Fig. 3.

This schematic diagram illustrates the putative mechanisms by which COVID-19 induces heart failure (HF). SARS-CoV-2 inclusions within the myocardium may cause infiltrative restrictive cardiomyopathy leading to HF. Moreover, pro-inflammatory cells surrounding SARS-CoV-2 inclusions release cytokines such as tumor necrosis alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-1β (IL-1β), interleukin-6 (IL-6) and many others. These cytokines increase the tissue levels of matrix metalloproteinases (MMPs), protease-activated receptor (PAR), nitric oxide synthase (NOS), severe oxidative stress, apoptosis, and edema in both the heart and lungs. All of these could lead to cardiac and pulmonary fibrosis and necrosis, eventually resulting in HF. In addition, SARS-CoV-2-induced lesion of the cardiovascular endothelium leads to the activation of thrombin and the complement systems. This activation causes disseminated intravascular coagulopathy (DIC) and many thrombi, which could block coronary arteries resulting in myocardial infarction and subsequently HF. Lung fibrosis and hypoxia stimulate further recruitment of pro-inflammatory cells, thereby initiating a vicious cycle