Emergence of the novel SARS-CoV-2 lineage P.4.1 and massive spread of P.2 in South Brazil

South Brazil has been the novel epicenter of Coronavirus Disease 2019 (COVID-19) in 2021, accounting for the greatest number of cumulative cases and deaths (per 100 thousand inhabitants in a week) worldwide. In this study, we analyzed 340 whole genomes of SARS-CoV-2, which were sampled between April and November 2020 in 33 cities in South Brazil. We demonstrated the circulation of two novel emergent lineages, described here as P.4 and P.4.1 (provisionally termed VUI-NP13L), and seven lineages that had already been assigned (B.1.1.33, B.1.1.28, P.2, B.1.91, B.1.1.94, B.1.195 and B.1.212). P.2 and P.4.1 demonstrated massive spread from approximately September/October 2020. Constant and consistent genomic surveillance is crucial to identify newly emerging SARS-CoV-2 lineages in Brazil and to guide decision making in the Brazilian Public Healthcare System.