Since early 2022 the Omicron variant has rapidly spread worldwide, becoming the dominant variant to date. The study aimed to investigate the clinical and epidemiological characteristics of COVID-19 patients and to reconstruct the genomic epidemiology of main SARS-CoV-2 Omicron sub-lineages in Italy in 2022. 8,970 SARS-CoV-2 samples were studied, and phylogenetic analyses were focused on BA.1, BA.2 and BA.5 sub-variants. More than half of subjects received three doses of vaccine and experienced a reinfection. A significant larger proportion of unvaccinated subjects presented reinfection compared to vaccinated. Clusters presented a tMRCA between September-November 2021 (BA.1), November 2021-January 2022 (BA.2) and October 2021-May 2022 (BA.5). R e values showed the highest level between September-October, January-February 2022, and May 2022 for BA.1, BA.2 and BA.5, respectively. Limited number of studied variant sequences are included in clusters. The analyses dissect the epidemiological dynamics of Omicron sub-lineages in Italy over a period of great epidemiological changes in the COVID-19 epidemic. The spread rate of the studied variant exceeded its evolutionary rate. No single sub-lineage had sufficient time to differentiate into large clusters, but only into small and fragmented groups sharing the same recent ancestor. These analyses dissect the epidemiological dynamics of Omicron sub-lineages in Italy over a period of great epidemiological changes in the COVID-19 epidemic.

Since the beginning of the pandemic, SARS-CoV-2 has shown a great genomic variability, resulting in the continuous emergence of new variants that has made their global monitoring and study a priority. This work aimed to study the genomic heterogeneity, the temporal origin, the rate of viral evolution and the population dynamics of the main circulating variants (20E.EU1, Alpha and Delta) in Italy, in August 2020-January 2022 period. For phylogenetic analyses, two datasets were evaluated for each variant, the former comprising international genomes and the latter focusing on clusters containing at least 70% of Italian sequences. The international dataset showed 26 (23% Italians, 23% singleton, 54% mixed), 40 (60% mixed, 37.5% Italians, 1 singleton) and 42 (85.7% mixed, 9.5% singleton, 4.8% Italians) clusters with at least one Italian sequence, in 20E.EU1 clade, Alpha and Delta variants, respectively. International clusters presented tMRCAs between 13/06/2020-27/07/2021. R e values showed the highest level between May-June until autumn 2020 in 20E.EU1 clade. The Alpha variant showed an increase in the R e in December 2020, when the highest mean value was estimated. Delta variant presented two peaks: the first between March-May, and the second between June-July 2021. The present work highlighted a different evolutionary dynamic of studied lineages with a high concordance between epidemiological parameters estimation and phylodynamic trends suggesting that the mechanism of replacement of the SARS-CoV-2 variants must be related to a complex of factors involving the transmissibility, as well as the implementation of control measures, and the level of cross-immunization within the population.