Adverse Birth Outcomes Associated with SARS-CoV-2 Infection Among Pregnant Women with and without HIV: A Longitudinal Cohort Study

Introduction Both COVID-19 disease and HIV infection in utero are associated with increased risk of adverse pregnancy outcomes. However, there is limited evidence on the impact of mild SARS-CoV-2 infection during pregnancy in sub-Saharan Africa, particularly among women living with HIV (WLWH), who may face heightened risk of adverse effects due to immune dysregulation and elevated obstetric risks. Methods We conducted a prospective cohort study of pregnant women enrolled at 20–36 weeks gestation at two health facilities in southern Malawi between 2018 and 2022. SARS-CoV-2 infection was determined via serologic testing at enrollment and delivery. Participants were enrolled into three groups based on HIV status and viral suppression: (1) WLWH with detectable viral load (VL), (2) WLWH with undetectable VL, and (3) HIV-negative women. We used multivariable logistic regression with adjustment for confounding to evaluate the impact of SARS-CoV-2 infection on the following adverse birth outcomes: low birth weight (LBW), preterm birth, small-for-gestational-age (SGA), stillbirth or early neonatal death, and a composite outcome. We further assessed any interaction between SARS-CoV-2 infection and HIV infection on adverse birth outcomes. Results Among 905 women, 29% tested positive for SARS-CoV-2 during pregnancy. Most (87%) infections were mild or asymptomatic. In the total population, SARS-CoV-2 infection was significantly associated with SGA births (adjusted OR [aOR]: 1.49, 95% CI: 1.03–2.13) but was not associated with other adverse outcomes. Among WLWH, SARS-CoV-2 positivity was significantly associated with increased odds of LBW (aOR: 2.07, 95% CI: 1.10–3.91) and SGA births (aOR: 1.73, 95% CI: 1.01–2.91). The effect of SARS-CoV-2 infection among WLWH did not differ based on VL. Conclusion Mild SARS-CoV-2 infection during pregnancy was associated with adverse birth outcomes, particularly among WLWH, suggesting HIV-related immune modulation may heighten vulnerability to adverse pregnancy outcomes in the context of other infectious exposures. These findings underscore the need for integrated antenatal care and targeted infection prevention strategies for pregnant women with HIV in high-burden settings. Additionally, in light of recent changes in recommendations for COVID-19 vaccinations, these findings highlight the ongoing need for infection prevention among pregnant women globally.