Elevated Plasma Levels of ICAM1 Predict Mortality in COVID-19 and Sepsis Patients with Liver Cirrhosis

Background: An increased covid-19 mortality has been reported in patients with liver cirrhosis. Given a significant association of endothelial damage with both liver disease and covid-19 severity, we investigated key endothelial injury markers in covid-19 patients with and without cirrhosis. Methods: A cross-sectional study with PCR-confirmed moderate/severe covid-19 hospitalized patients with and without cirrhosis was performed. Cirrhosis patients with bacterial sepsis were also recruited. Soluble plasma bio-markers of endothelial cell injury, including intercellular adhesion molecule 1 (ICAM1), von Willebrand Factor (vWF) antigen, vascular endothelial growth factor receptor 1 (vegfr1), angiopoietin 1 and 2 (Ang1, 2) were measured. Findings: A total of 56 hospitalized patients were included belonging to patients in moderate covid-19 category [covid-19 with liver cirrhosis (n=6); covid-19 without liver cirrhosis (n=8)] and severe covid-19 category [covid-19 with liver cirrhosis (n=10); severe covid-19 without liver cirrhosis (n=15)]. 17 patients were with liver cirrhosis plus bacterial sepsis. ICAM1 levels were increased (p=0.04) while vegfr1 (p<0.0001) and Ang1 (p<0.0001) were reduced in covid-19 patients with cirrhosis, as compared to that in covid-19 patients alone. On univariate logistic regression, ICAM1 (OR=9.81, 95%CI 11.69-155.9, p=0.03) and Ang2 levels (OR=3.72, 95%CI 1.29-21.92, p=0.04) predicted mortality in covid-19 patients with cirrhosis. Among severe covid-19, patients with covid-19 alone had a 28-day mortality of 76.7%, covid-19 plus cirrhosis had 48% while patients with cirrhosis had 23.8%. Endothelial injury biomarkers between cirrhosis patients with sepsis and those with covid-19 did not differ significantly. In cirrhosis patients with severe covid-19 and sepsis analysed together, elevated ICAM1 levels (OR=15, 95% CI 0.2-1380, P<0.05) and MELD score (OR=1.11, 95%CI=1.0-1.26, P<0.03) appeared to be significantly associated with mortality. For these patients, the area under the curve for ICAM1 was 0.721, while that of the MELD score was 0.621. An ICAM1 value higher than 182,150 pg/ml and MELD more than 31.5 was associated with higher mortality in liver cirrhosis patients with covid-19 and sepsis (ICAM1: HR: 5.65, 95% CI 2.16-14.83, p<0.01; MELD:HR: 1.09, 95% CI 1.02-1.16, p< 0.05). Interpretation: The study indicates that in patients with liver cirrhosis, altered levels of endothelial injury markers may be associated with a higher covid-19 and sepsis associated in-hospital mortality. Both elevated ICAM1 and MELD would serve as valuable predictors of covid-19 and sepsis associated mortality in cirrhosis patients. Funding: The study was funded by research funds from the Institute of liver and biliary Sciences (ILBS).Declaration of Interests: All authors declare no competing interestsEthics Approval Statement: The institutional review board approved this study (Ethics protocol no IEC/2020/82/NA01).