Effect of Direct Bilirubin Level on Clinical Outcome and Prognoses in Severely/Critically Ill Patients With COVID-19

Wensen Chen; Hanting Liu; Gang Yang; Wei Wang; Qiongfang Liu; Chaolin Huang; Zhuoru Zou; Yun Liu; Guihua Zhuang; Lei Zhang

doi:10.3389/fmed.2022.843505

Effect of Direct Bilirubin Level on Clinical Outcome and Prognoses in Severely/Critically Ill Patients With COVID-19

Front Med (Lausanne). 2022 Mar 28:9:843505. doi: 10.3389/fmed.2022.843505. eCollection 2022.

Authors

Wensen Chen^{1

2}, Hanting Liu³, Gang Yang⁴, Wei Wang⁵, Qiongfang Liu⁶, Chaolin Huang⁷, Zhuoru Zou³, Yun Liu⁸, Guihua Zhuang^{1

3}, Lei Zhang^{3

9

10}

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China.
² Office of Infection Management, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
³ China-Australia Joint Research Centre for Infectious Diseases, School of Public Health, Xi'an Jiaotong University Health Science Centre, Xi'an, China.
⁴ Department of Cardiology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
⁵ Department of Information Management, Wuhan No. 1 Hospital, Wuhan, China.
⁶ Department of Infection Management, Wuhan Hankou Hospital, Wuhan, China.
⁷ Center for Translational Medicine, Wuhan Jinyintan Hospital, Wuhan, China.
⁸ School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China.
⁹ Faculty of Medicine, Nursing and Health Sciences, Central Clinical School, Monash University, Melbourne, VIC, Australia.
¹⁰ Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia.

Abstract

Objectives: We aimed to investigate how changes in direct bilirubin (DBiL) levels in severely/critically ill the coronavirus disease (COVID-19) patients during their first week of hospital admission affect their subsequent prognoses and mortality.

Methods: We retrospectively enrolled 337 severely/critically ill COVID-19 patients with two consecutive blood tests at hospital admission and about 7 days after. Based on the trend of the two consecutive tests, we categorized patients into the normal direct bilirubin (DBiL) group (224), declined DBiL group (44) and elevated DBiL group (79).

Results: The elevated DBiL group had a significantly larger proportion of critically ill patients (χ²-test, p < 0.001), a higher risk of ICU admission, respiratory failure, and shock at hospital admission (χ²-test, all p < 0.001). During hospitalization, the elevated DBiL group had significantly higher risks of shock, acute respiratory distress syndrome (ARDS), and respiratory failure (χ²-test, all p < 0.001). The same findings were observed for heart damage (χ²-test, p = 0.002) and acute renal injury (χ²-test, p = 0.009). Cox regression analysis showed the risk of mortality in the elevated DBiL group was 2.27 (95% CI: 1.50-3.43, p < 0.001) times higher than that in the normal DBiL group after adjusted age, initial symptom, and laboratory markers. The Receiver Operating Characteristic curve (ROC) analysis demonstrated that the second test of DBiL was consistently a better indicator of the occurrence of complications (except shock) and mortality than the first test in severely/critically ill COVID-19 patients. The area under the ROC curve (AUC) combined with two consecutive DBiL levels for respiratory failure and death was the largest.

Conclusion: Elevated DBiL levels are an independent indicator for complication and mortality in COVID-19 patients. Compared with the DBiL levels at admission, DBiL levels on days 7 days of hospitalization are more advantageous in predicting the prognoses of COVID-19 in severely/critically ill patients.

Keywords: COVID-19; direct bilirubin; mortality; prognoses; severely/critically disease.