Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan, China

This case series was approved by the institutional ethics board of Zhongnan Hospital of Wuhan University and Xishui People’s Hospital (No. 2020020). All the discharged (alive at home and dead) patients with confirmed COVID-19 from Zhongnan Hospital of Wuhan University and Xishui People’s Hospital up to February 10, 2020, were enrolled. Oral consent was obtained from patients or patients’ relatives. Zhongnan Hospital, located in Wuhan, Hubei Province, the endemic areas of COVID-19, is one of the major tertiary teaching hospitals and responsible for the treatments for COVID-19 assigned by the government. Xishui People’s Hospital is located in Huanggang city, another early endemic center of COVID-19 in Hubei province. In total, about 340 heath care workers provided care to COVID-19 patients in the two medical centers from January to February 2020. All patients with COVID-19 enrolled in this study were diagnosed according to World Health Organization interim guidance [14]. The methodology of RT-PCR used has been previously reported [12]. The time frame was overlapped with the JAMA cohort, and 88 patients in the current report have been included in the JAMA cohort [12].

The medical records of patients were analyzed by the research team of the Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University. Epidemiological, clinical, laboratory, and radiological characteristics and treatment and outcomes data were obtained with data collection forms from electronic medical records and reviewed by a trained team of physicians. The information recorded included demographic data, medical history, exposure history, underlying comorbidities, symptoms, signs, laboratory findings, chest computed tomographic (CT) scans, treatment measures (i.e., antiviral therapy, corticosteroid therapy, respiratory support, kidney replacement therapy), and outcomes. The date of disease onset was defined as the day when the first symptom was noticed. Acute respiratory distress syndrome (ARDS) was defined according to the Berlin definition [15]. Acute kidney injury (AKI) was identified according to the Kidney Disease: Improving Global Outcomes definition [16]. Cardiac injury was defined if the serum levels of cardiac biomarkers (e.g., troponin I) were above the 99th percentile of the upper reference limit or if new abnormalities were shown in echocardiography. Times from onset of disease to hospital admission, dyspnea, ARDS, ICU admission, and hospital discharge were recorded.

Categorical variables were described using frequencies and percentages, while continuous variables were described using mean, median, and interquartile range (IQR) values. Means for continuous variables were compared using independent group Student’s t tests when the data were normally distributed and the Mann-Whitney test when they were not. Proportions for categorical variables were compared using the χ² test, although Fisher’s exact test was used when the data were sparse. Univariate analyses were performed to evaluate the risk factors associated with death. Multiple logistic regression analysis was used to identify independent predictors of mortality. All the tests were two-tailed, and P value less than 0.05 was considered statistically significant. All analyses were processed by SPSS for Windows version 17.0 (SPSS, Chicago, IL, USA).

As of February 10, 2020, 544 patients were admitted to Zhongnan Hospital and Xishui Hospital, and 107 patients were discharged. The basic characteristics of the 107 patients (95 from Zhongnan and 12 from Xishui) are shown in Table 1. There were 88 survivors and 19 non-survivors. The median age was 51 years (IQR, 36–65; range, 19–92 years); 57 (53.3%) were male. The median times from first symptoms to hospital admission, dyspnea, and ARDS were 7 days (IQR, 3.5–9), 5.5 days (IQR, 2–9.3), and 7.5 days (IQR, 4.3–11), respectively. The median length of hospital stay was 11 days (IQR, 7–15). In this cohort of 107 patients, hypertension (26 [24.3%]), cardiovascular disease (13 [12.1%]), and diabetes (11 [10.3%]) were the most common coexisting conditions. The most common symptoms at onset of illness were fever (104 [97.2%]), dry cough (67 [62.6%]), fatigue (69 [64.5%]), dyspnea (35 [32.7%]), anorexia (33 [30.8%]), and myalgia (33 [30.8%]). Less common symptoms were sore throat, headache, dizziness, abdominal pain, diarrhea, nausea, and vomiting. At hospital admission, the median respiratory rate was 20/min [IQR, 19–21], and the mean arterial pressure was 89 mmHg [IQR, 83–98].

In comparison with the 88 hospital survivors, the 19 non-survivors were significantly older (median age, 73 years [IQR, 64–81] vs 44.5 years [IQR, 35–58.8]; P < .001) and were predominantly male (16 [84.2%] vs 41 [46.6%]; P = .003). Non-survivors were more likely to have underlying comorbidities, including hypertension (10 [52.6%] vs 16 [18.2%]; P = .001) and other cardiovascular diseases (7 [36.8%] vs 6 [6.8%]; P = .002). Compared with the survivors, non-survivors were more likely to report dyspnea (15 [78.9%] vs 20 [22.7%]; P < .001) and diarrhea (4 [21.1%] vs 3 [3.4%]; P = .018) at presentation. At hospital admission, the respiratory rate was higher in survivors than in non-survivors (22 [IQR 20–24] vs 20 [17–19]; P = .003). Similarly, the mean arterial pressure was higher in non-survivors than in survivors (95 mmHg [IQR 89–101] vs 88 mmHg [83–96]; P = .019).

Laboratory values and radiographic findings at hospital admission are shown in Table 2. Lymphopenia (0.9 × 10⁹/L [0.7–1.2]) and prolonged prothrombin time (12.8 [11.9–13.5]) at admission were prominent features. Ninety (84.1%) patients showed multi-lobar involvement on initial radiographs. One hundred five (98.1%) patients showed bilateral involvement on chest CT scan during hospitalization. Compared with survivors, on admission, non-survivors had higher neutrophil counts (5.4 × 10⁹/L [3.2–8.5] vs 2.8 × 10⁹/L [2–3.9], P < 0.001), lower platelet count (122 × 10⁹/L [83–178] vs 178 [139–207], P = 0.006), and higher D-dimer level (439 mg/L [202–1991] vs 191 mg/L [108–327], P = 0.003). Admission values of blood urea, creatinine, highly sensitive troponin I, serum creatine kinase, creatine kinase-MB, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase were also significantly higher in the non-survivors.

Temporal clinical profiles in 107 patients with COVID-19 are shown in Fig. 1. Trends of temperature and onset of positive nucleic acid amplification test (NAAT) were consistent. Fever typically lasts for about 10 days. Most patients (about 75%) demonstrated positive NAAT results (measured every 2–3 days) within 9 days after symptom onset. The median time from illness onset to the first positive result of NAAT was 7 days (3.0–10.0), and the duration of active viral shedding was 13 days (IQR, 10–22.3) in survivors. In the majority of cases, the development of ARDS and the need for endotracheal intubation occurred within 9 days after symptom onset.

Dynamic body temperature and laboratory findings in 107 COVID-19 patients are shown in supplementary Fig. 1. During the first week after symptom onset, fever was prominent and more severe in the non-survivors. Body temperature gradually normalized in the second week. In general, white blood cell counts and neutrophil counts were in normal range during week 1, with leukocytosis and neutrophilia as later findings. Lymphopenia was common throughout the disease’s course, and the lymphocyte count dropped more in non-survivors. Platelet counts decreased slightly in the first week, then rose back to normal range rapidly in survivors, but remained low in non-survivors. Mild prolongation of prothrombin time (PT) during the illness course was observed, with no difference between survivors and non-survivors. The D-dimer level was elevated in the non-survivors during the late stage of illness. In the early stage of the illness, higher levels of creatine kinase, creatine kinase-MB, lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase were observed in the non-survivors than in the survivors. In non-survivors, blood urea and creatinine levels progressively increased until death.

Common complications included ARDS (28 [26.2%]), shock (22 [20.6%]), AKI (14 [13.1%]), and acute cardiac injury (12 [11.2%]) (Table 3). Non-survivors were more likely to have one of these complications than survivors. Secondary infection included 1 case of bacteremia caused by Staphylococcus caprae and 4 cases of bacterial pneumonia caused by Acinetobacter baumannii. Co-infection with virus included 1 patient tested positive for influenza A, two for influenza B, three for respiratory syncytial virus, three for parainfluenza, and 3 for adenovirus. Almost all patients received antiviral therapy (105 [98.1%]). Among them, 95 (88.8%) patients received oseltamivir and 33 (30.8%) patients received arbidol. Glucocorticoids were administered in 62 [57.9%] patients. Oxygen therapy was applied in (80 [74.8%] patients. In total, 20 patients required invasive mechanical ventilation. On day 1 of invasive mechanical ventilation, the median PaO₂/FiO₂ ratio was 103 (IQR 58–172) and the median APACHE II score was 25 (IQR 17–32). Three patients received extracorporeal membrane oxygenation (ECMO) therapy, Two of them survived and were discharged at day 26 and day 32, and one died due to sudden cardiac arrest after connection to the ECMO circuit. The causes of death included refractory ARDS (15 [78.9%]), septic shock (1 [5.3%]), sudden cardiac arrest (1 [5.3%]), hemorrhagic shock (1 [5.3%]), and acute myocardial infarction (1 [5.3%]).

On the univariate analysis, the risk factors associated with death at hospital admission were older age, male gender, hypertension, diabetes, cardiovascular disease, raised white blood cell counts, elevated level of neutrophil counts, thrombocytopenia, creatine kinase-MB, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, and creatinine (Table 4). On the multivariable analysis, older age and male gender remained the significant independent risk factors for death (Table 5).