Our patient has fulfilled the suspect case criteria for COVID-19 by WHO guideline as followed: A patient with acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough, shortness of breath), AND a history of travel to or residence in a location reporting community transmission of COVID-19 disease or having been in contact with a confirmed or probable COVID-19 case during the 14 days prior to symptom onset or patients with severe acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough, shortness of breath; AND requiring hospitalization) AND in the absence of an alternative diagnosis that thoroughly explains the clinical presentation [5]. This was also supported by the laboratory abnormalities found in our patient, which were lymphopenia, leucopenia, thrombocytopenia, elevated creatinine, AST and ALT, and hypoxemia from blood gas analysis, and also pneumonia by chest X-ray and CT scan findings (bilateral, peripheral, patchy opacities on chest X-ray and bilateral ground-glass opacities, crazy paving, and multifocal consolidation from chest CT scan) that suggest high probable for COVID-19 infection. It is suggested that findings from chest CT scans usually peak around 9–13 days [6, 7].
WHO criteria for confirmed COVID-19 was based on the detection of unique sequences of virus SARS-CoV-2 RNA by nucleic acid amplification tests such as real-time RT-PCR and needed at least two positive results [8]. For initial diagnostic testing, Centers for Disease Control and Prevention (CDC) recommends collecting and testing an upper respiratory specimen with a nasopharyngeal swab as the preferred specimen choice [9]. However, multiple negative tests are required to exclude a diagnosis of COVID-19.
CDC also stated that negative SARS-CoV-2 results from RT-PCR do not preclude COVID-19 infection and should not be used as the sole basis for patient treatment decisions, especially when it is not supported with the clinical observations, patient history, and epidemiological information [9]. It is because RT-PCR has the sensitivity as low as 6-70% for initial diagnosis despite its high specificity [10]. In our case, although the initial SARS-CoV-2 RT-PCR showed a negative result, the chest CT scan showed a typical manifestation of COVID-19. This might be explained by the findings from previous study that the sensitivity of the initial chest CT scan is greater than the initial RT-PCR assay (98% vs 71%, p < 0.001) [11].
To establish the diagnosis of Wellens’ syndrome, it is suggested that several criteria be fulfilled, which includes (1) deep symmetrically inverted T waves or biphasic T waves in lead V2 and V3, (2) isoelectric or minimally elevated (< 1 mm) ST-segment, (3) absence of precordial Q waves, (4) history of angina, (5) pattern present during pain-free period, and (6) normal or mildly elevated creatine phosphokinase (less than two times normal upper limit) [12]. In our case, the patient fulfilled all criteria for Wellens’ syndrome except the cardiac marker. However, since the cardiac marker is known to be frequently abnormal in patients with COVID-19 [13], we argued that the cardiac marker criterion could be exempted in this situation.
There were some reports regarding the association between COVID-19 infection and cardiovascular complications including myocardial injury, myocarditis, deep vein thrombosis (DVT), and pulmonary embolism (PE) [14]. Our case might be correlated to COVID-19 infection-induced myocardial injury, infarction, or inflammation due to systemic inflammation response, marked by an elevated CK-MB level. However, it is unlikely that our patient had DVT because there were no supporting clinical findings such as warmth or pain in the extremity or asymmetrical swelling [15]. PE could also be ruled out because there was also no filling defect in the pulmonary artery in the chest CT scan evaluation [16].
It could be argued that this type of case is usually diagnosed as high-risk anterior NSTEMI. However, we would like to stress out the use of Wellens’ syndrome nomenclature to underline the high probability of total or near-total LAD occlusion that is not commonly found in high-risk NSTEMI patients. Patients with Wellens’ syndrome will develop extensive anterior wall infarction if aggressive intervention is not undertaken, despite the relief of symptoms with medical management. Half of the patients will develop the infarction within 1 week after the admission [1]. Thus, in normal situation, our patient should have undergone emergency cardiac catheterization. Other than that, our patient also had a GRACE score of 159. European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association recommend an invasive strategy should be performed in less than 24 h in patient with high-risk NSTEMI (GRACE score more than 140) [17, 18].
However, in patients with suspected COVID-19 infection, the algorithm management is different. National guideline published by the Indonesian Heart Association recommends conservative treatment in the isolated hospital ward if the patients have stable hemodynamic to reduce transmission risk of COVID-19, especially when a special standardized facility is not available [4]. This recommendation was in line with the Chinese Society of Cardiology guideline that recommends patients with high-risk NSTEMI to be hospitalized and treated conservatively in designated hospital [19]. American College of Cardiology suggests that in patient with stable NSTEMI, conservative therapy may be sufficient on the basis of patient risk [3]. In contrary, guideline published by ESC recommends patients with high-risk NSTEMI to still be treated with an early invasive strategy in less than 24 h after admission in COVID-19 designated hospital [20]. According to the Egyptian Society of Cardiology guidelines, patients with high-risk NSTEMI should undergo early catheterization in less than 24 h. However, it is only possible if the hospital is not overwhelmed and all the precautions to prevent the dissemination of infection and protect the medical staff are adopted. Nevertheless, if the prevalence of COVID-19 increases and causes overburden of the health system resources, patients with high-risk NSTEMI should be hospitalized and treated conservatively in isolation wards or ICU in non-designated hospital [21].
According to the national guideline, DAPT (clopidogrel or ticagrelor and aspirin) and high-dose statin should be given for conservative treatment during hospitalization [4]. We opted to treat our patient with clopidogrel because of the moderate bleeding risk (CRUSADE score 37). Recent meta-analysis study showed that ticagrelor was associated with a higher risk of major bleeding compared to clopidogrel in East Asian patients with acute coronary syndrome [22]. In addition to those recommended treatment, the patient also received fondaparinux. After the hospitalization, the patient had been given DAPT for take-home medicine. It is recommended that DAPT should be given for 1 year after discharged home [17].
The limitations of this report were the absence of coronary angiography and echocardiography evaluation. Therefore, the diagnosis of the patients could not be confirmed and the differential diagnosis such as PE and myocarditis could not be totally excluded. The coronary angiography was not performed because it was not recommended by the Indonesian Heart Association. Echocardiography evaluation was not performed because there was no published guideline in performing echocardiography to patients with suspected COVID-19 infection and there was also a shortage of standardized personal protective equipment when this case report occurred.
