Clara Eunyoung Lee, Natalie J Wilson, David N Fisman
Increased population-level SARS-CoV-2 activity is associated with a heightened risk of PE, peaking at approximately the third week. This delayed peak suggests a protracted thrombo-inflammatory window, likely driven by sustained endothelial injury. These findings highlight the vascular burden of COVID-19 and suggest that infection prevention measures, including vaccination, may provide significant downstream protection against thromboembolic disease.
OBJECTIVES: SARS-CoV-2 infection is an established prothrombotic trigger, yet the population-level temporal relationship between circulating viral activity and pulmonary embolism (PE) remains poorly characterized. We aimed to evaluate the short-term association between respiratory viral activity and PE, accounting for specific temporal lags.
STUDY DESIGN: Ecological time-series study.
METHODS: We conducted a population-level time-series analysis of incident PE hospitalizations in Ontario, Canada, from 2011 to 2024. Using distributed lag non-linear models, we assessed associations between standardized weekly activity of SARS-CoV-2, influenza A/B, and respiratory syncytial virus (RSV) and PE risk over a 5-week lag. RR per SD increase in viral activity were estimated via negative binomial regression with cross-basis terms, capturing exposure-response and lag-response non-linearities, and adjusted for Fourier seasonal terms and secular trends. A single-virus model assessed SARS-CoV-2 alone, while a multi-pathogen model additionally adjusted for influenza A and RSV.
RESULTS: Among 70,599 PE cases, SARS-CoV-2 activity demonstrated a significant temporal association with PE. Cumulative RR increased 12% per SD over five weeks (RR 1.12; 95% CI 1.00-1.25). The risk followed a distinct delay trajectory, with weekly cumulative RRs peaking at week 3 (RR 1.22; 95% CI 1.04-1.43). The multi-pathogen model, SARS-CoV-2 showed a higher cumulative RR of 1.26 (95% CI 1.11-1.44), with a lower, non-significant peak at week 3 (RR 1.13; 95% CI 0.96-1.32).
CONCLUSIONS: Increased population-level SARS-CoV-2 activity is associated with a heightened risk of PE, peaking at approximately the third week. This delayed peak suggests a protracted thrombo-inflammatory window, likely driven by sustained endothelial injury. These findings highlight the vascular burden of COVID-19 and suggest that infection prevention measures, including vaccination, may provide significant downstream protection against thromboembolic disease.