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

Franziska Legler; Lil Meyer-Arndt; Lukas Mödl; Claudia Kedor; Helma Freitag; Elisa Stein; Uta Hoppmann; Rebekka Rust; Kirsten Wittke; Nadja Siebert; Janina Behrens; Andreas Thiel; Frank Konietschke; Friedemann Paul; Carmen Scheibenbogen; Judith Bellmann-Strobl

doi:10.1016/j.eclinm.2023.102146

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

EClinicalMedicine. 2023 Aug 19:63:102146. doi: 10.1016/j.eclinm.2023.102146. eCollection 2023 Sep.

Authors

Franziska Legler^{1

2}, Lil Meyer-Arndt^{1

2

3}, Lukas Mödl⁴, Claudia Kedor⁵, Helma Freitag⁵, Elisa Stein⁵, Uta Hoppmann^{1

2

3}, Rebekka Rust^{1

2}, Kirsten Wittke⁵, Nadja Siebert², Janina Behrens², Andreas Thiel^{6

7}, Frank Konietschke⁴, Friedemann Paul^{1

2}, Carmen Scheibenbogen⁵, Judith Bellmann-Strobl^{1

2}

Affiliations

¹ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin and Berlin Institute of Health, Max Delbrück for Molecular Medicine, Experimental and Clinical Research Centre, 13125 Berlin, Germany.
² Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin and Berlin Institute of Health, NeuroCure Research Centre, 10117 Berlin, Germany.
³ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin and Berlin Institute of Health, Department for Neurology with Experimental Neurology, 10117 Berlin, Germany.
⁴ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Biometry and Clinical Epidemiology, 10117 Berlin, Germany.
⁵ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin and Berlin Institute of Health, Institute of Medical Immunology, 13353 Berlin, Germany.
⁶ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Regenerative Immunology and Aging, BIH Centre for Regenerative Therapies, 13353 Berlin, Germany.
⁷ Si-M / "Der Simulierte Mensch" a Science Framework of Technische Universität Berlin and Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.

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.

Keywords: Canadian consensus criteria; Chronic fatigue; Exertion intolerance; Hand grip strength; Myalgic encephalomyelitis/chronic fatigue syndrome (ME-CFS); Post-COVID-19 syndrome; Post-exertional malaise (PEM).