Clinical MedicineIn-Press PreviewInfectious diseasePulmonology Open Access | 10.1172/jci.insight.177518
1Medical Scientist Training Program, The University of Alabama at Birmingham, Birmingham, United States of America
2Department of Radiology, The University of Alabama at Birmingham, Birmingham, United States of America
3Department of Medicine, Pulmonary, Allergy, and Critical Care Medicine Divi, The University of Alabama at Birmingham, Birmingham, United States of America
4Department of Epidemiology, The University of Alabama at Birmingham, Birmingham, United States of America
5Hugh Kaul Precision Medicine Institute, The University of Alabama at Birmingham, Birmingham, United States of America
6Department of Medicine, The University of Alabama at Birmingham, Birmingham, United States of America
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1Medical Scientist Training Program, The University of Alabama at Birmingham, Birmingham, United States of America
2Department of Radiology, The University of Alabama at Birmingham, Birmingham, United States of America
3Department of Medicine, Pulmonary, Allergy, and Critical Care Medicine Divi, The University of Alabama at Birmingham, Birmingham, United States of America
4Department of Epidemiology, The University of Alabama at Birmingham, Birmingham, United States of America
5Hugh Kaul Precision Medicine Institute, The University of Alabama at Birmingham, Birmingham, United States of America
6Department of Medicine, The University of Alabama at Birmingham, Birmingham, United States of America
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1Medical Scientist Training Program, The University of Alabama at Birmingham, Birmingham, United States of America
2Department of Radiology, The University of Alabama at Birmingham, Birmingham, United States of America
3Department of Medicine, Pulmonary, Allergy, and Critical Care Medicine Divi, The University of Alabama at Birmingham, Birmingham, United States of America
4Department of Epidemiology, The University of Alabama at Birmingham, Birmingham, United States of America
5Hugh Kaul Precision Medicine Institute, The University of Alabama at Birmingham, Birmingham, United States of America
6Department of Medicine, The University of Alabama at Birmingham, Birmingham, United States of America
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1Medical Scientist Training Program, The University of Alabama at Birmingham, Birmingham, United States of America
2Department of Radiology, The University of Alabama at Birmingham, Birmingham, United States of America
3Department of Medicine, Pulmonary, Allergy, and Critical Care Medicine Divi, The University of Alabama at Birmingham, Birmingham, United States of America
4Department of Epidemiology, The University of Alabama at Birmingham, Birmingham, United States of America
5Hugh Kaul Precision Medicine Institute, The University of Alabama at Birmingham, Birmingham, United States of America
6Department of Medicine, The University of Alabama at Birmingham, Birmingham, United States of America
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1Medical Scientist Training Program, The University of Alabama at Birmingham, Birmingham, United States of America
2Department of Radiology, The University of Alabama at Birmingham, Birmingham, United States of America
3Department of Medicine, Pulmonary, Allergy, and Critical Care Medicine Divi, The University of Alabama at Birmingham, Birmingham, United States of America
4Department of Epidemiology, The University of Alabama at Birmingham, Birmingham, United States of America
5Hugh Kaul Precision Medicine Institute, The University of Alabama at Birmingham, Birmingham, United States of America
6Department of Medicine, The University of Alabama at Birmingham, Birmingham, United States of America
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1Medical Scientist Training Program, The University of Alabama at Birmingham, Birmingham, United States of America
2Department of Radiology, The University of Alabama at Birmingham, Birmingham, United States of America
3Department of Medicine, Pulmonary, Allergy, and Critical Care Medicine Divi, The University of Alabama at Birmingham, Birmingham, United States of America
4Department of Epidemiology, The University of Alabama at Birmingham, Birmingham, United States of America
5Hugh Kaul Precision Medicine Institute, The University of Alabama at Birmingham, Birmingham, United States of America
6Department of Medicine, The University of Alabama at Birmingham, Birmingham, United States of America
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1Medical Scientist Training Program, The University of Alabama at Birmingham, Birmingham, United States of America
2Department of Radiology, The University of Alabama at Birmingham, Birmingham, United States of America
3Department of Medicine, Pulmonary, Allergy, and Critical Care Medicine Divi, The University of Alabama at Birmingham, Birmingham, United States of America
4Department of Epidemiology, The University of Alabama at Birmingham, Birmingham, United States of America
5Hugh Kaul Precision Medicine Institute, The University of Alabama at Birmingham, Birmingham, United States of America
6Department of Medicine, The University of Alabama at Birmingham, Birmingham, United States of America
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1Medical Scientist Training Program, The University of Alabama at Birmingham, Birmingham, United States of America
2Department of Radiology, The University of Alabama at Birmingham, Birmingham, United States of America
3Department of Medicine, Pulmonary, Allergy, and Critical Care Medicine Divi, The University of Alabama at Birmingham, Birmingham, United States of America
4Department of Epidemiology, The University of Alabama at Birmingham, Birmingham, United States of America
5Hugh Kaul Precision Medicine Institute, The University of Alabama at Birmingham, Birmingham, United States of America
6Department of Medicine, The University of Alabama at Birmingham, Birmingham, United States of America
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1Medical Scientist Training Program, The University of Alabama at Birmingham, Birmingham, United States of America
2Department of Radiology, The University of Alabama at Birmingham, Birmingham, United States of America
3Department of Medicine, Pulmonary, Allergy, and Critical Care Medicine Divi, The University of Alabama at Birmingham, Birmingham, United States of America
4Department of Epidemiology, The University of Alabama at Birmingham, Birmingham, United States of America
5Hugh Kaul Precision Medicine Institute, The University of Alabama at Birmingham, Birmingham, United States of America
6Department of Medicine, The University of Alabama at Birmingham, Birmingham, United States of America
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1Medical Scientist Training Program, The University of Alabama at Birmingham, Birmingham, United States of America
2Department of Radiology, The University of Alabama at Birmingham, Birmingham, United States of America
3Department of Medicine, Pulmonary, Allergy, and Critical Care Medicine Divi, The University of Alabama at Birmingham, Birmingham, United States of America
4Department of Epidemiology, The University of Alabama at Birmingham, Birmingham, United States of America
5Hugh Kaul Precision Medicine Institute, The University of Alabama at Birmingham, Birmingham, United States of America
6Department of Medicine, The University of Alabama at Birmingham, Birmingham, United States of America
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1Medical Scientist Training Program, The University of Alabama at Birmingham, Birmingham, United States of America
2Department of Radiology, The University of Alabama at Birmingham, Birmingham, United States of America
3Department of Medicine, Pulmonary, Allergy, and Critical Care Medicine Divi, The University of Alabama at Birmingham, Birmingham, United States of America
4Department of Epidemiology, The University of Alabama at Birmingham, Birmingham, United States of America
5Hugh Kaul Precision Medicine Institute, The University of Alabama at Birmingham, Birmingham, United States of America
6Department of Medicine, The University of Alabama at Birmingham, Birmingham, United States of America
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1Medical Scientist Training Program, The University of Alabama at Birmingham, Birmingham, United States of America
2Department of Radiology, The University of Alabama at Birmingham, Birmingham, United States of America
3Department of Medicine, Pulmonary, Allergy, and Critical Care Medicine Divi, The University of Alabama at Birmingham, Birmingham, United States of America
4Department of Epidemiology, The University of Alabama at Birmingham, Birmingham, United States of America
5Hugh Kaul Precision Medicine Institute, The University of Alabama at Birmingham, Birmingham, United States of America
6Department of Medicine, The University of Alabama at Birmingham, Birmingham, United States of America
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Published April 23, 2024 - More info
BACKGROUND
Persistent cough and dyspnea are prominent features of post-acute sequelae of SARS-CoV-2 (also termed ’Long COVID’); however, physiologic measures and clinical features associated with these pulmonary symptoms remain poorly defined. Using longitudinal pulmonary function testing (PFTs) and CT imaging, this study aimed to identify the characteristics and determinants of pulmonary Long COVID.
METHODS
This single-center retrospective study included 1,097 patients with clinically defined Long COVID characterized by persistent pulmonary symptoms (dyspnea, cough, and chest discomfort) lasting for ≥1 month after resolution of primary COVID infection.
RESULTS
After exclusion, a total of 929 patients with post-COVID pulmonary symptoms and PFTs were stratified diffusion impairment and restriction as measured by percent predicted diffusion capacity for carbon monoxide (DLCO) and total lung capacity (TLC). Dyspnea was the predominant symptom in the cohort (78%) and had similar prevalence regardless of degree of diffusion impairment or restriction. Longitudinal evaluation revealed diffusion impairment (DLCO ≤80%) and pulmonary restriction (TLC ≤80%) in 51% of the cohort overall (n=479). In multivariable logistic regression analysis (adjusted odds ratio; aOR, 95% confidence interval [CI]), invasive mechanical ventilation during primary infection conferred the greatest increased odds of developing pulmonary Long COVID with diffusion impairment and restriction (aOR=10.9 [4.09-28.6]). Finally, a sub-analysis of CT imaging identified radiographic evidence of fibrosis in this patient population.
CONCLUSIONS
Longitudinal PFT measurements in patients with prolonged pulmonary symptoms after SARS-CoV-2 infection revealed persistent diffusion impaired restriction as a key feature of pulmonary Long COVID. These results emphasize the importance of incorporating PFTs into routine clinical practice for evaluation of patients with prolonged pulmonary symptoms after resolution of SARS-CoV-2. Subsequent clinical trials should leverage combined symptomatic and quantitative PFT measurements for more targeted enrollment of pulmonary Long COVID patients.
FUNDING
This work was supported by the National Institute of Allergy and Infectious Diseases (AI156898, K08AI129705), the National Heart, Lung, and Blood Institute (HL153113, OTA21-015E, HL149944), and the COVID-19 Urgent Research Response Fund established by the Hugh Kaul Precision Medicine Network at the University of Alabama at Birmingham.