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High antibody levels in cord blood from pregnant women vaccinated against COVID-19

Published:September 21, 2021DOI:https://doi.org/10.1016/j.ajogmf.2021.100481
      OBJECTIVE: Current data suggest that the transplacental passage of immunoglobulin (Ig) G antibodies to the SARS-CoV-2 virus occurs following natural infection,
      • Flannery DD
      • Gouma S
      • Dhudasia MB
      • et al.
      Assessment of maternal and neonatal cord blood SARS-CoV-2 antibodies and placental transfer ratios.
      and there is emerging evidence that antibody transfer may occur following COVID-19 messenger RNA (mRNA) vaccination.
      • Mithal LB
      • Otero S
      • Shanes ED
      • Goldstein JA
      • Miller ES.
      Cord blood antibodies following maternal coronavirus disease 2019 vaccination during pregnancy.
      • Gray KJ
      • Bordt EA
      • Atyeo C
      • et al.
      Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study.
      • Collier A-RY
      • McMahan K
      • Yu J
      • et al.
      Immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women.
      However, existing studies analyzed antibodies to the spike protein (anti-S IgG) alone, which could be present either after natural infection or vaccination. They do not include antibodies to the nucleocapsid protein (anti-N IgG), which is only present following natural infection.
      Centers for Disease Control and Prevention
      Interim guidelines for COVID-19 antibody testing.
      This study aimed to determine the presence of transplacental antibody transmission and the levels of detectable antibodies in cord blood in women vaccinated against COVID-19 during pregnancy.
      STUDY DESIGN: This was an institutional review board-approved prospective study of pregnant women who received at least 1 dosage of either mRNA COVID-19 vaccine, that is, from Pfizer/BioNTech (Mainz, Germany) or Moderna (Cambridge, MA), from the time of the US Food and Drug Administration Emergency Use Authorization till June 4, 2021. Eligible women were identified through a search of the electronic medical records and recruited via email. Informed consent was obtained electronically. The umbilical cord blood was collected at delivery and analyzed for both anti-N and anti-S IgG.
      IgG anti-N antibodies were analyzed using the Abbott SARS-CoV-2 assay (Abbott Laboratories, Abbott Park, IL) on the ARCHITECT i system (Abbott Laboratories, Abbott Park, IL) using chemiluminescent microparticle immunoassay. The results were considered positive if the index (S/C) was ≥1.4. Anti-S antibodies were tested by Viracor laboratories (Lee's Summit, MO) using Elecsys anti-SARS-CoV-2 assay (Roche Diagnostics, Basel, Switzerland) on the cobas e analyzers. The assay predominantly detected IgG, but it also detected IgA and IgM antibodies, providing semiquantitative results in units per mililiter. The samples with reactivity ≥0.8 U/mL were considered positive. When the sample result exceeded the upper limit of the analytical measurable interval (250 U/mL), the results were reported as >250 U/mL.
      The charts were reviewed for maternal demographics, vaccination information, gestational age at delivery, and antibody results. The time interval between the administration of the second vaccine injection and delivery was calculated. Descriptive analyses were performed using R Version 4.0.2 (Boston, MA).
      RESULTS: The maternal characteristics and vaccination information are shown in the Table. The umbilical cord blood was collected from 36 deliveries. All 36 neonates (100%) were positive for anti-S IgG at high titers—34 with a titer of >250 U/mL and 2 with titers of 201 U/mL and 249 U/mL, respectively.The median interval from the completion of the vaccine series to delivery was 13 weeks, with the range being 5.9 to 24.9 weeks. Both the mothers of the neonates that had cord blood titers <250 U/mL received their second vaccine dosage >20 weeks before delivery. Furthermore, 3 women had an interval of >20 weeks from vaccination to delivery, and their neonates had anti-S IgG titers >250 U/mL. Among the 36 samples, 31 were also tested for anti-N IgG; all were negative. All but 1 of the subjects received both the doses of their mRNA vaccines before delivery. The neonate born to the woman who received only 1 dosage was still positive for anti-S IgG at a titer of >250 U/mL.
      TableMaternal characteristics and vaccination information of the study cohort
      Trostle. COVID-19 antibodies in cord blood. Am J Obstet Gynecol MFM 2021.
      CharacteristicValue (N=36)
      Age (y)35.5 (26–46)
      Body mass index (kg/m2)29.9 (23.1–45.0)
      History of COVID-19 infection0 (0)
      Vaccine type
       Pfizer/BioNTech26 (72)
       Moderna10 (28)
      Trimester of vaccine initiation
       First2 (6)
       Second30 (83)
       Third4 (11)
      Interval from second vaccine to delivery (wk)13.0 (5.9–24.9)
      Gestational age at delivery (wk)39.1 (36.3–40.4)
      Data are presented as number (percentage) or median (range).
      CONCLUSION: These findings demonstrate transplacental antibody transfer following mRNA COVID-19 vaccination during pregnancy, with 100% of cord blood specimens having high levels of anti-S antibodies. Given the combination of positive anti-S IgG and negative anti-N IgG, the neonatal antibodies were secondary to the vertical transfer of antibodies from maternal vaccination rather than natural infection. The moderately high anti-S IgG titers in the 2 women with a longer latency between vaccination and delivery suggests that cord blood antibody level may correlate with the interval of the time from vaccine administration to delivery. Further investigation is needed to determine if vaccination in the second half of pregnancy may confer higher levels of antibody transfer than vaccination earlier in pregnancy.
      Our data are novel as they distinguish between passive immunity from natural infection and immunity from mRNA vaccination by testing for anti-N IgG in our cohort of pregnant women. Other studies have evaluated the association of anti-S IgG levels with protection from COVID-19 illness and have determined that a high anti-S IgG level correlates with immune protection against SARS-CoV-2.
      • Feng S
      • Phillips DJ
      • White T
      • et al.
      Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection.
      The robust cord blood levels observed in our population suggest that the high degree of vertical transmission of these antibodies may protect the infant, at least in the neonatal period.This point is especially important, because after discharge, the infants may come into contact with family members or caretakers who have not received the vaccine (ie, siblings below the age threshold for vaccination). A limitation of this study is that we did not obtain maternal blood to correlate maternal and neonatal antibody levels, though others have found that a correlation may exist.
      • Mithal LB
      • Otero S
      • Shanes ED
      • Goldstein JA
      • Miller ES.
      Cord blood antibodies following maternal coronavirus disease 2019 vaccination during pregnancy.
      However, with the observed high levels in cord blood, such a correlation becomes less clinically relevant.
      Recent data suggest that only 16.3% of pregnant women have been vaccinated, despite the evidence of prenatal vaccine safety.
      • Razzaghi H
      • Meghani M
      • Pingali C
      • et al.
      COVID-19 vaccination coverage among pregnant women during pregnancyeight integrated health care organizations, United States, December 14, 2020-–May 8, 2021.
      Most of the guidance on the importance on vaccination during pregnancy stems from the concern for pregnancy as a risk factor for severe COVID-19 illness in the mother. Our findings add to a growing list of the important reasons why women should be advised to receive the COVID-19 vaccine during pregnancy, indicating its neonatal benefit and potential protection from COVID-19 illness in the first days of life. Future study should focus on vertical antibody transmission in a larger population and the durability of antibody detection during infancy.

      Acknowledgments

      The authors would like to thank Gerard Kick, the director of operations at the clinical laboratories at New York University Langone Health; he worked to make this antibody testing possible.

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