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.

Background: Enhanced safety surveillance (ESS) of seasonal influenza vaccines is required by the European Medicines Agency (EMA). ESS is conducted during each Northern Hemisphere (NH) influenza season and aims to monitor the reactogenicity of influenza vaccines early in the season. A cell culture-based quadrivalent influenza vaccine (QIVc; Flucelvax® Tetra), which has an advantage of avoiding egg-adaptive mutations that may reduce vaccine effectiveness, has been available in Europe since the 2019/20 influenza season. The objective of this manuscript is to summarize ESS activity across three seasons for QIVc in all age groups. Methods: As per EMA guidelines, an enhanced passive safety surveillance (EPSS) approach was adopted. The EPSS envisages near-real-time surveillance of adverse events (AEs) that are reported spontaneously by vaccinees. The EPSS was conducted in primary care setting in Genoa (Italy) during the seasons 2019/20, 2020/21 and 2021/22. All AEs registered within the first 7 days following immunization were analyzed by season, type, age group and seriousness. Results: Over three seasons, a total of 3,603 QIVc exposures were recorded within EPSS. No safety signals were identified. The overall reporting rates of individual case safety reports (ICSRs) for the seasons 2019/20, 2020/21 and 2021/22 were 1.75% (18/1030), 0.48% (5/1032) and 0.40% (4/1001), respectively. The average number of AEs per ICSR was similar (range 3.3–3.8) across the three seasons. Most AEs were reactogenic in nature. The rate of AEs was similarly low in all age groups. Conclusions: These results support the favorable safety profile of QIVc in all indicated age groups.