This retrospective study described the clinical characteristics and cardiovascular implications in hospitalized patients with COVID-19 in Wuhan. By April 13, 2020, of the 116 patients included in this study, 69% were male, 47% were severe cases, 90.5% were discharged, 6.0% (7) died, and 3.4% remained hospitalized. Most severe patients were older and had more underlying conditions. Common symptoms at onset of illness were fever, dry cough, fatigue, dyspnea, and chest discomfort. Local and/or bilateral patchy shadowing was a typical hallmark of CT imaging for COVID-19. Lymphopenia and elevated levels of neutrophil count, C-reactive protein, interleukin 6, D-dimer, creatinine, lactate dehydrogenase, cTnT, and NT-proBNP were more commonly seen in severe cases. During hospitalization, the prevalence of new onset hypertension, acute heart injury, and heart failure was significantly higher in severe patients.
In our cohort, 69% (80) of COVID-19 patient were male. Severe patients were older and had a greater number of comorbid conditions. Evidence from previous studies suggest that older, male patients are the most susceptible to SARS-CoV-2 infection [4, 5, 7, 13], which is supported by our data. It has been confirmed that increased age was associated with death in COVID-19 patients , and the coexistence of agedness and comorbidity could lead to an even higher risk of death . Older age has been regarded as an important independent predictor of mortality in COVID-19.
Cardiovascular diseases have a high incidence rate in the middle aged and elderly population . As previously reported , we observed that many COVID-19 patients had a comorbidity, with hypertension being the most common (45 [38.8%]), followed by diabetes (19 [16.4%]) or coronary heart disease (17 [14.7%]). The morbidity rates of coronary heart disease and cerebrovascular diseases were significantly higher in the severe group. Thus, older people with comorbidities, such as coronary heart disease and hypertension were thought to be more vulnerable to SARS-CoV-2 and result in more severe outcomes and elevated case-fatality rate[5, 9, 15]. In the present study, 4 of 7 dead patients had preexisting hypertension and coronary heart disease. Previously, coronary heart disease has also been found to be correlated with acute cardiac events and poor outcomes in influenza and other respiratory viral infections [16, 17], Multivariate logistic regression analysis demonstrated that coronary heart disease and heart injury were the independent risk factors for critical disease status in COVID-19 patients . More intense clinical care is in need for COVID-19 patients with cardiac-related chronic diseases.
Incident cardiovascular complications including new or worsening heart failure, new or worsening arrhythmias, or myocardial infarction are common in patients with pneumonia and are associated with increased short-term mortality . Acute pneumonia brings important effects on the status of cardiovascular system irrespective of severities of infection [16, 19]. Risk factors for cardiac complications after pneumonia include older age, preexisting cardiovascular diseases, and greater severity of pneumonia [16, 19]. An analysis of 112 cardiovascular disease patients with COVID-19 found that, COVID-19 patients combined with cardiovascular disease were associated with a higher risk of mortality . In this study, compared with non-severe patients with COVID-19, severe patients showed abnormalities in numerous cardiac markers. During hospitalization, the morbidity of new onset hypertension, acute heart injury, and heart failure was significantly higher in severe patients. Increased level of myocardial enzymes and cTnT was found in all 3 dead cases. As far as we know, this is the first study that reports the prevalence rate of new onset hypertension was significantly higher in hospitalized severe patients with COVID-19. These findings suggest a higher possibility of cardiovascular complications in severe patients with COVID-19. Outcomes of patients with COVID-19 may be improved by prevention of the development and progression of associated cardiac complications.
Angiotensin-converting enzyme 2 (ACE2) acts as a receptor for SARS-CoV-2 entry into cells and contributes to the pathogenesis of COVID-19 . Meanwhile, ACE2 is widely expressed in myocytes and vascular endothelial cells. At least, these is theoretically a possibility of direct cardiovascular involvement induced by the virus. The only pathological result of heart biopsy in a fatal case with COVID-19 showed a few interstitial mononuclear inflammatory infiltration, but no other substantial damage in the heart tissue . However, given that this patient had no clinical manifestations of myocardial injury during the whole course of this disease, it could not be concluded whether myocardium was involved in SARS-CoV-2 infection yet. We speculated that the potential pathogenesis of myocardial injury in COVID-19 may include several processes, SARS-CoV-2 may directly invade myocytes via ACE2 and cause viral myocarditis; the imbalance between supply and demand in oxygen further results in myocardial injury; and inflammatory cytokines storm. In order to further clarify the etiology of SARS-CoV-2 infection related myocardial injury, it is of great need to obtain pathological evidence from COVID-19 patients showing definite myocardial injury.
Recently, the safety of treatment applying angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) in relation to COVID-19 has been concerned. An observational study containing 112 patients with cardiovascular diseases infected by COVID-19 reported that there was no significant difference in the proportion of ACEI/ARB medication between the critical group and the general group or between non-survivors and survivors . Currently, it is in lack of any experimental or clinical evidence suggesting adverse or beneficial outcomes with background use of ACEI, ARBs or other RAAS antagonists in COVID-19 or among COVID-19 patients with a history of cardiovascular disease treated with such agents. Statements of ACC and ESC Council on Hypertension do not recommend to discontinue ACEI/ARB treatment in the lack of any evidence supporting adverse effect of ACEI and ARB in the context of the pandemic COVID-19 outbreak[22, 23]. Individualized treatment strategies should be approached according to each patient's hemodynamic status and clinical manifestations.
Our study has some limitations. First, only 116 patients with laboratory-confirmed COVID-19 were included. It would be better to include a large population of patients from other centers in Wuhan, and even in other cities in China to get a more comprehensive understanding of COVID-19. Second, not all laboratory tests were dynamically performed in all patients, including the counts of lymphocyte subsets and inflammatory cytokines, therefore their role in the pathogenesis of COVID-19 might be underestimated. Third, due to the retrospective study design, echocardiography and electrocardiograph were only performed in some of the patients. The detailed information of ACEI/ARB medication was incomplete. Therefore, we could not further asses the changes of cardiac structure and function during the progression of COVID-19, and the possible effect of ACEI/ARB on SARS-CoV-2 infection. Last but not least, we were unable to obtain myocardial tissues from deceased COVID-19 patients with heart injury. The characteristics of myocardial damage should be further demonstrated by pathologists.