Longitudinal serological detection of exposure to SARS-CoV-2 in a cohort of pregnant women in Malawi: a secondary analysis from a randomised controlled trial.

Abstract

To investigate whether IgG to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens could reveal undetected SARS-CoV-2 exposure in a cohort of Malawian pregnant women participating in the REVAMP clinical trial. A secondary analysis of serological samples from a randomised controlled trial of iron supplementation in pregnancy, which began recruiting women in November 2018 and had its last visit occurring in September 2021. Resource-limited setting in Zomba and Blantyre, Southern Malawi. Pregnant women with ultrasound-confirmed singleton pregnancies in the second trimester, with haemoglobin <100 g/L and randomised at enrolment to receive either intravenous ferric carboxymaltose or standard oral iron, where no coronavirus disease 2019 (COVID-19) clinical cases or SARS-CoV-2 positive tests were reported during the pandemic (April 2020-September 2021). Primary outcome was the levels of antibodies and seropositivity to SARS-CoV-2 antigens in the cohort of women across the duration of the trial. Secondary outcomes were the impact of IgG levels and seropositivity to SARS-CoV-2 on pregnancy outcomes. At delivery, IgG levels to SARS-CoV-2 antigens increased sharply by 18.5%-29.7% every 30 days during COVID-19 waves 2 and 3. Overall seropositivity reached 39.3% during the pandemic; however, 14.7% pre-pandemic seropositivity demonstrates cross-reactive antibody responses. Pandemic pregnancies showed improved outcomes with longer gestations (mean difference: 0.6 weeks (95% CI 0.2 to 0.9)) and higher birth weights (mean difference: 169.3 g (65.9-272.6)). SARS-CoV-2 IgG levels were not associated with pregnancy outcomes. Serological testing was able to detect exposure to SARS-CoV-2 in a population without clinical indications of the disease, suggesting that serosurveillance is more sensitive than relying on clinical data to monitor pathogen exposure in the community. Additionally, this highlights pregnancy cohorts as valuable sentinel populations for infectious disease surveillance in resource-limited settings. This trial was prospectively registered at ANZCTR: ACTRN12618001268235.