Population attributable mortality associated with respiratory viruses in Ontario, Canada: a population-based ecological analysis

Respiratory viruses are major contributors to population mortality, but cause-of-death coding undercounts their impact. Ecological regression linking viral circulation to mortality fluctuations can address this. We estimated the population attributable fraction (PAF) of mortality associated with influenza A and B, respiratory syncytial virus (RSV), and SARS-CoV-2 in Ontario, Canada, over 1993-2025, across the pandemic transition.

We analysed monthly all-cause mortality with laboratory surveillance indicators for influenza A, influenza B, RSV, and SARS-CoV-2. Negative binomial models with secular trends, Fourier seasonal terms, and population offsets were fitted for pre-pandemic (1993-2020) and combined pandemic (2020-2025) periods. PAFs were derived from counterfactual predictions. Further analyses examined temporal stratification, exclusion of the early pandemic period, and models without Fourier adjustment.

Pre-pandemic, influenza A was associated with 1.8% (95% CI 1.4-2.3) of mortality; influenza B showed no association; RSV showed positive associations (1.9%, 1.3-2.4) only without seasonal adjustment. Amid elevated pandemic mortality (IRR 1.052, p < 0.0001), SARS-CoV-2 was associated with 6.48% (4.5-8.4) of deaths, 3-4-fold the pre-pandemic influenza A burden. Attributable deaths (18,052) fell within 3% of 18,594 independently adjudicated Ontario COVID-19 deaths. Post-Public Health Emergency of International Concern (PHEIC) SARS-CoV-2 mortality (9.8%, 1.1-17.7) did not differ from PHEIC estimates; post-PHEIC influenza did not differ from pre-pandemic baselines.

SARS-CoV-2 was associated with a 3-4-fold higher population mortality burden than seasonal influenza A despite available countermeasures, and continued to contribute beyond the formal emergency period, underscoring the importance of sustained respiratory virus prevention.

Canadian Institutes of Health Research.