Pathophysiology of Cardiac Cell Injury in Post-COVID-19 Syndrome

Basheer      Abdullah Marzoog
Abstract

Recently, the scientific community has realized that COVID-19 effects are not limited to the acute period of infection but continue beyond that to cause more prolonged pathological changes. Post-COVID syndrome is a novel concept that describes the sequelae/persistent pathophysiological changes of post-COVID-19 infection. The current hypothesis suggests the involvement of severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) in cardiac arrhythmias, coronary artery aneurism, acute renal injury, central nervous system degenerative diseases, vascular endothelial cell dysfunction, and pulmonary dyspnea, as well as fibrotic lung damage. Therefore, COVID-19 has been identified as a poly-syndromic and polysystemic inflammatory disease. Post-COVID extrapulmonary complications have been observed in approximately 85% of hospitalized COVID-19 survivors and 35% of COVID-19 outpatients. Furthermore, 25% of hospitalised COVID-19 survivors developed myocardiopathy.
[1]
Carfì A, Bernabei R, Landi F. Persistent symptoms in patients after acute COVID-19. JAMA  2020; 324(6): 603-5.
 [http://dx.doi.org/10.1001/jama.2020.12603] [PMID: 32644129]

[2]
Vojdani A, Vojdani E, Kharrazian D. Reaction of human monoclonal antibodies to SARS-CoV-2 proteins with tissue antigens: Implications for autoimmune diseases. Front Immunol  2021; 11: 617089.
 [http://dx.doi.org/10.3389/fimmu.2020.617089] [PMID: 33584709]

[3]
Maltezou HC, Pavli A, Tsakris A. Post-COVID syndrome: An insight on its pathogenesis. Vaccines  2021; 9(5): 497.
 [http://dx.doi.org/10.3390/vaccines9050497] [PMID: 34066007]

[4]
Halpin S, O’Connor R, Sivan M. Long COVID and chronic COVID syndromes. J Med Virol  2021; 93(3): 1242-3.
 [http://dx.doi.org/10.1002/jmv.26587] [PMID: 33034893]

[5]
Mahase E. COVID-19: What do we know about “long covid”? BMJ  2020; 370
 [http://dx.doi.org/10.1136/bmj.m2815]

[6]
Wu Q, Zhou L, Sun X, et al. Altered lipid metabolism in recovered SARS patients twelve years after infection. Sci Rep  2017; 7(1): 9110.
 [http://dx.doi.org/10.1038/s41598-017-09536-z] [PMID: 28831119]

[7]
Bilaloglu S, Aphinyanaphongs Y, Jones S, Iturrate E, Hochman J, Berger JS. Thrombosis in hospitalized patients with COVID-19 in a New York City health system. JAMA  2020; 324(8): 799-801.
 [http://dx.doi.org/10.1001/jama.2020.13372] [PMID: 32702090]

[8]
Klok FA, Kruip MJHA, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res  2020; 191: 145-7.
 [http://dx.doi.org/10.1016/j.thromres.2020.04.013] [PMID: 32291094]

[9]
Cui S, Chen S, Li X, Liu S, Wang F, Cui S. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost  2020; 18(6): 1421-4.
 [http://dx.doi.org/10.1111/jth.14830] [PMID: 32271988]

[10]
Shi S, Qin M, Shen B, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol  2020; 5(7): 802-10.
 [http://dx.doi.org/10.1001/jamacardio.2020.0950] [PMID: 32211816]

[11]
Siripanthong B, Nazarian S, Muser D, et al. Recognizing COVID-19–related myocarditis: The possible pathophysiology and proposed guideline for diagnosis and management. Heart Rhythm  2020; 17(9): 1463-71.
 [http://dx.doi.org/10.1016/j.hrthm.2020.05.001] [PMID: 32387246]

[12]
Akhmerov A, Marbán E. COVID-19 and the Heart Circulation Research.  Lippincott Williams and Wilkins 2020; pp. 1443-55.
 [http://dx.doi.org/10.1161/CIRCRESAHA.120.317055]

[13]
Bhatraju PK, Ghassemieh BJ, Nichols M, et al. COVID-19 in critically ill patients in the seattle region — case series. N Engl J Med  2020; 382(21): 2012-22.
 [http://dx.doi.org/10.1056/NEJMoa2004500] [PMID: 32227758]

[14]
Liu PP, Blet A, Smyth D, Li H. The Science Underlying COVID-19: Implications for the Cardiovascular System Circulation.  Lippincott Williams and Wilkins 2020; pp. 68-78.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047549]

[15]
Zheng Y Y, Ma Y T, Zhang J Y, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol  2020; 17: 259-60.
 [http://dx.doi.org/10.1038/s41569-020-0360-5]

[16]
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(7): 811-8.
 [http://dx.doi.org/10.1001/jamacardio.2020.1017] [PMID: 32219356]

[17]
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet  2020; 395(10229): 1054-62.
 [http://dx.doi.org/10.1016/S0140-6736(20)30566-3] [PMID: 32171076]

[18]
Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ  2020; 368: m1091.
 [http://dx.doi.org/10.1136/bmj.m1091] [PMID: 32217556]

[19]
Liu PP, Blet A, Smyth D, Li H. The science underlying COVID-19. Circulation  2020; 142(1): 68-78.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047549] [PMID: 32293910]

[20]
Rajpal S, Tong MS, Borchers J, et al. Cardiovascular magnetic resonance findings in competitive athletes recovering From COVID-19 infection. JAMA Cardiol  2021; 6(1): 116-8.
 [http://dx.doi.org/10.1001/jamacardio.2020.4916] [PMID: 32915194]

[21]
Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA  2020; 323(20): 2052-9.
 [http://dx.doi.org/10.1001/jama.2020.6775] [PMID: 32320003]

[22]
Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically Ill patients with COVID-19 in Washington State. JAMA  2020; 323(16): 1612-4.
 [http://dx.doi.org/10.1001/jama.2020.4326] [PMID: 32191259]

[23]
Myers LC, Parodi SM, Escobar GJ, Liu VX. Characteristics of hospitalized adults With COVID-19 in an integrated health care system in California. JAMA  2020; 323(21): 2195-8.
 [http://dx.doi.org/10.1001/jama.2020.7202] [PMID: 32329797]

[24]
Ishibashi Y, Yoneyama K, Tsuchida T, J Akashi Y. Post-COVID-19 postural orthostatic tachycardia syndrome. Intern Med  2021; 60(14): 2345.
 [http://dx.doi.org/10.2169/internalmedicine.7626-21] [PMID: 34053992]

[25]
Nehme M, Braillard O, Alcoba G, et al. COVID-19 Symptoms: Longitudinal evolution and persistence in outpatient settings. Ann Intern Med  2021; 174(5): 723-5.
 [http://dx.doi.org/10.7326/M20-5926] [PMID: 33284676]

[26]
Tenforde MW, Kim SS, Lindsell CJ, et al. Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network-United States, March–June 2020. MMWR Morb Mortal Wkly Rep  2020; 69(30): 993-8.
 [http://dx.doi.org/10.15585/mmwr.mm6930e1] [PMID: 32730238]

[27]
Stavem K, Ghanima W, Olsen MK, Gilboe HM, Einvik G. Persistent symptoms 1.5–6 months after COVID-19 in non-hospitalised subjects: A population-based cohort study. Thorax  2021; 76(4): 405-7.
 [http://dx.doi.org/10.1136/thoraxjnl-2020-216377] [PMID: 33273028]

[28]
Taquet M, Geddes JR, Husain M, Luciano S, Harrison PJ. 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: A retrospective cohort study using electronic health records. Lancet Psychiatry  2021; 8(5): 416-27.
 [http://dx.doi.org/10.1016/S2215-0366(21)00084-5] [PMID: 33836148]

[29]
Chopra V, Flanders SA, O’Malley M, et al. Sixty-day outcomes among patients hospitalized with COVID-19. Ann Intern Med  2021; 174(4): 576-8.
 [http://dx.doi.org/10.7326/M20-5661] [PMID: 33175566]

[30]
Arnold DT, Hamilton FW, Milne A, et al. Patient outcomes after hospitalisation with COVID-19 and implications for follow-up: Results from a prospective UK cohort. Thorax  2021; 76(4): 399-401.
 [http://dx.doi.org/10.1136/thoraxjnl-2020-216086] [PMID: 33273026]

[31]
Halpin SJ, McIvor C, Whyatt G, et al. Postdischarge symptoms and rehabilitation needs in survivors of COVID‐19 infection: A cross‐sectional evaluation. J Med Virol  2021; 93(2): 1013-22.
 [http://dx.doi.org/10.1002/jmv.26368] [PMID: 32729939]

[32]
Jacobs LG, Gourna Paleoudis E, Lesky-Di Bari D, et al. Persistence of symptoms and quality of life at 35 days after hospitalization for COVID-19 infection. PLoS One  2020; 15(12): e0243882.
 [http://dx.doi.org/10.1371/journal.pone.0243882] [PMID: 33306721]

[33]
Garrigues E, Janvier P, Kherabi Y, et al. Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. J Infect  2020; 81(6): e4-6.
 [http://dx.doi.org/10.1016/j.jinf.2020.08.029] [PMID: 32853602]

[34]
Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: A cohort study. Lancet  2021; 397(10270): 220-32.
 [http://dx.doi.org/10.1016/S0140-6736(20)32656-8] [PMID: 33428867]

[35]
Carvalho-Schneider C, Laurent E, Lemaignen A, et al. Follow-up of adults with noncritical COVID-19 two months after symptom onset. 2021  27(2): 258-63.
 [http://dx.doi.org/10.1016/j.cmi.2020.09.052]

[36]
Mandal S, Barnett J, Brill SE, et al. ‘Long-COVID’: A cross-sectional study of persisting symptoms, biomarker and imaging abnormalities following hospitalisation for COVID-19. Thorax  2021; 76(4): 396-8.
 [http://dx.doi.org/10.1136/thoraxjnl-2020-215818] [PMID: 33172844]

[37]
Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med  2021; 27(4): 601-15.
 [http://dx.doi.org/10.1038/s41591-021-01283-z] [PMID: 33753937]

[38]
Lu J, Sun PD. High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity. J Biol Chem  2020; 295(52): 18579-88.
 [http://dx.doi.org/10.1074/jbc.RA120.015303] [PMID: 33122196]

[39]
Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. The proximal origin of SARS-CoV-2. Nat Med  2020; 26(4): 450-2.
 [http://dx.doi.org/10.1038/s41591-020-0820-9] [PMID: 32284615]

[40]
Moreno-Pérez O, Merino E, Leon-Ramirez JM, et al. Post-acute COVID-19 syndrome. Incidence and risk factors: A Mediterranean cohort study. J Infect  2021; 82(3): 378-83.
 [http://dx.doi.org/10.1016/j.jinf.2021.01.004] [PMID: 33450302]

[41]
Gupta A, Madhavan MV, Sehgal K, et al. Extrapulmonary manifestations of COVID-19. Nat Med  2020; 26(7): 1017-32.
 [http://dx.doi.org/10.1038/s41591-020-0968-3] [PMID: 32651579]

[42]
Ambardar SR, Hightower SL, Huprikar NA, Chung KK, Singhal A, Collen JF. Post-COVID-19 pulmonary fibrosis: Novel sequelae of the current pandemic. J Clin Med  2021; 10(11): 2452.
 [http://dx.doi.org/10.3390/jcm10112452] [PMID: 34205928]

[43]
Khoury MK, Gupta K, Franco SR, Liu B. Necroptosis in the pathophysiology of disease. Am J Pathol  2020; 190(2): 272-85.
 [http://dx.doi.org/10.1016/j.ajpath.2019.10.012] [PMID: 31783008]

[44]
Puntmann VO, Carerj ML, Wieters I, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol  2020; 5(11): 1265-73.
 [http://dx.doi.org/10.1001/jamacardio.2020.3557] [PMID: 32730619]

[45]
Xu K, Wei Y, Giunta S, Zhou M, Xia S. Do inflammaging and coagul-aging play a role as conditions contributing to the co-occurrence of the severe hyper-inflammatory state and deadly coagulopathy during COVID-19 in older people? Exp Gerontol  2021; 151: 111423.
 [http://dx.doi.org/10.1016/j.exger.2021.111423] [PMID: 34048906]

[46]
Bikdeli B, Madhavan MV, Jimenez D, et al. COVID-19 and thrombotic or thromboembolic disease: Implications for prevention, antithrombotic therapy, and follow-up. J Am Coll Cardiol  2020; 75(23): 2950-73.
 [http://dx.doi.org/10.1016/j.jacc.2020.04.031] [PMID: 32311448]

[47]
Vukusic K, Thorsell A, Muslimovic A, et al. Overexpression of the SARS-CoV-2 receptor angiotensin converting enzyme 2 in cardiomyocytes of failing hearts. Sci Rep  2022; 12(1): 965.
 [http://dx.doi.org/10.1038/s41598-022-04956-y] [PMID: 35046458]

[48]
Lindner D, Fitzek A, Bräuninger H, et al. Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases. JAMA Cardiol  2020; 5(11): 1281-5.
 [http://dx.doi.org/10.1001/jamacardio.2020.3551] [PMID: 32730555]

[49]
Oudit GY, Kassiri Z, Jiang C, et al. SARS-coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS. Eur J Clin Invest  2009; 39(7): 618-25.
 [http://dx.doi.org/10.1111/j.1365-2362.2009.02153.x] [PMID: 19453650]

[50]
Marzoog BA, Vlasova TI. The possible puzzles of BCG vaccine in protection against COVID-19 infection. Egypt J Bronchol  2021; 15(1): 7.
 [http://dx.doi.org/10.1186/s43168-021-00052-3]

[51]
Marzoog BA. Recent advances in molecular biology of metabolic syndrome pathophysiology: Endothelial dysfunction as a potential therapeutic target. J Diabetes Metab Disord  2022; 21(2): 1903-11.
 [http://dx.doi.org/10.1007/s40200-022-01088-y] [PMID: 36065330]

[52]
Marzoog BA, Vlasova TI. Systemic and local hypothermia in the context of cell regeneration. Cryo Lett  2022; 43(2): 66-73.
 [http://dx.doi.org/10.54680/fr22210110112] [PMID: 36626147]

[53]
Marzoog BA, Vlasova TI. Membrane lipids under norm and pathology. Eur J Clin Exp Med  2021; 19(1): 59-75.
 [http://dx.doi.org/10.15584/ejcem.2021.1.9]

[54]
Marzoog B. Anticoagulant status under COVID-19: The potential pathophysiological mechanism. J App Hematol  2022; 13(4): 167.
 [http://dx.doi.org/10.4103/joah.joah_154_21]

[55]
Marzoog BA. Coagulopathy and brain injury pathogenesis in post-COVID-19 syndrome. Cardiovasc Hematol Agents Med Chem  2022; 20(3): 178-88.
 [http://dx.doi.org/10.2174/1871525720666220405124021] [PMID: 35382728]

[56]
Marzoog B. Lipid behavior in metabolic syndrome pathophysiology. Curr Diabetes Rev  2022; 18(6): e150921196497.
 [http://dx.doi.org/10.2174/1573399817666210915101321] [PMID: 34525924]

[57]
Marzoog BA, Vlasova TI. The metabolic syndrome puzzles; Possible pathogenesis and management. Curr Diabetes Rev  2022; 18
 [http://dx.doi.org/10.2174/1573399818666220429100411] [PMID: 35507784]

[58]
Marzoog BA. Tree of life: Endothelial cell in norm and disease, the good guy is a partner in crime! Anat Cell Biol 2023. Available at:
 [http://dx.doi.org/10.5115/acb.22.190]

[59]
Marzoog BA. Endothelial cell autophagy in the context of disease development. Anat Cell Biol  2023; 56(1): 16-24.
 [http://dx.doi.org/10.5115/acb.22.098] [PMID: 36267005]

[60]
Marzoog BA. Transcription Factors-the essence of heart regeneration: A potential novel therapeutic strategy. Curr Mol Med  2022; 23(3): 232-8.
 [http://dx.doi.org/10.2174/1566524022666220216123650] [PMID: 35170408]

[61]
Abdullah Marzoog B. Autophagy as an anti-senescent in aging neurocytes. Curr Mol Med  2023; 23 epub ahead of print.
 [http://dx.doi.org/10.2174/1566524023666230120102718] [PMID: 36683318]

[62]
Marzoog BA. Local lung fibroblast autophagy in the context of lung fibrosis pathogenesis. Curr Respir Med Rev  2023; 19(1): 6-11.
 [http://dx.doi.org/10.2174/1573398X19666221130141600]

[63]
Marzoog B A. Autophagy behavior in post-myocardial infarction injury. Cardiovasc Hematol Disord Drug Targets 2023. epub ahead of print.

[64]
Marzoog BA, Vlasova TI. Myocardiocyte autophagy in the context of myocardiocytes regeneration: A potential novel therapeutic strategy. Egypt J Med Hum Genet  2022; 23(1): 41.
 [http://dx.doi.org/10.1186/s43042-022-00250-8]

[65]
Marzoog BA. Autophagy in cancer cell transformation: A potential novel therapeutic strategy. Curr Cancer Drug Targets  2022; 22(9): 749-56.
 [http://dx.doi.org/10.2174/1568009622666220428102741] [PMID: 36062863]

[66]
Samidurai A, Das A. Cardiovascular complications associated with COVID-19 and potential therapeutic strategies. Int J Mol Sci  2020; 21(18): 6790.
 [http://dx.doi.org/10.3390/ijms21186790] [PMID: 32947927]

[67]
Chen L, Li X, Chen M, Feng Y, Xiong C. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res  2020; 116(6): 1097-100.
 [http://dx.doi.org/10.1093/cvr/cvaa078] [PMID: 32227090]

[68]
Bozkurt B, Kovacs R, Harrington B. Joint HFSA/ACC/AHA statement addresses concerns re: Using RAAS antagonists in COVID-19. J Card Fail  2020; 26(5): 370.
 [http://dx.doi.org/10.1016/j.cardfail.2020.04.013] [PMID: 32439095]

[69]
Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin–angiotensin–aldosterone system inhibitors in patients with COVID-19. N Engl J Med  2020; 382(17): 1653-9.
 [http://dx.doi.org/10.1056/NEJMsr2005760] [PMID: 32227760]

[70]
Lopes RD, Macedo AVS, de Barros E Silva PGM, et al. Effect of discontinuing vs continuing angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on days alive and out of the hospital in patients admitted With COVID-19. JAMA  2021; 325(3): 254-64.
 [http://dx.doi.org/10.1001/jama.2020.25864] [PMID: 33464336]

[71]
Humphrey TJL, James G, Wittbrodt ET, Zarzuela D, Hiemstra TF. Adverse clinical outcomes associated with RAAS inhibitor discontinuation: Analysis of over 400 000 patients from the UK Clinical Practice Research Datalink (CPRD) Clin Kidney J  2021; 14(10): 2203-12.
 [http://dx.doi.org/10.1093/ckj/sfab029] [PMID: 34804520]

[72]
Kociol RD, Cooper LT, Fang JC, et al. Recognition and initial management of fulminant myocarditis. Circulation  2020; 141(6): e69-92.
 [http://dx.doi.org/10.1161/CIR.0000000000000745] [PMID: 31902242]
Cite As
New Emirates Medical Journal

Pathophysiology of Cardiac Cell Injury in Post-COVID-19 Syndrome

Abstract
