Clinical Characteristics and Cardiovascular Implications of 116 Hospitalized Patients with COVID-19 in Wuhan, China: A single-Centered, Retrospective, Observational Study


 Background Corona Virus Disease 2019 (COVID-19) caused by 2019 novel coronavirus (SARS-CoV-2), has become a global pandemic. Aged population with cardiovascular diseases are more likely be to infected with SARS-CoV-2 and result in more severe outcomes and elevated case-fatality rate. Meanwhile, cardiovascular diseases have a high prevalence in the middle-aged and elderly population. However, despite of several researches in COVID-19, cardiovascular implications related to it still remains largely unclear. Methods 116 patients with laboratory-confirmed COVID-19 were enrolled, who admitted to the General Hospital of Central Theater Command (Wuhan, China) from January 20 to March 8, 2020. The demographic data, underlying comorbidities, clinical symptoms and signs, laboratory findings, chest computed tomography, treatment measures, and outcome data were collected from electronic medical records. Data were compared between non-severe and severe cases.Results Of 116 hospitalized patients with COVID-19, the median age was 58.5 years (IQR, 47.0-69.0), and 36 (31.0%) were female. Hypertension (45 [38.8%]), diabetes (19 [16.4%]), and coronary heart disease (17 [14.7%]) were the most common coexisting conditions. Common symptoms included fever [99 (85.3%)], dry cough (61 [52.6%]), fatigue (60 [51.7%]), dyspnea (52 [44.8%]), anorexia (50 [43.1%]), and chest discomfort (50 [43.1%]). Lymphopenia (lymphocyte count, 1.0 × 109/L [IQR, 0.7-1.3]) was observed in 66 patients (56.9%), and elevated lactate dehydrogenase (245.5 U/L [IQR, 194.3-319.8]) in 69 patients (59.5%). Compared with non-severe cases, severe cases were older (64.0 years [IQR, 53.0-76.0] vs 56.0 years [IQR, 37.0-64.0]), more likely to have comorbidities (35 [63.6%] vs 24 [39.3%]), and more likely to develop acute cardiac injury (19 [34.5%] vs 4 [6.6%]), acute heart failure (18 [32.7%] vs 3 [4.9%]), and ARDS (20 [36.4%] vs 0 [0%]). During hospitalization, the prevalence of new onset hypertension was significantly higher in severe patients (55.2% vs 19.0%) than in non-severe ones. Conclusions We found that the infection of SARS-CoV-2 was more likely to occur in aged population with cardiovascular comorbidities. Cardiovascular complications, including new onset hypertension and heart injury were common in severe patients. More detailed researches in cardiovascular involvement in COVID-19 are urgently needed to further understand the disease.

Cardiovascular diseases have a high prevalence in middle-aged and elderly population. [8] aged population with comorbidities, such as cardiovascular diseases are more susceptible to COVID-19 and result in severe outcomes and elevated case-fatality rate [5,9]. Acute cardiac injury is one of the common complications in COVID-19 patients [7]. These findings suggest that cardiovascular system is tightly implicated in COVID- 19

Data Collection
We obtained the demographic data, medical history, underlying comorbidities, clinical symptoms and signs, laboratory findings, chest computed tomography (CT), treatment measures, and outcome data from electronic medical records for all hospitalized patients with laboratory confirmed COVID-19.
ARDS and shock were defined in accordance with the guidance of WHO for COVID-19.
[10] The diagnosis of acute kidney injury was based on the highest serum creatinine level and urine output [11]. Cardiac injury was defined if the serum concentration of hypersensitive cardiac troponin T (cTnT) was above the upper limit of the reference range ( 0.02 ng/mL). Acute heart failure was defined based on the typical symptoms that may be accompanied by signs caused by a structural and/or functional cardiac abnormality [12]. Hypertension is defined in adults as the results of systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg three times on different days.

Baseline Characteristics
The study population included 116 hospitalized patients with laboratory-confirmed COVID-19 (   (Table 1).    There were numerous differences in laboratory findings between severe and non-severe cases (Table 3). Laboratory abnormalities were more obviously seen in severe cases, including lower counts of lymphocyte, T cells, CD4 + and CD8 + T cells, and elevated levels of neutrophil count, procalcitonin, c-reactive protein, interleukin 6, D-dimer, creatinine, blood urea nitrogen, lactate dehydrogenase, myoglobin, cTnT, and NT-proBNP (all P < 0.05). Hypokalemia (20.7%) was prevailing in both severe and non-severe patients, though no statistical difference was found between them.

Dynamic profile of blood pressure and cardiac markers
To determine the cardiovascular implications during COVID-19 progression, the dynamic changes in heart rate, blood pressure, and 5 clinical laboratory parameters, including creatine kinase-MB, αhydroxybutyric dehydrogenase, lactate dehydrogenase, cTnT, and NT-proBNP were tracked in survivors (Figure 1, 2). The results of heart rate and blood pressure were recorded every day at the same time. Laboratory parameters were examined once every 3 days. During hospitalization, higher levels of systolic blood pressure were observed in server cases ( Figure 1B). A total of 8 patients from non-severe group and 16 patients from severe group were diagnosed with new onset hypertension ( Figure 1D) Figure 1E).
During hospitalization, severe cases exhibited higher levels of cardiac markers ( Figure 2). The prevalence of cardiac complications, including acute cardiac injury and heart failure was significantly higher in severe cases ( Table 4). Increases of lactate dehydrogenase and α-hydroxybutyric dehydrogenase were also more likely to occur in severe patients ( Figure 2B, 2C). Myocardial enzymes increased rapidly in the early stage of illness, but gradually decreased with the disease progression.
In the end period of the 28-day time frame, abnormal results of cTnT and NT-proBNP were still common in some of the severe patients because of progression of COVID-19 (( Figure 2D, 2E).

Discussion
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 [14], and the coexistence of agedness and comorbidity could lead to an even higher risk of death [13]. 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 [8]. As previously reported [14], 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 [18]. 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 [19]. 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 [15]. 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 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 [15]. Currently, it is in lack of any

Conclusions
In this single-centered, retrospective, observational study, we found that the infection of SARS-CoV-2 were more likely to occur in older population with cardiovascular comorbidities. Cardiovascular complications, including new onset hypertension and heart injury were common in severe patients with COVID-19. More comprehensive and in-depth researches are in need to unveil the cardiovascular involvement in COVID-19 to further understand the disease.

Ethics approval and consent to participate
The Ethics Commission of General Hospital of Central Theater Command approved this study ([2020]025-1).

Consent for publication
interpreted the patient data. All authors participated in collecting data, designing the analyses, and interpreting the results. SD had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved the final manuscript.

Figure 1
Dynamic monitoring heart rate and blood pressure of patients hospitalized with COVID-19 During hospitalization, heart rate and blood pressure were recorded every day at the same time by nurses. The dynamic monitoring results of heart rate (A), systolic blood pressure (B), and diastolic blood pressure (C) were compared between non-severe and severe cases.
D, the counts of normal blood pressure, preexisting hypertension, and new onset hypertension cases in non-severe and severe groups. E, rate of preexisting hypertension, new onset hypertension, and the total hypertension were compared between non-severe and severe subgroups. *P<0.05, **P<0.01, ***P<0.001 for Non-severe vs Severe.