Long-term health outcomes in elderly COPD patients with long COVID: a 2-year prospective cohort study

Elderly chronic obstructive pulmonary disease (COPD) patients often face long-term adverse health issues post-COVID-19, but longitudinal and comprehensive assessments are limited. The study aimed to assess 2-year trajectories of both self-reported symptoms and lung function in elderly COPD patients after SARS-CoV-2 infection and to explore potential molecular mechanisms underlying long COVID progression through serum proteomic analysis. This longitudinal cohort study followed up elderly COPD patients at 1, 1.5, and 2 years post-COVID-19. Patients were assigned to the Control or Long-COVID group based on the presence of new-onset and significant fatigue. They completed questionnaires, pulmonary function tests, routine laboratory tests, and serum proteomic analysis. Patients in the Long-COVID group consistently experienced a heavier symptom burden throughout the follow-up period, including lower EQ-VAS scores, higher mMRC and CAT scores, and experienced more frequent adverse events. Several parameters of both pulmonary ventilation function and small airway function were lower in the Long-COVID group at 1-year and 1.5-year follow-ups. Although not statistically significant, the Long-COVID group showed slightly poorer diffusion capacity at all three follow-up visits. The phenomenon of lung function improvement at the 1.5-year follow-up, which was conducted in summer, was not observed in the Long-COVID group. Additionally, at the 2-year follow-up, serum proteomic analysis revealed upregulation of blood coagulation and platelet activation, as well as complement system dysregulation in patients with long COVID. Proteins associated with coagulation and thrombosis (FLNA, FN1, ITGA2B, FGB, and ITGB3) and complement system (C8A, C8B, VTN, C3, and CFH) were identified as hub differentially expressed proteins (DEPs). Elderly COPD patients with long COVID showed a persistently greater symptom burden and more frequent adverse outcomes, even up to two years post-infection. These individuals exhibited worse pulmonary ventilation function, particularly at the first and second follow-up visits, along with slightly lower diffusion capacity throughout all three follow-up visits. Disordered coagulation, platelet activation, and complement system may be the underlying molecular mechanisms and therapeutic targets.