The COVID-19 pandemic overwhelmed health systems, resulting in a surge in excess deaths. This study clustered countries based on excess mortality to understand their response to the pandemic and the influence of various factors on excess mortality within each cluster. This ecological study is part of the COVID-19 MORtality (C-MOR) Consortium. Mortality data were gathered from 21 countries and were previously used to calculate weekly all-cause excess mortality. Thirty exposure variables were considered in five categories as factors potentially associated with excess mortality: population factors, health care resources, socioeconomic factors, air pollution, and COVID-19 policy. Estimation of Latent Class Linear Mixed Model (LCMM) was used to cluster countries based on response trajectory and Generalized Linear Mixture Model (GLMM) for each cluster was run separately. Using LCMM, two clusters were reached. Among 21 countries, Brazil, the USA, Georgia, and Poland were assigned to a separate cluster, with the mean of excess mortality z-score in 2020 and 2021 around 4.4, compared to 1.5 for all other countries assigned to the second cluster. In both clusters the population incidence of COVID-19 had the greatest positive relationship with excess mortality while interactions between the incidence of COVID-19, fully vaccinated people, and stringency index were negatively associated with excess mortality. Moreover, governmental variables (government revenue and government effectiveness) were the most protective against excess mortality. This study highlighted that clustering countries based on excess mortality can provide insights to gain a broader understanding of countries' responses to the pandemic and their effectiveness.
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