Summary Background Throughout the COVID-19 pandemic, the SARS-CoV-2 virus has continued to evolve, with new variants outcompeting existing variants and often leading to different dynamics of disease spread. Methods In this paper, we performed a retrospective analysis using longitudinal sequencing data to characterize differences in the speed, calendar timing, and magnitude of 13 SARS-CoV-2 variant waves/transitions for 215 countries and sub-country regions, between October 2020 and October 2022. We then clustered geographic locations in terms of their variant behavior across all Omicron variants, allowing us to identify groups of locations exhibiting similar variant transitions. Finally, we explored relationships between heterogeneity in these variant waves and time-varying factors, including vaccination status of the population, governmental policy, and the number of variants in simultaneous competition. Findings This work demonstrates associations between the behavior of an emerging variant and the number of co-circulating variants as well as the demographic context of the population. We also observed an association between high vaccination rates and variant transition dynamics prior to the Mu and Delta variant transitions. Interpretation These results suggest the behavior of an emergent variant may be sensitive to the immunologic and demographic context of its location. Additionally, this work represents the most comprehensive characterization of variant transitions globally to date. Funding Laboratory Directed Research and Development (LDRD), Los Alamos National Laboratory Research in context Evidence before this study SARS-CoV-2 variants with a selective advantage are continuing to emerge, resulting in variant transitions that can give rise to new waves in global COVID-19 cases and changing dynamics of disease spread. While variant transitions have been well studied individually, more work is needed to better understand how variant transitions have occurred in the past and how properties of these transitions may relate to vaccination rates, natural immunity, and population demographics. Added value of this study Our retrospective study integrates metadata based on 12.8 million SARS-CoV-2 sequences available through the Global Initiative on Sharing All Influenza Data (GISAID) with clinical and demographic data to characterize heterogeneity in variant waves/transitions across the globe throughout the COVID-19 pandemic. We demonstrate that properties of the variant transitions (e.g., speed, timing, and magnitude of the transition) are associated with vaccination rates, prior COVID-19 cases, and the number of co-circulating variants in competition. Implications of all the available evidence Our results indicate that there is substantial heterogeneity in how an emerging variant may compete with other viral variants across locations, and suggest that each location’s contemporaneous immunologic landscape may play a role in these interactions.

SARS-CoV-2 variant transition dynamics are associated with vaccination rates, number of co-circulating variants, and natural immunity