Shuangyan Li,1,* Hui Zhao,2,* Min Zhang,3 Tingting Yuan,4 Di Chai,5 Zhengyin Shen,3 Chengfeng Qin,2,6 Yanming Li,5 Mingming Pan5 

1Beijing Hospital, National Centre of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, People’s Republic of China; 3Department of Radiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Clinical Laboratory, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 6Research Unit of Discovery and Tracing of Natural Focus Diseases, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Mingming Pan, Department of Respiratory and Critical Care Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1 Dongdan Dahua Road, Beijing, People’s Republic of China, Tel +86-13661129402, Email panmm6@163.com

Background: Elderly patients with chronic obstructive pulmonary disease (COPD) face a heightened risk of developing long coronavirus disease (COVID); however the exact clinical characteristics and underlying mechanisms remain unclear.
Methods: We enrolled 85 elderly COPD patients, of whom 43 reported newly onset persistent fatigue (the most dominant complaint of long COVID) within 1 year after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and they were allocated to the Long-COVID group. The remaining 42 patients were assigned to the Control group. Patients completed questionnaires, pulmonary function tests, chest CT, routine laboratory tests, and blood proteomic analysis.
Results: Long-COVID patients had a longer course of COPD (> 5 years, 76.8% vs 52.4%) and duration of SARS-CoV-2 infection (10.0 days vs 7.0 days) (All P < 0.05), higher symptom burden, worse pulmonary ventilation function and a more rapid decrease in DLCO (All P < 0.05). Proteomic analysis indicated disruptions in inflammation and energy metabolism, potentially underlying long COVID in these patients. The machine learning model identified wheezing, the duration of SARS-CoV-2 infection, EIF2S3 (eukaryotic translation initiation factor 2 subunit gamma), current FEV1/FVC (%), and the course of COPD as key features distinguishing Long-COVID patients, and exhibited excellent performance.
Conclusion: Elderly COPD patients with a longer COPD course and duration of COVID-19 are more prone to develop long COVID, with decreased pulmonary ventilation and diffusion ability. Disordered inflammation regulation and energy metabolism may be the potential mechanisms, highlighting the importance of monitoring inflammation and metabolic dysregulation in elderly COPD patients after recovery from COVID-19.

Keywords: elderly, COPD, long COVID, risk factors, proteomics