Shifts in seasonal timing of respiratory diseases and causes of death following a natural pandemic event.

Seasonal respiratory infections typically surge within a limited time window, but what determines the exact timing within a given year is not well understood. Major causes of death show a similar seasonal pattern, but whether this pattern is linked to respiratory infections is unclear. The disruptions caused by the COVID-19 pandemic led to dramatic changes in the transmission dynamics of many respiratory pathogens, providing a unique opportunity to study the determinants of seasonal epidemics and the role of infectious diseases in driving seemingly unrelated causes of mortality. We analyzed publicly available data on weekly incidences of respiratory infections and all-cause mortality in Germany for the last 14 years. The analysis was complemented with results from an epidemiological model to determine the main drivers of seasonal timing. The timing of the seasonal epidemic of respiratory infections in Germany has been remarkably consistent for years, peaking during just few weeks in late winter. During the COVID-19 pandemic the seasonal surge in respiratory infections occurred substantially earlier, initially driven by the emerging COVID-19 and during later seasons by the resurgence of influenza and RSV. Remarkably, this shift was accompanied by a similar shift in the seasonality of all-cause mortality, and in particular mortality due to cardiovascular disease. The observed shift in epidemic timing is a consistent, but transient, outcome of disrupted epidemic seasonality, predictable from basic epidemiological principles. Our study reinforces that the buildup of susceptibles after the pandemic disruption was responsible for the shift in timing of the seasonal epidemic of respiratory infections. We show that more generally the rate of immune waning is the main determinant of the exact timing of seasonal epidemics of infectious diseases. The corresponding shift in seasonality of cardiovascular mortality suggests a connection between recent respiratory infections and severe cardiovascular events. This highlights the importance of monitoring individual infection history and improving vaccination coverage, in particular against influenza.