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

Abstract

Background and Aims Endothelial injury and dysfunction play a detrimental role in the pathogenesis of infections. Endothelium-related molecules have been reported as potential biomarkers for early diagnosis and/or prognosis of infections. The prognostic value of these biomarkers in patients with liver cirrhosis and infections however remain 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) antigen, vascular endothelial growth factor receptor 1 (vegfr1), angiopoietin 1 and 2 (Ang1, 2) as mortality predictors in liver cirrhosis patients with severe covid-19 or bacterial sepsis. Results A total of 66 hospitalized patients [admitted in covid-19 ward or liver intensive care unit (ICU)] were included. 22 patients had covid-19 alone while 20 patients had cirrhosis plus covid-19. 24 patients had liver cirrhosis plus bacterial sepsis. Among cirrhosis patients, most common aetiology was alcohol. ICAM1 was increased (p=0.003) while vegfr1 (p<0.0001) and Ang1 (p<0.0001) were reduced in covid-19 patients with cirrhosis, as compared to covid-19 patients alone. Endothelial biomarkers between cirrhosis patients with severe covid-19 or with bacterial sepsis in the ICUs did not differ significantly. In these patients, ICAM1 levels significantly and independently predicted mortality (HR:3.24;1.19-8.86) along with MELD, renal and coagulation failures. The area under the curve 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 liver cirrhosis, elevated plasma ICAM1 serve 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 cirrhosis patients. 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 having severe covid-19 or bacterial sepsis.

Redox imbalance in COVID-19 pathophysiology

“…A significantly greater ICAM-1 levels were measured in the serum of ICU subjects and multivariate analyses confirmed it as a significant predictor of mortality. These findings agree with a previous report demonstrating its significance in predicting mortality in SARS-CoV-2 infected subjects [ 101 ].…”

Gene Networks of Hyperglycemia, Diabetic Complications, and Human Proteins Targeted by SARS-CoV-2: What Is the Molecular Basis for Comorbidity?

“…The clinical evidence supports the role of some molecules revealed in this work in COVID-19 pathogenesis: ANGPT2 [48,49], CCL2 [50], ICAM1 [52,53], VCAM-1 [52], MIR21 [54], MMP9 [55,56], STAT3 [57], HMGB1 [58,59], SIRT1 [62,63], AGTR1 [66], APOE4 [69,70], ACE [73], CCL11 [86,87], FGF2 [89], TNF [92], PPAR-γ [95], CASP8 [115], IL8 [117], IL6 [118], PRL [119], SP1 [122], TLR4 [123], BDNF [124], CASP1 [125], CASP3 [126,127], IL18 [128], IL10 [129], TGFB1 [130], ANXA2 [131,132], HPSE [162], MAPK1 [163], CDH1 [166], FBN1 [180], GDF15 [182,183], PLAT [195][196][197], RHOA…”

“…The serum levels of ICAM-1 and VCAM-1 were elevated in patients with COVID-19, especially in severe cases; the molecules demonstrated relations with coagulation disorders [52]. Enhanced ICAM-1 concentration was an independent predictor of mortality in COVID-19 [53]. The fibrosis-associated miRNA-21 was increased in the acute phase of COVID-19 infection and its upregulation turned out to be a predictor of chronic myocardial damage and inflammation in COVID-19 survivors [54].…”

Covid‐19 and Liver Injury: Role of Inflammatory Endotheliopathy, Platelet Dysfunction, and Thrombosis

“…More broadly, elevated plasma ICAM1, indicative of endothelial damage, has been recently defined as a predictor of mortality in patients with both cirrhosis and COVID-19 or sepsis. (95) IL-6 trans-signaling induced ICAM1 up-regulation by LSECs in our study, indicating that this pathway of inflammatory endotheliopathy may be broadly important for key outcomes in our patients with infection and inflammation.…”