DISCUSSION

Recent epidemiologic and clinical studies of influenza and other acute inflammatory conditions have demonstrated an association of an event leading towards acute coronary syndrome in patients with long-standing coronary artery disease and those with risk factors for atherosclerotic cardiovascular disease, i.e., diabetes, hypertension, dyslipidemia, smoking obesity, inactive lifestyle and significant family history of heart disease.^7-12 Both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), formerly referred to as the 2019 novel coronavirus (2019-nCoV), and the Middle East Respiratory Syndrome coronavirus (MERSCoV) share the same pathobiochemical and biomechanical mechanisms of myocardial damage which increase the difficulty and complexity of patient treatment.¹³

It was also shown that during acute infections, the following risk factors for atherosclerotic cardiovascular disease, like hypertension, cigarette smoking, diabetes mellitus, hyperlipidemia, and obesity, further add to the already heightened risk for acute coronary events among those with long term coronary artery disease.^14-1

Bonow et al recognized that patients with underlying cardiovascular disease which can be mostly seen in older people had more unfavorable outcomes and death during serious and aggressive inflammatory reactions to COVID-19 compared to younger and healthier individuals.[18] Likewise, two cohorts demonstrated the association of myocardial injury with increased fatality rate among older patients with preexisting cardiovascular comorbidities and diabetes.^19-20 ​

Myocardial injury is one of the more clinically significant manifestations of COVID-19. It is not yet well known how this is brought about by SARS-CoV-2 infection due to a lack of randomized controlled trials and the acuteness of this global pandemic. Current data suggest that the interaction between SARS-CoV-2 and cardiac angiotensin-converting enzyme 2 (ACE-2) receptors may precipitate myocardial damage. One of the proposed mechanisms is that cardioprotection provided by angiotensin 1-7 is hindered by the downregulation of ACE-2 receptors thereby resulting in increased inflammatory cytokines such as tumor necrosis factor-alpha (TNFα).[21] Other hypothesized mechanisms of myocardial injury include induction of interstitial fibrosis in the myocardium by activation of TGFβsignaling by SARS-CoV-2, exaggerated cytokine response by T-Helper cells (both type 1 and type 2), as well as strong interferon-mediated immune reactions.²¹

​ These acute coronary events result from the severe increase in myocardial demand triggered by infections that precipitate myocardial injury or type 2 myocardial infarction.^14-17 Additionally, during severe systemic inflammatory stress, the circulating cytokines released could also lead to atherosclerotic plaque instability and rupture.^14-17 Wang et al postulated that the increase in metabolic demand brought about by the viral infection potentiates the imbalance and reduce the cardiac reserve thereby making chronic cardiovascular diseases unstable.¹³

​ Most epidemiologic studies enrolled more severe cases than non-severe ones,^8-10 but in this study, there were more cases in the non-severe category than in the severe category. The findings in this study of marked elevation of acute inflammatory markers, i.e., neutrophil count, AST, serum ferritin, LDH, creatine kinase, D-dimer, and hs-CRP among subjects with COVID-19 who developed complications were all in congruence with other international and local studies.^22-26

This study showed similar findings that older patients with co-morbid conditions were predisposed to increase adverse events.^{12, 26, 28-33} Additionally, it was shown that creatine kinase and hsTnI had a direct association with disease severity and the primary composite endpoints (ICU admission, intubation, and mortality). The strength of correlation was generally weak, except for that of hsTnI with in-hospital mortality where it was moderate. Direct correlations of both tCK and hsTnI with disease severity and the primary composite endpoints were shown in this study. These could be ascribed to the actual myocardial injury caused by the SARS-CoV-19 similar to what was observed in other previous studies.^{13, 15, 19, 20} ​

As with other international and local studies, this study also demonstrated that the majority of the mortalities have acute myocardial injury as evidenced by increased levels of hsTnI.^{12, 13, 15, 20, 26, 34} The demonstration of the value of cardiac troponin to in-hospital mortality among COVID-19 patients resembles other previous investigations.^{12, 13, 15, 19, 20} Those laboratory-confirmed patients with elevated hsTnI levels were eight times more likely to succumb to the disease relative to those who did not. Also, the odds that COVID patients were more likely to die when they have elevated levels of tCK was increased four times as opposed to those who have normal levels.

​ The AUC analysis of the ROC curve further showed that hsTnI was a good predictor for in-hospital mortality, while creatine kinase was a poor significant predictor of in-hospital mortality. Evaluating the 95% CI showed that the lower limit of tCK was 0.531. Anything below the threshold limit of 0.6 would have no value as an instrument, hence nullifying its significance as a tool for predicting in-hospital mortality.

​ As with other previous studies, the severity of damage to the myocardium was reflected by the increase in hsTnI levels, where the more severe the damage, the more the patient was predisposed to adverse clinical outcome and mortality.^{12, 13, 15, 19, 20} The extent of insult might affect myocardial function which could draw hemodynamic instability anytime. Hence, the positive association of the biomarker with in-hospital mortality among patients with COVID infection existed.

​ Studies have shown that high specificity is one characteristic of an extremely good screening test to avoid large numbers of false positives.^{36, 37} The cutoff analysis revealed an optimal cutoff value for hsTnI of 0.010 ng/ml in predicting myocardial injury which was directly associated with in-hospital mortality among COVID-19 patients, and it was specific to as high as 83%, and was sensitive to as high as 97% at the most. If the test was negative, one can be 99% confident that there was no myocardial injury resulting from COVID-19 infection. Seventy-six percent of those who will exceed the threshold will be correctly classified as having myocardial damage. The probability of having myocardial injury is increased by 20% when hsTnI levels exceed 0.010 ng/ml among COVID-19 patients, whereas it is decreased by 30% when hsTnI levels are below 0.010 ng/ml. ​

CONCLUSION

In this small study of 90 rRT-PCR positive COVID-19 patients with cardiac biomarker determinations, high sensitivity troponin I level is a good tool in significantly predicting in-hospital mortality.

​ LIMITATIONS
A much bigger sample size will ensure more robust conclusions. There were missing data on some of the variables, such as symptoms pre-admission (4/90, [4.4%]) and eventual disposition (5/90, [5.5%]).