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

RATIONALE: Increased risk of COVID-19 hospitalization and death has been reported among patients with clinical lung disease.

OBJECTIVE: To test the association of objective measures of pre-pandemic lung function and structure with COVID-19 outcomes in US adults.

METHODS: Pre-pandemic obstruction (FEV1/FVC<0.70) and restriction (FEV1/FVC≥0.7, FVC<80%) were defined based on the most recent spirometry exam conducted in 11 prospective US general population-based cohorts. Severe obstruction was classified by FEV1<50%. Percent emphysema, percent high attenuation areas (HAA), and interstitial lung abnormalities (ILA) were defined on computed tomography (CT) in a subset. Incident COVID-19 was ascertained via questionnaires, serosurvey, and medical records from 2020-2023, and classified as severe (hospitalized or fatal) or non-severe. Cause-specific hazards models were adjusted for socio-demographics, anthropometry, smoking, comorbidities, and COVID-19 vaccination status.

MEASUREMENTS AND MAIN RESULTS: Among 29,323 participants (mean age, 67 years), 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, aHR=2.11;95%CI:1.02-1.27), restriction (vs normal, aHR=1.40;95%CI:1.12-1.76), and percent emphysema (highest vs lowest quartile, aHR= 1.64;95%CI:1.03-2.61), but not greater HAA or ILAs. COVID-19 vaccination provided greater absolute risk reduction in these groups. Results were similar in participants without smoking, obesity, or clinical cardiopulmonary disease.

CONCLUSIONS: Pre-pandemic severe spirometric obstruction, spirometric restriction, and greater percent emphysema lung on CT 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. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).