Involvement of cardiovascular system as the critical point in coronavirus disease 2019 (COVID-19) prognosis and recovery

Abstract

The novel coronavirus disease 2019 (COVID-19) pandemic has already caused more than 300,000 deaths worldwide. Several studies have elucidated the central role of cardiovascular complications in the disease course. Herein, we provide a concise review of current knowledge regarding the involvement of cardiovascular system in the pathogenesis and prognosis of COVID-19. We summarize data from 21 studies involving in total more than 21,000 patients from Asia, Europe, and the USA indicating that severe disease is associated with the presence of myocardial injury, heart failure, and arrhythmias. Additionally, we present the clinical and laboratory differences between recovered and deceased patients highlighting the importance of cardiac manifestations. For the infected patients, underlying cardiovascular comorbidities and particularly existing cardiovascular disease seem to predispose to the development of cardiovascular complications, which are in turn associated with higher mortality rates. We provide mechanistic insights into the underlying mechanisms including direct myocardial damage by the virus and the consequences of the hyperinflammatory syndrome developed later in the disease course. Finally, we summarize current knowledge on therapeutic modalities and recommendations by scientific societies and experts regarding the cardiovascular management of patients with COVID-19.

Keywords: COVID-19; Cardiovascular comorbidities; Cardiovascular complications; Pandemic; SARS-CoV-2.

Graphical abstract

Figure 1

Clinical manifestations of cardiovascular disease after infection with SARS-CoV-2. (1) High ACE2 expression is detected in cardiac and vascular tissue and may therefore facilitate cellular entry of SARS-CoV-2 resulting in myocardial and vascular damage. (2) An aberrant T-cell and monocyte activation has been observed in patients with COVID-19 leading to a systemic hyperinflammatory response. Increased circulating proinflammatory cytokines may result in inflammatory cardiomyopathy or atherothrombosis, causing an acute coronary syndrome. Systemic inflammatory response can also activate the microvascular endothelium, provoking the dysfunction of the coronary microvasculature, and consequently resulting in myocardial ischemia and myocardial injury. (3) Decreased myocardial oxygen supply, due to severe COVID-19 respiratory complications and hypoxia, along with increased myocardial oxygen demand, mainly due to high systemic metabolic needs, can provoke myocardial injury and type 2 myocardial infarction. (4) The binding of SARS-CoV-2 to ACE2 is expected to lead to the internalization of ACE2 and loss of the external ACE2 catalytic effect. Therefore, the possible downregulation of ACE2 and the subsequent decrease of angiotensin 1-7 in patients with COVID-19 may also compromise heart function. This figure was created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License; https://smart.servier.com. ACE2: angiotensin-converting enzyme 2, MI: myocardial infarction, and SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.

Figure 2

Mechanistic insights into viral and inflammatory myocardial and vascular tissue damage in COVID-19. Two phases of COVID-19 have been described: a) an early phase where tissue damage is mainly induced directly by the virus and b) in some severe cases a 2^nd phase, where aberrant immune response (hyperinflammation) is the cause of tissue damage (upper panel). A large number of proinflammatory cytokines (TNFα, IL-2, IL-6, and IL-7) and chemokines (MCP-1 and IP-10) have been found increased in the circulation of patients with more severe disease. Circulating cytokines can activate endothelial cells and upregulate the expression of leukocyte adhesion molecules such as E-selectin, ICAM-1, and VCAM-1. This could lead to the transmigration of leukocytes into peripheral tissues, such as the myocardium, and cause inflammatory tissue damage (lower panel). This figure was created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License; https://smart.servier.com. ACE2: angiotensin-converting enzyme 2, CVD: cardiovascular disease, DM: diabetes mellitus, HTN: hypertension, ICAM-1: intercellular adhesion molecule 1, IL: interleukin, IP10: interferon γ-induced protein 10, MCP1: monocyte chemoattractant protein-1, mono: monocytes, TNFα: tumor necrosis factor alpha, and VCAM-1: vascular cell adhesion molecule.

Figure 3

Comparative analysis of myocardial injury frequency between total and severe patients with COVID-19. The number of patients included in the whole cohort vs. severe cases in the depicted cohort studies (n whole cohort/severe cases): Huan et al. 41/13, Wang et al. 138/36, Shi et al. 416/97, Guo et al. 187/46, Wei et al. 101/37, Guan et al. 1099/173, Zhang et al. 140/58, Wu et al. 201/84, Guan et al. 1590/254, Huang et al. 221/25, and Goyal et al. 393/130. Bar graphs represent: (A) the percentage of patients who developed myocardial injury, (B) median age of patients, (C) the percentage of patients with arterial hypertension, (D) the percentage of patients with DM and (E) the percentage of patients with preexisting CVD in the whole cohort (black) and among the severe COVID-19 cases (red) per study. DM: diabetes mellitus and CVD: cardiovascular disease.

Figure 4

Comparative analysis of myocardial injury frequency between recovered and deceased patients with COVID-19. The number of recovered patients vs. deceased patients in the depicted cohort studies (n recovered patients/deceased patients): Yang et al. 20/32, Zhou et al. 37/54, Shi et al. 40/57, Chen et al. 161/113, Ruan et al. 82/68, Mehra et al. 8395/515, and Shi et al. 609/62. Bar graphs represent: (A) the percentage of patients who developed myocardial injury, (B) the median (Zhou, Ruan, Chen, and Shi¹¹⁷) or mean (Yang and Mehra¹⁷⁰) age of patients, (C) the percentage of patients with arterial hypertension, (D) the percentage of patients with DM, and (E) the percentage of patients with preexisting CVD in recovered (green) and deceased patients with COVID-19 (red) per study. DM: diabetes mellitus and CVD: cardiovascular disease.