The COVID-19 pandemic caused major global health and economic disruption, yet many African countries reported relatively high numbers of mild or asymptomatic cases. Although underreporting and limited testing complicate estimates of the true burden, researchers have explored whether immune and genetic factors in African populations may help explain these patterns.
A systematic review following PRISMA guidelines analysed studies published between 2019 and January 2026 that investigated immune responses and host genetic variation linked to COVID-19 in African populations. Searches across PubMed, Scopus, and African Journals Online identified more than 4,000 records, of which 40 studies met the inclusion criteria. These studies covered 19 African populations and examined cytokine responses, T-cell activity, antibody responses, and host genetic variants.
Many studies reported evidence of pre-existing immunity, including cross-reactive antibodies and diverse T-cell responses. These immune patterns may be influenced by prior exposure to pathogens such as malaria parasites, helminths, and other coronaviruses. Severe COVID-19 cases were associated with increased inflammatory cytokines, including IL-6, TNF-α, and IFN-γ, while asymptomatic individuals tended to show milder and broader immune responses. Antibody responses were generally strong across different disease severities.
Genetic studies also identified several variants that may influence susceptibility. Certain HLA alleles were linked to either increased risk or protection against severe disease, while polymorphisms in the ACE2 receptor gene, important for viral entry, were associated with differences in receptor expression and potential disease outcomes.
Overall, the review suggests that a combination of immune history and genetic variation may have contributed to differences in COVID-19 severity observed across African populations.
Journal article: Manu, P.G., et al. 2026. Reduced COVID-19 Severity in Africa: A Systematic Review of Host Genetic and Immunological Responses to SARS-CoV-2 Infection. Frontiers Immunology.
Summary by Stefan Botha
