ISSN : 2146-3123
E-ISSN : 2146-3131

"When," "Where," and "How" of SARS-CoV-2 Infection Affects the Human Cardiovascular System: A Narrative Review
Nicholas G. Kounis1, Christos Gogos2, Cesare de Gregorio3, Ming-Yow Hung4, Sophia N. Kounis5, Efthymios P. Tsounis6, Stelios F. Assimakopoulos7, Soheila Pourmasumi8, Virginia Mplani9, George Servos10, Periklis Dousdampanis11, Panagiotis Plotas1, Marina A. Michalaki12, Grigorios Tsigkas1, Gerasimos Grammatikopoulos13, Dimitrios Velissaris14, Ioanna Koniar15
1Department of Cardiology, University of Patras Medical School, Rio, Greece
2Clinic of Cardiology, COVID-19 Unit, Papageorgiou General Hospital, Pavlos Melas, Greece
3Department of Clinical and Experimental Medicine, University of Messina Medical School, Messina, Italy
4Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
5Speech Therapy Practice, Rio, Greece
6Division of Gastroenterology, Department of Internal Medicine, Medical School, University Hospital of Patras, Rio, Greece
7Department of Internal Medicine, Division of Infectious Diseases, University of Patras Medical School, Rio, Greece
8Social Determinants of Health Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
9Intensive Care Unit, Patras University Hospital, Rio, Greece
10Pediatric Cardiology Unit, “P. & A. Kyriakou” Children’s Hospital, Athina, Greece
11Department of Nephrology, Saint Andrews State General Hospital, Patras, Greece
12Department of Internal Medicine, Division of Endocrinology, University of Patras, School of Health Sciences, Rio, Greece
13Private Practice Neuroncenter, Neuron Neurology Center, Rio, Greece
14Department of Internal Medicine, University of Patras Medical School, Rio, Greece
15Electrophysiology and Device Department, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom
DOI : 10.4274/balkanmedj.galenos.2023.2023-10-25
Pages : 7-22


Coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory coronavirus-2 (SARS-CoV-2). Several explanations for the development of cardiovascular complications during and after acute COVID-19 infection have been hypothesized. The COVID-19 pandemic, caused by SARS-CoV-2, has emerged as one of the deadliest pandemics in modern history. The myocardial injury in COVID-19 patients has been associated with coronary spasm, microthrombi formation, plaque rupture, hypoxic injury, or cytokine storm, which have the same pathophysiology as the three clinical variants of Kounis syndrome. The angiotensin-converting enzyme 2 (ACE2), renin-aldosterone system (RAAS), and kinin-kallikrein system are the main proposed mechanisms contributing to cardiovascular complications with the COVID-19 infection. ACE receptors can be found in the heart, blood vessels, endothelium, lungs, intestines, testes, neurons, and other human body parts. SARS-CoV-2 directly invades the endothelial cells with ACE2 receptors and constitutes the main pathway through which the virus enters the endothelial cells. This causes angiotensin II accumulation downregulation of the ACE2 receptors, resulting in prothrombotic effects, such as hemostatic imbalance via activation of the coagulation cascade, impaired fibrinolysis, thrombin generation, vasoconstriction, endothelial and platelet activation, and pro-inflammatory cytokine release. The KKS system typically causes vasodilation and regulates tissue repair, inflammation, cell proliferation, and platelet aggregation, but SARS-CoV-2 infection impairs such counterbalancing effects. This cascade results in cardiac arrhythmias, cardiac arrest, cardiomyopathy, cytokine storm, heart failure, ischemic myocardial injuries, microvascular disease, Kounis syndrome, prolonged COVID, myocardial fibrosis, myocarditis, new-onset hypertension, pericarditis, postural orthostatic tachycardia syndrome, pulmonary hypertension, stroke, Takotsubo syndrome, venous thromboembolism, and thrombocytopenia. In this narrative review, we describe and elucidate when, where, and how COVID-19 affects the human cardiovascular system in various parts of the human body that are vulnerable in every patient category, including children and athletes.

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