A novel coronavirus (2019-nCoV) was identified as the cause associated with emerging pneumonia (COVID-19) detected in Wuhan on Jan 7 th . Since the number of patients rising rapidly worldwide, COVID-19 has become a throny international public health event. As of Mar 24 th , China has cumulatively diagnosed 81747 cases and 147 new cases, while the number of cases in other countries is growing rapidly with a total of 291070 cases confirmed and 22027 new cases identified that day.
Emerging studies suggest that COVID-19 preferentially afflicts the elderly, particularly those with chronic comorbidities 1, 2 . However, the clinical profiles of COVID-19 in refractory heart failure patients is unknown. Herein, we reported the clinical features in a group of end-stage heart failure patients with COVID-19, providing strong evidence of cardiac injury by the virus. We retrospectively included four hospitalized severe heart failure patients infected with COVID-19 between Jan 7 th and Mar 15 th in our department. All patients were transferred to isolation ward since confirmed diagnosis or highly suspected.
Three patients were suspected as hospital-related transmission because they were once in the same ward. None of the patients had fever during the illness, and they had just mild cough or fatigue at the time of diagnosis. Significantly enlarged left ventricle ( Figure 1 ) and reduced left ventricular ejection fraction was observed in four patients, and all of them had New York Heart Function grade IV. Interestingly, patient 1 was negative for two consecutive nucleic acid tests but positive for serum antibodies (IgM 69.12 AU/ml). Only two patients had typical ground-glass imaging changes in lung CT ( Figure 1 ). With exacerbations, patient 3 and 4 were transferred to ICU and both died on ten days after the first positive nucleic acid test. Three patients had elevated troponin I (TNI) in the later period, especially in patient 3 and 4, TNI increased significantly a few days before death. Moreover, the levels of C-reactive protein (CRP) and brain natriuretic peptide of patient 3 and 4 were significantly higher than the rest two patients. It is also worth mentioning that patient 2 turned positive again after two consecutive negative test for nucleic acid. The detailed information and treatment on patients were shown in Table 1 .
In this study, we reported for the first time four end-stage heart failure patients who were infected with COVID-19, two severe presentation and others mild. These patients showed some similar characteristics as described in previous reports 3 . For instance, all four patients were male, consistent with previous findings that higher percentages of infection in men than women. In addition, critically ill COVID-19 patients with heart failure also had typical lymphopenia and significantly increased CRP level.
Patients with end-stage heart failure seemed to have a high mortality rate after infection with the pneumonia. Older age, more comorbidities, poor general condition and severe myocardial injury may be risk factors. The most novel finding was that the TNI level of the two critically ill patients increased significantly by more than 20 folds, indicating myocardial injury. Although there have been previous reports of myocardial damage in COVID-19 patients 4,5 , they mostly chose non-specific indicators such as CK-MB and LDH which could be confounded by many other factors in clinic. In addition, CK-MB and LDH were not significantly increased in those reports in fact. Our findings provided definitely stronger evidence of myocardial injury by COVID-19.
The exact mechanism of myocardial injury caused by 2019-nCoV is not completely clear, but through previous and our findings, it is clear that 2019-nCoV infection can cause myocardial injury and is closely related to disease progression.
The study was limited by small sample size, longitudinal studies on a larger cohort of heart failure patients would help to understand the prognosis of the disease. 