Risk of severe influenza in people with a history of injection drug use in Ontario: a population-based nested case control study

Background — People who inject drugs may be at risk for influenza due to comorbidities and social determinants of health. We aimed to determine if a history of injection drug use is a risk factor for severe influenza.

Methods — We conducted a nested case-control study using the ICES (formerly Institute for Clinical Evaluative Sciences) database. Adults in Ontario, Canada were followed from July 1, 2022 to March 31, 2025. Cases consisted of adults admitted to hospital with severe influenza. Controls were adults who were not hospitalized for influenza. Each case was matched to 10 controls on age and sex. The exposure of injection drug use was determined based on a validated algorithm using hospitalization or emergency department visit diagnoses, physician billing codes, and opioid agonist treatment. A multivariable conditional logistic regression model was used to adjust for other known risk factors including sociodemographics, comorbidities, vaccination, and healthcare utilization.

Results — The study included 9514 cases and 95,140 matched controls. For both cases and controls, the median (interquartile) age was 74 (61–84) years and 53% were female. There were 559 (5.9%) cases and 1288 (1.4%) controls who had a history of injection drug use. In a multi-variable conditional logistic regression model, persons with a history of injection drug use had an adjusted odds ratio of 2.59 (95% CI 2.29–2.92, P<0.0001) of being hospitalized for influenza.

Conclusions — People who inject drugs are at a substantial increased risk for severe influenza. Public health efforts including vaccination campaigns should be targeted towards this population.