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To investigate the introductions and spread of SARS-CoV-2 in Mozambique, 1 142 whole genome sequences sampled within Mozambique were phylogenetically analyzed against a globally representative set, reflecting the first 25 months of the epidemic. The epidemic in the country was marked by four waves of infection, the first associated with B.1 ancestral lineages, while the Beta, Delta, and Omicron Variants of Concern (VOCs) were responsible for most infections and deaths during the second, third, and fourth waves. Large-scale viral exchanges occurred during the latter three waves and were largely attributed to southern African origins. Not only did the country remain vulnerable to the introductions of new variants but these variants continued to evolve within the borders of the country. Due to the Mozambican health system already under constraint, and paucity of data in Mozambique, there is a need to continue to strengthen and support genomic surveillance in the country as VOCs and Variants of interests (VOIs) are often reported from the southern African region.<\/jats:p>","DOI":"10.1371\/journal.pgph.0001593","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T18:21:48Z","timestamp":1678126908000},"page":"e0001593","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgph.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genomic epidemiology of SARS-CoV-2 during the first four waves in Mozambique"],"prefix":"10.1371","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1793-9471","authenticated-orcid":true,"given":"Nalia","family":"Ismael","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"van 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