The Cardiac pathophysiology of Covid-19
Article Sidebar
Main Article Content
Abstract
The heart is a key target organ in SARS-CoV-2 infection. During the illness stage of acute Covid-19, fibrin thrombi frequently form within the coronary microcirculation, including the vasa vasorum. These thrombi are predominantly located in the abluminal spaces, the sites of pericyte location, of the vessel wall, in both the microvascular and epicardial vessels. A hallmark histopathological finding is the presence of diffuse, focal fibrin deposits surrounding myocardial fibres, which exhibit varying degrees of degeneration and atrophy. This process contributes to myocardial injury, which is reflected both biochemically and clinically in the acute and long-term phases of Covid-19. Myocardial fibrosis results from this pathological cascade, without a concurrent cellular inflammatory response associated with the myocardial stromal fibrin deposits. During the convalescent stage of acute Covid-19, focal myocardial fibrosis and the presence of thrombi within myocardial vessels remain apparent but sparse. Vascular changes, such as fibrin thrombi within the cardiac microcirculation, exhibit similarities to those observed in the pulmonary microcirculation in Covid-19.
In Covid-19, the vascular findings of fibrin thrombi deposits within the cardiac micro vascular circulation are like those seen within the pulmonary microcirculation.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
Lowenstein CJ, Solomon SD. Severe COVID-19 Is a Microvascular Disease. Circulation. 2020 Oct 27;142(17):1609-1611. doi: 10.1161/CIRCULATIONAHA.120.050354. Epub 2020 Sep 2. PMID: 32877231; PMCID: PMC7580651.
Karakasis P, Nasoufidou A, Sagris M, Fragakis N, Tsioufis K. Vascular Alterations Following COVID-19 Infection: A Com-prehensive Literature Review. Life (Basel). 2024 Apr 24;14(5):545. doi: 10.3390/life14050545. PMID: 38792566; PMCID: PMC11122535.
Çalışkan M, Baycan ÖF, Çelik FB, Güvenç TS, Atıcı A, Çağ Y, Konal O, İrgi T, Bilgili ÜZ, Ağırbaşlı MA. Coronary microvascular dysfunction is common in patients hospitalized with COVID‐19 infection. Microcirculation [Internet]. 2022 Apr 19;29(4–5). Available from: https://doi.org/10.1111/micc.12757.
Wadowski PP, Panzer B, Józkowicz A, Kopp CW, Gremmel T, Panzer S, Koppensteiner R. Microvascular thrombosis as a critical factor in severe COVID-19. International Journal of Molecular Sciences [Internet]. 2023 Jan 27;24(3):2492. Available from: https://doi.org/10.3390/ijms24032492.
Azevedo RB, Botelho BG, Hollanda JVG, Ferreira LVL, Junqueira de Andrade LZ, Oei SSML, Mello TS, Muxfeldt ES. Covid-19 and the cardiovascular system: a comprehensive review. J Hum Hypertens. 2021 Jan;35(1):4-11. doi: 10.1038/s41371-020-0387-4. Epub 2020 Jul 27. PMID: 32719447; PMCID: PMC7384729.
Kole C, Stefanou Ε, Karvelas N, Schizas D, Toutouzas KP. Acute and Post-Acute COVID-19 Cardiovascular Complications: A Comprehensive review. Cardiovascular Drugs and Therapy [Internet]. 2023 May 20; Available from: https://doi.org/10.1007/s10557-023-07465-w.
Bangalore S, Sharma A, Slotwiner A, Yatskar L, Harari R, Shah B, Ibrahim H, Friedman GH, Thompson C, Alviar CL, Chadow HL, Fishman GI, Reynolds HR, Keller N, Hochman JS. ST-Segment Elevation in Patients with Covid-19 — A Case Series. New England Journal of Medicine [Internet]. 2020 Apr 17;382(25):2478–2480. Available from: https://doi.org/10.1056/nejmc2009020.
Bois MC, Boire NA, Layman AJ, Aubry MC, Alexander MP, Roden AC, Hagen CE, Quinton RA, Larsen C, Erben Y, Majumdar R, Jenkins SM, Kipp BR, Lin PT, Maleszewski JJ. COVID-19–Associated nonocclusive fibrin microthrombi in the heart. Cir-culation [Internet]. 2020 Nov 16;143(3):230–243. Available from: https://doi.org/10.1161/circulationaha.120.050754.
Yin J, Wang S, Liu Y, Chen J, Li D, Xu T. Coronary microvascular dysfunction pathophysiology in COVID‐19. Microcirculation [Internet]. 2021 May 20;28(7). Available from: https://doi.org/10.1111/micc.12718.
Guagliumi G, Sonzogni A, Pescetelli I, Pellegrini D, Finn AV. Microthrombi and ST-Segment–Elevation myocardial infarction in COVID-19. Circulation [Internet]. 2020 Jul 17;142(8):804–809. Available from: https://doi.org/10.1161/circulationaha.120.049294.
Daisley H, Rampersad A, Daisley M, Ramdin A, Acco O, Narinesingh F, Humphrey O. COVID-19: a closer look at the pathology in two autopsied cases. Is the pericyte at the center of the pathological process in COVID-19? Autopsy and Case Reports [In-ternet]. Hospital Universitário da Universidade de São Paulo; 2021 May 6;11. Available from: http://www.scielo.br/pdf/acrep/v11/2236-1960-acrep-11-e2021262.pdf.
Daisley H, Acco O, Daisley M, George D, Paul L, Rampersad A, Daisley J. COVID-19 shed light on Virchow’s law of thrombosis. Autopsy and Case Reports [Internet]. 2024 Jan 1;14:e2024512. Available from: https://doi.org/10.4322/acr.2024.512.
Pellegrini D, Kawakami R, Guagliumi G, Sakamoto A, Kawai K, Gianatti A, Nasr A, Kutys R, Guo L, Cornelissen A, Faggi L, Mori M, Sato Y, Pescetelli I, Brivio M, Romero M, Virmani R, Finn AV. Microthrombi as a major cause of cardiac injury in COVID-19. Circulation [Internet]. 2021 Jan 22;143(10):1031–1042. Available from: https://doi.org/10.1161/circulationaha.120.051828.
Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nature Medicine [Internet]. 2022 Feb 7;28(3):583–590. Available from: https://doi.org/10.1038/s41591-022-01689-3.
Cremer S, Jakob C, Berkowitsch A, Borgmann S, Pilgram L, Tometten L, Classen A, Wille K, Weidlich S, Gruener B, Dimmeler S, Massberg S, Rieg S, Zeiher AM. Elevated markers of thrombo-inflammatory activation predict outcome in patients with cardiovascular comorbidities and COVID-19 disease: insights from the LEOSS registry. Clinical Research in Cardiology [Internet]. 2020 Nov 19;110(7):1029–1040. Available from: https://doi.org/10.1007/s00392-020-01769-9.
Gyöngyösi M, Alcaide P, Asselbergs FW, Brundel BJJM, Camici GG, Da Costa Martins P, Ferdinandy P, Fontana M, Girao H, Gnecchi M, Gollmann-Tepeköylü C, Kleinbongard P, Krieg T, Madonna R, Paillard M, Pantazis A, Perrino C, Pesce M, Schiattarella GG, Sluijter JPG, Steffens S, Tschöpe C, Van Linthout S, Davidson SM. Long COVID and the cardiovascular sys-tem—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. Cardiovascular Research [Internet]. 2022 Jul 25;119(2):336–356. Available from: https://doi.org/10.1093/cvr/cvac115.
Gössl M, Rosol M, Malyar NM, Fitzpatrick LA, Beighley PE, Zamir M, Ritman EL. Functional anatomy and hemodynamic characteristics of vasa vasorum in the walls of porcine coronary arteries. The Anatomical Record Part a Discoveries in Mo-lecular Cellular and Evolutionary Biology [Internet]. 2003 Apr 23;272A(2):526–537. Available from: https://doi.org/10.1002/ar.a.10060).
Williams JK, Heistad DD. Structure and function of vasa vasorum. Trends in Cardiovascular Medicine [Internet]. 1996 Feb 1;6(2):53–57. Available from: https://doi.org/10.1016/1050-1738(96)00008-4.
Daisley H Junior, Rampersad A, Daisley M, Ramdin A, Acco O, Narinesingh F, Humphrey O, James E. The vasa vasorum of the large pulmonary vessels are involved in COVID-19. Autopsy and Case Reports [Internet]. 2021 Jan 1;11:e2021304. Available from: https://doi.org/10.4322/acr.2021.304.
Daisley H, Acco O, Daisley M, George D, Paul L, James E, Rampersad A, Narinesingh F, Humphrey O, Daisley J, Nathan M. Thrombosis of the vasa vasorum of the large and medium size pulmonary artery and vein leads to pulmonary throm-boembolism in COVID-19. Autopsy and Case Reports [Internet]. 2024 Jan 1;14:e2024491. Available from: https://doi.org/10.4322/acr.2024.491.
Huang W, Richards TD, Kaczorowski DJ, Noda K, Bartholow T, Sanchez PG, Phillippi JA. Pulmonary artery vasa vasorum damage in severe COVID-19 induced pulmonary fibrosis. Annals of Thoracic Surgery Short Reports [Internet]. 2024 Jan 1; Available from: https://doi.org/10.1016/j.atssr.2023.12.019.
Tsigkas G, Bozika M, Nastouli KM, Apostolos A, Routoula M, Georga AM, Latta A, Papageorgiou A, Papafaklis MI, Leven-topoulos G, Karamasis GV, Davlouros P. Spontaneous Coronary Artery Dissection and COVID-19: A Review of the Literature. Life (Basel). 2024 Feb 28;14(3):315. doi: 10.3390/life14030315. PMID: 38541641; PMCID: PMC10970992.
Faa G, Gerosa C, Fanni D, Barcellona D, Cerrone G, Orrù G, Scano A, Marongiu F, Suri JS, Demontis R, Nioi M, D’Aloja E, La Nasa G, Saba L. Aortic vulnerability to COVID-19: is the microvasculature of vasa vasorum a key factor? A case report and a review of the literature. DOAJ (DOAJ: Directory of Open Access Journals) [Internet]. 2021 Oct 1;25(20):6439–6442. Available from: https://doaj.org/article/36b047c3471d421eacc0ef4fe94365ef.
Irilouzadian R, Salehi Omran H, Alirezaei T. Fatal association of COVID-19 and acute type A aortic dissection. Clin Case Rep. 2022 Mar 22;10(3):e05617. doi: 10.1002/ccr3.5617. PMID: 35356160; PMCID: PMC8939039.
Engin M, Aydın U, Eskici H, Ata Y, Türk T. Type 1 Acute Aortic Dissection in the Early Period After COVID-19 Infection. Cureus. 2021 Mar 7;13(3):e13751. doi: 10.7759/cureus.13751. PMID: 33842128; PMCID: PMC8023408.
Gorecka M, Thirunavukarasu S, Levelt E, Greenwood JP. Multiple etiologies to myocardial injury in COVID-19. JACC Case Reports [Internet]. 2021 Jun 1;3(6):971–972. Available from: https://doi.org/10.1016/j.jaccas.2021.05.003.
Das M, Chung MK. Cardiac pericytes. JACC Basic to Translational Science [Internet]. 2023 Feb 1;8(2):121–123. Available from: https://doi.org/10.1016/j.jacbts.2023.01.010.
Zhang ZS, Zhou HN, He SS, Xue MY, Li T, Liu LM. Research advances in pericyte function and their roles in diseases. Chinese Journal of Traumatology [Internet]. 2020 Mar 6;23(2):89–95. Available from: https://doi.org/10.1016/j.cjtee.2020.02.006
Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A, Li WW, Li VW, Mentzer SJ, Jonigk D. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. New England Journal of Medicine [Internet]. 2020 May 21;383(2):120–128. Available from: https://doi.org/10.1056/nejmoa2015432.
Cardot-Leccia N, Hubiche T, Dellamonica J, Burel-Vandenbos F, Passeron T. Pericyte alteration sheds light on mi-cro-vasculopathy in COVID-19 infection. Intensive Care Medicine [Internet]. 2020 Jun 12;46(9):1777–1778. Available from: https://doi.org/10.1007/s00134-020-06147-7.
Cadamuro M, Lasagni A, Radu CM, Calistri A, Pilan M, Valle C, Bonaffini PA, Vitiello A, Toffanin S, Venturin C, Friòn-Herrera Y, Sironi S, Alessio MG, Previtali G, Seghezzi M, Gianatti A, Strazzabosco M, Strain AJ, Campello E, Spiezia L, Palù G, Frigo AC, Tosoni A, Nebuloni M, Parolin C, Sonzogni A, Simioni P, Fabris L. Procoagulant phenotype of virus-infected pericytes is associated with portal thrombosis and intrapulmonary vascular dilations in fatal COVID-19. Journal of Hepatology [Internet]. 2024 Jun 1; Available from: https://doi.org/10.1016/j.jhep.2024.06.014
Unipd Research. Microthrombosis, Severe Liver Disease, and Fatal COVID-19. 5th July 2024. Available from: https://www.unipd.it/news/unipd-research-microthrombosis-severe-liver-disease-and-fatal-covid-19unipd-research.
Juchem G, Weiss DR, Gansera B, Kemkes BM, Mueller-Hoecker J, Nees S. Pericytes in the macrovascular intima: possible physiological and pathogenetic impact. AJP Heart and Circulatory Physiology [Internet]. 2009 Dec 19;298(3):H754–H770. Available from: https://doi.org/10.1152/ajpheart.00343.2009.
Andreeva ER, Pugach IM, Gordon D, Orekhov AN. Continuous subendothelial network formed by pericyte-like cells in human vascular bed. Tissue and Cell [Internet]. 1998 Feb 1;30(1):127–135. Available from: https://doi.org/10.1016/s0040-8166(98)80014-1.
Brumback BD, Dmytrenko O, Robinson AN, Bailey AL, Ma P, Liu J, Hicks SC, Ng S, Li G, Zhang DM, Lipovsky CE, Lin CY, Diamond MS, Lavine KJ, Rentschler SL. Human cardiac pericytes are susceptible to SARS-COV-2 infection. JACC Basic to Translational Science [Internet]. 2022 Sep 14;8(2):109–120. Available from: https://doi.org/10.1016/j.jacbts.2022.09.001.
Avolio E, Carrabba M, Milligan R, Williamson MK, Beltrami AP, Gupta K, Elvers KT, Gamez M, Foster RR, Gillespie K, Hamilton F, Arnold D, Berger I, Davidson AD, Hill D, Caputo M, Madeddu P. The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease. Clinical Science [Internet]. 2021 Nov 22;135(24):2667–2689. Available from: https://doi.org/10.1042/cs20210735.
Tsai EJ, Čiháková D, Tucker NR. Cell-Specific mechanisms in the heart of COVID-19 patients. Circulation Research [Internet]. 2023 May 11;132(10):1290–1301. Available from: https://doi.org/10.1161/circresaha.123.321876.
Beaser SB, Rudy A, Seligman A. CAPILLARY FRAGILITY IN RELATION TO DIABETES MELLITUS, HYPERTENSION AND AGE. Archives of Internal Medicine [Internet]. 1944 Jan 1;73(1):18. Available from: https://doi.org/10.1001/archinte.1944.002101300260.