Endotheliitis after COVID-19 Infection Requires Optimization of Chronic Disease Prevention

Main Article Content

Gumpanart Veerakul, MD

Abstract

The outbreak of a new coronavirus–infection (2019-nCoV, so-called COVID-19) started in Wuhan, China1 and shortly became a pandemic to create an enormous burden on the global health care and economic system.2,3 In August 2021, the cumulative infected cases and the cumulative death, per world health organization (WHO) reporting, were over 266 million and almost 4.4 million worldwide, respectively.2 In Thailand, the number of polymerase chain reaction (PCR) confirmed COVID -19 cases increased beyond one million cases in August 2021.4 Although the majority of cases had only mild symptoms, critical cases developed severe pneumonia with respiratory failure, and many died.5,6 Most of the deaths occurred in elderly patients who had chronic illness (non-communicable disease (NCD)) including diabetes mellitus (DM), hypertension (HT), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD).6-8 Studies revealed that the endothelial and epithelial cells that express angiotensin-converting enzyme 2 (ACE-2) receptor are the entry site for COVID -19 viral invasion. The subsequent inflammation, so-called endotheliitis, induces micro thrombi generation in capillary beds of lungs, kidneys, and myocardium, and contributes to cardiovascular morbidity and mortality.8-11 This review summarizes the link between COVID -19 virus induced endotheliitis and poor prognosis in those with prior endothelial dysfunction. This relationship urges improvements in strategies to control and prevent these chronic conditions.

Article Details

How to Cite
1.
Veerakul, MD G. Endotheliitis after COVID-19 Infection Requires Optimization of Chronic Disease Prevention. BKK Med J [Internet]. 2022 Feb. 26 [cited 2024 Dec. 3];18(1):47. Available from: https://he02.tci-thaijo.org/index.php/bkkmedj/article/view/254747
Section
Reviews Article

References

1. World Health Organization (WHO). Novel Coronavirus (2019- nCoV) Situation Report-1, 21 Janaury 2020. (Accessed August 22, 2021, at https://apps.who.int/iris/bitstream/han dle/10665/330760/nCoVsitrep21Jan2020-eng. pdf?sequence=3&isAllowed=y).

2. Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20. doi: 10.1056/NEJMoa200203.

3. World Health Organization (WHO). Weekly epidemiological update on COVID-19 - 17 August 2021. (Accessed August 22, 2021, at https://www.who.int/publications/m/item/ weekly-epidemiological-update-on-covid-19---17-au gust-2021).

4. Congressional Research Service. Global economic effects of COVID-19: Updated July 9, 2021. (Accessed August 22, 2021, at https://sgp.fas.org/crs/row/R46270.pdf).

5. The World Bank Press release, June 20, 2020: Major Impact from COVID-19 to Thailand’s Economy, Vulnerable Households, Firms: Report. 2020. (Accessed August 22, 2021, at https:// www.worldbank.org/en/news/press-release/2020/06/30/ma jor-impact-from-covid-19-to-thailands-economy-vulnerable households-firms-report).

6. World Health Organization (WHO). Coronavirus disease 2019 (COVID-19): WHO Thailand Situation Update No.198 August 26,2021. (Accessed September 7, 2021, at https://cdn.who. int/media/docs/default-source/searo/thailand/2021_08_26_ eng-sitrep-198-covid19.pdf?sfvrsn=465abbe5_6).

7. Du RH, Liang LR, Yang CQ, et al. Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study. Eur Respir J 2020:55(5);2000524. doi:10.1183/13993003.00524-2020.

8. Qiu P, Zhou Y, Wang F, et al. Clinical characteristics, laboratory outcome characteristics, comorbidities, and complications of related COVID-19 deceased: a systematic review and meta-analysis. Aging Clin Exp Res 2020; 30(9):1– 10. doi:10.1007/s40520-020-01664-3.

9. Mehraeen E, Karimi A, Barzegary A. et al. Predictors of mortality in patients with COVID-19-a systematic review. Eur J Integr Med 2020;40:101226. doi: 10.1016/j.eu jim.2020.101226

10. Nikoloski Z, Alqunaibet AM, Alfawazal RA et al. Covid-19 and non-communicable diseases: evidence from a systematic literature review. BMC Public Health 2021;21:1068. doi:10.1186/s12889-021-11116-w.

11. Bermejo-Martin J. F, Almansa R, Torres, A, et al. COVID-19 as a cardiovascular disease: the potential role of chronic endothelial dysfunction. Cardiovasc Res 2020;116(10); e132–e133. doi: 10.1093/cvr/cvaa140.

12. Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 Patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA 2020;323(16):1574-81. doi:10.1001/jama.2020.5394.

13. Tipnis SR, Hooper NM, Hyde R, et al. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem 2000;275:33238-43. doi: 10.1074/jbc.M002615200.

14. Donoghue M, Hsieh F, Baronas E, et al. A novel angiotensin converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res 2000; 87:E1–E9. doi:10.1161/01.RES.87.5.e1.

15. Harmer D, Gilbert M, Borman R, et al. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett 2002;532 (1-2):107-11. doi: 10.1016/s0014-5793(02)03640-2.

16. Ferrario CM. Angiotensin-coverting enzyme 2 and Angiotensin-(1-7). an evolving story in cardiovascular Regulation. Hypertension 2005; 47(3):515-21. doi: 10.1161/01. HYP.0000196268.08909.fb.

17. Ksiazek TG, Erdman D, Cynthia S, et al. A Novel Coronavirus Associated with Severe Acute Respiratory Syndrome. N Engl J Med 2003; 348:1953-66. doi: 10.1056/NEJMoa030781.

18. Hamming I, Timens W, Bulthuis MLC, et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first-step in understanding SARS pathogenesis. J Pathol. 2004; 203(2): 631–7. doi:10.1002/path.1570.

19. Li WH, Moore MJ, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003; 426:450-4. doi: 10.1038/nature02145.

20. Wan Y, Shang J, Graham R, et al. Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. J Virol 2020;94(7):e00127-20. doi:10.1128/JVI.00127-20

21. Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nature Microbiol 2020;5(4):562-9. doi: 10.1038/s41564-020-0688-y.

22. Wrapp D, Wang N, Corbett KS, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 2020;367(6483):1260-3. doi:10.1126/science.abb2507.

23. Hoffmann M, Kleine-Weber H, Schroeder, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181(2): 271–280.e8. doi:10.1016/j.cell.2020.02.052.

24. Bayati A, Kumar R, Francis V, et al. SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis. J Biol Chem 2021;296:100306.doi: 10.1016/j.jbc.2021.100306.

25. Lebeau G, Vagner D, Frumence E, et al. Deciphering SARS-CoV-2 virologic and immunologic features. Int J Mol Sci 2020;21(16):5932. doi: 10.3390/ijms21165932.

26. Chistiakov DA, Orekhov AN, Bobryskov YV. Endothelial barrier and its abnormalities in cardiovascular disease. Front Physiol 2015;6:365. doi: 10.3389/fphys.2015.00365.

27. Armulik A, Genove G, Betshaltz C, et al. Pericytes: develop mental, physiological, and pathological perspectives, problems, and promises. Dev Cell 2011;21(2):193-21. doi: 10.1016/j.devcel.2011.07.001.

28. Godo S, Shimokawa H. Endothelial functions. Arterioscler Thromb Vasc Biol 2017;37:e108–e114. doi: 10.1161/ ATVBAHA.117.309813.

29. Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020; 395: 1417–8. doi:10.1016/S0140-6736.

30. Puelles VG, Lütgehetmann M, Lindenmeyer MT, et al. Multiorgan and Renal Tropism of SARS-CoV-2. N Engl J Med 2020; 383:590-2. doi: 10.1056/NEJMc2011400.

31. Maccio U, Zinkernagel AS, Shambat SM, et al. SARS-CoV-2 leads to a small vessel endotheliitis in the heart. EBioMedicine 2021;63:103182. doi:10.1016/j.ebiom. 2020.103182

32. Rhodes RH, Love GL, Da Silva Lameira F et al. Acute endotheliitis (Type 3 hypersensitivity vasculitis) in ten COVID-19 autopsy brains. MedRxiv preprint doi:10.1101/2 021.01.16.21249632.

33. Ilonzo N, Kumar S, Borazan N, et al. Endotheliitis in Coronavirus disease 2019-positive patients after extremity amputation for acute thrombotic events. Ann Vasc Surg 2021;72:209-15. doi: 10.1016/j.avsg.2020.12.004.

34. Hanspetera B, Cockcroft J, Deanfield J. Endothelial function and dysfunction. Part II: Association with cardiovascular risk factors and diseases. A statement by the Working Group on Endothelins and Endothelial Factors of the European Society of Hypertension. J Hypertens 2005 ;23(2):233-46. doi: 10.1097/00004872-200502000-00001.

35. Zeiher AM, Schachinger V, Minners J. Long-term cigarette smoking impairs endothelium-dependent coronary arterial vasodilator function. Circulation 1995; 92:1094-100. doi: 10.1161/01.cir.92.5.1094.

36. Newby DE, Wright RA, Labinjoh C, et al. Endothelial dysfunction, impaired endogenous fibrinolysis, and cigarette smoking: a mechanism for arterial thrombosis and myocardial infarction. Circulation 1999; 99:1411-5. doi: 10.1161/01. cir.99.11.1411.

37. Chan NN, Vallance P, Colhoun HM. Endothelium-dependent and -independent vascular dysfunction in type 1 diabetes: role of conventional risk factors, sex, and glycemic control. Arterioscler Thromb Vasc Biol 2003;23:1048–54. doi: 10.1161/01.ATV.0000072968.00157.6B

38. Williams SB, Cusco JA, Roddy MA, et al. Impaired nitric oxide-mediated vasodilation in patients with non-insulin dependent diabetes mellitus. J Am Coll Cardiol 1996; 27: 567-74. doi: 10.1016/0735-1097(95)00522-6.

39. Makimattila S, Liu ML, Vakkilainen J, et al. Impaired endothelium-dependent vasodilation in type 2diabetes. Relation to LDL size, oxidized LDL, and antioxidants. Diabetes Care 1999;22:973-81. doi: 10.2337/diacare.22.6.973.

40. Krentz AJ, Clough G, Byrne CD. Interactions between microvascular and macrovascular disease in diabetes: patho physiology and therapeutic implications. Diabetes Obes Metab 2007;9:781-91. doi: 10.1111/j.1463-1326.2007.00670.x.

41. Walther G, Obert P, Dutheil CF, et al. Metabolic syndrome individuals with and without type 2 diabetes mellitus present generalized vascular dysfunction. Arterioscler Thromb Vasc Biol 2015; 35(4):1022-9. doi:10.1161/ATVBAHA.114.304591.

42. Jonk AM, Houben AJ, Schaper NC, et al. Obesity is associated with impaired endothelial function in the postprandial state. Microvasc Res.2011; 82(3):423-9. doi: 10.1016/j. mvr.2011.08.006.

43. Panza JA, Quyyumi AA, Brush JE Jr. et al. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 1990; 323:22-7. doi: 10.1056/NEJM199007053230105.

44. Taddei S, Salvetti A. Endothelial dysfunction in essential hypertension: clinical implications. J Hypertens 2002;20:1671-4. doi: 10.1097/00004872-200209000-00001.

45. Watson T, Goon PK, Lip GY. Endothelial progenitor cells, endothelial dysfunction, inflammation, and oxidative stress in hypertension. Antioxid Redox Signal 2008;10:1079-88. doi: 10.1089/ars.2007.1998.

46. Brandes RP. Endothelial dysfunction and hypertension. Hy pertension 2014;64:924-8. doi: 10.1161/HYPERTENSIO NAHA.114.03575.

47. Casino PR, Kilcoyne CM, Quyyumi AA, et al. The role of nitric oxide in endothelium-dependent vasodilation of hyper cholesterolemic patients. Circulation 1993;88:2541-7. doi: 10.1161/01.cir.88.6.2541.

48. de Jongh S, Lilien MR, Bakker HD, et al. Family history of cardiovascular events and endothelial dysfunction in children with familial hypercholesterolemia. Atherosclerosis 2002; 163:193-7. doi: 10.1016/s0021-9150(02)00003-5.

49. de Man FH, Weverling-Rijnsburger AW, van der Laarse A, et al. Not acute but chronic hypertriglyceridemia is associated with impaired endothelium-dependent vasodilation: reversal after lipid-lowering therapy by atorvastatin. Arterioscler Thromb Vasc Biol 2000;20:744-75. doi: 10.1161/01. atv.20.3.744.

50. Ludmer PL, Selwyn AP, Shook TL, et al. Paradoxical vaso constriction induced by acetylcholine in atherosclerotic coro nary arteries. N Engl J Med 1986;315:1046-51. doi: 10.1056/ NEJM198610233151702.

51. Zeiher AM, Drexler H, Wollschlager H, et al. Endothelial dysfunction of the coronary microvasculature is associated with coronary blood flow regulation in patients with early atherosclerosis. Circulation 1991;84:1984-92. doi: 10.1161/01. cir.84.5.1984.

52. Suwaidi JA, Hamasaki S, Higano ST, et al. Long-term follow up of patients with mild coronary artery disease and endothe lial dysfunction. Circulation 2000;101:948-54. doi: 10.1161/01.cir.101.9.948.

53. Katz SD, Schwarz M, Yuen J, et al. Impaired acetylcholine mediated vasodilation in patients with congestive heart failure. Role of endothelium-derived vasodilating and vasoconstrict ing factors. Circulation 1993;88:55-61. doi: 10.1161/01. cir.88.1.55.

54. Brandes R, Fleming I, Busse R. Endothelial aging. Cardiovas Res 2005; 66(2): 286–94. doi: 10.1016/j.cardiores.2004.12.027.

55. Altabas V. Diabetes, endothelial dysfunction, and vascular repair: What should a diabetologist keep his eye on? Int J Endocrinol 2015;2015:848272 doi: 10.1155/2015/848272.

56. Lee PSS, Poh KK. Endothelial progenitor cell in cardiovas cular disease. World J Stem Cells 2014; 6(3): 355-66. doi: 10.4252/wjsc.v6.i3.355.

57. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275: 964-7. doi: 10.1126/science.275.5302.964.

58. Garmy-Susini B, Varner JA. Circulating endothelial progeni tor cells. Br J Cancer 2005; 93:855–8. doi: 10.1038/sj. bjc.6602808.

59. Radenković M, Stojanović M, Potpara T, et al. Therapeutic approach in the improvement of endothelial dysfunction: the current state of the art. Biomed Res Int. 2013;2013:252158. doi: 10.1155/2013/252158.

60. Laufs U, Werner N, Link A, et al. Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis. Circulation 2004; 109(2):220-6. doi: 10.1161/01.CIR.0000109141.48980.37.

61. Sandri M, Adams V, Gielen S, et al. Effects of exercise and ischemia on mobilization and functional activation of blood derived progenitor cells in patients with ischemic syndromes: results of 3 randomized studies. Circulation 2005;111(25):3391-9. doi:10.1161/CIRCULATIONAHA.104.527135.

62. Volaklis KA, Tokmakidis SP, Halle M. Acute and chronic effects of exercise on circulating endothelial progenitor cells in healthy and diseased patients. Clin Res Cardiol 2013;102(4):249-57. doi: 10.1007/s00392-012-0517-2.

63. Kondo T, Hayashi M, Takeshita K, et al. Smoking Cessation Rapidly Increases Circulating Progenitor Cells in Peripheral Blood in Chronic Smokers. Arterioscler Thromb Vasc Biol 2004;24:1442–7. https://doi.org/10.1161/01. ATV.0000135655.52088.c5.

64. Marin C, Ramirez R, Delgado-Lista J, et al. Mediterranean diet reduces endothelial damage and improves the regenerative capacity of endothelium. Am J Clin Nutr 2011; 93(2):267-4. doi: 10.3945/ajcn.110.006866.

65. Rizza S, Cardellini M, Porzio O, et al. Pioglitazone improves endothelial and adipose tissue dysfunction in pre-diabetic CAD subjects. Atherosclerosis 2011; 215(1):180–3. doi: 10.1016/j.atherosclerosis.2010.12.021.

66. Chen LL, Yu F, Zeng TS, Liao YF, Li YM, Ding HC. Effects of gliclazide on endothelial function in patients with newly diagnosed type 2 diabetes. Eur J. Pharmacol. 2011;659: 296–301. doi: 10.1016/j.ejphar.2011.02.044.

67. KayaaltI F, Kalay N, Basar E, et al. Effects of nebivolol therapy on endothelial functions in cardiac syndrome X. Heart and Vessels 2010;25(2):92–6. doi: 10.1016/j. ejphar.2011.02.044.

68. Xiaozhen H, Yun Z, Mei Z, et al. Effect of carvedilol on coronary flow reserve in patients with hypertensive left-ventricular hypertrophy. Blood Press 2010; 19(1):40–7. doi: 10.3109/08037050903450492

69. Perl S, Schmölzer I, Sourij H, et al. Telmisartan improves vascular function independently of metabolic and antihyper tensive effects in hypertensive subjects with impaired glucose tolerance. Inter J Cardiol 2010; 139(3):289–96. doi: 10.1016/j. ijcard.2008.10.048.

70. Cangiano E, Marchesini J, Campo G, et al. ACE inhibition modulates endothelial apoptosis and renewal via endothelial progenitor cells in patients with acute coronary syndromes. Am J Cardiovasc Drugs. 2011; 11(3):189–98. doi: 10.2165/11589400-000000000-00000.

71. Inanc MT, Kalay N, Heyit T, et al. Effects of atorvastatin and lisinopril on endothelial dysfunction in patients with Behçet’s disease. Echocardiography. 2010; 27(8):997–1003. doi: 10.1111/j.1540-8175.2010.01180.x

72. Erbs S, Beck EB, Linke A, et al. High-dose rosuvastatin in chronic heart failure promotes vasculogenesis, corrects endothelial function, and improves cardiac remodeling—re sults from a randomized, double-blind, and placebo-controlled study. Int J Cardiol 2011; 146(1):56–6. doi: 10.1016/j.ij card.2010.02.019.

73. Nagashima H, Endo M. Pitavastatin prevents postprandial endothelial dysfunction via reduction of the serum triglycer ide level in obese male subjects. Heart Vessels 2011; 26(4):428–34. doi: 10.1007/s00380-010-0071-7.

74. Vasa M, Fichtlscherer S, Adler K, et al. Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation 2001;103: 2885-90. doi: 10.1161/hc2401.092816.

75. Hibbert B, Simard T, Ramirez FD, et al. The effect of statins on circulating endothelial progenitor cells in humans. J Car diovasc Pharmacol 2013; 62(5):491-6. doi: 10.1097/ FJC.0b013e3182a4027f.

76. Lee HY, Ahn J, Park J, et al. Beneficial effect of statins in COVID-19-related outcomes: a national population-based cohort sudy. Arterioscler Thromb Vasc Biol 2021;41(3):e175- e182. doi: 10.1161/ATVBAHA.120.315551

77. Gupta, A., Madhavan, M.V., Poterucha, T.J. et al. Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19. Nat Commun 2021;12(1):1325. doi: 10.1038/s41467-021-21553-1.

78. Hariyanto TI, Kurniawan A. Statin therapy did not improve the in-hospital outcome of coronavirus disease 2019 (COVID-19) infection. D i a b e t e s M e t a b S y n d r 2020;14(6):1613-5. doi: 10.1016/j.dsx.2020.08.023

79. Diaz-Arocutipa C, Melgar-Talavo B, Alvarado-Yarasca A, et al. Statins reduce mortality in patients with COVID-19: an updated meta-analysis of 147,824 patients. Inter Infectious Dis 2021;110:374-81. doi: 10.1016/j.ijid.2021.08.004.

80. Pal R, Banerjee M, Yadav U, et al. Statin use and clinical outcomes in patients with COVID-19: An updated systematic review and meta-analysis. Postgrad Med J 2021;postgrad medj-2020-139172. doi: 10.1136/postgradmedj-2020-139172.

81. Oesterle A, Laufs U, Liao JK. Pleiotropic effects of statins on the cardiovascular system. Circ Res 2017;120: 229-43. doi: 10.1161/CIRCRESAHA.116.308537.

82. Tikoo K, Patel G, Kumar S, et al. Tissue specific up regulation of ACE2 in rabbit model of atherosclerosis by atorvastatin: role of epigenetic histone modifications. Biochem Pharmacol 2015;93:343-51. doi: 10.1016/j.bcp.2014.11.013.

83. Carfì A, Bernabei R, Landi F. Persistent symptoms in patients after acute COVID-19. JAMA 2020;324: 603–5. doi: 10.1001/ jama.2020.12603.

84. Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med 2021;27:601-5. doi: 10.1038/s41591-021- 01283-z.

85. Di Toro A, Bozzani A, Tavazzi G, et al. Long COVID: long-term effects? Eur Heart J 2021, 23(Suppl E):E1-E5. doi: 10.1093/eurheartj/suab080.

86. Satterfield, B.A., Bhatt, D.L. & Gersh, B.J. Cardiac involvement in the long-term implications of COVID-19. Nat Rev Cardiol 2021. doi: 10.1038/s41569-021-00631-3

87. Guo T, fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020;5: 811–8. doi: 10.1001/ jamacardio.2020.1017.

88. Long B, Brady W J, Koyfman A, et al. Cardiovascular complications in COVID-19. Am. J. Emerg. Med.2020;38:1504–7. doi: 10.1016/j.ajem.2020.04.048.

89. Bavishi C, Bonow EO, Trivadi V, et al. Acute myocardial injury in patients hospitalized with COVID-19 infection: a review. Prog. Cardiovasc. Dis. 2020;63:682–9. doi: 10.1016/j. pcad.2020.05.013.

90. O’Connell TF, Bradley CJ, Abbas AE, et al. Hydroxychloro quine/azithromycin therapy and QT prolongation in hospitalized patients with COVID-19. JACC Clin Electrophysiol 2021;7(1):16-25. doi: 10.1016/j.jacep.2020.07.016.

91. Are ́valos V, Ortega-Paz L, Fernandez-Rodrı ́guez D, et al. Long-term effects of coronavirus disease 2019 on the cardiovascular system, CV COVID registry: A structured summary of a study protocol. PLoS One 29;16(7):e0255263. doi: 10.1371/journal.pone.0255263.