Long COVID and the cardiovascular system—elucidating causes and cellular mechanisms in order to develop targeted diagnostic and therapeutic strategies: a joint Scientific Statement of the ESC Working Groups on Cellular Biology of the Heart and Myocardial and Pericardial Diseases

Author:

Gyöngyösi Mariann1,Alcaide Pilar2,Asselbergs Folkert W34,Brundel Bianca J J M5,Camici Giovanni G67,Martins Paula da Costa89ORCID,Ferdinandy Péter1011,Fontana Marianna12ORCID,Girao Henrique13ORCID,Gnecchi Massimiliano1415ORCID,Gollmann-Tepeköylü Can16,Kleinbongard Petra17ORCID,Krieg Thomas18ORCID,Madonna Rosalinda19,Paillard Melanie20,Pantazis Antonis2122,Perrino Cinzia23ORCID,Pesce Maurizio24ORCID,Schiattarella Gabriele G25262728,Sluijter Joost P G2930ORCID,Steffens Sabine3132ORCID,Tschöpe Carsten33,Van Linthout Sophie33ORCID,Davidson Sean M34

Affiliation:

1. Division of Cardiology, 2nd Department of Internal Medicine, Medical University of Vienna , Waehringer Guertel 18-20, 1090 Vienna , Austria

2. Department of Immunology, Tufts University School of Medicine , Boston, MA , USA

3. Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University , Utrecht , The Netherlands

4. Health Data Research UK and Institute of Health Informatics, University College London , London , UK

5. Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam , The Netherlands

6. Center for Molecular Cardiology, University of Zurich , Schlieren , Switzerland

7. Department of Cardiology, University Heart Center, University Hospital , Zurich , Switzerland

8. Department of Cardiology, CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University , Maastricht , The Netherlands

9. Department of Molecular Genetics, Faculty of Sciences and Engineering, Maastricht University , Maastricht , The Netherlands

10. Department of Pharmacology and Pharmacotherapy, Semmelweis University , Budapest , Hungary

11. Pharmahungary Group , Szeged , Hungary

12. Division of Medicine, Royal Free Hospital London, University College London , London , UK

13. Center for Innovative Biomedicine and Biotechnology (CIBB), Clinical Academic Centre of Coimbra (CACC), Faculty of Medicine, Univ Coimbra, Institute for Clinical and Biomedical Research (iCBR) , Coimbra , Portugal

14. Department of Molecular Medicine, Unit of Cardiology, University of Pavia , Pavia , Italy

15. Unit of Translational Cardiology, Division of Cardiology, Fondazione IRCCS Policlinico San Matteo , Pavia , Italy

16. Department of Cardiac Surgery, Medical University of Innsbruck , Innsbruck , Austria

17. Institut für Pathophysiologie, Westdeutsches Herz- und Gefäßzentrum, Universitätsklinikum Essen , Essen , Germany

18. Department of Medicine, University of Cambridge, Addenbrooke's Hospital , Cambridge , UK

19. Department of Pathology, Institute of Cardiology, University of Pisa , Pisa , Italy

20. Laboratoire CarMeN-équipe IRIS, INSERM, INRA, Université Claude Bernard Lyon-1 , INSA-Lyon, Univ-Lyon, 69500 Bron , France

21. National Heart and Lung Institute, Imperial College London , London , UK

22. Cardiovascular Research Centre at Royal Brompton and Harefield Hospitals , London , UK

23. Department of Advanced Biomedical Sciences, Federico II University , Via Pansini 5, 80131 Naples , Italy

24. Unità di Ingegneria Tissutale cardiovascolare, Centro Cardiologico Monzino, IRCCS , Milan , Italy

25. Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University , Naples , Italy

26. Center for Cardiovascular Research (CCR), Department of Cardiology, Charité—Universitätsmedizin Berlin , Berlin , Germany

27. DZHK (German Centre for Cardiovascular Research), Partner Site Berlin , Berlin , Germany

28. Translational Approaches in Heart Failure and Cardiometabolic Disease, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) , Berlin , Germany

29. Laboratory of Experimental Cardiology, Cardiology, UMC Utrecht Regenerative Medicine Center , Utrecht , The Netherlands

30. Circulatory Health Laboratory, Utrecht University, University Medical Center Utrecht , Utrecht , The Netherlands

31. Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-Universität , Munich , Germany

32. Germany and Munich Heart Alliance, DZHK Partner Site Munich , Munich , Germany

33. Berlin Institute of Health (BIH) at Charité, Universitätmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), German Center for Cardiovascular Research (DZHK), Partner site Berlin and Dept Cardiology (CVK), Charité , Berlin , Germany

34. The Hatter Cardiovascular Institute, University College London , 67 Chenies Mews, WC1E 6HX London , UK

Abstract

Abstract Long COVID has become a world-wide, non-communicable epidemic, caused by long-lasting multiorgan symptoms that endure for weeks or months after SARS-CoV-2 infection has already subsided. This scientific document aims to provide insight into the possible causes and therapeutic options available for the cardiovascular manifestations of long COVID. In addition to chronic fatigue, which is a common symptom of long COVID, patients may present with chest pain, ECG abnormalities, postural orthostatic tachycardia, or newly developed supraventricular or ventricular arrhythmias. Imaging of the heart and vessels has provided evidence of chronic, post-infectious perimyocarditis with consequent left or right ventricular failure, arterial wall inflammation, or microthrombosis in certain patient populations. Better understanding of the underlying cellular and molecular mechanisms of long COVID will aid in the development of effective treatment strategies for its cardiovascular manifestations. A number of mechanisms have been proposed, including those involving direct effects on the myocardium, microthrombotic damage to vessels or endothelium, or persistent inflammation. Unfortunately, existing circulating biomarkers, coagulation, and inflammatory markers, are not highly predictive for either the presence or outcome of long COVID when measured 3 months after SARS-CoV-2 infection. Further studies are needed to understand underlying mechanisms, identify specific biomarkers, and guide future preventive strategies or treatments to address long COVID and its cardiovascular sequelae.

Funder

UCL Hospitals NIHR Biomedical Research Center

National Institutes of Health

Austrian Scientific Fund

British Heart Foundation

Università e Ricerca Scientifica

Swiss Heart Foundation and Swiss National Science Foundation

National Research, Development and Innovation Office of Hungary

Dutch CardioVascular Alliance

Dutch Heart Foundation grant

Publisher

Oxford University Press (OUP)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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