AUTHOR=Liu Zeming , Li Jinpeng , Long Wei , Zeng Wen , Gao Rongfen , Zeng Guang , Chen Danyang , Wang Shipei , Li Qianqian , Hu Di , Guo Liang , Li Zhengwei , Wu Xiaohui 

TITLE=Bilirubin Levels as Potential Indicators of Disease Severity in Coronavirus Disease Patients: A Retrospective Cohort Study

JOURNAL=Frontiers in Medicine

VOLUME=7

YEAR=2020

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.598870

DOI=10.3389/fmed.2020.598870

ISSN=2296-858X

ABSTRACT=<p><bold>Objectives:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> In total, 1,788 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% (11/1,719) 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 <italic>p</italic> &lt; 0.05). Patients with an elevated STB level showed increased mortality [hazard ratio (HR): 9.45, <italic>P</italic> = 0.002], elevated conjugated bilirubin (CB) levels (HR: 4.38, <italic>P</italic> = 0.03), and an elevated ratio of CB to unconjugated bilirubin (UCB, CB/UCB) (HR: 2.49, <italic>P</italic> = 0.01). CB/UCB was positively correlated with disease severity (odds ratio: 2.21, <italic>P</italic> = 0.01).</p><p><bold>Conclusions:</bold> 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.</p>