COVID-19 vaccine effectiveness in patients with lung cancer: challenges in the Omicron era

Background — During the Omicron era, COVID-19 vaccines demonstrated over 90% effectiveness against severe disease in the general population. However, vaccine effectiveness (VE) in patients with lung cancer, who are at high risk for severe COVID-19, has not been well characterized.

Methods — In this population-based cohort, we employed a test-negative design using linked data from the Ontario Cancer Registry, health administrative databases, and the Ontario vaccination registry. We included all patients with active lung cancer or mesothelioma residing in Ontario, Canada, who were symptomatic and underwent SARS-CoV-2 RT-PCR testing from January 2, 2022, to June 30, 2025. The outcome of interest was a severe outcome, defined as hospitalization within 14 days or death within 30 days following SARS-CoV-2 test. We constructed an analytic cohort that included the earliest testing episode among test-positive and test-negative patients with severe outcomes. We also performed a sensitivity analysis comparing test-positive patients with severe outcomes to randomly selected testing episodes among test-negative patients.

Results — Among 47,344 tested patients, 3,332 (7.0%) were SARS-CoV-2 test-positive, of whom 1,967 (59%) experienced severe outcomes; 16,257 test-negative patients also developed severe outcomes. Adjusted VE against severe COVID-19 was 52% (95% CI: 42%, 60%) within 7–179 days post-vaccination, declining to 16% (95%CI: 0%, 30%) thereafter. In sensitivity analyses comparing 1,967 test-positive patients with severe outcomes to 18,922 randomly selected test-negative patients, adjusted VE was 49% (95% CI: 39%, 58%), declining to 12% (95% CI: −4% 26%) thereafter.

Conclusions — In this large population-based study of patients with lung cancer and mesothelioma, COVID-19 vaccination was associated with moderate protection against severe outcomes, including hospitalization and death. These findings emphasize the importance of optimizing alternative preventive strategies, such as masking, social distancing, ensuring household and caregiver vaccinations, and improving post-infection management through early antiviral therapy and close monitoring for severe disease.