Tropical medicine & international health : TM & IH · 2026
Life Course Malaria Exposure and SARS-CoV-2 Seroepidemiology in Ugandan Adolescents: A Longitudinal Study Nested in a Birth Cohort.
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Zirimenya Ludoviko, Nayebare Doreen, Baine Claire, Nassuuna Jacent, Namutebi Milly, Zziwa Christopher, Nsubuga Denis, Kiwudhu Fred, Akello Florence, Tumusiime Josephine, Oduru Gloria, Kabami Grace, Akurut Hellen, Nakyesige Rachel, Natukunda Agnes, Wajja Anne, Lubyayi Lawrence, Kimuda Simon, Nkurunungi Gyaviira, Serwanga Jennifer, Doores Katie J, Webb Emily L, Elliott Alison M
Аннотация
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: We found no consistent evidence that life-course malaria exposure was associated with SARS-CoV-2 infection as measured by serology or antibody levels.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: We found no consistent evidence that life-course malaria exposure was associated with SARS-CoV-2 infection as measured by serology or antibody levels.