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The cytokines HGF and CXCL13 predict the severity and the mortality in COVID-19 patients.

ABSTRACT: The objective of the present study was to identify biological signatures of severe coronavirus disease 2019 (COVID-19) predictive of admission in the intensive care unit (ICU). Over 170 immunological markers were investigated in a 'discovery' cohort (n = 98 patients) of the Lausanne University Hospital (LUH-1). Here we report that 13 out of 49 cytokines were significantly associated with ICU admission in the three cohorts (P < 0.05 to P < 0.001), while cellular immunological markers lacked power in discriminating between ICU and non-ICU patients. The cytokine results were confirmed in two 'validation' cohorts, i.e. the French COVID-19 Study (FCS; n = 62) and a second LUH-2 cohort (n = 47). The combination of hepatocyte growth factor (HGF) and C-X-C motif chemokine ligand 13 (CXCL13) was the best predictor of ICU admission (positive and negative predictive values ranging from 81.8% to 93.1% and 85.2% to 94.4% in the 3 cohorts) and occurrence of death during patient follow-up (8.8 fold higher likelihood of death when both cytokines were increased). Of note, HGF is a pleiotropic cytokine with anti-inflammatory properties playing a fundamental role in lung tissue repair, and CXCL13, a pro-inflammatory chemokine associated with pulmonary fibrosis and regulating the maturation of B cell response. Up-regulation of HGF reflects the most powerful counter-regulatory mechanism of the host immune response to antagonize the pro-inflammatory cytokines including CXCL13 and to prevent lung fibrosis in COVID-19 patients.

SUBMITTER: Perreau M

PROVIDER: S-EPMC8352963 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Introduction The most dreaded pandemic grappling world now, the Coronavirus Disease 2019 (COVID-19), chiefly involves the respiratory system; nevertheless, it is a multisystem disorder. Its involvement of the hepatic system is considerable; however, still emerging are its clinical implications and effects on morbidity and mortality. The aim of this study is to report on the various aspects of its hepatic involvement by describing the alterations in tests of liver function and its significance in the disease outcome in a cohort of hospitalized COVID-19 patients at a tertiary centre in northern India. Methods This is a retrospective cohort study conducted in a tertiary-care hospital in northern India. All confirmed hospitalized COVID-19 cases aged 15 and above from Apr till Oct 2020 with no pre-existing liver disease were included. The primary endpoint was death at 28 days. Statistical analysis included descriptive analysis, sensitivity-specificity, and univariable and multivariable regression analysis as well as survival analysis. Results A total of 708 COVID-19 patients fulfilled the inclusion criteria included 561 (79.2%) males and 147 (20.8%) females. The median age was 49 (IQR=25) years. Mild and moderate/severe disease were seen in 508 (71.8%) and 200 (28.2) patients respectively. Serum bilirubin, Aspartate-aminotransferase (AST) and Alanine-aminotransferase (ALT) were elevated in 6.92%, 69.91% and 80.22% of patients respectively. In univariable logistic regression, AST [odds ratio; OR 1.008 95% CI (1.005-1.012) per 1 IU/L increase] and ALT [OR 1.005 95% CI (1.002-1.007) per 1 IU/L increase] were significantly associated with the odds of moderate-to-severe disease but only AST was significant after adjustment to age, sex, and comorbidity [adjusted odds ratio; aOR 1.007 95% CI (1.003-1.011) per 1IU/L increase]. Serum albumin was negatively associated with the odds of moderate to severe disease and remained significant in the adjusted model [aOR 0.217 95%CI (0.149-0.316) per 1g/dL increase]. Ninety-six patients succumbed to illness [case fatality rate; CFR 13.6%). In adjusted Cox Proportional-Hazards Model for mortality, AST [adjusted hazard ratio; aHR 1.002 95% CI (1.000-1.003) per 1 IU/L increase] and serum albumin [aHR 0.396 95% CI (0.285-0.549) per 1g/dL increase] showed significant association with mortality. Conclusion Liver function abnormalities are common in COVID 19 patients. In particular, AST and serum albumin levels are effective predictors of disease severity and mortality and can be used as markers of fatal disease in the management as well as prognostication of COVID-19.

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The cytokines HGF and CXCL13 predict the severity and the mortality in COVID-19 patients.

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