Proportions of COVID-19 variants.

<div> The COVID-19 pandemic has had varying impacts across different regions, necessitating localised data-driven responses. SARS-CoV-2 was first identified in a person in Wuhan, China, in December 2019 and spread globally within three months. While there were similarities in the pandemic’s impact across regions, key differences motivated systematic quantitative analysis of diverse geographical data to inform responses. Malawi reported its first COVID-19 case on 2 April 2020 but had significantly less data than Global North countries to inform its response. Here, we present a modelling analysis of SARS-CoV-2 epidemiology and phylogenetics in Malawi between 2 April 2020 and 19 October 2022. We carried out this analysis using open-source tools and open data on confirmed cases, deaths, geography, demographics, and viral genomics. R was used for data visualisation, while Generalised Additive Models (GAMs) estimated incidence trends, growth rates, and doubling times. Phylogenetic analysis was conducted using IQ-TREE, TreeTime, and interactive tree of life. This analysis identifies five major COVID-19 waves in Malawi, driven by different lineages: (1) Early variants, (2) Beta, (3) Delta, (4) Omicron BA.1, and (5) Other Omicron. While the Alpha variant was present, it did not cause a major wave, likely due to competition from the more infectious Delta variant, since Alpha circulated in Malawi when Beta was phasing out and Delta emerging. Case Fatality Ratios were higher for Delta, and lower for Omicron, than for earlier lineages. Phylogeny reveals separation of the tree into major lineages as would be expected, and early emergence of Omicron, as is consistent with proximity to the likely origin of this variant. Both variant prevalence and overall rates of confirmed cases and confirmed deaths were highly geographically heterogeneous. We suggest that real-time analyses should be considered in Malawi and other countries, where similar computational and data resources are available. </div>