The number of COVID-19 cases was greater in early autumn 2022 in contrast to in autumn 2021. Therefore, we decided to examine the factors that may have affected differences in the number of COVID-19 cases between the time periods 2021/2022 and 2022/2023 with consideration of the occurrence of influenza. In this cross-sectional study, we conducted a multiple factor analysis using data from publicly available databases for weeks 35–14 in 2022/2023 and 2021/2022 for Austria, Germany, Greece, Italy, and Slovenia. In the 2021/2022 season, the analyzed countries had similar profiles and were characterized by restrictions, health system policies, and SARS-CoV-2 variants, such as Alpha, Beta, Delta, Kappa, Eta, as well as Omicron sublineages (BA.1, BA.2), which were positively correlated with the number of new cases of COVID-19 per million people. However, in the 2022/2023 season, the analyzed countries were described by groups of variables corresponding to vaccination, influenza, the number of flights, and the Omicron SARS-CoV-2 subvariant. In summary, crucial factors correlated with the increasing of number of COVID-19 cases in the 2021/2022 season were the presence of dominant SARS-CoV-2 variants as well as the lifting of restrictions and strict health system policies.