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Maternal hybrid immunity to SARS-CoV-2 during pregnancy provides more durable infant antibody responses compared to natural infection alone

Presenter: Associate Professor, Sylvia M. LaCourse, MD, MPH, University of Washington, Seattle, WA, United States.


In infants up to 6 months of age born to women with prior SARS-CoV-2 infection, infection alone did not provide persistent antibody responses, in a study reported in an oral presentation at ID Week 2023. More durable antibody response was provided by maternal hybrid immunity (vaccine + infection), according to associate professor Sylvia M. LaCourse, MD, MPH, University of Washington, Seattle, WA, United States.

In pregnancy, SARS-CoV-2 infection is associated with increased risk of severe COVID-19 disease, intensive care unit admission, and death. COVID-19 vaccination has been shown to be safe in pregnancy and is recommended, even with previous SARS-CoV-2 infection. Infants less than 6 months of age are not eligible for COVID-19 vaccination, and for protection they rely on maternally derived antibodies. While immunity from natural infection and vaccination (“hybrid immunity”) appears to provide more durable SARS-CoV-2 antibody responses in the general population, whether hybrid immunity from both natural infection and vaccination in mothers provides more durable SARS-CoV-2 antibody responses in infants has remained not well characterized, LaCourse said.

She and colleagues enrolled a prospective cohort of 107 pregnant women (median age 32 years, interquartile range [IQR] 30–35) with prior SARS-CoV-2 infection (anti-nucleocapsid [anti-N] IgG-positive on enrollment or prior reverse transcriptase polymerase chain reaction-positive or antigen-positive testing from the medical record) from January 2021 through August 2022. Investigators collected blood samples during pregnancy, at delivery or birth, at 0 to less than 3 months, and at 3 to 6 months, testing for anti-spike (anti-S) IgG by Abbott Architect (positive: ≥ 50 AU/mL) and neutralizing antibodies (serum dilution inhibited infection by 50% [ND50 heat] ≥ 20 and R2 ≥ 0.9).

COVID-19 severity was characterized as asymptomatic in 27%, mild or moderate in 71%, and severe or critical in 2%. Median gestational age at enrollment was 31 weeks (IQR 19.1–37.9). Median time from SARS CoV-2 diagnosis at delivery was 19.7 weeks (IQR 19.1–37.9). At delivery, LaCourse reported, 35% of women were unvaccinated (infection alone) and 65% had one or more vaccination (hybrid immunity—vaccine plus infection). Also at delivery, LaCourse said, both unvaccinated participants and their infants were less likely to have anti-S IgG (maternal 87%, cord 86%) or neutralizing antibodies (maternal 86%, cord 75%) than vaccinated participants and their infants (maternal and cord both 100% anti-S IgG-positive and neutralizing antibodies, all P ≤ .01).

The proportion of infants of mothers who remained unvaccinated at birth who still had anti-S IgG had declined by 6 months to 50%, and those who still had  neutralizing antibody declined to 14%, compared with 100% (anti-S IgG and neutralizing antibody) among infants with vaccinated mothers (all P < .01). Also, median antibody levels at birth were lower among infants born to unvaccinated mothers than among infants with mothers vaccinated prior to delivery (anti-S IgG log10 2.95 vs 4.40 AU/mL; neutralization log10 1:2.37 vs 1:4.00, all P < .01). The patterns persisted through 6 months of age (anti-S IgG log10 1.95 vs 3.84 AU/mL, P < .01; log10 neutralization 1:1.34 vs 1:3.20, P = .11).

LaCourse also pointed out that with later-gestation SARS CoV-2 infection, the likelihood of neutralizing antibodies at birth was lower than with earlier infections.

LaCourse and colleagues concluded that SARS-CoV-2 infection alone during pregnancy did not provide persistent antibody responses in infants through 6 months of age. “Maternal vaccination provided more durable antibody responses in participants with prior SARS-CoV-2 than infection alone during pregnancy. Vaccination potentially provides protection to vulnerable infants in the months prior to their own COVID-19 vaccine eligibility,” Lacourse added.

Disclosures. Dr. LaCourse has disclosed grant support from Merck through the Investigator Studies Program for this work.

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