Effect of COVID-19 vaccination and SARS-CoV-2 infection status on mortality risk in patients with chronic obstructive pulmonary disease: a nationwide population-based cohort study

Background: The coronavirus disease 2019 (COVID-19) vaccination is suggested to be effective in improving outcomes of chronic obstructive pulmonary disease (COPD). However, real-world evidence on long-term mortality among individuals with COPD, accounting for both vaccination and COVID-19 infection status, remains sparse. Methods: A retrospective cohort study was conducted using datasets from the Korean National Health Insurance system. Through two-step propensity score matching, 716 individuals with COPD were included in the analysis and classified into four groups according to COVID-19 vaccination and severe acute respiratory syndrome coronavirus 2 infection status: 125 COVID-19 vaccinated/uninfected, 125 vaccinated/infected, 233 unvaccinated/uninfected, and 233 unvaccinated/infected. A multivariable Cox proportional hazards regression analysis was conducted to assess the risk of mortality following COVID-19 vaccination and SARS-CoV-2 infection status. Results: The median follow-up period was 420 days, during which 79.6% of study participants completed follow-up. Mortality rates were lowest in the vaccinated/uninfected individuals (281/10,000 person-years), followed by the vaccinated/infected individuals (661/10,000 person-years) and unvaccinated/uninfected individuals (2,106/10,000 person-years) and highest in unvaccinated/infected individuals (4,510/10,000 person-years). Compared with vaccinated/uninfected individuals, unvaccinated/infected individuals had a significantly higher annual risk of mortality (adjusted hazard ratio [aHR] = 13.51, 95% confidence interval [CI] = 4.91–37.13). The annual mortality risk was also significantly higher among unvaccinated/uninfected individuals (aHR = 6.01, 95% CI = 2.15–16.81). On the other hand, vaccinated/infected individuals (aHR = 2.32, 95% CI = 0.71–7.55) did not exhibit a significantly increased annual mortality risk compared with vaccinated/uninfected individuals. Conclusion: COVID-19 vaccination is associated with reduced long-term COPD-related mortality, whereas mortality risk was higher in unvaccinated/uninfected individuals than in vaccinated/infected individuals. Vaccination-related factors may confer broader benefits on COPD outcomes beyond direct protection against COVID-19.