Baseline Characteristics
The study population included 116 hospitalized patients with laboratory-confirmed COVID-19 (Table 1). The median age was 58.5 years (IQR, 47.0-69.0), and 36 (31.0%) were females. Fifty-nine (50.9%) patients had at least one underlying disorder. Hypertension (45 [38.8%]), diabetes (19 [16.4%]), coronary heart disease (17 [14.7%]), and cerebrovascular diseases (8 [6.9%]) were the most common coexisting conditions (Table 1). Fever (85.3%), dry cough (52.6%), fatigue (51.7%), anorexia (43.1%), dyspnea (44.8%), and chest discomfort (43.1%) were the most common symptoms, whereas dizziness (6.0%), nasal obstruction (5.2%), abdominal pain (2.6%), hemoptysis (0.9%) were less common (Table 1). The median durations from first symptoms to dyspnea and hospital admission were 4.5 days (IQR, 0-9.0), and 8.0 days (IQR, 4.0-11.0) respectively (Table 1).
On admission, 61 and 55 patients were categorized into non-severe and severe subgroups, respectively. The age differed significantly between the two groups (median age, non-severe vs severe, 56.0 years [IQR, 37.0-64.0] vs 64.0 years [IQR, 53.0-76.0]; P<0.001). Severe cases were more prone to having underlying comorbidities, including coronary heart disease (13 [23.6%] vs 4 [6.6%], cerebrovascular diseases (7 [12.7%] vs 1 [1.6%]), and malignancy (4 [7.3%] vs 0 [0.0%]). Compared with the non- severe group, dyspnea and fatigue were more frequently reported in severe patients. Vital signs were recorded on the day of admission to hospital for all patients. Respiratory rate was higher in severe cases as compared with non-severe cases (20.0 [IQR, 18.0-25.0] vs 19.0 [IQR, 18.0-20.0; P=0.030]). While, heart rate, mean arterial pressure, and body temperature showed no significant difference between the two groups (all P>0.05).
Laboratory and radiologic findings at presentation
The most common pattern on chest CT was bilateral patchy shadowing (69.9%). These imaging alterations were more prominent in severe patients (47 [85.5%] vs 36 [59.0%]; P=0.002) (Table 2).
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.
Complications, main interventions, and outcomes
The organ dysfunction and treatment of the 116 patients were shown in Table 4. On April 21, 2020, a total of 109 patients (94.0%) had been discharged, and 7 patients (6.0%) had died. Among the 116 patients, the most common complication was acute cardiac injury (23 [19.8%]), followed by acute heart failure (21 [18.1%]), ARDS (20 [17.2%]), shock (16 [13.8%]), or liver dysfunction (15 [12.9%]). Severe cases were more liable to having one of these complications than non- severe cases.
All patients were treated in isolation. 112 (96.6%) patients received antiviral treatment, including oseltamivir phosphatecas (91, [78.4%]), lopinave/litonawe (74, [63.8%]), arbidol hydrochloride (27, [21.4%]), and ribavirin Injection (71, [61.2%]). Antibacterial therapy was performed for most patients (113, [97.4%]). Twelve (10.3%) patients adopting antifungal medications were all enrolled in severe group. Systemic corticosteroid was given to 47.4% of cases and more so in the severe patients than in the non-severe group (74.5% vs 23.0%, P<0.0001). Obviously, more severe cases received mechanical ventilation (non-invasive: 32.7% vs. 0%, P<0.0001; invasive: 18.2% vs. 0%, P<0.0001) as compared with non-severe cases. Three severe patients were treated with extracorporeal membrane oxygenation. Traditional Chinese medical herbal treatment and immune support therapy were applied in most cases. Overall, all these interventions were initiated in significantly higher percentages of severe patients.
Of the 7 deceased patients, all patients developed ARDS, 4 had sepsis or sepsis shock, 1 had gastrointestinal and cerebral hemorrhage. As the disease progressed and clinical status deteriorated, the levels of D-dimer, creatinine, blood urea, lactate dehydrogenase, and cTnT progressively increased before death. Among the dead patients, all received antiviral therapy, antibacterial therapy, and immune support therapy (use of intravenous immunoglobin and/or thymopeptides injection). Based on the 6th edition guideline issued by the National Health Commission of China, Hydroxychloroquine had not been recommend in the treatment of COVID-19 yet. Meanwhile, traditional Chinese medical herbal treatment, including Lianhua Qingwen Capsule and oral use of Chinese herbal decoction, like Lung cleansing and detoxification soup, were recommended and applied in most hospitalized patients. This part of treatment was managed by the doctor majoring in traditional Chinese medicine. In the present study, 5 non-survivors received Lianhua Qingwen Capsule therapy.
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, α-hydroxybutyric 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). The morbidity rate of hypertension was significantly higher in severe cases (42 [76.4%] vs 27 [44.3%]; P=0.0006) (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).