The association of neonatal SARS-CoV-2 anti-spike protein receptor-binding domain antibodies at delivery with infant SARS-CoV-2 infection under the age of 6 months: a prospective cohort study

Abstract

Objectives: The aim of this study was to assess the association between neonatal SARS-CoV-2 antibody level at delivery and infant SARS-CoV-2 infection under the age of 6 months and to identify predictive factors for neonatal antibody level at delivery.

Methods: In a prospective observational study, conducted between September 2021 and mid-February 2022, cord blood sera were tested for SARS-CoV-2 anti-spike receptor-binding domain antibodies after maternal BNT162b2 vaccination or infection. Infants were followed up for 6 months for SARS-CoV-2 infection.

Results: Sixty-seven mother-infant dyads were enrolled; nine of those did not meet the eligibility criteria. Of the 58 mother-infant dyads included, 6-month follow-up data were available for 57 mother-infant dyads. The mean ± standard deviation log SARS-CoV-2 anti-spike antibody level at delivery was lower among infants who were COVID-19 positive versus negative during follow-up (3.41 ± 0.74 AU/mL, n = 12; vs. 3.87 ± 0.84 AU/mL, n = 46; p 0.036); a log titre of ≥4.07 AU/mL (11 750) at delivery was associated with a significantly lower likelihood of infant infection (1/26 vs. 11/32 in infants with antibody level of <4.07 log AU/mL, OR = 0.076 [95% CI, 0.076, 0.64], p 0.018). A spline curve model showed a linear decrease in antibody levels when the last dose was administered at ≤30 weeks of gestation (50 days before delivery), after which the antibody levels increased (R² = 0.50). In multivariate analysis, more vaccine doses, prior maternal infection, and last administered dose at ≥31 weeks of gestation were associated with higher antibody levels at delivery.

Discussion: Higher anti-spike antibodies at delivery were associated with decreased risk of COVID-19 at the age of <6 months; the antibody level decreased linearly when the last dose was administered at ≤30 weeks of gestation. Future research should assess the effectiveness of a second booster during pregnancy against infant infection.

Keywords: Antibody; Cord blood; Maternal; Natural infection; mRNA vaccine.