Elevated Plasma ICAM1 Levels Predict 28-day Mortality In cirrhotic Patients with COVID-19 or Bacterial Sepsis

Overview

Journal JHEP Rep

Specialty Gastroenterology

Date 2021 May 17

PMID 33997748

Citations 14

Authors

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

Affiliations

Soon will be listed here.

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 ( 0.003) while VEGFR1 (0.0001) and Ang1 (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.

Citing Articles

Utility of Protein Markers in COVID-19 Patients.

Alicia L, Maria Angeles O, Desiree M, Maximino R, Marilina G Int J Mol Sci. 2025; 26(2).

PMID: 39859366 PMC: 11766239. DOI: 10.3390/ijms26020653.

Sustained Vascular Inflammatory Effects of SARS-CoV-2 Spike Protein on Human Endothelial Cells.

Gultom M, Lin L, Brandt C, Milusev A, Despont A, Shaw J Inflammation. 2024; .

PMID: 39739157 DOI: 10.1007/s10753-024-02208-x.

Association between serum endocan levels and organ failure in hospitalized patients with cirrhosis.

Wejnaruemarn S, Suksawatamnuay S, Vanichanan J, Komolmit P, Treeprasertsuk S, Thanapirom K PLoS One. 2024; 19(12):e0315619.

PMID: 39724169 PMC: 11671009. DOI: 10.1371/journal.pone.0315619.

Bioinformatics study of the TNFRSF1A mechanism involved in acute liver injury in sepsis through the mTOR signaling pathway.

Chen Z, Tang K, Zhang H Histol Histopathol. 2024; 40(3):401-409.

PMID: 39044690 DOI: 10.14670/HH-18-789.

ICAMs in Immunity, Intercellular Adhesion and Communication.

Guerra-Espinosa C, Jimenez-Fernandez M, Sanchez-Madrid F, Serrador J Cells. 2024; 13(4.

PMID: 38391953 PMC: 10886500. DOI: 10.3390/cells13040339.

References

Goshua G, Pine A, Meizlish M, Chang C, Zhang H, Bahel P . Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Lancet Haematol. 2020; 7(8):e575-e582. PMC: 7326446. DOI: 10.1016/S2352-3026(20)30216-7. View

Ranucci M, Ballotta A, Di Dedda U, Baryshnikova E, Dei Poli M, Resta M . The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. J Thromb Haemost. 2020; 18(7):1747-1751. PMC: 9906332. DOI: 10.1111/jth.14854. View

Lambden S, Laterre P, Levy M, Francois B . The SOFA score-development, utility and challenges of accurate assessment in clinical trials. Crit Care. 2019; 23(1):374. PMC: 6880479. DOI: 10.1186/s13054-019-2663-7. View

Wang H, Babic A, Mitchell H, Liu K, Wagner D . Elevated soluble ICAM-1 levels induce immune deficiency and increase adiposity in mice. FASEB J. 2005; 19(8):1018-20. DOI: 10.1096/fj.04-3094fje. View

Bastug A, Bodur H, Erdogan S, Gokcinar D, Kazancioglu S, Kosovali B . Clinical and laboratory features of COVID-19: Predictors of severe prognosis. Int Immunopharmacol. 2020; 88:106950. PMC: 7480980. DOI: 10.1016/j.intimp.2020.106950. View

Mandi Y, Nagy I . Circulating ICAM-1 in alcoholic liver cirrhosis. Int Arch Allergy Immunol. 1995; 106(3):302-4. DOI: 10.1159/000236859. View

Kasztelan-Szczerbinska B, Surdacka A, Slomka M, Rolinski J, Celinski K, Cichoz-Lach H . Angiogenesis-related biomarkers in patients with alcoholic liver disease: their association with liver disease complications and outcome. Mediators Inflamm. 2014; 2014:673032. PMC: 4052180. DOI: 10.1155/2014/673032. View

Kaur S, Tripathi D, Yadav A . The Enigma of Endothelium in COVID-19. Front Physiol. 2020; 11:989. PMC: 7417426. DOI: 10.3389/fphys.2020.00989. View

Albillos A, Lario M, Alvarez-Mon M . Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol. 2014; 61(6):1385-96. DOI: 10.1016/j.jhep.2014.08.010. View

10.

Mendez-Guerrero O, Calle-Rodas D, Cervantes-Alvarez E, Alatorre-Arenas E, Perez-Escobar J, Navarro-Alvarez N . Renal and brain failure predict mortality of patients with acute-on-chronic liver failure admitted to the intensive care unit. Ann Hepatol. 2020; 22:100270. DOI: 10.1016/j.aohep.2020.09.014. View

11.

Smadja D, Guerin C, Chocron R, Yatim N, Boussier J, Gendron N . Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of COVID-19 patients. Angiogenesis. 2020; 23(4):611-620. PMC: 7250589. DOI: 10.1007/s10456-020-09730-0. View

12.

Galley H, Webster N . Physiology of the endothelium. Br J Anaesth. 2004; 93(1):105-13. DOI: 10.1093/bja/aeh163. View

13.

Hernandez-Bartolome A, Lopez-Rodriguez R, Borque M, Gonzalez-Moreno L, Real-Martinez Y, Garcia-Buey L . Angiopoietin-2/angiopoietin-1 as non-invasive biomarker of cirrhosis in chronic hepatitis C. World J Gastroenterol. 2016; 22(44):9744-9751. PMC: 5124979. DOI: 10.3748/wjg.v22.i44.9744. View

14.

Sarin S, Choudhury A, Sharma M, Maiwall R, Al Mahtab M, Rahman S . Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update. Hepatol Int. 2019; 13(4):353-390. PMC: 6728300. DOI: 10.1007/s12072-019-09946-3. View

15.

Dong V, Karvellas C . Acute-on-chronic liver failure: Objective admission and support criteria in the intensive care unit. JHEP Rep. 2020; 1(1):44-52. PMC: 7001553. DOI: 10.1016/j.jhepr.2019.02.005. View

16.

Schmidt E, Yang Y, Janssen W, Gandjeva A, Perez M, Barthel L . The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nat Med. 2012; 18(8):1217-23. PMC: 3723751. DOI: 10.1038/nm.2843. View

17.

Hernaez R, Liu Y, Kramer J, Rana A, El-Serag H, Kanwal F . Model for end-stage liver disease-sodium underestimates 90-day mortality risk in patients with acute-on-chronic liver failure. J Hepatol. 2020; 73(6):1425-1433. PMC: 10424237. DOI: 10.1016/j.jhep.2020.06.005. View

18.

Iavarone M, DAmbrosio R, Soria A, Triolo M, Pugliese N, Del Poggio P . High rates of 30-day mortality in patients with cirrhosis and COVID-19. J Hepatol. 2020; 73(5):1063-1071. PMC: 7280108. DOI: 10.1016/j.jhep.2020.06.001. View

19.

Marjot T, Moon A, Cook J, Abd-Elsalam S, Aloman C, Armstrong M . Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: An international registry study. J Hepatol. 2020; 74(3):567-577. PMC: 7536538. DOI: 10.1016/j.jhep.2020.09.024. View

20.

Ackermann M, Verleden S, Kuehnel M, Haverich A, Welte T, Laenger F . Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 2020; 383(2):120-128. PMC: 7412750. DOI: 10.1056/NEJMoa2015432. View