from endothelial dysfunction to myocardial dysfunction.
Cardiovasc Res. 2020 Apr 30. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Guzik TJ1,2, Mohiddin SA3,4, Dimarco A3, Patel V3, Savvatis K3, Marelli-Berg FM4, Madhur MS5, Tomaszewski M6, Maffia P7,8, D’Acquisto F9, Nicklin SA1, Marian AJ10, Nosalski R1,2, Murray EC1, Guzik B11, Berry C1, Touyz RM1, Kreutz R12, Wang DW13, Bhella D14, Sagliocco O15, Crea F16, Thomson EC7,14,17, McInnes IB7. Author information Abstract The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: firstname.lastname@example.org. KEYWORDS: ACE2; Acute coronary syndrome; COVID-19; Cardiac; Endothelium; Microvascular; Myocardial infarction; Myocarditis; Vascular; Virus
Cardiovascular involvement in COVID-19—key manifestations and hypothetical mechanisms. SARS-CoV-2 anchors on transmembrane ACE2 to enter the host cells including type 2 pneumocytes, macrophages, endothelial cells, pericytes, and cardiac myocytes, leading to inflammation and multiorgan failure. In particular, the infection of endothelial cells or pericytes could lead to severe microvascular and macrovascular dysfunction. Furthermore, in conjunction with the immune over-reactivity, it can potentially destabilize atherosclerotic plaques and explain the development of the acute coronary syndromes. Infection of the respiratory tract, particularly of type 2 pneumocytes, by SARS-CoV-2 is manifested by the progression of systemic inflammation and immune cell overactivation, leading to a ‘cytokine storm’, which results in an elevated level of cytokines such as IL-6, IL-7, IL-22, and CXCL10. Subsequently, it is possible that activated T cells and macrophages may infiltrate infected myocardium, resulting in the development of fulminant myocarditis and severe cardiac damage. This process could be further intensified by the cytokine storm. Similarly, the viral invasion could cause cardiac myocyte damage directly leading to myocardial dysfunction and contribute to the development of arrhythmia.