Long-term symptom severity and clinical biomarkers in post-COVID-19/chronic fatigue syndrome: results from a prospective observational cohort

Background Post-COVID-19 syndrome (PCS) is characterised by a wide range of symptoms, primarily fatigue and exertion intolerance. While disease courses in the early months post-infection have been well-described, the longterm health consequences for patients with PCS with disabling fatigue remain unclear. Methods In this prospective observational cohort study, we evaluated symptom severity and various biomarkers, including hand grip strength (HGS), cardiovascular function, and laboratory parameters, in 106 patients with PCS with moderate to severe fatigue and exertion intolerance at three time points after infection (3-8, 9-16, and 17-20 months). The study was conducted at the Charite's Fatigue Centre and the Charite's outpatient clinic for neuroimmunology at Berlin, Germany from July 16, 2020, to February 18, 2022. A subset of patients (PCS-ME/CFS) met the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome according to the Canadian Consensus Criteria (CCC). The aim was to determine differences in the disease course between the two patient groups (i.e., PCS vs PCS-ME/CFS) and identify correlating biomarkers. Findings Patients with PCS-ME/CFS reported persistently high severity of most symptoms up to 20 months after infection, while patients with PCS showed overall health improvement. Although fatigue and post-exertional malaise (PEM), hallmarks of post-infectious fatigue syndromes, were still evident in both groups, they remained more pronounced in PCS-ME/CFS. Inflammatory biomarkers decreased in both groups, but not antinuclear antibodies. Lower HGS at onset correlated with symptom persistence, particularly in patients with PCS-ME/CFS. Interpretation Our findings suggest that PCS can persist beyond 20 months post-infection and encompass the full scope of post-infectious ME/CFS as defined by the CCC. Sub-classifying patients with PCS based on the CCC can assist in the management and monitoring of patients with PCS-ME/CFS due to their persistently higher symptom severity. 2023;63: Published https://doi.org/10. 1016/j.eclinm.2023. 102146

Automated summary

This study examined the long-term health consequences of Post-COVID-19 syndrome (PCS) in patients with moderate to severe fatigue and exertion intolerance. It found that PCS symptoms could persist beyond 20 months after infection and that patients with PCS-ME/CFS had higher and more persistent symptom severity compared to PCS patients. Subclassifying PCS based on the Canadian Consensus Criteria (CCC) can aid in the management and monitoring of PCS-ME/CFS patients.