**2. Epidemiology**

The COVID-19 pandemic ranks as one of the most devastating events of the 21st century. Since 2019, the virus has spread rapidly across the globe with a reported case burden of upwards of 219 million with 4.5 million deaths. The United States of America, India, and Brazil reported the highest mortality among countries across the globe. The Centers for Disease Control and Prevention (CDC) estimates put the total number of COVID-19 cases in the United States at 44 million with 709,000 deaths. There is emerging data regarding the incidence and prevalence of cardiac injury in COVID-19 infection. Systematic reviews and meta-analyses have shown wide-ranging results. One meta-analysis demonstrated a 19% prevalence of cardiac injury in total COVID-19 cases, with 36% prevalence in severe cases, and 48% prevalence in non-survivors. Another meta-analysis showed a cardiac injury prevalence of 7.2% in total COVID-19 survivors, and 77% in non-survivors. While further analysis needs to be carried out to establish a more accurate prevalence of cardiac injury in COVID-19 infection, the prevalence of cardiac injury tends to increase along with the severity of the infection and poorer prognosis.

## **3. Pathogenesis**

The pathobiology of elevation of cardiac enzymes in patients with COVID-19 can be divided into two major categories: (1) direct damage to the heart by downregulation of ACE2, microvascular dysfunction, pericyte injury, and hypoxemia causing: myocarditis, heart failure, arrhythmias; and (2) indirect damage of cytokine storm by the release of cytokines, hyper inflammation, insulin resistance, coagulopathy causing: myocarditis, metabolic effect, thromboembolism. These are elucidated in **Figures 1** and **2**. Potential mechanisms of myocardial injury in COVID-19 include binding of the SARS-CoV2 virus to the endothelial angiotensinconverting enzyme 2 (ACE-2) receptor [3]. Given the low overall expression of angiotensin-converting enzyme 2 receptor in myocardial cells, the tropism of severe acute respiratory coronavirus 2 for the heart may be less likely. Myocardial injury has been reported in 36% patients hospitalized with COVID-19. Although clinical COVID-19 cases with myocardial injury and normal coronary arteries have been thought to be caused by myocarditis, ST-segment elevation myocardial infarctions (STEMI) may be caused by extensive microvascular thrombosis in the absence of epicardial coronary obstruction. On the other hand, indirect injury can occur as a consequence of a proinflammatory state, stress cardiomyopathy, and

#### *COVID-19 and Cardiac Enzymes DOI: http://dx.doi.org/10.5772/intechopen.101402*

**Figure 1.** *Cardiac phenotypes of manifestations of COVID-19.*

#### **Figure 2.**

*Mechanisms of cardiac Injury of COVID-19 with clinical sequelae.*

tachyarrhythmia attributable to endogenous or exogenous adrenergic stimulation. Systemic infections such as pneumonia have a profound effect on the cardiovascular system, including an increase in oxygen consumption and coronary plaque vulnerability. Myocardial involvement caused by cytokine storm or cardiomyocyte apoptosis triggered by excessive intracellular calcium in response to tissue hypoxia constitutes the indirect response of COVID-19 [4]. Myocardial ischemia occurs in the setting of shock, prolonged tachycardia, or severe respiratory failure, known as type 2 acute myocardial injury (AMI) or acute atherothrombosis, known as type 1 AMI. Type 1 myocardial infarction occurs in the setting of atherothrombosis, which may be triggered by a proinflammatory and prothrombotic state. Type 2 myocardial infarction is most likely in patients with prolonged oxygen supply or demand imbalance with hypoxia, hypotension, or tachycardia. Finally, both myocarditis and takotsubo syndrome have been reported in patients with confirmed COVID-19 and in those without COVID-19 who had experienced severe anxiety due to the pandemic or with concomitant infections.
