Baseline characteristics of enrolled patients with COVID-19
The clinical characteristics of enrolled patients with COVID‑19 are shown in Table 1. A total of 63 patients were enrolled in the study. The average age of the patients was 56.75 years and 41 patients (65.08%) were male. According to the severity of the disease, subjects were classified into the severe group (36, 57.14%) or the critical group (27, 42.86%). There were significant differences between the two groups in drug use and oxygen therapy except for the requirement of high flow oxygen or non-invasive ventilator use. In terms of laboratory results, blood indices including peripheral white blood cell count, neutrophil, C-reactive protein (CRP), blood urea nitrogen (BUN), and lactate dehydrogenase (LDH) were significantly higher in critical patients than severe patients (p＜0.05). In contrast, lymphocytes, percentage of monocytes, hemoglobin, and hematocrit were significantly lower in critical patients than severe patients (p＜0.05).
Clinical features of enrolled patients with COVID-19 and liver function tests during hospitalization
The serum liver enzyme parameters of enrolled patients were further analyzed. Results showed that there were no differences between severe and critical group in AST, ALT, TBIL, INR, albumin, and A/G ratio on admission (Supplemental Table), whereas the extreme values of these parameters had significant differences, except for ALT (Table 2). The incidence of abnormal AST, ALT, and TBIL in the critical group was significantly higher than in the severe group (81.48%, 81.49%, 62.67%, and 45.71%, 63.88%, 22.86%, respectively, p＜0.05) during hospitalization. Based on the test of liver function, subjects were further classified as normal liver (11, 17.46%), abnormal liver (32, 50.79%), and liver injury group (20, 31.75%) (Table 3). Patients in the three groups were not significantly different in distributions of gender or age. The CRP, percentage of neutrophils, BUN, and LDH in the liver injury group were significantly higher than in the normal liver group, while the percentages of lymphocytes and monocytes were significantly lower (p＜0.05). Additionally, the oxygenation index of the liver injury group was significantly lower than that of the other groups (p=0.015), while the CURB-65 score, sequential organ failure assessment (SOFA) scores, the incidence of ARDS, and the application of an invasive ventilator were significantly higher in the liver injury group than in the non-liver group (p＜0.05) (Table 3, Fig. 1a).
Dynamic profile of liver function indicators and viral clearance
To explore the correlation of dynamic changes in liver function parameters and virus clearance in enrolled patients, data of liver enzymes and Ct values were monitored during hospitalization. Results showed that the plasma levels of AST, TBIL, and INR were significantly higher in the critical group than in the severe group, and the time for these indicators to reach their peak was approximately 2-3 weeks after admission (Fig. 1b-d). Compared with AST, the plasma TBIL level more slowly reached its peak at about 4 weeks, then gradually decreased. Conversely, the levels of ALT, albumin and A/G ratio, were significantly lower in the critical group than in the severe group, the time for these parameters to reach their extremes was also approximately 2-3 weeks (Fig. 1b-d, f). The liver injury group had similar characteristics (Supplemental Fig. 1a-c). The level of Ct values in the critical group was higher than in the severe group, but there was no significant difference either on admission or at the peak level(Table 1, Supplemental Fig. 2a). In addition, there was no significant difference in the level of Ct values among liver injury group, abnormal group and normal group (Table 3, Supplemental Fig. 2b). The Ct values of PCR increased gradually during hospitalization and the time of virus clearance was approximately 2-3 weeks after admission (Fig. 2a-b).
Independent factors associated with severity of liver function
As shown in Fig. 3a-d, the severity of damage to liver function was positively correlated with the percentage of neutrophils, CRP, CURB-65 score and SOFA score, and negatively correlated with percentage of lymphocytes and oxygenation index. To further analyze the correlation between the severity of liver injury and clinical or laboratory index, and identify independent factors associated with severity of damage to liver function, we conducted ordinal logistic regression analysis. The variables included in the ordinal logistic regression and statistical univariate analysis results are shown in Table 3. Variables with p-values of <0.05 in univariate analyses were included in the ordinal logistic analysis to identify the significant indicators affecting liver function in enrolled COVID-19 patients (Table 4). Results revealed that SOFA score ≥ 2 [OR=165.41, 95% confidence interval (CI)= (1.57, 8.64); p=0.005] was positively associated with abnormality or injury as indicated by liver tests. After adjustment for age, sex, and comorbidities, patients with invasive ventilators, decreased percentages of neutrophils, lymphocytes and monocytes, and SOFA score ≥ 2 were the independent factors associated with abnormal liver tests or liver tests showing injury.