Genomic epidemiology of SARS-CoV-2 in Peru from 2020 to 2024

Background: Peru recorded one of the world’s highest COVID-19 mortality rates, with nearly 4.5 million reported cases and 220,000 deaths by March 2024. Understanding the emergence and spread of SARS-CoV-2 variants in this context is key to informing effective public health responses. This study describes the genomic diversity, transmission dynamics, and geographic spread of SARS-CoV-2 in Peru from 2020 to 2024. Methods: We analyzed nearly 50,000 high-quality public SARS-CoV-2 genome sequences collected nationwide between March 2020 and March 2024. Phylogeographic and mutational analyses were performed to identify variant lineages, trace their origins, and map viral movements within and beyond Peru. Results: We show that Peru’s epidemic waves were shaped by the emergence of locally evolved variants, including Lambda (C.37), Gamma (P.1.12), and Omicron (XBB.2.6 and DJ.1) sub-lineages. The city of Lima acted as the primary hub for inter-regional spread, accounting for 47.3% of inferred viral movements to other departments, notably Ancash, Cusco, and Piura. Peru was the source of various lineages that spread internationally, primarily to Chile, the USA, and Europe. Mutational analysis highlighted critical mutations in the spike protein, including L452Q and F490S in Lambda, associated with immune evasion and increased transmissibility. Conclusions: This work demonstrates the capacity of genomic surveillance in Peru to detect and track emerging SARS-CoV-2 variants, providing insights into regional and global transmission dynamics in a high-transmission, middle-income country setting. Sustained, cost-effective genomic monitoring, combined with strengthened bioinformatics and laboratory capacity, is essential for pandemic preparedness in resource-limited settings.