key: cord-0847357-hoqcd9wp
authors: Rottenstreich, A.; Zarbiv, G.; Oiknine-Djian, E.; Zigron, R.; Wolf, D. G.; Porat, S.
title: Efficient maternofetal transplacental transfer of anti- SARS-CoV-2 spike antibodies after antenatal SARS-CoV-2 BNT162b2 mRNA vaccination
date: 2021-03-12
journal: nan
DOI: 10.1101/2021.03.11.21253352
sha: 542b34f176fc5fe4a26da61249bb395b2b0ede54
doc_id: 847357
cord_uid: hoqcd9wp

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy and early infancy can result in severe disease. Evaluating the serologic response after maternal vaccination during pregnancy and subsequent transplacental antibody transfer has important implications for maternal care and vaccination strategies. Objective To assess maternal and neonatal SARS-CoV-2 antibody levels after antenatal mRNA vaccination. Design, Setting, and Participants This study took place at Hadassah Medical Center in Jerusalem, Israel in February 2021. Maternal and cord blood sera were collected for antibody measurement from mother/newborn dyads following antenatal vaccination. Exposure SARS-CoV-2 BNT162b2 mRNA vaccination. Main outcome and measures Spike protein (S) and receptor binding domain (RBD)- specific, IgG levels were evaluated in maternal and cord blood sera. Results The study cohort consisted of 20 parturients, with a median maternal age of 32 years and a median gestational age of 393/7 weeks at the time of delivery. The median time lapsed from the first and second doses of vaccine administration until delivery was 33 [IQR 30-37] and 11 [IQR 9-15] days, respectively. Of the 20 dyads, all women and infants were positive for anti S- and anti-RBD-specific IgG. Anti-S and anti-RBD-specific IgG levels in maternal sera were positively correlated to their respective concentrations in cord blood (Rs= 0.72; P<0.001 and Rs = 0.72; P <0.001, respectively). Anti-S and anti-RBD-specific IgG titers in cord blood were directly correlated with time lapsed since the administration of the first vaccine dose (Rs = 0.71; P =0.001 and Rs= 0.63; P=0.004, respectively). Conclusion and Relevance In this study, SARS-CoV-2 mRNA vaccine administered during pregnancy induced adequate maternal serologic response with subsequent efficient transplacental transfer. Our findings highlight that vaccination of pregnant women may provide maternal and neonatal protection from SARS-CoV-2 infection.

The rapidly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has afflicted over 113 million individuals resulting in over 2.5 million deaths, since it was declared a pandemic by the World Health Organization on March 2020. The pressing need for effective tools to combat Coronavirus Disease 19 (COVID-19) has led to the accelerated development and recent approval of several targeted vaccines including two novel mRNAbased vaccines [1, 2] . A mass vaccination campaign using the BNT162b2 mRNA vaccine has commenced in Israel in December 2020.

Pregnant women are at higher risk for COVID-19 related illness [3, 4] . In addition, recent data show that severe SARS-CoV-2 infection is more common among infants as compared to older children [4, 5] Nevertheless, as pregnant women were excluded from the pivotal trials evaluating the aforementioned vaccines [1, 2] , their safety and efficacy in the setting of pregnancy remain unknown.

Despite these uncertainties and given the risk for severe disease course, the Center for Disease Control and Prevention (CDC), the world Health Organization (WHO), and other agencies support offering pregnant women to receive the SARS-CoV-2 vaccine following shared decision making [6, 7] . Due to the paucity of literature and the high clinical relevance, we aimed to investigate the maternal serologic response after SARS-CoV-2 vaccination during pregnancy and its related subsequent transplacental antibody transfer.

A prospective study following women admitted for delivery was performed in February 2021 at Hadassah Medical Center, a university affiliated hospital in Jerusalem, Israel. Women who received two doses of SARS-CoV-2 BNT162b2 mRNA vaccine during pregnancy were eligible for this study. Demographic and clinical data, were collected at the time of All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in 

Following delivery, maternal and cord blood sera were collected for antibody measurement.

Spike protein (S) (Liaison SARS-CoV-2 S1/S2 IgG, DiaSorin, Saluggia, Italy) and receptor binding domain (RBD)-specific (Architect SARS-CoV-2 IgG II Quant assay, Abbott Diagnostics, Chicago, USA), IgG levels were evaluated in maternal and cord blood sera.

Maternal and cord blood sera were also tested for SARS-CoV-2 IgM (Liaison, DiaSorin, Saluggia, Italy).

Patient characteristics are described as proportions for categorical variables and medians and interquartile range (IQR) for continuous variables without a normal distribution. Antibody levels and placental transfer ratios are expressed as medians and IQR. Correlations were reported using the Spearman's test with the correspondent s and P values. The data were analyzed using Software Package for Statistics and Simulation (IBM SPSS version 24, IBM Corp, Armonk, NY).

During the study period, 20 parturients who received two doses of SARS-CoV-2 BNT162b2 mRNA vaccine were approached and agreed to participate. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in 

We measured SARS-CoV-2 anti-S and anti-RBD IgG in 20 mother/newborn dyads at a single center in Israel, following antenatal SARS-CoV-2 BNT162b2 mRNA vaccination. IgG antibodies were detected in all 20 maternal and cord blood sera. The current study finding may support the role of vaccination of pregnant women to induce both maternal and neonatal immunity.

Currently, there is lack of data regarding SARS-CoV-2 vaccination among pregnant women in terms of safety and efficacy. In addition, the degree of transplacental passive immunity induced by maternal SARS-CoV-2 vaccination is unestablished. In this regard, studies among pregnant women with SARS-CoV-2 infection reported conflicting results [8, 9] , with some suggesting compromised transplacental transfer of naturally acquired antibodies [9], questioning the potential role of vaccination during pregnancy to confer neonatal protection against COVID-19. All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in Finally, larger studies are warranted to better assess the safety and efficacy of the different SARS-CoV-2 vaccines in the setting of pregnancy. All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in This study has several caveats, including its small sample size and single-site nature. In addition, the association between gestational age at delivery with transplacental transfer requires further investigation. Moreover, as previously stated, the effect of SARS-CoV-2 vaccination at different times throughout gestation remains to be explored.

Our findings demonstrate that antenatal SARS-CoV-2 vaccination induces an adequate maternal serologic response and has the potential to provide neonatal protection through transplacental transfer of vaccine-stimulated maternally-derived antibodies. These encouraging results have important implications for maternal care and the development of appropriate vaccination strategies. Further studies will be needed to better delineate the safety and efficacy of the different maternal SARS-CoV-2 vaccines available and better define transplacental antibody dynamics at earlier gestational ages.

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine

Efficacy and safety of the mRNA-1273 SARSCoV-2 vaccine

Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status -United States

CDC COVID-19 Response Pregnancy and Infant Linked Outcomes Team; COVID-19 Pregnancy and Infant Linked Outcomes Team (PILOT)

COVID-NET Surveillance Team. Hospitalization rates and characteristics of children aged <18 years hospitalized with laboratory-confirmed COVID-19-COVID-NET, 14 states

COVID-19 (coronavirus disease): people with certain medical conditions

The coronavirus disease 2019 vaccine in pregnancy: risks, benefits, and recommendations

Dr Rottenstreich had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.Concept and design: Porat, Rottenstreich, Wolf. Acquisition, analysis, or interpretation of data: All authors.Drafting of the manuscript: Rottenstreich, Zigron, Zarbiv, Porat, Wolf.Laboratory analyses: Oiknine-Djian, Wolf.Statistical analysis: Rottenstreich.All authors read and approved the final manuscript.

All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in Naama Lessens and Dr. Roy Alter for their assistance in patients' enrollment. We also thank Rimma Barsuk and Yulia Yachnin for their technical assistance..

The authors declare that they have no conflicts of interest.

No external funding was used for this study.All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted March 12, 2021. ; https://doi.org/10.1101/2021.03.11.21253352 doi: medRxiv preprint All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The dotted lines are the 95% confidence intervals.All rights reserved. No reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted March 12, 2021. ; https://doi.org/10.1101/2021.03.11.21253352 doi: medRxiv preprint