The overlapping impacts of heat and COVID-19 on mortality in Flanders, Belgium: a time-stratified case-crossover analysis.

The compound occurrence of extreme heat and the COVID-19 pandemic may have increased mortality risk beyond the impact of each factor alone. However, the interaction between these two risk factors and their combined effect on mortality has not been adequately quantified. We conducted a time-stratified case-crossover analysis of daily all-cause mortality, minimum temperature, and COVID-19 case counts in Flanders over the period 2018-2021. We applied a distributed lag nonlinear model (DLNM) with a conditional quasi-Poisson regression to estimate the cumulative effects (lag 0-14 days) of extreme heat. The relative risk (RR) was quantified at the 99th percentile (P99) of minimum temperature compared to 50th percentile (P50). To assess effect modification, we used a binary interaction approach (pre-COVID-19 and during COVID-19) and a linear interaction approach. We used a 15-day moving average of daily confirmed cases and centered it at three reference points representing 25th, 75th and 95th percentiles of the distribution, corresponding to low, mild and high intensity levels, respectively. We observed that during the COVID-19 pandemic, the risk of mortality associated with extreme heat was significantly elevated (RR = 1.55; 95% CI: 1.18-2.02), compared to a weaker and non-significant association during pre-COVID-19 (RR = 1.07; 95% CI: 0.72-1.58). The heat-mortality curve showed a sharper increase during the pandemic, specifically above the 14 °C (P50). An increased association was observed together with rising COVID-19 incidence. On days when COVID-19 intensity was low, the relative risk (RR) of heat-related mortality was 1.18 (95% CI: 0.64-2.18). This risk increased under moderate incidence, with an RR of 1.95 (95% CI: 1.1.03-3.70), and rose markedly during high cases, reaching an RR of 3.57 (95% CI: 1.10-11.61). Our findings suggest an increased risk of heat-related mortality during the COVID-19 pandemic, especially as COVID-19 transmission intensified.