Authors

Discussion

Background: The emergence of the SARS-CoV-2 virus as a global pandemic has led to millions of deaths worldwide, yet Africa has shown notably lower infection and mortality rates compared to other continents. Various factors have been proposed to explain this difference, including demographic, lifestyle, and climatic variations. However, the role of the immune system, which plays a significant role in SARS-CoV-2 infection and COVID-19 outcomes, has been overlooked. Recent research suggests that pre-existing cross-reactive immune responses in African populations, potentially induced by previous exposure to other Human Coronaviruses (HCoVs) or endemic pathogens like Plasmodium falciparum, could contribute to this epidemiological pattern.

Methods: To investigate pre-existing cross-reactive immunity to SARS-CoV-2 in an African population, we conducted a cross-sectional study using pre-pandemic serum samples collected from adults living in Zimbabwe. Serum samples from four villages were analyzed for SARS-CoV-2 serological cross-reactivity using rapid diagnostic tests and screened for cross-reactivity with peptides from the proteomes of seven human coronaviruses. Peptide analysis revealed complex IgM and IgG response profiles against peptides from various coronaviruses, including the spike, nucleocapsid, and polyprotein 1AB proteins. Additionally, we compared identified peptides to the Human Immune Epitope Database (HIED) to assess potential cross-reactivity with antigens from endemic pathogens and food immunogens.

Findings: The overall prevalence of cross-reactivity with SARS-CoV-2 among pre-pandemic serum samples from two villages was 31.9%. Peptide analysis highlighted the presence of IgM and IgG responses against peptides across coronaviruses, with some peptides sharing motifs with antigens from pathogens endemic to Zimbabwe, including Trypanosoma spp and Plasmodium spp, as well as plant and food immunogens, and human autoantigens.

Interpretation: The implications of these cross-reactive antibodies on SARS-CoV-2 infection and COVID-19 outcomes remain uncertain. However, their presence underscores the importance of considering pre-existing immunity in interpreting SARS-CoV-2 seroepidemiology studies and evaluating COVID-19 vaccine efficacy in Africa. Further characterization of SARS-CoV-2 immune phenotypes and responses in African populations is warranted. This study sheds light on the potential role of pre-existing immunity in shaping the epidemiological landscape of COVID-19 in Africa and underscores the need for continued research in this area.