Genomic Surveillance of SARS‐CoV‐2 in Senegal (2020–2024): Variant Turnover, Omicron Introductions, and Interregional Spread

ABSTRACT Background Genomic surveillance is central to tracking SARS‐CoV‐2 evolution, variant replacement, and transmission dynamics. In Senegal, the Institut Pasteur de Dakar generated one of the largest national longitudinal SARS‐CoV‐2 genomic datasets, offering a unique view of viral spread from the first pandemic wave to the post‐Omicron period. Aims This study aimed to reconstruct SARS‐CoV‐2 evolution and dissemination in Senegal from March 2020 to September 2024, assess variant and Omicron sublineage dynamics, infer introduction and interregional spread patterns, and describe the national mutational landscape. Material and Methods A total of 4820 SARS‐CoV‐2 genomes generated by the Institut Pasteur de Dakar were analyzed. Lineage assignment, temporal and regional distribution, time‐scaled phylogenetics, discrete phylogeographic reconstruction, and mutation profiling were used to assess variant turnover, international seeding, intranational dissemination, and genomic diversification. Results Ancestral A/B lineages predominated in 2020 before replacement by Alpha and Beta in early 2021, followed by Delta in mid‐2021, which coincided with the highest case burden. From late 2021, Omicron became dominant, with rapid turnover of BA.1/BA.2, BA.4/BA.5, BQ.1.1, XBB, and BA.2.86, while later waves were smaller. Dakar contributed 64.7% of genomes and emerged as the main hub for inferred introductions and interregional spread, with Kaolack and Diourbel as secondary hubs. Major Omicron sublineages resulted from multiple introductions, mainly from Africa and Europe, with BA.1/BA.2 seeded from a broader range of continents than later lineages. Mutation profiling showed strong enrichment in Spike, with recurrent changes in ORF1a/ORF1b and nucleocapsid. Discussion The findings reveal repeated variant replacement, shifting international seeding routes, and a hub‐and‐spoke pattern of national dissemination centered on Dakar. Declining later waves may reflect increasing hybrid population immunity, although interpretation remains influenced by heterogeneous sequencing intensity. Conclusions This study provides an integrated national picture of SARS‐CoV‐2 evolution in Senegal and supports decentralized sequencing, stronger metadata capture, and routine use of genomic evidence for public health decision‐making.