti-N-positive, suggesting past unknown infection (Supplemental Table 2).

Supplemental Table 1

Demographic and clinical data

Demographics	Vaccinated (28)	Recovered (12)	P value
Age (y)	30.4±5.2	26±4.3	.014
BMI (kg/m2)a	28.4±3.4	30.1±3.9	.257
Nulliparous	5 (17.9%)	4 (33.3%)	.411
Gestational age (wk)	39±1.1	39.9±1	.027
Cesarean delivery	11 (39.3%)	2 (16.7%)	.271
Interval to delivery (d)b	11.1 (9.3–15)	20.6 (17.6–36.9)	<.001
Birthweight	3258±436	3650±465	.015
Male/female ratio	14/14	7/5	.629
Low 1-min Apgarc	0	1 (8.3%)	.3
Low 5-min Apgarc	0	0	1

Continuous variables are represented as mean±standard deviation or median (interquartile range) according to distribution. Categorical variables are represented as number (percentage). P values were calculated using the t test, Mann–Whitney, or Fisher exact test, as appropriate.

BMI, body mass index.

Treger. Transplacental transfer of SARS-CoV-2 antibodies in recovered and BNT162b2-vaccinated patients. Am J Obstet Gynecol 2022.

BMI data were missing in 10 cases

Days to delivery were calculated from date of COVID-19 diagnosis to date of delivery in the recovered group and from date of second vaccination to date of delivery in the vaccinated group

Low 1- or 5-minute Apgar score was defined as a score <7.

Supplemental Table 2

Qualitative antibody assays

Assay			Vaccinated (28)	Recovered (12)	P value
Maternal	Positive anti-N		2 (7.1)	11 (91.7)	<.001
	Anti-S	Positive	27 (96.4)	10 (83.3)	.238
		Borderline	0	1 (8.3)
		Negative	1 (3.6)	1 (8.3)
Neonatal	Positive anti-N		2 (7.1)	12 (100)	<.001
	Anti-S	Positive	27 (96.4)	10 (83.3)	.238
		Borderline	0	1 (8.3)
		Negative	1 (3.6)	1 (8.3)

Categorization of serologic results in maternal and neonatal serum. Anti-N antibodies results were categorized as positive or negative. Anti-S antibodies results were categorized as positive, borderline, and negative. P values were calculated using the chi-squared test or Fisher exact test, as appropriate.

Anti-N, anti-nucleocapsid; anti-S, anti-spike.

Treger. Transplacental transfer of SARS-CoV-2 antibodies in recovered and BNT162b2-vaccinated patients. Am J Obstet Gynecol 2022.

Overall, maternal anti-S antibody levels were significantly higher in the vaccinated group than in the recovered group (145, IQR, 113–202 vs 41, IQR, 19–95 AU/mL, respectively; P=.008), as were neonatal anti-S antibody levels (216, IQR, 155–316 vs 64, IQR, 23–219 AU/mL, respectively; P=.026). Neonatal antibody levels were significantly higher than maternal levels in both groups (185, IQR, 85–316 vs 131, IQR, 59–198; P<.001). There was no significant difference in the neonatal to maternal anti-S ratio between the groups (Table ).

Table

Anti-spike antibody levels

Antibody	Vaccinated (28)	Recovered (12)	P value
Maternal anti-S (AU/mL)	145 (113–202)	41 (19–95)	.008
Neonatal anti-S (AU/mL)	216 (155–316)	64 (23–219)	.026
Neonatal/maternal anti-S ratio	1.48 (1.18–1.82)	1.35 (1.19–1.84)	.919

Anti-S antibody levels in maternal and neonatal serum. Data are presented as median (interquartile range). P values were calculated using the Mann–Whitney U test.

Anti-S, anti-spike.

Treger. Transplacental transfer of SARS-CoV-2 antibodies in recovered and BNT162b2-vaccinated patients. Am J Obstet Gynecol 2022.

There was a significant correlation between maternal and neonatal anti-S antibody levels (r=0.922, P<.001). However, there was no correlation between maternal anti-S levels and the neonatal to maternal anti-S ratio, nor between maternal anti-S levels and the interval to delivery. Moreover, the lack of correlation between maternal anti-S levels and the interval to delivery was also apparent when assessing the vaccinated and the recovered groups separately (Supplemental Table 3).

Supplemental Table 3

Correlation of maternal anti-spike levels

Correlation		Correlation coefficient	P value
	Neonatal anti-S	0.922	<.001
	Anti-S ratio	0.268	.094
Days to delivery	All	−0.277	.087
	Recovered	0.014	.966
	Vaccinated	−0.136	.500

Spearman correlations between maternal anti-S levels to neonatal levels ratio, neonatal to maternal anti-S ratio, and time from exposure to either the virus causing COVID-19 or vaccine to delivery.

Anti-S, anti-spike.

Treger. Transplacental transfer of SARS-CoV-2 antibodies in recovered and BNT162b2-vaccinated patients. Am J Obstet Gynecol 2022.

Regarding factors that may affect transplacental anti-S antibody transfer, using a linear regression model (Figure ), we found that only birthweight had a significant positive impact on the neonatal to maternal anti-S ratio (β-coefficient, 0.509; 95% confidence interval, 0.032–0.986; P=.037).

Figure

Linear regression assessing the factors affecting the neonatal to maternal anti-S ratio

Circles and error bars represent the β-coefficients and 95% confidence intervals, respectively.

Treger. Transplacental transfer of SARS-CoV-2 antibodies in recovered and BNT162b2-vaccinated patients. Am J Obstet Gynecol 2022.

Conclusion

This study assessed the maternal to neonatal transfer of SARS-CoV-2 antibodies in women vaccinated during the second trimester. Previously published studies assessed the transfer of anti-SARS-CoV-2 antibodies in women vaccinated in the late third trimester,2, 3, 4 in some cases without completing the vaccination course (ie, 1 week after the second dose). The fact that vaccinations were given close to delivery may explain the low neonatal to maternal antibody ratio found in all these studies. By contrast, our study found a high neonatal to maternal antibody ratio, similar to that found in studies on other vaccines.

The median gestational week at second dose was 26 (24–30 weeks; IQR, 14–34), enabling us to show that despite the long interval between vaccination and delivery, a high level of antibodies was maintained. We did not find an association between vaccination-to-delivery or infection-to-delivery interval and antibody levels. This can be explained by the relatively short time frame of our study and the fact that the study’s population comprised young, healthy women.

Birthweight was found to affect transplacental antibody transfer. This is in accordance with previous data showing a correlation between birthweight and antibody transfer. We could not assess the correlation between gestational age and antibody transfer because all cases in this study were term deliveries.

Our study has a few limitations. The small sample size may have prevented us from detecting a time-dependent decrease in antibody levels or other factors that may have affected transplacental antibody transfer in addition to birthweight. Differences between the vaccinated and recovered groups may have been a source of bias. The risk of residual bias cannot be eliminated, although the use of multivariate analyses reduces that risk. We have no data regarding vaccines other than the BNT162b2, which was used exclusively in Israel. Lastly, waning of antibody titers in neonates remains yet to be determined.

Neonatal SARS-CoV-2 antibody levels were higher than maternal levels in both vaccinated and recovered patients. Antibody levels in newborns of vaccinated mothers were 3.4-fold higher than those in newborns of recovered mothers. Given that the protection afforded to neonates is based solely on maternal antibody transfer, vaccination of women during pregnancy might have an impact on the protection of their newborns.