Recurrent COVID-19 infection and the risk of exacerbation, mortality and long covid in patients with chronic obstructive pulmonary disease: a nationwide retrospective cohort study

Objectives To evaluate how recurrent COVID-19 infections influence the clinical course of patients with chronic obstructive pulmonary disease (COPD), focusing on moderate-to-severe symptom flare-ups, all-cause mortality and long covid. Design Nationwide retrospective cohort study. Setting Korean Health Insurance Review and Assessment database covering the entire Korean population between January 2020 and December 2023. Participants A total of 313 760 patients aged ≥40 years who met an established operational definition of COPD based on diagnostic codes and inhaled therapy prescriptions. Patients were stratified by the number of COVID-19 events: none, one, two or three or more. Primary and secondary outcome measures The primary outcomes were moderate-to-severe COPD exacerbations and all-cause mortality. The secondary outcome was long covid, defined by WHO criteria using International Classification of Diseases (ICD)-10 codes persisting ≥2 months within 3 months after infection. Results Among 313 760 patients, 154 095 (49.1 %) experienced at least one COVID-19 event. COVID-19 infection was associated with increased risk of exacerbations (adjusted HR (aHR) 1.64, 95% CI 1.62 to 1.66) and mortality (aHR 2.25, 95 % CI 2.19 to 2.31). Risk rose progressively with repeated infections, reaching an aHR of 2.41 for exacerbations and 2.93 for mortality after three or more events. Long covid was more frequent in patients with multiple infections, but most cases occurred after the first event, with diminishing occurrence after subsequent infections. Conclusion Recurrent COVID-19 infections in patients with COPD were linked to progressively higher risk of exacerbations and mortality, whereas the burden of long covid was greatest after the first infection. Preventing the initial infection and reducing reinfection risk remain critical components of COPD care in the post-COVID-19 era.