Cardiovascular manifestations of COVID-19: An evidence-based narrative review

Abstract

The recent outbreak of coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization on March 11, 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, primarily involves the respiratory system with viral pneumonia as a predominant manifestation. In addition, SARS-CoV-2 has various cardiovascular manifestations which increase morbidity and mortality in COVID-19. Patients with underlying cardiovascular diseases and conventional cardiovascular risk factors are predisposed for COVID-19 with worse prognosis. The possible mechanisms of cardiovascular injury are endothelial dysfunction, diffuse microangiopathy with thrombosis and increased angiotensin II levels. Hyperinflammation in the myocardium can result in acute coronary syndrome, myocarditis, heart failure, cardiac arrhythmias and sudden death. The high level of cardiac troponins and natriuretic peptides in the early course of COVID-19 reflects an acute myocardial injury. The complex association between COVID-19 and cardiovascular manifestations requires an in-depth understanding for appropriate management of these patients. Till the time a specific antiviral drug is available for COVID-19, treatment remains symptomatic. This review provides information on the cardiovascular risk factors and cardiovascular manifestations of COVID-19.

Keywords: ACE inhibitors/angiotensin receptor blockers; ACE-2; MERS; SARS-CoV-2; coronavirus disease 2019; cytokine storm; endothelial dysfunction; heart failure; myocarditis.

Fig. 1

Pathogenesis of SARS-CoV-2 in COVID-19.The S1 subunit of spike S protein on the virus surface engages with membrane-bound cellular receptor carboxypeptidase ACE2 present over the cell membrane of lung epithelial cells (pulmonary alveolar type II cells), and S2 subunit stalk helps in cell fusion. TMPRSS2 protease aids in the attachment of ACE2 with virus S protein. After entry inside the cell, the virus replicates and destroys ACE2. The decrease in ACE2 (transmembranous and circulatory) perpetuates the RAAS pathway. Increase in angiotensin II levels in COVID-19 causes widespread injury by activation of ATR1 receptors. Activation of ATR1 causes vasoconstriction, inflammation, endothelial dysfunction, acute lung injury and myocardial injury. The physiological function of ACE2 is to degrade angiotensin II to angiotensin 1-7, and angiotensin I to angiotensin 1-9. Angiotensin 1-7 acts on MasR receptors on cell membranes, and has vasodilatory and antifibrotic effects. Black arrows represent upregulation and red arrows represent downregulation in COVID-19. ACE2, angiotensin-converting enzyme 2; ATR1, angiotensin II receptor 1; cACE2, circulatory angiotensin-converting enzyme 2; MasR, mitochondrial assembly receptor; RAAS, rennin-angiotensin-aldosterone system; TMPRSS2, transmembrane protease serine 2. Source: Refs .

Fig. 2

The proposed mechanism of cardiovascular manifestations of COVID-19. Hyperinflammatory state secondary to cytokine storm, increased angiotensin II, low ACE2 levels and APLA contribute to thrombus formation in coronary and pulmonary vasculature. APLA, antiphospholipid antibodies; IL, interleukin; IFN-γ, interferon-gamma; MCP, monocyte chemoattractant protein; TNF-α, tumour necrosis factor-alpha. Source: Refs .

Fig. 3

Complex interaction of ACE-i/ARBs and COVID-19. In COVID-19, the virus downregulates ACE2, which acts as a receptor of SARS-CoV-2. The physiological function of ACE2 is to catalyze angiotensin II to angiotensin 1-7, and acts like a gatekeeper of the RAAS pathway. This leads to angiotensin surge in COVID-19. The ACE-i/ARBs inhibit RAAS pathway and upregulate the ACE2 level. Red arrows represent downregulation and blue arrows represent upregulation. ACE-i, angiotensin-converting enzyme inhibitors; ARBs, angiotensin receptor blockers.

Fig. 4

Management of STEMI during the COVID-19 pandemic. ECG, electrocardiography; PPE, personal protective equipment. Source: Ref. . [Case classification: COVID-19 positive: any person meeting the laboratory criteria (reverse transcription-polymerase chain reaction positive for SARS-CoV-2); COVID-19 possible: any person meeting the clinical criteria (cough, fever, shortness of breath and sudden onset of anosmia, ageusia or dysgeusia) and COVID-19 probable case: any person meeting the clinical criteria with an epidemiological link or any person meeting the diagnostic criteria].