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

Abstract

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 long-term 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 Charité's  Fatigue Centre and the Charité'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. FUNDING: C. S. was supported by a grant from the  Weidenhammer-Zoebele Foundation. F. K. was supported by the Volkswagen  Foundation.