Prepandemic cross-reactive humoral immunity to SARS-CoV-2 in Africa: Systematic review and meta-analysis

OBJECTIVES: To assess the evidence on the presence of antibodies cross-reactive with SARS-CoV-2 antigens in prepandemic samples from African populations. METHODS: We performed a systematic review and meta-analysis of studies evaluating prepandemic African samples using pre-set assay-specific thresholds for SARS-CoV-2 seropositivity. RESULTS: In total, 26 articles with 156 datasets were eligible, including 3437 positives among 29,923 measurements (11.5%) with large between-dataset heterogeneity. Positivity was similar for anti-nucleocapsid (14%) and anti-spike antibodies (11%), higher for anti-spike1 (23%), and lower for anti-receptor-binding domain antibodies (7%). Positivity was similar, on average, for immunoglobulin M and immunoglobulin G. Positivity was seen prominently in countries where malaria transmission occurs throughout and in datasets enriched in malaria cases (14%, 95% confidence interval, 12-15% vs 2%, 95% confidence interval 1-2% in other datasets). Substantial SARS-CoV-2 reactivity was seen in high malaria burden with or without high dengue burden (14% and 12%, respectively), and not without high malaria burden (2% and 0%, respectively). Lower SARS-CoV-2 cross-reactivity was seen in settings of high HIV seroprevalence. More sparse individual-level data showed associations of higher SARS-CoV-2 cross-reactivity with Plasmodium parasitemia and lower SARS-CoV-2 cross-reactivity with HIV seropositivity. CONCLUSION: Prepandemic samples from Africa show high levels of anti-SARS-CoV-2 seropositivity. At the country level, cross-reactivity tracks especially with malaria prevalence.