Life Course Malaria Exposure and SARS-CoV-2 Seroepidemiology in Ugandan Adolescents: A Longitudinal Study Nested in a...

COVID-19 has had major global health impacts, yet reported morbidity and mortality have been lower in Africa despite serological evidence of widespread infection. Malaria has been proposed as a potential modifier of susceptibility to and outcomes of SARS-CoV-2 infection. We investigated whether prospectively measured life-course malaria exposure was associated with serologically defined SARS-CoV-2 infection among adolescents in a malaria-endemic setting and explored symptomatic COVID-19 during follow-up.

We conducted a longitudinal study nested within the Entebbe Mother and Baby Study birth cohort in Uganda. Adolescents were enrolled and followed up 6 and 12 months later. Blood samples were collected at each visit for SARS-CoV-2 serology. Malaria exposure was defined using prospectively collected data on clinical malaria (from birth to 10 years), asymptomatic parasitaemia at annual visits and antibody responses to Plasmodium falciparum merozoite surface protein 2 (PfMSP-2) and apical membrane antigen 1 (PfAMA-1). The primary outcome was SARS-CoV-2 seropositivity, based on spike and nucleocapsid IgG responses, with seropositivity cut-offs derived from pre-pandemic samples. Secondary outcomes, including antibody concentrations and symptomatic PCR-confirmed disease, were explored. Vaccinated participants were excluded from subsequent serological analyses. Logistic and linear regression models assessed associations with seropositivity and log₁₀-transformed antibody concentrations, adjusting for key demographic, socioeconomic and exposure-related confounders.

Between August and November 2021, 476 adolescents (mean age 16.4 years (SD = 0.75); 205 (43.1%) female) were enrolled. Overall, 12.0% had ever had asymptomatic parasitaemia, and 61.3% had experienced clinical malaria. SARS-CoV-2 seropositivity among unvaccinated participants increased from 63% at baseline to 89.3% at 6 months and 94.9% at 12 months; no PCR-positive cases were reported. Multivariable analyses showed no consistent association between malaria exposure and SARS-CoV-2 seropositivity or antibody concentration levels.

We found no consistent evidence that life-course malaria exposure was associated with SARS-CoV-2 infection as measured by serology or antibody levels.