Basic characteristics, clinical features, laboratory findings and outcomes in total patients
In this study, from February 4th to March 9th 2020, we enrolled 1646 COVID-19 confirmed patients, who hospitalized in Wuhan Huoshenshan Hospital. The median age was 60.0 years (IQR 50.0-68.0), 830 (50.4%) patients were male, 93 (5.7%) were current smoker and 56 (3.4%) addicted to alcohol. The initial symptom included fever (1034 [62.8%]), cough/sputum (277 [16.8%]), fatigue (108 [6.6%]) or short of breath (71 [4.3%]). Gastrointestinal symptoms such as nausea, vomiting, diarrhea might occur in early as well. In addition, 48 patients (2.9%) showed no significant discomfort. Hypertension (490 [29.8%]) and diabetes (220 [13.4%]) were the common comorbidities. 1312 (79.7%) patients showed bilateral pneumonia while 133 (8.1%) patients showed unilateral pneumonia, and 1482 (90.0%) patients exhibited ground-glass opacity. COVID-19 patients showed elevated hs-CRP (2.7 [IQR 1.0-10.3] mg/L), the mean levels of other laboratory results in all patients were within the reference ranges. However, 294 (17.9%), 19 (1.2%), 117 (7.1%) and 28 (1.7%) patients suffered from liver injury, kidney injury, myocardial injury and coagulation disorder, respectively. (Table 1)
Most patients received antivirus therapy, including abidor hydrochloride (751 [45.6%]), oseltamivir phosphate (194 [11.8%]), and ribavirin (77 [4.7%]). Moxifloxacin hydrochloride was used in 493 (30.0%) patients to anti-infection. Vitamin C (481 [29.2%]), thymalfasin (123 [7.5%]) and recombinant interference (104 [6.3%]) were used to regulate immune function. In addition, a small percentage of patients were treated with glucocorticoid (215 [13.1%]).
The median hospital length of stay was 14.0 days (IQR 9.0-19.0), the median time from illness onset to normothermia was 24.0 days (IQR 17.0-32.0), the median time from illness onset to inflammatory resorption was 30.0 days (IQR 23.0-36.0), and the median time from illness onset to viral shedding was 29.0 days (IQR 24.0-36.0). 73 (4.4%) subjects were complicated with ARDS, 57 (3.5%) subjects progressed into respiratory failure, 60 (3.7%) subjects were admitted to ICU, and 43 (2.6%) subjects received mechanical ventilation. The median time from illness onset to severe illness was 20.0 days (IQR 14.0-26.0), the median time from illness onset to ARDS was 18.0 days (IQR 14.0-26.5), the median time from illness onset to respiratory failure was 18.5 days (IQR 14.0-25.0), and the median time from illness onset to use mechanical ventilation was 20.0 days (IQR 13.0-26.0). The median time from illness onset to ICU admission was 18.0 days (IQR 14.0-25.0) and the median ICU length of stay was 5.5 days (IQR 3.0-9.0). 23 (1.4%) patients died during hospitalization, and the median time from illness onset to death was 26.0 days (IQR 17.0-31.0). (Table 2)
Differences of basic characteristics, clinical features, laboratory findings and outcomes between common patients and severe patients
327 (19.9%) individuals developed into severe cases. Compared to common cases, severe patients showed older age (65.0 [IQR 56.0-72.0] vs 58.0 [IQR 48.0-67.0] years, p<0.0001), lower proportion of fever (184 [56.3%] vs 850 [64.4%], p=0.0062), on the contrary, higher proportion of short of breath (24 [7.3%] vs 47 [3.6%], p=0.0026), more comorbidities including hypertension (138 [42.2%] vs 352 [26.7%], p<0.0001), diabetes (66 [20.2%] vs 154 [11.7%], p<0.0001), arrhythmia (25 [7.6%] vs 28 [2.1%], p<0.0001), and malignant neoplasm (10 [3.1%] vs 18 [1.4%], p=0.034).
In addition, severe patients exhibited higher leucocytes (6.7 [IQR 5.3-8.3] vs 5.7 [IQR 4.7-6.8] × 109/L, p<0.0001), neutrophil percentage (69.9 [IQR 62.6-78.0] vs 60.7 [IQR 54.8-66.5] %, p<0.0001) but lower lymphocyte percentage (18.9 [IQR 12.9-26.1] vs 28.2 [IQR 23.0-33.6] %, p<0.0001), monocyte percentage (7.6 [IQR 6.0-8.9] vs 7.7 [IQR 6.6-9.0] %, p=0.010), eosinophil percentage (1.6 [IQR 0.9-2.6] vs 2.0 [IQR 1.3-3.1] %, p<0.0001), basophil percentage (0.28 [IQR 0.15-0.40] vs 0.40 [IQR 0.28-0.50] %, p<0.0001), and hemoglobin concentration (116.3 [IQR 104.5-127.7] vs 125.5 [IQR 116.0-136.0] g/L, p<0.0001). Particularly, the hs-CRP concentrations in severe patients were significantly higher (15.6 [IQR 4.5-45.0] vs 2.0 [IQR 0.8-5.9] mg/L, p<0.0001) than those in common patients. Moreover, compared to common cases, severe patients showed higher ALT (29.3 [IQR 17.6-50.4] vs 23.9 [IQR 15.3-38.9] IU/L, p<0.0001), aspartate aminotransferase (22.4 [IQR 18.3-32.5] vs 19.4 [IQR 15.6-25.7] IU/L, p<0.0001), total bilirubin (9.5 [IQR 7.2-12.4] vs 9.0 [IQR 7.2-11.5] μmol/L, p=0.044), gamma-glutamyl transpeptidase (37.0 [IQR 23.1-60.4] vs 30.2 [IQR 20.1-48.4] IU/L, p<0.0001), urea nitrogen (5.0 [IQR 4.0-6.5] vs 4.3 [IQR 3.6-5.2] mmol/L, p<0.0001), and cystatin C (1.0 [IQR 0.9-1.2] vs 0.9 [IQR 0.8-1.0] mg/L, p<0.0001), lower total protein (60.9 [IQR 57.5-65.0] vs 64.8 [60.9-68.3] g/L, p<0.0001). Besides, creatine kinase-MB (9.5 [IQR 7.3-13.4] vs 8.2 [IQR 6.6-10.2] IU/L, p<0.0001), lactate dehydrogenase (219.1 [IQR 180.9-273.6] vs 172.1 [IQR 150.4-202.8] IU/L, p<0.0001), α-hydroxybutyrate dehydrogenase (181.6 [IQR 150.9-232.9] vs 140.6 [IQR 123.3-164.8] IU/L, p<0.0001), and hs-cTnI (0.02 [IQR 0.01-0.06] vs 0.01 [IQR 0.01-0.01] ng/mL, p<0.0001) were elevated in severe patients. PT (13.1 [IQR 12.4-14.0] vs 12.7 [IQR 12.1-13.4] s, p<0.0001), thrombin time (15.5 [IQR 14.7-16.4] vs 15.3 [IQR 14.5-16.0] s, p=0.0086), and fibrinogen (3.2 [IQR 2.8-3.7] vs 3.0 [IQR 2.6-3.3] g/L, p<0.0001) were elevated in severe patients. More severe patients suffered from liver injury, kidney injury, myocardial injury, and coagulation disorder. (Table 1)
Furthermore, all clinical adverse events were derived from severe cases and the length of hospitalization was longer in severe patients (16.0 [IQR 11.0-21.0) vs 14.0 [IQR 8.0-18.0] days, p<0.0001) than in common cases. (Table 2)
Risk factors for the incidence of severe patients
In univariable regression, age, hypertension, diabetes, arrhythmia, malignant neoplasm, white blood cell count, lymphocyte percentage, hs-CRP, liver injury, acute kidney injury, cardiac injury as well as coagulation disorder were associated with the incidence of severe cases. (Table 3) The initial chest CT imaging and symptoms did not show significant correlations with severe cases of COVID-19 (Supplement table 1, 2). Importantly, results from multivariable analysis showed that age (OR: 1.02, 95% confidence interval [95% CI]: 1.01-1.03, p=0.0003), arrhythmia (OR: 2.91, 95% CI: 1.45-5.86, p=0.0027), lymphocyte percentage (OR: 3.48, 95% CI: 2.58-4.69, p<0.0001), hs-CRP (OR: 3.73, 95% CI: 2.74-5.09, p<0.0001), and myocardial injury (OR: 3.02, 95% CI: 1.91-4.77, p<0.0001) were independently associated with the incidence of severe cases. (Table 3)
Clinical outcomes in patients with or without myocardial injury
After follow-up, the mortality rate was higher in patients with myocardial injury (16.2%) than those without myocardial injury (0.3%) (log-rank p value <0.0001, Figure 1A). What’s more, the event-free survival rates (including the incidences of severe cases, ARDS and ICU admission) were similarly lower in patients with myocardial injury than those without myocardial injury (log-rank p value <0.0001, Figure 1B-D). Furthermore, patients with myocardial injury showed significantly higher mortality rate, percentage of ARDS and ICU admission than those without myocardial injury irrespective of age (log-rank p value <0.0001, Figure 2A, C, D), whereas the incidence of severe cases seemed to be higher in patients with myocardial injury and age≥75 years old than those with myocardial injury and age <75 years old (Figure 2B). Moreover, the event-free survival rates (including mortality, the incidences of severe cases, ARDS and ICU admission) were even lower in patients with myocardial injury and arrhythmia than those with myocardial injury but without arrhythmia (log-rank p value <0.0001, Figure 3A-D). Interestingly, if myocardial injury co-existed with elevated hs-CRP, the clinical outcomes [mortality (Figure 4A), the incidences of severe cases (Figure 4B), ARDS (Figure 4C) and ICU admission (Figure 4D)] were extremely poor. Similar outcomes were found in patients with myocardial injury co-existed with abnormal lymphocyte percentage (log-rank p value <0.0001, Figure 5A-D) .