Antibody surveillance provided valuable public health insights during the Coronavirus Disease 2019 (COVID-19) pandemic. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, vaccination, and cross-reactive responses from endemic coronaviruses (human coronaviruses [HCoVs]) can influence SARS-CoV-2 antibody responses, impacting reliability and interpretation of serological findings. Here, we investigated population-level SARS-CoV-2 and HCoV IgA and IgG responses following SARS-CoV-2 infection among unvaccinated and vaccinated pregnant individuals over 3 months. Using residual sera from routine antenatal screening of pregnant individuals in British Columbia between March 2020 to May 2022, we designed a retrospective repeated cross-sectional cohort of infected individuals either unvaccinated (UV + COV, N = 171) or two- to three-dose vaccinated (V + COV, N = 137). A total of 30 pre-pandemic sera served as negative controls. Sera were collected within 3 months of respiratory PCR-positivity in half-month intervals and tested for IgA and IgG against Spike (S) of alpha-HCoV (HCoV-229E, HCoV-NL63) and beta-HCoV (HCoV-HKU1, HCoV-OC43) and S, receptor binding domain, and nucleocapsid (N) of SARS-CoV-2 using a multiplex immunoassay. Following SARS-CoV-2 infection, V + COV had lower anti-N IgG levels ( P = 0.004) and seropositivity rates than UV + COV. One month post-infection, V + COV (38%) had lower anti-N IgA seropositivity than UV + COV (73%). Both groups had significantly higher anti-S IgA and IgG levels against beta-HCoV vs controls, with signals correlating positively with SARS-CoV-2 anti-S levels for each isotype. These results suggest that neither IgA nor IgG can reliably identify recent infections in vaccinated populations, emphasizing the importance of considering complex interplay of antibody responses when interpreting serological data and recognizing the potential and limitations of serological testing for diagnostics and surveillance. IMPORTANCE: This study provides key insights into how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination and infection shape the magnitude and longevity of IgA and IgG antibody responses following infection in pregnant individuals. It also highlights the interplay of serological responses to related viruses, such as the human coronaviruses. By leveraging population-level antenatal sera, our findings highlight important considerations for the design and interpretation of future seroprevalence studies, antibody-based surveillance, and diagnostic strategies. As SARS-CoV-2 transitions into endemic circulation, understanding the complexity of SARS-CoV-2 antibody responses provides additional insights into the strengths and limitations of serological data interpretation in a real-world setting.

Breast milk can provide passive immunity to infants, serving as a valuable source of maternal antibodies while remaining a non-invasive sample for investigating maternal immune responses. To date, no studies have evaluated SARS-CoV-2 and potentially cross-reactive HCoV antibodies in breast milk following bamlanivimab administration. A 36-year-old postpartum female was PCR-positive for SARS-CoV-2 four days post-delivery. Bamlanivimab was administered intravenously two days later. Breast milk was collected before bamlanivimab infusion, daily for two weeks post-infusion, then weekly until 102 days post-infusion. Mother and infant sera were collected only at 102 days post-infusion. All milk and serum samples were tested for IgG antibodies against SARS-CoV-2 and HCoV. We observed two distinct SARS-CoV-2 antibody peaks at days 3 and 29 post-infusion, likely representing bamlanivimab transfer and the post-infection antibody response. Beta-HCoV antibodies showed two peaks at days 6 and 29, potentially representing backboosted beta-HCoV responses and/or antibody cross-reactivity with SARS-CoV-2. Infant seropositivity for SARS-CoV-2 102 days post-infusion may represent antibodies from passive transfer via breastfeeding or a subclinical infection. This case highlights the value of breast milk as a non-invasive and repeatable sample to help understand maternal immune responses post-infection, exogenous antibody infusion, and passive antibody transfer during breastfeeding, which can provide insights into maternal–infant health research.

There is a limited understanding of the immunological differences between children and adults that protect children from developing severe coronavirus disease 2019 (COVID-19) following SARS-CoV-2 infection. Previous infection with endemic human coronaviruses (HCoVs) has been suggested as a factor. In this study, we used 100 paired residual samples collected before and during the COVID-19 pandemic from children in Bangladesh. We compared the changes in their sero-status (no COVID-19 vs. COVID-19) and quantified antibody levels to HCoVs. We found that although 45% of the children seroconverted for IgG antibodies against SARS-CoV-2, there was no correlation between evidence of previous infection with HCoVs and the magnitude of SARS-CoV-2 antibody responses post-infection. Moreover, no differences in the anti-HCoV antibody levels were found pre- and post-SARS-CoV-2 infection.