Cord blood IgA/M reveals in utero response to SARS-CoV-2 with fluctuations in relation to circulating variants

It is estimated that in utero SARS-CoV-2 infection is rare. However, few studies have systematically assessed for IgA and IgM antibodies indicating potential in utero response to SARS-CoV-2 infection using multi-isotype serology, and no studies have assessed in utero infection markers in relation to circulating variants. Between October 21, 2021 and February 15, 2023, remnant cord blood samples (CBS) from neonates born at a single hospital in Los Angeles, were systematically tested for serological markers suggesting in utero infection. SARS-CoV-2 specific fetal IgA and/or IgM antibodies were detected in 28.7% (298/1038 CBS, 95% CI: 26.0, 31.6), higher than previous in utero infection estimates that used only PCR and/or IgM. Importantly, the probability of detecting markers of in utero infection varied by month (P-value = 0.0144). The prevalence of fetal IgA/IgM varied with the emergence of new variants, increasing during the BA.1 wave with a peak in February 2022 at 36% (18/50, 95% CI: 22.7-49.3) and again during the BA.4/5 wave, with a peak at 48.8% in September 2022 (39/80, 95% CI 37.8-59.7), suggesting variant-related fluctuations. These data suggest it may be useful to identify SARS-Cov-2 in utero exposure at birth so these newborns may be more closely followed for adverse clinical outcomes.