Waning of the Humoral Response to SARS-CoV-2 in Pregnancy is Variant-Dependent

  1. Romina Plitman Mayo
  2. Tal Raz
  3. Bar Ben David
  4. Gila Meir
  5. Haim Barr
  6. Leonardo J. Solmesky
  7. Rony Chen
  8. Ana Idelson
  9. Lucilla Zorzetti
  10. Rinat Gabbay-Benziv
  11. Yuval Jaffe Moshkovich
  12. Tal Biron-Shental
  13. Gil Shechter-Maor
  14. Hen Yitzhak Sela
  15. Itamar Glick
  16. Hedi Benyamini Raischer
  17. Raed Salim
  18. Yariv Yogev
  19. Ofer Beharier
  20. Debra Goldman-Wohl
  21. Ariel Many
  22. Michal Kovo
  23. Simcha Yagel
  24. Michal Neeman
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Abstract

Importance

TheSARS-CoV-2 alpha variant posed increased risk for COVID-19 complications in pregnant women. However, its impact on the maternal humoral response and placental IgG transport remains unclear.

Objective

To characterize the maternal humoral waning and neonate immunity acquired during the 3rdCOVID-19 wave in Israel, dominated by the Alpha variant, as compared to earlier Wildtype infections and humoral response to vaccination across gestation.

Design

Maternal and fetal blood serum were collected at delivery since April 2020 from parturients. Sera IgG and IgM titers were measured using the Milliplex MAP SARS-CoV-2 Antigen Panel supplemented with additional HA-coupled microspheres.

Setting

A nationwide multicenter cohort study on SARS-CoV-2 infections and vaccination during pregnancy.

Participants

Expectant women presenting for delivery were recruited at 8 medical centers across Israel and assigned to 3 primary groups: SARS-CoV-2 positive (n= 157) and fully vaccinated during pregnancy (n= 125), and unvaccinated noninfected controls matched to the infected group by BMI, maternal age, comorbidities and gestational age (n =212). Eligibility criteria included pregnant women without active COVID-19 disease, age ≥18 years and willingness to provide informed consent.

Main Outcome(s) and Measure(s)

Pregnant women’s humoral response is dependent on the SARS-CoV-2 strain.

Results

The humoral response to infection as detected at birth, showed a gradual and significant decline as the interval between infection/vaccination and delivery increased. Significantly faster decay of antibody titers was found for infections occurring during the 3rdwave compared to earlier infections/vaccination. Cord blood IgG antigens levels correlated with maternal IgG. However, cord IgG-HA variance significantly differed in SARS-CoV2 infections as compared to the other groups. No sexual dimorphism in IgG transfer was observed. Lastly, high fetal IgM response to SARS-CoV-2 was detected in 17 neonates, all showing elevated IgM to N suggesting exposure to SARS-Cov-2 antigens.

Conclusions and Relevance

Infections occurring during the 3rdwave induced a faster decline in humoral response when compared to Wildtype infections or mRNA BNT162b2 vaccination during pregnancy, consistent with a shift in disease etiology and severity induced by the Alpha variant. Vaccination policies in previously infected pregnant women should consider the timing of exposure along pregnancy as well as the risk of infection to specific variants of concern.

Key Points

Question

What is the difference in the maternal-fetal humoral response between Alpha variant and SARS-CoV-2 Wildtype infections?

Findings

In this nationwide multicenter study including 494 pregnant women, the maternal humoral response to Alpha variant infection was weaker and shorter when compared to Wildtype infections. Placental transport compensated for the maternal waning of immunity. Fetal sex did not affect humoral response.

Meaning

Vaccination policies should be adjusted to account for the timing of infection and the SARS-CoV-2 variant.

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