Fighting Post-COVID and ME/CFS - development of curative therapies

doi:10.3389/fmed.2023.1194754

. 2023 Jun 15:10:1194754.

doi: 10.3389/fmed.2023.1194754. eCollection 2023.

Fighting Post-COVID and ME/CFS - development of curative therapies

Carmen Scheibenbogen¹, Judith Theresia Bellmann-Strobl^{2

3

4}, Cornelia Heindrich¹, Kirsten Wittke¹, Elisa Stein¹, Christiana Franke⁵, Harald Prüss^{5

6}, Hannah Preßler⁵, Marie-Luise Machule⁵, Heinrich Audebert⁵, Carsten Finke⁵, Hanna Gwendolyn Zimmermann^{2

3

4}, Birgit Sawitzki^{1

7}, Christian Meisel^{1

8}, Markus Toelle⁹, Anne Krueger⁹, Anna C Aschenbrenner¹⁰, Joachim L Schultze^{10

11

12}, Marc D Beyer^{10

11}, Markus Ralser^{13

14}, Michael Mülleder¹³, Leif Erik Sander¹⁵, Frank Konietschke¹³, Friedemann Paul^{2

3

4}, Silvia Stojanov¹⁶, Lisa Bruckert¹⁷, Dennis M Hedderich¹⁸, Franziska Knolle¹⁸, Gabriela Riemekasten¹⁹, Maria J G T Vehreschild²⁰, Oliver A Cornely^{21

22

23}, Uta Behrends^{16

24

25}, Susen Burock¹⁷

Affiliations

¹ Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany.
² Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin, Berlin, Germany.
³ NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁴ Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
⁵ Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany.
⁶ Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Berlin, Germany.
⁷ Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Immunomics, Berlin, Germany.
⁸ Department of Immunology, Labor Berlin - Charité Vivantes GmbH, Berlin, Germany.
⁹ Department of Nephrology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany.
¹⁰ Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.
¹¹ PRECISE Platform for Single Cell Genomics and Epigenomics, DZNE and University of Bonn, Bonn, Germany.
¹² Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
¹³ Institute of Biochemistry, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
¹⁴ The Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
¹⁵ Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
¹⁶ Childrens' Hospital, School of Medicine, Technical University of Munich, Munich, Germany.
¹⁷ Clinical Trial Office, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany.
¹⁸ Department of Neuroradiology, School of Medicine, Technical University of Munich, Munich, Germany.
¹⁹ Department of Rheumatology, University Medical Center Schleswig-Holstein Campus Lübeck, Lübeck, Germany.
²⁰ Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany.
²¹ Department of Internal Medicine, University Hospital Cologne, Cologne, Germany.
²² German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Germany.
²³ University of Cologne, Faculty of Medicine, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.
²⁴ German Center for Infection Research (DZIF), Berlin, Germany.
²⁵ AGV Research Unit Gene Vectors, Helmholtz Center Munich (HMGU), Munich, Germany.

PMID: 37396922
PMCID: PMC10309204
DOI: 10.3389/fmed.2023.1194754

Fighting Post-COVID and ME/CFS - development of curative therapies

Carmen Scheibenbogen et al. Front Med (Lausanne). 2023.

. 2023 Jun 15:10:1194754.

doi: 10.3389/fmed.2023.1194754. eCollection 2023.

Authors

Affiliations

¹ Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany.
² Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin, Berlin, Germany.
³ NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁴ Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
⁵ Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany.
⁶ Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Berlin, Germany.
⁷ Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Immunomics, Berlin, Germany.
⁸ Department of Immunology, Labor Berlin - Charité Vivantes GmbH, Berlin, Germany.
⁹ Department of Nephrology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany.
¹⁰ Systems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.
¹¹ PRECISE Platform for Single Cell Genomics and Epigenomics, DZNE and University of Bonn, Bonn, Germany.
¹² Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
¹³ Institute of Biochemistry, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
¹⁴ The Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
¹⁵ Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
¹⁶ Childrens' Hospital, School of Medicine, Technical University of Munich, Munich, Germany.
¹⁷ Clinical Trial Office, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany.
¹⁸ Department of Neuroradiology, School of Medicine, Technical University of Munich, Munich, Germany.
¹⁹ Department of Rheumatology, University Medical Center Schleswig-Holstein Campus Lübeck, Lübeck, Germany.
²⁰ Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany.
²¹ Department of Internal Medicine, University Hospital Cologne, Cologne, Germany.
²² German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Germany.
²³ University of Cologne, Faculty of Medicine, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.
²⁴ German Center for Infection Research (DZIF), Berlin, Germany.
²⁵ AGV Research Unit Gene Vectors, Helmholtz Center Munich (HMGU), Munich, Germany.

PMID: 37396922
PMCID: PMC10309204
DOI: 10.3389/fmed.2023.1194754

Abstract

The sequela of COVID-19 include a broad spectrum of symptoms that fall under the umbrella term post-COVID-19 condition or syndrome (PCS). Immune dysregulation, autoimmunity, endothelial dysfunction, viral persistence, and viral reactivation have been identified as potential mechanisms. However, there is heterogeneity in expression of biomarkers, and it is unknown yet whether these distinguish different clinical subgroups of PCS. There is an overlap of symptoms and pathomechanisms of PCS with postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). No curative therapies are available for ME/CFS or PCS. The mechanisms identified so far provide targets for therapeutic interventions. To accelerate the development of therapies, we propose evaluating drugs targeting different mechanisms in clinical trial networks using harmonized diagnostic and outcome criteria and subgrouping patients based on a thorough clinical profiling including a comprehensive diagnostic and biomarker phenotyping.

Keywords: COVID-19; ME/CFS; autoantibodies; clinical trials; endothelial dysfunction; inflammation; post-COVID.

Copyright © 2023 Scheibenbogen, Bellmann-Strobl, Heindrich, Wittke, Stein, Franke, Prüss, Preßler, Machule, Audebert, Finke, Zimmermann, Sawitzki, Meisel, Toelle, Krueger, Aschenbrenner, Schultze, Beyer, Ralser, Mülleder, Sander, Konietschke, Paul, Stojanov, Bruckert, Hedderich, Knolle, Riemekasten, Vehreschild, Cornely, Behrends and Burock.

PubMed Disclaimer

Conflict of interest statement

The Charité Universitaetsmedizin Berlin holds a patent for the use of vericiguat in Post-COVID Syndrome. CS, JB-S, CH, KW, ES, CaF, HPru, HPre, M-LM, HA, ChF, HZ, BS, CM, MT, AK, MR, MM, LS, FKo, FP, LB, and SB are employed at Charité Universitaetsmedizin Berlin. CM was employed by Labor Berlin - Charité Vivantes GmbH. The remaining authors declare that the research was conducted in the absence of any comercial or financial relationships that could be construed as a potential conflict of interest. The Handling Editor NS declared a past collaboration with the Author CS.

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References

1. Ballering AV, van Zon SKR, Olde Hartman TC, Rosmalen JGM. Persistence of somatic symptoms after COVID-19 in the Netherlands: an observational cohort study. Lancet. (2022) 400:452–61. doi: 10.1016/S0140-6736(22)01214-4, PMID: - DOI - PMC - PubMed
1. Al-Aly Z, Bowe B, Xie Y. Long COVID after breakthrough SARS-CoV-2 infection. Nat Med. (2022) 28:1461–7. doi: 10.1038/s41591-022-01840-0, PMID: - DOI - PMC - PubMed
1. Tran VT, Porcher R, Pane I, Ravaud P. Course of post COVID-19 disease symptoms over time in the ComPaRe long COVID prospective e-cohort. Nat Commun. (2022) 13:1812. doi: 10.1038/s41467-022-29513-z, PMID: - DOI - PMC - PubMed
1. Nittas V, Gao M, West EA, Ballouz T, Menges D, Wulf Hanson S, et al. . Long COVID through a public health Lens: an umbrella review. Public Health Rev. (2022) 43:1604501. doi: 10.3389/phrs.2022.1604501, PMID: - DOI - PMC - PubMed
1. Behnood SA, Shafran R, Bennett SD, Zhang AXD, O'Mahoney LL, Stephenson TJ, et al. . Persistent symptoms following SARS-CoV-2 infection amongst children and young people: a meta-analysis of controlled and uncontrolled studies. J Infect. (2022) 84:158–70. doi: 10.1016/j.jinf.2021.11.011 - DOI - PMC - PubMed

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[1] Ballering AV, van Zon SKR, Olde Hartman TC, Rosmalen JGM. Persistence of somatic symptoms after COVID-19 in the Netherlands: an observational cohort study. Lancet. (2022) 400:452–61. doi: 10.1016/S0140-6736(22)01214-4, PMID: - DOI - PMC - PubMed

[2] Ballering AV, van Zon SKR, Olde Hartman TC, Rosmalen JGM. Persistence of somatic symptoms after COVID-19 in the Netherlands: an observational cohort study. Lancet. (2022) 400:452–61. doi: 10.1016/S0140-6736(22)01214-4, PMID: - DOI - PMC - PubMed

[3] Al-Aly Z, Bowe B, Xie Y. Long COVID after breakthrough SARS-CoV-2 infection. Nat Med. (2022) 28:1461–7. doi: 10.1038/s41591-022-01840-0, PMID: - DOI - PMC - PubMed

[4] Al-Aly Z, Bowe B, Xie Y. Long COVID after breakthrough SARS-CoV-2 infection. Nat Med. (2022) 28:1461–7. doi: 10.1038/s41591-022-01840-0, PMID: - DOI - PMC - PubMed

[5] Tran VT, Porcher R, Pane I, Ravaud P. Course of post COVID-19 disease symptoms over time in the ComPaRe long COVID prospective e-cohort. Nat Commun. (2022) 13:1812. doi: 10.1038/s41467-022-29513-z, PMID: - DOI - PMC - PubMed

[6] Tran VT, Porcher R, Pane I, Ravaud P. Course of post COVID-19 disease symptoms over time in the ComPaRe long COVID prospective e-cohort. Nat Commun. (2022) 13:1812. doi: 10.1038/s41467-022-29513-z, PMID: - DOI - PMC - PubMed

[7] Nittas V, Gao M, West EA, Ballouz T, Menges D, Wulf Hanson S, et al. . Long COVID through a public health Lens: an umbrella review. Public Health Rev. (2022) 43:1604501. doi: 10.3389/phrs.2022.1604501, PMID: - DOI - PMC - PubMed

[8] Nittas V, Gao M, West EA, Ballouz T, Menges D, Wulf Hanson S, et al. . Long COVID through a public health Lens: an umbrella review. Public Health Rev. (2022) 43:1604501. doi: 10.3389/phrs.2022.1604501, PMID: - DOI - PMC - PubMed

[9] Behnood SA, Shafran R, Bennett SD, Zhang AXD, O'Mahoney LL, Stephenson TJ, et al. . Persistent symptoms following SARS-CoV-2 infection amongst children and young people: a meta-analysis of controlled and uncontrolled studies. J Infect. (2022) 84:158–70. doi: 10.1016/j.jinf.2021.11.011 - DOI - PMC - PubMed

[10] Behnood SA, Shafran R, Bennett SD, Zhang AXD, O'Mahoney LL, Stephenson TJ, et al. . Persistent symptoms following SARS-CoV-2 infection amongst children and young people: a meta-analysis of controlled and uncontrolled studies. J Infect. (2022) 84:158–70. doi: 10.1016/j.jinf.2021.11.011 - DOI - PMC - PubMed

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Fighting Post-COVID and ME/CFS - development of curative therapies

Affiliations

Fighting Post-COVID and ME/CFS - development of curative therapies

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Affiliations

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