Associations of Prepandemic Lung Function and Structure with COVID-19 Outcomes: The C4R Study.

Increased risk of coronavirus disease (COVID-19) hospitalization and death has been reported among patients with clinical lung disease. To test the association of objective measures of prepandemic lung function and structure with COVID-19 outcomes in U.S. adults. Prepandemic obstruction (FEV/FVC < 0.70) and restriction (FEV/FVC ⩾ 0.7, FVC < 80%) were defined based on the most recent spirometry exam conducted in 11 prospective U.S. general population-based cohorts. Severe obstruction was classified by FEV < 50%. Percentage emphysema, percentage high-attenuation areas, and interstitial lung abnormalities were defined on computed tomography in a subset. Incident COVID-19 was ascertained via questionnaires, serosurvey, and medical records from 2020 to 2023 and classified as severe (hospitalized or fatal) or nonsevere. Cause-specific hazard models were adjusted for sociodemographics, anthropometry, smoking, comorbidities, and COVID-19 vaccination status. Among 29,323 participants (mean age, 67 yr), there were 748 severe incident COVID-19 cases over median follow-up of 17.3 months from March 1, 2020. Greater hazards of severe COVID-19 were associated with severe obstruction (vs. normal; adjusted hazard ratio [aHR], 2.11; 95% confidence interval [CI], 1.02-1.27), restriction (vs. normal; aHR, 1.40; 95% CI, 1.12-1.76), and percentage emphysema (highest vs. lowest quartile; aHR, 1.64; 95% CI, 1.03-2.61), but not greater high-attenuation areas or interstitial lung abnormalities. COVID-19 vaccination provided greater absolute risk reduction in these groups. Results were similar in participants without smoking, obesity, or clinical cardiopulmonary disease. Prepandemic severe spirometric obstruction, spirometric restriction, and greater percentage emphysema lung on computed tomography were associated with risk of severe COVID-19. These findings support enhanced COVID-19 risk mitigation for individuals with impaired lung health and warrant further mechanistic studies on interactions of lung function, structure, and vulnerability to acute respiratory illnesses.