Pre-pandemic cross-reactive humoral immunity to SARS-CoV-2 in Africa: systematic review and meta-analysis

ABSTRACT Objective To assess the evidence on the presence of antibodies cross-reactive with SARS-CoV-2 antigens in pre-pandemic samples from African populations. Methods We performed a systematic review and meta-analysis of studies evaluating pre-pandemic African samples using pre-set assay-specific thresholds for SARS-CoV-2 seropositivity. Results 26 articles with 156 datasets were eligible, including 3,437 positives among 29,923 measurements (11.5%) with large between-dataset heterogeneity. Positivity was similar for anti-N (14%) and anti-S antibodies (11%), higher for anti-S1 (23%) and lower for anti-RBD antibodies (7%). Positivity was similar, on average, for IgM and IgG. Positivity was seen prominently in countries where malaria transmission occurs throughout and in datasets enriched in malaria cases (14%, 95% CI, 12-15% versus 2%, 95% CI 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 countries and cohorts 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. Conclusions Pre-pandemic samples from Africa show high levels of anti-SARS-CoV-2 seropositivity. Levels of cross-reactivity tracks especially with malaria prevalence.