Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and chronic fatigue syndrome (ME/CFS)

Milan Haffke; Helma Freitag; Gordon Rudolf; Martina Seifert; Wolfram Doehner; Nadja Scherbakov; Leif Hanitsch; Kirsten Wittke; Sandra Bauer; Frank Konietschke; Friedemann Paul; Judith Bellmann-Strobl; Claudia Kedor; Carmen Scheibenbogen; Franziska Sotzny

doi:10.1186/s12967-022-03346-2

Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and chronic fatigue syndrome (ME/CFS)

J Transl Med. 2022 Mar 22;20(1):138. doi: 10.1186/s12967-022-03346-2.

Authors

Milan Haffke¹, Helma Freitag², Gordon Rudolf², Martina Seifert^{2

3

4}, Wolfram Doehner^{3

4

5

6}, Nadja Scherbakov^{3

4

5

6}, Leif Hanitsch², Kirsten Wittke², Sandra Bauer², Frank Konietschke⁷, Friedemann Paul^{8

9

10}, Judith Bellmann-Strobl^{8

9

10}, Claudia Kedor², Carmen Scheibenbogen^#², Franziska Sotzny^#²

Affiliations

¹ Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu Berlin, Berlin, Germany. milan.haffke@charite.de.
² Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu Berlin, Berlin, Germany.
³ Berlin Institute of Health at Charité-Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany.
⁴ DZHK (German Center for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.
⁵ Department of Cardiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu Berlin, Berlin, Germany.
⁶ Center for Stroke Research Berlin (CSB), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu Berlin, Berlin, Germany.
⁷ Institute of Biometry and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt Universität Zu Berlin, Berlin, Germany.
⁸ Experimental and Clinical Research Center (ECRC), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu Berlin, Berlin, Germany.
⁹ NeuroCure Clinical Research Center (NCRC), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu Berlin, Berlin, Germany.
¹⁰ Max Delbrueck Center for Molecular Medicine, Experimental and Clinical Research Center (ECRC), Berlin, Germany.

^# Contributed equally.

Abstract

Background: Fatigue, exertion intolerance and post-exertional malaise are among the most frequent symptoms of Post-COVID Syndrome (PCS), with a subset of patients fulfilling criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). As SARS-CoV-2 infects endothelial cells, causing endotheliitis and damaging the endothelium, we investigated endothelial dysfunction (ED) and endothelial biomarkers in patients with PCS.

Methods: We studied the endothelial function in 30 PCS patients with persistent fatigue and exertion intolerance as well as in 15 age- and sex matched seronegative healthy controls (HCs). 14 patients fulfilled the diagnostic criteria for ME/CFS. The other patients were considered to have PCS. Peripheral endothelial function was assessed by the reactive hyperaemia index (RHI) using peripheral arterial tonometry (PAT) in patients and HCs. In a larger cohort of patients and HCs, including post-COVID reconvalescents (PCHCs), Endothelin-1 (ET-1), Angiopoietin-2 (Ang-2), Endocan (ESM-1), IL-8, Angiotensin-Converting Enzyme (ACE) and ACE2 were analysed as endothelial biomarkers.

Results: Five of the 14 post-COVID ME/CFS patients and five of the 16 PCS patients showed ED defined by a diminished RHI (< 1.67), but none of HCs exhibited this finding. A paradoxical positive correlation of RHI with age, blood pressure and BMI was found in PCS but not ME/CFS patients. The ET-1 concentration was significantly elevated in both ME/CFS and PCS patients compared to HCs and PCHCs. The serum Ang-2 concentration was lower in both PCS patients and PCHCs compared to HCs.

Conclusion: A subset of PCS patients display evidence for ED shown by a diminished RHI and altered endothelial biomarkers. Different associations of the RHI with clinical parameters as well as varying biomarker profiles may suggest distinct pathomechanisms among patient subgroups.

Keywords: Endothelial dysfunction; Endothelin-1; Myalgic encephalomyelitis/chronic fatigue syndrome; Post-COVID syndrome; Reactive hyperaemia index.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
COVID-19* / complications
Endothelial Cells
Endothelium
Fatigue Syndrome, Chronic*
Humans
Post-Acute COVID-19 Syndrome
SARS-CoV-2

Substances

Biomarkers