Elevated plasma ICAM1 levels predict 28-day mortality in cirrhotic patients with COVID-19 or bacterial sepsis

Savneet Kaur; Sadam Hussain; Kailash Kolhe; Guresh Kumar; Dinesh M Tripathi; Arvind Tomar; Pratibha Kale; Ashad Narayanan; Chaggan Bihari; Meenu Bajpai; Rakhi Maiwall; Ekta Gupta; Shiv K Sarin

doi:10.1016/j.jhepr.2021.100303

Elevated plasma ICAM1 levels predict 28-day mortality in cirrhotic patients with COVID-19 or bacterial sepsis

JHEP Rep. 2021 Aug;3(4):100303. doi: 10.1016/j.jhepr.2021.100303. Epub 2021 May 8.

Authors

Savneet Kaur¹, Sadam Hussain¹, Kailash Kolhe^{1

2}, Guresh Kumar^{1

3}, Dinesh M Tripathi¹, Arvind Tomar⁴, Pratibha Kale⁵, Ashad Narayanan⁶, Chaggan Bihari⁷, Meenu Bajpai⁸, Rakhi Maiwall⁹, Ekta Gupta¹⁰, Shiv K Sarin⁹

Affiliations

¹ Department of Molecular and Cellular Medicine, Institute of liver and biliary Sciences, New Delhi, India.
² Department of Gastroenterology, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai, India.
³ Department of Research and Biostatistics, Institute of liver and biliary Sciences, New Delhi, India.
⁴ Department of Pulmonary Medicine, Institute of liver and biliary Sciences, New Delhi, India.
⁵ Department of Microbiology, Institute of liver and biliary Sciences, New Delhi, India.
⁶ Department of Emergency, Institute of liver and biliary Sciences, New Delhi, India.
⁷ Department of Pathology, Institute of liver and biliary Sciences, New Delhi, India.
⁸ Department of Transfusion Medicine, Institute of liver and biliary Sciences, New Delhi, India.
⁹ Department of Hepatology, Institute of liver and biliary Sciences, New Delhi, India.
¹⁰ Department of Virology, Institute of liver and biliary Sciences, New Delhi, India.

Abstract

Background & aims: Endothelial injury and dysfunction play a detrimental role in the pathogenesis of infections. Endothelium-related molecules have been reported as potential diagnostic and/or prognostic biomarkers of infection. The prognostic value of these biomarkers in patients with cirrhosis and infections remains elusive.

Methods: In this study, we investigated the performance of key soluble endothelial injury biomarkers, including intercellular adhesion molecule 1 (ICAM1), von Willebrand factor (vWF), vascular endothelial growth factor receptor 1 (VEGFR1), and angiopoietin 1 and 2 (Ang1, 2) as mortality predictors in patients with cirrhosis and severe COVID-19 or bacterial sepsis.

Results: A total of 66 hospitalized patients (admitted to the COVID-19 ward or liver intensive care unit [ICU]) were included. Twenty-two patients had COVID-19 alone, while 20 patients had cirrhosis plus COVID-19. Twenty-four patients had cirrhosis plus bacterial sepsis. Among patients with cirrhosis, the most common aetiology of liver disease was alcohol. ICAM1 was increased (p = 0.003) while VEGFR1 (p <0.0001) and Ang1 (p <0.0001) were reduced in patients with COVID-19 and cirrhosis, compared to patients with COVID-19 alone. Endothelial biomarker levels did not differ significantly between patients with cirrhosis and severe COVID-19 or bacterial sepsis in the ICU. In these patients, ICAM1 levels significantly and independently predicted mortality (hazard ratio 3.24; 95% CI 1.19-8.86) along with model for end-stage liver disease (MELD) score, renal and coagulation failures. The AUC for ICAM1 was 0.74, MELD was 0.60 and combined ICAM1 and MELD was 0.70. ICAM1 also positively correlated with the composite organ failure scores recorded 3-5 days post ICU admission (CLIF-OF and SOFA) in this subgroup of patients.

Conclusion: The study indicates that in patients with cirrhosis, elevated plasma ICAM1 serves as an independent predictor of severe COVID-19- or sepsis-associated 28-day mortality.

Lay summary: Bacterial sepsis and COVID-19 lead to increased mortality in patients with cirrhosis. In this study, we demonstrate that high plasma levels of ICAM1, an endothelial injury biomarker, is one of the important factors predicting mortality in critically ill cirrhotic patients with severe COVID-19 or bacterial sepsis.

Keywords: ACLF, acute-on-chronic liver failure; AST, aspartate aminotransferase; Ang1, angiopoietin 1; Ang2, angiopoietin 2; Biomarkers; CCI, Charlson comorbidity index; COVID-19; Endothelial Injury; HR, hazard ratio; ICAM1, intercellular adhesion molecule 1; ICU, intensive care unit; LDH, lactate dehydrogenase; Liver Cirrhosis; MELD, model for end-stage liver disease; NLR, neutrophil to lymphocyte ratio; PCT, procalcitonin; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SOFA, sequential organ failure assessment; Sepsis; VEGFR1, vascular endothelial growth factor receptor 1; vWF, von Willebrand factor.