Bilirubin Levels as Potential Indicators of Disease Severity in Coronavirus Disease Patients: A Retrospective Cohort Study
Zeming Liu, Jinpeng Li, Wei Long, Wen Zeng, Rongfen Gao, Guang Zeng, Danyang Chen, Shipei Wang, Qianqian Li, Di Hu, Liang Guo, Zhengwei Li, Xiaohui Wu
Abstract
Objectives: The coronavirus disease (COVID-19) pandemic has caused a large number of deaths. Some patients with severe or critical COVID-19 have been observed to have elevated bilirubin levels. Studies on the association of bilirubin level and mortality in patients with COVID-19 are limited. This study aimed to examine the role of bilirubin levels in COVID-19 severity and mortality. Methods: A retrospective cohort study was conducted in patients hospitalized with COVID-19 in Leishenshan Hospital in Wuhan, China. Cox regression analyses and logistic regression analyses were conducted to investigate the risks for mortality and disease severity, respectively. Kaplan–Meier analyses with log-rank tests were performed to assess the association between bilirubin level and survival. Results: In total, 1788 patients with COVID-19 were included in the analysis. 5.8% (4/69) of patients in the elevated serum total bilirubin (STB) group died, compared to 0.6% (11/1719) of patients in the non-elevated STB group. The median alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in the elevated STB group were 29 U/L (interquartile range [IQR]: 16–45 U/L ) and 22 U/L (IQR: 13–37 U /L), respectively, which were significantly higher than the median ALT (median: 23, IQR: 15–37) and AST (median: 20, IQR: 16–26) activities in the non-elevated STB group (both p<0.05). Patients with an elevated STB level showed increased mortality (hazard ratio [HR]: 9.45, P=0.002), elevated conjugated bilirubin (CB) levels (HR: 4.38, P=0.03), and an elevated ratio of CB to unconjugated bilirubin (UCB, CB/UCB) (HR: 2.49, P=0.01). CB/UCB was positively correlated with disease severity (odds ratio: 2.21, P=0.01). Conclusions: COVID-19 patients with elevated STB and CB levels had a higher mortality, and CB/UCB was predictive of disease severity and mortality. Thus, it is necessary to pay special attention to COVID-19 patients with elevated bilirubin levels in clinical management.