Symptom burden, lung function, exercise tolerance and inflammation in patients post COVID-19: results from the prospective COVID-19 Chronic Morbidity (CCHROMO) study

BACKGROUND: Post-COVID syndrome is common and associated with substantial morbidity, yet its pathophysiology and predictors of disease course remain incompletely understood. This study aimed to quantify symptom burden in patients attending a post-COVID outpatient clinic and to evaluate associations with pulmonary function parameters, exercise capacity, and circulating biomarkers. METHODS: The prospective CCHROMO cohort collects longitudinal clinical data, detailed pulmonary function testing, and blood samples from patients with persistent symptoms following SARS-CoV-2 infection, with planned follow-up of up to three years. We present an interim analysis of 253 patients contributing 561 study visits (median follow-up 273 days after COVID-19 diagnosis; interquartile range [IQR] 177-332). Assessments included standardized symptom questionnaires, spirometry, inspiratory muscle strength testing, cardiopulmonary exercise testing (CPET), and serum biomarker measurements reflecting inflammation as well as epithelial and endothelial injury. RESULTS: At study entry, the most prevalent symptoms were fatigue (84.6% reporting at least moderate severity), dyspnoea (70.3%), headache (69.8%), and neurocognitive impairment (66.4%). Spirometric values were within normal ranges in most participants. In contrast, reduced inspiratory muscle strength was observed in 54.8% of visits, and impaired exercise capacity on CPET in 28.8%. Correlations between symptom severity, pulmonary function, CPET parameters, and circulating biomarkers were weak. Serum club cell protein-16 (CC-16) levels were lower in patients with severe fatigue (median [IQR] 6.6 [4.7-8.4] ng/mL) compared with those without fatigue (7.6 [6.3-10.1] ng/mL; p = 0.039). CONCLUSIONS: Patients with post-COVID syndrome show a high and persistent symptom burden, frequently accompanied by reduced inspiratory muscle strength and impaired exercise capacity despite preserved spirometry. Associations between symptoms, physiological measures, and biomarkers were weak and suggest heterogenous post-COVID manifestations. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00022475, Date of Registration 2020-07-27).