Long-term COVID-19 syndrome and endotheliopathy: pathophysiological mechanisms and therapeutic strategies


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Abstract

The article presents an overview of the significance of endothelial dysfunction in the pathogenesis of coronavirus infection and long-term COVID-19 syndrome. The mechanisms of endothelial damage are considered, data on the significance of glycocalyx damage in the formation of endotheliopathy in COVID-19 are presented. The analysis of modern therapeutic strategies for restoring endothelial function and preventing hypercoagulation after coronavirus infection is presented.

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About the authors

Tatiana Vladimirovna Adasheva

A.I. Yevdokimov Moscow State University of Medicine and Dentistry of the Ministry of Healthcare of Russia

Email: adashtv@mail.ru
Dr med. habil., professor, professor of the Department of polyclinic therapy

Elena I. Samorukova

A.I. Yevdokimov Moscow State University of Medicine and Dentistry of the Ministry of Healthcare of Russia

Email: wlrad@bk.ru
PhD in Medicine, assistant at the Department of polyclinic therapy

Ekaterina E. Gubernatorova

A.I. Yevdokimov Moscow State University of Medicine and Dentistry of the Ministry of Healthcare of Russia

Email: creativone@list.ru
PhD in Medicine, assistant at the Department of polyclinic therapy

Elena G. Lobanova

A.I. Yevdokimov Moscow State University of Medicine and Dentistry of the Ministry of Healthcare of Russia

Email: e.g.lobanova@mail.ru
Dr. med. habil., professor of the Department of pharmacology

Ekaterina I. Goruleva

Moscow Medical University «Reaviz»

Email: ekaterina.gorulyova@gmail.com
PhD in Medicine, associate professor of the Department of internal diseases

References

  1. Daniel Ayoubkhani, Kamlesh Khunti, Vahe Nafilyan, Thomas Maddox, Ben Humberstone, Sir Ian Diamond, Amitava Banerjee Epidemiology of post-COVID syndrome following hospitalisation with coronavirus: a retrospective cohort study doi: https://doi.org/10.1101/2021.01.15.21249885
  2. Yan Xie, Evan, Benjamin Bowe and Ziyad Al-Aly. Long-term cardiovascular outcomes of COVID-19. Nature Medicine / www.nature.com/naturemedicine. 07 February 2022. https://doi.org/10.1038/s41591-022-01689-3.
  3. Varga Z. et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 395, 1417-1418 (2020)
  4. Akwii R.G., Sajib M.S., Zahra F.T. & Mikelis C.M. Role of angiopoietin-2 in Vascular physiology and pathophysiology. Cells 8, 471 (2019).
  5. Scholz A., Plate K.H. & Reiss Y. Angiopoietin-2: a multifaceted cytokine that functions in both angiogenesis and inflammation. Ann. N. Y. Acad. Sci. 1347, 45-51 (2015).
  6. Didion S.P. Cellular and oxidative mechanisms associated with interleukin-6 signaling in the vasculature. Int J. Mol. Sci. 18, 2563 (2017).
  7. De Mello W.C. Chemical communication between heart cells is disrupted by intracellular renin and angiotensin II: implications for heart development and disease. Front. Endocrinol. 6, 72 (2015).
  8. Figueroa C.D. et al. Kinin B1 receptor regulates interactions between neutrophils and endothelial cells by modulating the levels of Mac-1, LFA-1 and intercellular adhesion molecule-1. Innate Immun. 21, 289-304 (2015).
  9. Lopatko Fagerstrom I. et al. Blockade of the kallikrein-kinin system reduces endothelial complement activation in vascular inflammation. 2020. EBioMedicine 47
  10. Pennathur S. & Heinecke J.W. Oxidative stress and endothelial dysfunction in vascular disease. Curr. Diabetes Rep. 7, 257-264 (2007).
  11. Di A., Mehta D. & Malik A.B. ROS-activated calcium signaling mechanisms regulating endothelial barrier function. Cell Calcium 60, 163-171 (2016).
  12. Scioli M.G. et al. Oxidative stress and new pathogenetic mechanisms in endothelial dysfunction: potential diagnostic biomarkers and therapeutic targets. J. Clin. Med. 9, 1995 (2020).
  13. Violi F. et al. Nox2 activation in covid-19. Redox Biol. 36, 101655 (2020).,
  14. Didion S.P. Cellular and oxidative mechanisms associated with interleukin-6 signaling in the vasculature. Int J. Mol. Sci. 18, 2563 (2017).
  15. Noris M., Benigni A. & Remuzzi G. The case of complement activation in COVID- 19 multiorgan impact. Kidney Int. 98, 314-322 (2020).
  16. Cugno M. et al. Complement activation in patients with COVID-19: A novel therapeutic target. J. Allergy Clin. Immunol. 146, 215-217 (2020).
  17. Wang L. C-reactive protein levels in the early stage of COVID-19. Med Mal. Infect. 50, 332-334 (2020).
  18. Luo X. et al. Prognostic value of C-reactive protein in patients with COVID-19. Clin. Infect. Dis. 71, 2174-2179 (2020).
  19. Devaraj S., Kumaresan P.R. & Jialal I. C-reactive protein induces release of both endothelial microparticles and circulating endothelial cells in vitro and in vivo: further evidence of endothelial dysfunction. Clin. Chem. 57, 1757-1761 (2011).
  20. Verma S. et al. A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation 106, 913-919 (2002).
  21. Verma S. et al. Endothelin antagonism and interleukin-6 inhibition attenuate the proatherogenic effects of C-reactive protein. Circulation 105, 1890-1896 (2002).
  22. Ohishi M.; Yamamoto K.; Rakugi H. Angiotensin (1-7) and other angiotensin peptides. Curr. Pharm. Des. 2013, 19, 3060-3064.
  23. Teuwen L.A.; Geldhof V.; Pasut A.; Carmeliet P. COVID-19: The vasculature unleashed. Nat. Rev. Immunol 2020, 20, 389-391.
  24. Pons S.; Fodil S.; Azoulay E.; Zafrani L. The vascular endothelium: The cornerstone of organ dysfunction in severe SARS-CoV-2 infection. Crit. Care 2020, 24, 353.
  25. Okada H.; Yoshida S.; Hara A.; Ogura S.; Tomita H. Vascular endothelial injury exacerbates coronavirus disease 2019: The role of endothelial glycocalyx protection. Microcirculation 2020, e12654.
  26. Uchimido R.; Schmidt E.P.; Shapiro N.I. The glycocalyx: A novel diagnostic and therapeutic target in sepsis. Crit. Care 2019, 23, 16.
  27. Yamaoka-Tojo М. Vascular Endothelial Glycocalyx Damage in COVID-19 Int. J. Mol. Sci. 2020, 21, 9712; doi: 10.3390/ijms21249712
  28. Yamaoka-Tojo M. A note on systemic inflammatory-reactive microvascular endotheliopathy (SIRME): Prevention of cardiovascular disease and COVID-19. JJCDP 2020, 55, 1-14.].
  29. Butler P.J.; Bhatnagar A. Mechanobiology of the abluminal glycocalyx. Biorheology 2019, 56, 101-112.
  30. Betteridge K.B.; Arkill K.P.; Neal C.R.; Harper S.J.; Foster R.R.; Satchell S.C.; Bates D.O.; Salmon A.H.J. Sialic acids regulate microvessel permeability, revealed by novel in vivo studies of endothelial glycocalyx structure and function. J. Physiol. 2017, 595, 5015-5035. [CrossRef]
  31. Butler M.J.; Ramnath R.; Kadoya H.; Desposito D.; Riquier-Brison A.; Ferguson J.K.; Onions K.L.; Ogier A.S.; ElHegni H.; Coward R.J. et al. Aldosterone induces albuminuria via matrix metalloproteinase-dependent damage of the endothelial glycocalyx. Kidney Int. 2019, 95, 94-107.
  32. Curry F.E. Layer upon layer: The functional consequences of disrupting the glycocalyx-endothelial barrier in vivo and in vitro. Cardiovasc. Res. 2017, 113, 559-561
  33. Thi M.M.; Tarbell J.M.; Weinbaum S.; Spray D.C. The role of the glycocalyx in reorganization of the actin cytoskeleton under fluid shear stress: A "bumper-car" model. Proc. Natl. Acad. Sci. USA 2004, 101, 16483-16488.
  34. Bar A.; Targosz-Korecka M.; Suraj J.; Proniewski B.; Jasztal A.; Marczyk B.; Sternak M.; Przybylo M.; Kurpinska A.;Walczak M. et al. Degradation of Glycocalyx and Multiple Manifestations of Endothelial Dysfunction Coincide in the Early Phase of Endothelial Dysfunction Before Atherosclerotic Plaque Development in Apolipoprotein E/Low-Density Lipoprotein Receptor-Deficient Mice. J. Am. Heart Assoc. 2019, 8, e011171. ].
  35. Tang T.H.; Alonso S.; Ng L.F.; Thein T.L.; Pang V.J.; Leo Y.S.; Lye D.C.; Yeo T.W. Increased Serum Hyaluronic Acid and Heparan Sulfate in Dengue Fever: Association with Plasma Leakage and Disease Severity. Sci. Rep. 2017, 7, 46191.
  36. Chelazzi C., Villa G., Mancinelli P., De Gaudio A.R., Adembri C. Glycocalyx and sepsis-induced alterations in vascular permeability. Crit Care 2015;19:26.
  37. Hideshi Okada 1, Shozo Yoshida, Akira Hara, Shinji Ogura, Hiroyuki Tomita. Vascular endothelial injury exacerbates coronavirus disease 2019: The role of endothelial glycocalyx protection PULMONARY AND CRITICAL CARE PERSPECTIVES. doi:10.1111/ MICC.12654
  38. Helen Fogarty 1, Liam Townsend 2, 3, Hannah Morrin1 Persistent Endotheliopathy in the Pathogenesis of Long COVID Syndrome. Journal of Thrombosis and Haemostasis. 10 August 2021. doi: 10.1111/jth.15490
  39. Временные методические рекомендации «Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19). Версия 15, 22.02.2022.
  40. Hasan K. Siddiqi, Peter Libby, Paul M. Ridker. COVID-19 - A vascular disease. Trends in Cardiovascular Medicine 31 (2021) 1-5 https://doi.org/10.1016/j.tcm.2020.10.005
  41. Broekhuizen L.N., Lemkes B.A., Mooij H.L. et al. Effect of sulodexide on endothelial glycocalyx and vascular permeability in patients with type 2 diabetes mellitus. Diabetologia. 2010; 53 (12): 2646-2655.
  42. V. Masola et al. Glycosaminoglycans, proteoglycans and sulodexide and the endothelium: biological roles and pharmacological effects International angiology: a journal of the International Union of Angiology ■ June 2014
  43. F. Mannello D. Ligi M. canale and J. Raffetto, "Sulodexide Down-Regulates the Release of Cytokines, Chemokines, and Leukocyte Colony Stimulating Factors from Human Macrophages: Role of Glycosaminoglycans in Inflammatory Pathways of Chronic Venous," Current Vascular Pharmacology, vol. 12, no. 1, pp. 173-185, 2014
  44. ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Epub 2020 Jan 30
  45. Management of chronic venous disorders of the lower limbs. Guidelines
  46. According to Scientific Evidence. Part II. journal of the International Union of Angiology ■ March 2020 doi: 10.23736/S0392-9590.20.04388-6
  47. Alejandro J. Gonzalez-Ochoa, Joseph D. Raffetto, Ana G. Hernandez, Nestor Zavala, Obed Gutierrez, Arturo Vargas, Jorge Loustaunau, Sulodexide in the Treatment of Patients with Early Stages of COVID-19: A Randomized Controlled Trial, Thromb Haemost. 2021 Mar 7. doi: 10.1055/a-1414-5216

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