Background: Low numbers of recorded COVID-19 deaths in Africa may be due to undercounting and/or protection due to demographic and/or other factors, including pre-existing immunity. Several studies have assessed pre-pandemic samples for anti-SARS-CoV-2 antibodies with heterogeneous results.
Methods: We performed a systematic review and meta-analysis of studies evaluating pre-pandemic African samples for anti-SARS-CoV-2 antibody activity using pre-set assay-specific thresholds for seropositivity. Data where assay thresholds were calibrated on African populations were excluded. Searches used PubMed (September 13, 2022), reference lists of retrieved papers and citing articles (Google Scholar). Data were extracted independently by two authors on study and assay characteristics, and number of positive and tested samples. Datasets were classified according to malaria, dengue, and HIV burden. Proportions of seropositivity were combined with random effects meta-analysis.
Results: 22 articles with 117 datasets were eligible, including 2,971 positives among 21,988 measurements (13.5%) with large between-dataset heterogeneity. Positivity was higher for anti-S1 (25%) and lower for anti-RBD antibodies (8%). Positivity was non-significantly higher for IgM than for IgG antibodies. Positivity was seen prominently in countries where malaria transmission occurs throughout and in datasets enriched in malaria cases (17%, 95% CI, 15-19%) versus 1%, 95% CI 0-2% in other datasets). There were modest differences according to dengue burden (15% versus 11%). Substantial SARS-CoV-2 reactivity was seen in high malaria burden with or without high dengue burden (seropositivity 19% and 12%, respectively), and not without high malaria burden (seropositivity 2% and 0% with and without high dengue burden, respectively). There were modestly lower proportions of positivity in datasets with >10% of HIV-infected participants (8% versus 15% in others), but no association according to HIV serostatus in individual samples (summary odds ratio 0.97, 95% CI, 0.55-1.70).
Interpretation: Pre-pandemic samples from Africa show high levels of anti-SARS-CoV-2 seropositivity that tracks especially with malaria.
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