key: cord-0752380-yqpu79wn
authors: Nevo, Lea; Cahen-Peretz, Adva; Vorontsov, Olesya; Frenkel, Rachelli; Kabessa, Maor; Cohen, Sarah M.; Hamrani, Adar; Oiknine-Djian, Esther; Lipschuetz, Michal; Goldman-Wohl, Debra; Walfisch, Asnat; Kovo, Michal; Neeman, Michal; Yagel, Simcha; Wolf, Dana G.; Beharier, Ofer
title: Boosting maternal and neonatal humoral immunity following SARS-CoV-2 infection using a single mRNA vaccine dose
date: 2022-04-14
journal: Am J Obstet Gynecol
DOI: 10.1016/j.ajog.2022.04.010
sha: d676bf178b5082f0df7ad86c3a8992d18b1618c1
doc_id: 752380
cord_uid: yqpu79wn

Background Post-COVID-19 boosting is a potent tool in the ongoing pandemic. Relevant data regarding this approach during pregnancy are lacking, affecting vaccination policy guidance, public acceptance, and vaccine uptake during pregnancy. We aimed to investigate the dynamics of anti-SARS-CoV-2 antibody levels following SARS-CoV-2 infection during pregnancy, and characterize the effect of a single post-infection boosting dose in parturients, as compared to naïve vaccinated and convalescent, non-boosted parturients. Methods Serum samples prospectively collected from parturients and umbilical cords at delivery in our university-affiliated urban medical center in Jerusalem, Israel from May-October, 2021, were selected and analyzed in case-control manner. Study groups were comprised of 1: Consecutive sample of parturients with PCR-confirmed history of COVID-19 disease at all stages of pregnancy; 2: Comparison groups selected by time of exposure, a: PCR-confirmed COVID-19 convalescent non-boosted parturients; b: PCR-confirmed COVID-19 convalescent parturients who received a single BNT162b2 mRNA vaccine boosting dose; and c: infection-naïve fully vaccinated parturients who received two doses of BNT162b2 mRNA vaccine. Outcome measures included maternal and cord blood anti-SARS-CoV-2 antibody levels detected at delivery, reported side effects, and pregnancy outcomes. Results 228 parturients aged 18-45 years were included: 64 were studied to characterize titer dynamics following COVID-19 at all stages of pregnancy; boosting effect was determined by comparing a: convalescent (n=54); b: boosted convalescent (n=60); and c: naïve fully vaccinated (n=114) parturients. Anti-SARS-CoV-2 antibody levels detected upon delivery showed a gradual and significant decline over time from infection to delivery (r = 0.4371; p = 0.0003). Of gravidae infected in the first trimester 34.6% (9/26) tested negative at delivery, vs. 9.1% (3/33) following second trimester infection (p=0.023). Significantly higher anti-SARS-CoV-2 antibody levels were observed among boosted convalescent vs. non-boosted convalescent (17.6 fold, p<0.001) and naïve vaccinated parturients (3.2 fold, p<0.001). Similar patterns were observed in cord blood. Side effects in convalescent gravidae resembled previous reports of mild symptoms following COVID-19 vaccination during pregnancy. Conclusions Post-infection maternal humoral immunity wanes during pregnancy, resulting in low or absent protective titers for a significant proportion of patients. A single boosting dose of BNT162b2 mRNA vaccine induced a robust increase in protective titers for both mother and newborn with modest reported side effects.

Anti-SARS-CoV-2 antibody levels detected upon delivery showed a gradual and significant 76 decline over time from infection to delivery (r = 0.4371; p = 0.0003). Of gravidae infected in the 77 first trimester 34.6% (9/26) tested negative at delivery, vs. 9.1% (3/33) following second 78 trimester infection (p=0.023). Significantly higher anti-SARS-CoV-2 antibody levels were 79 observed among boosted convalescent vs. non-boosted convalescent (17.6 fold, p<0.001) and 80 naïve vaccinated parturients (3.2 fold, p<0.001). Similar patterns were observed in cord blood. 81 Side effects in convalescent gravidae resembled previous reports of mild symptoms following 82 COVID-19 vaccination during pregnancy. The COVID-19 pandemic remains an ongoing and evolving threat, with novel variants emerging 93 across the globe. 1 As the pandemic evolves we learn that decline in anti-SARS-CoV-2 antibody 94 titers 2 and the emergence of new variants, challenge our long lasting immunity following 95 primary infection 3 . Importantly, recent data have indicated that a single boosting dose of an 96 mRNA vaccine significantly enhances resistance against variants of concern, including the supports the notion that pregnancy is a time of immune system modulation, affecting many 126 aspects of the maternal immune response, including the humoral response 18, 19 . 127 In the present study we aimed to provide essential data regarding the dynamics of anti SARS- significantly increase the uptake of immunization in the peripartum period and augment 295 immunity for parturients and offspring. 296 We also examined patient-reported side effects of post-COVID-19 vaccine boosting in 297 pregnancy. We found that most reports did not differ from those of naïve vaccinees during 298 pregnancy among our cohort. In fact, there were lower rates of myalgia, injection site pain, and level. This patient delivered two weeks following boosting. We speculate that the time elapsed 470 from boosting dose to delivery was insufficient for optimal vertical transmission. Significant 471 difference between maternal and cord blood antibodies within the same group was determined 472 by a Wilcoxon matched-pairs signed rank test, ***p < 0.001, ****p < 0.0001. Significant 473 differences between maternal vs. maternal (# p < 0.0001) and cord blood vs. cord blood ($$ p < 474 0.0001) groups were found only when comparing titers to convalescent titers; (Kruskal-Wallis 1-475 way ANOVA test, following by Dunn's all-pairwise comparisons test). B. Maternal (M) and cord 476 blood (C) sera neutralizing activity, reflected by NT50 values (see Methods section), presented 477 as maternal-cord pairs. Significant difference between maternal and cord blood neutralizing 478 activity within the same group was determined by a Wilcoxon matched-pairs signed rank test, 479 and unpaired t test for comparisons between groups **p < 0.01, *p < 0.05. Interval between delivery and postpartum sampling in weeks

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Data are presented as % or median (inter quartile range, IQR); Continuous parameters were analyzed by Kruskal-Wallis 1-way ANOVA test