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ImportanceCOVID-19 vaccination is recommended during pregnancy for the protection of the mother. Little is known about the immune response to booster vaccinations during pregnancy. ObjectiveTo measure immune responses to COVID-19 primary and booster mRNA vaccination during pregnancy and transplacental antibody transfer to the newborn. DesignProspective cohort study of pregnant participants enrolled from July 2021 to January 2022, with follow up through and up to 12 months after delivery. SettingMulticenter study conducted at 9 academic sites. ParticipantsPregnant participants who received COVID-19 vaccination during pregnancy and their newborns. Exposure(s)Primary or booster COVID-19 mRNA vaccination during pregnancy. Main Outcome(s) and Measure(s)SARS-CoV-2 binding and neutralizing antibody (nAb) titers after primary or booster COVID-19 mRNA vaccination during pregnancy and antibody transfer to the newborn. Immune responses were compared between primary and booster vaccine recipients in maternal sera at delivery and in cord blood, after adjusting for days since last vaccination. ResultsIn this interim analysis, 167 participants received a primary 2-dose series and 73 received a booster dose of mRNA vaccine during pregnancy. Booster vaccination resulted in significantly higher binding and nAb titers, including to the Omicron BA.1 variant, in maternal serum at delivery and cord blood compared to a primary 2-dose series (range 0.55 to 0.88 log10 higher, p<0.0001 for all comparisons). Although levels were significantly lower than to the prototypical D614G variant, nAb to Omicron were present at delivery in 9% (GMT ID50 12.7) of Pfizer and 22% (GMT ID50 14.7) of Moderna recipients, and in 73% (GMT ID50 60.2) of boosted participants (p<0.0001). Transplacental antibody transfer was efficient regardless of vaccination regimen (median transfer ratio range: 1.55-1.77 for binding IgG and 1.00-1.78 for nAb). Conclusions and RelevanceCOVID-19 mRNA vaccination during pregnancy elicited robust immune responses in mothers and efficient transplacental antibody transfer to the newborn. A booster dose during pregnancy significantly increased maternal and cord blood antibody levels, including against Omicron. Findings support continued use of COVID-19 vaccines during pregnancy, including booster doses. Trial Registrationclinical trials.gov; Registration Number: NCT05031468; https://clinicaltrials.gov/ct2/show/NCT05031468 Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the immune response after COVID-19 booster vaccination during pregnancy and how does receipt of a booster dose impact transplacental antibody transfer to the newborn? FindingsReceipt of COVID-19 mRNA vaccines during pregnancy elicited robust binding and neutralizing antibody responses in the mother and in the newborn. Booster vaccination during pregnancy elicited significantly higher antibody levels in mothers at delivery and cord blood than 2-dose vaccination, including against the Omicron BA.1 variant. MeaningCOVID-19 vaccines, especially booster doses, should continue to be strongly recommended during pregnancy.
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BackgroundHIV may increase SARS-CoV-2 infection risk and COVID-19 severity generally, but data are limited about its impact on postpartum women and their infants. As such, we characterized SARS-CoV-2 infection among mother-infant pairs in Nairobi, Kenya. MethodsWe conducted a nested study of 53 HIV-uninfected and 51 healthy women living with HIV, as well as their HIV-exposed uninfected (N=41) and HIV-unexposed (N=48) infants, participating in a prospective cohort. SARS-CoV-2 serology was performed on plasma collected between 1 May-31 December 2020 to determine the incidence, risk factors, and symptoms of infection. SARS-CoV-2 RNA PCR and sequencing was also performed on stool samples from seropositive participants. ResultsSARS-CoV-2 seropositivity was found in 38% of the 104 mothers and in 17% of the 89 infants. There was no significant association between SARS-CoV-2 infection and maternal HIV (Hazard Ratio [HR]=1.51, 95% CI: 0.780-2.94) or infant HIV exposure (HR=1.48, 95% CI: 0.537-4.09). Maternal SARS-CoV-2 was associated with a >10-fold increased risk of infant infection (HR=10.3, 95% CI: 2.89-36.8). Twenty percent of participants had symptoms, but no participant experienced severe COVID-19 or death. Seroreversion occurred in [~]30% of mothers and infants. SARS-CoV-2 sequences obtained from stool were related to contemporaneously circulating variants. ConclusionsThese data indicate that postpartum Kenyan women and their infants were at high risk for SARS-CoV-2 infection in 2020, and that antibody responses waned rapidly. However, most cases were asymptomatic and healthy women living with HIV did not have a substantially increased risk of infection or severe COVID-19.
