Utilizing residual antenatal sera to investigate antibody responses to coronaviruses in pregnancy

SARS-CoV-2 emerged in a population with prior exposures and pre-existing immune responses to the seasonal human coronaviruses (HCoV). Because SARS-CoV-2 is closely related to HCoV, infection may preferentially recall memory responses against HCoV rather than generating antibody responses to SARS-CoV-2. This phenomenon, known as immune imprinting, may have beneficial or detrimental impacts on COVID-19 outcomes. As pregnant individuals are at increased risk of severe COVID-19 and adverse pregnancy outcomes, how pre-existing HCoV immunity shapes immune responses to SARS-CoV-2 in pregnancy is important to understand. The objective was to investigate how pre-existing HCoV antibody responses influence antibody responses following SARS-CoV-2 infection and/or vaccination, and their association with clinical outcomes in pregnancy. To address this, four observational cohorts with well-characterized infection and vaccination exposures were assembled by linking residual antenatal sera to laboratory and clinical data. Serum antibody levels to HCoV and SARS-CoV-2 were analyzed at both individual and population levels and correlated with antibody function and clinical outcomes. The findings suggested that pre-existing antibody responses to HCoV influenced the antibody response to SARS-CoV-2. Following acute SARS-CoV-2 infection, recall-like antibody response patterns were observed and associated with HCoV antibody levels. Stronger antibody responses to SARS-CoV-2 were also associated with higher pre-existing HCoV antibody levels. Elevated beta-HCoV antibody responses were observed following SARS-CoV-2 exposure at both individual and population-levels and were associated with more severe COVID-19 in pregnancy. This may reflect higher antibody responses associated with increased disease severity, antibody cross-reactivity and/or imprinting. SARS-CoV-2 infection and vaccination exhibited distinct antibody profiles, with vaccination eliciting stronger SARS-CoV-2-specific responses while infection was associated with broader HCoV responses. These patterns manifested as a sustained shift toward higher HCoV antibody levels over three years, suggesting that SARS-CoV-2 exposure has reshaped the broader coronavirus antibody landscape at the population-level. Understanding how repeated coronavirus exposures shape population-level immune responses, combined with the ability to assess functional activity and correlate these findings with clinical outcomes during pregnancy, remains important for public health and pandemic preparedness. Our findings, combined with antenatal sera and linked administrative and clinical outcome data in pregnancy, provides insights into studying the complexity of coronavirus immune responses.