Important differences in excess mortality between European countries during the COVID-19 pandemic have been reported. Understanding the drivers of these differences is essential to pandemic preparedness. We examined patterns in age- and sex-standardized cumulative excess mortality in 13 Western European countries during the first 30 months of the COVID-19 pandemic and the correlation of country-level characteristics of interest with excess mortality. In a timeline analysis, we identified notable differences in seeding events, particularly in early 2020 and when the Alpha variant emerged, likely contributing to notable differences in excess mortality between countries (lowest in Denmark during that period). These differences were more limited from July 2021 onwards. Lower excess mortality was associated with implementing stringent non-pharmaceutical interventions (NPIs) when hospital admissions were still low in 2020 (correlation coefficient rho = 0.65, p = 0.03) and rapid rollout of vaccines in the elderly in early 2021 (rho = − 0.76, p = 0.002). Countries which implemented NPIs while hospital admissions were low tended to experience lower gross domestic product (GDP) losses in 2020 (rho = − 0.55, p = 0.08). Structural factors, such as high trust in the national government (rho = − 0.77, p = 0.002) and low ratio of population at risk of poverty (rho = 0.55, p = 0.05), were also associated with lower excess mortality. These results suggest the benefit of early implementation of NPIs and swift rollout of vaccines to the most vulnerable. Further analyses are required at a more granular level to better understand how these factors impacted excess mortality and help guide pandemic preparedness plans.
While performing a large-scale analysis of mRNA transcripts in the murine thymus, our attention was drawn to the forkhead family transcription factor FKHR. Here we demonstrate that FKHR is expressed in thymocytes, most prominently in those that are undergoing positive selection. Interestingly, FKHR transcripts show a highly regionalized pattern of expression, concentrated in the innermost areas of the medulla. We define the FKHR binding site as (G/C)(A/C)N(G/a)T(A/c)AA(T/c) A(T/g)(T/g)(G/c), a sequence found in the regulatory elements of many genes, including certain that encode molecules crucial for thymocyte differentiation. To study the function of FKHR, we engineered mice expressing a dominant-negative mutant specifically in T cells in a tetracycline-regulatable fashion. In these animals, T cell differentiation appeared quite normal; however, total thymocyte numbers were decreased, owing to reductions in all four of the CD4/CD8 subsets, and incorporation of the thymidine analogue bromo-deoxyuridine was increased, again in all four subsets. These data suggest that, in thymocytes, FKHR may be involved in cell survival and/or cycling.
