Coronaviruses belong to the ribonucleic acid (RNA) viruses’ family named Coronaviridae, present in both humans and mammals. It is an enveloped virus that can cause respiratory, enteric, hepatic, and neurologic disease. Although it has been linked to diseases involving the pulmonary tract, there is also an association with cardiac pathologies [13]. Special attention was paid to the function of angiotensin-converting enzyme 2 (ACE2), a protein that is proposed to be the binding receptor for SARS-CoV-2 and allows its cellular entrance. ACE2 is found in epithelial cells of lung alveoli, and also highly expressed in adult human heart pericytes, suggesting an inherent heart vulnerability to SARS-CoV-2 infection. Despite ACE2 mediated entry, SARS-CoV-2 also down-regulates the expression of ACE2 receptors, resulting in a diminished conversion of angiotensin II (Ang-II) to cardioprotective angiotensin 1–7 protein. Besides the heart and lungs, Ang-II conversion to 1-7 in vascular endothelium, intestinal epithelium, and the kidneys leads to the inhibition of vasoconstrictor, pro-inflammatory, pro-oxidant, pro-proliferative, and pro-fibrotic functions mediated by Ang-II through AT1 receptors [14]. Thus, suppression of ACE2 expression and subsequent rise in Ang-II levels in COVID-19 patients may pose a further danger to both the heart and vessels.
Although mainly research has been done on pulmonary complications, few investigations have been done to evaluate the cardiovascular effects associated with Covid-19. Elevated cardiac troponin has been observed since the first data analyses in China, representing myocardial damage as a potential pathogenic pathway that contributes to disease severity and mortality among COVID-19 patients. The phenomenon of elevated cTn levels in COVID-19 patients may be explained by several mechanisms such as viral myocarditis, myocardial damage driven by cytokine syndrome, microangiopathy, and unmasked coronary artery disease. It has been proposed that microvascular injury in patients with COVID-19 causes perfusion disorders, hyper-permeability of the vessels, and vasospasm, resulting in myocardial injury [15].
Research conducted by Wang Z et al demonstrated the association between clinical comorbidities and disease severity among COVID-19 disease patients [16]. In our study, there was a significant association between clinical comorbidities and disease severity including diabetes, hypertension, obesity, and smoking. However, cancer patients did not show any significance. Although Robilotti et al [17], showed that there was a substantial rate (20%) of severe respiratory outcomes among cancer patients, there study results were contradictory to our findings. Evidence suggests that the development of cancer is linked with a blunted immune status depicted by an increase in immunosuppressive cytokines along with suppressed induction of pro-inflammatory danger signals, impairment in the maturation of dendritic cell, and role of immunosuppressive leukocytes [18].
Studies have shown that elevated troponin levels may be seen in 7–17% of patients hospitalized with COVID-19 and 22–31% of those admitted to the intensive care unit [19]. In this study, out of 201 patients, 54% had raised Trop-I levels suggesting myocardial injury, and 47.2% patients in the critical group. Trop-I were significantly higher >0.2ng/ml in critical patients, eventhough mean values were raised in both both groups. Increased levels of cTn were also associated with abnormal ECG findings. Other studies have also shown that heart injury and elevated troponin may contribute to complications including ventricular fibrillation, acute coagulopathy, electrolyte disturbances, acute kidney failure, and the necessity for mechanical ventilation [20]. Furthermore, the autopsy report of people who died due to the 2002 SARS outbreak revealed that 35% of heart specimens demonstrated the existence of viral RNA in the myocardium, and this, in turn, was linked to lower expression of ACE2 protein [21], SARS-CoV-2 can represent the same mechanism because the two viruses seem to be similar in the genome [22]. Also, patients with pre-existing or with risk factors for coronary artery disease have a high chance of developing severe coronary syndrome following acute infections, as shown in epidemiological and clinical influenza studies and other acute inflammatory conditions. This may arise due to an imbalance between myocardial oxygen supply and demand, such that the troponin elevation may be viewed as a type 2 myocardial infarction (MI). Decreased oxygen supply in COVID-19 patients is usually triggered by hypoxic respiratory failure and is a sign of disease severity. Infectious conditions, by comparison, are frequently followed by fever, tachycardia, and endocrine dysregulation, contributing to a marked rise in demand for myocardial oxygen. Besides, hypoxemia also results in elevated intracellular calcium with subsequent apoptosis of the cardiac myocytes [23].
Circulating cytokines produced during extreme systemic inflammatory stress may result in instability and breakup of atherosclerotic plaque with thrombus formation contributing to type 1 MI due to COVID-19 [24]. Furthermore, due to the expression of ACE2 in endothelial vascular cells, a direct viral vascular infection that contributes to plaque instability also contributes to type1 MI in patients with COVID-19 [25].
Coagulopathies seen in severe COVID 19 cases can be explained by endothelial dysfunction, cytokine storm, oxidative stress, and activation of Ang II. A postmortem report from Singapore states that 4 out of 8 patients infected with SARS had pulmonary thrombo-embolic lesions and 3 had deep vein thrombosis. To date, only 1 case of pulmonary embolism associated with COVID-1939 has been reported, but only half of the COVID-19 patients have raised levels of D Dimer which is associated with more deaths [26-27]. Increased D-dimer levels can be explained by inflammatory reactions, which stimulate severe fibrinolysis in the lungs with overspill into the bloodstream [28]. In our study, analysis of laboratory results revealed that D-dimers and inflammatory markers were significantly raised in critical patients. Also, critical patients presented with significantly low levels of WBC count, platelet counts, Lymphocyte counts. ALT and AST also showed increased mean values among critical patients.
Although, the incidence of the acute coronary syndrome and MI in infected patients during the first SARS outbreak was described. However, in COVID-19, very limited details are available on the changes in electrocardiogram linked to MI. Angeli F et al [29] showed from their study on 50 patients that ECG changes were present in patients with COVID-19 disease irrespective of the severity of the disease. Common ECG changes were seen in 43.7% of patients in our study, Sinus tachycardia was the common followed by Anteroseptal ST Depressions irrespective of disease severity. ECG changes also when correlated with the troponin level suggested that their values were higher as compared to ones having normal ECG (p-value <0.001). Also, ECG changes had a significant relation with the mortality as well (p-value < 0.001) among COVID-19 disease patients which are positively related to the severity of the disease. Furthermore, among patients with abnormal ECG patterns, we observed RV dilatation and RV dysfunction commonly among critical group category patients suggesting SARS-COV infection severity in cardiac damage, especially among critical group patients.
Limitations
There are a few limitations to our study. This was a single-center experience with a relatively small sample size therefore, further studies with a large population size may help to draw a definitive conclusion regarding the severity of disease and ECG changes. Further, a detailed evaluation of echocardiographic changes was not studied owing to the short study period and the limited amount of time due to the disease’s peak period going on, so observing more parameters with better modalities might give a broader picture of cardiac involvement. In addition, the reversibility of the electrocardiographic changes with an improvement of the clinical status could not be discerned.