Serum soluble Fas ligand is a severity and mortality prognostic marker for COVID-19 patients

Abstract

Finding cytokine storm initiator factors associated with uncontrolled inflammatory immune response is necessary in COVID-19 patients. The aim was the identification of Fas/Fas Ligand (FasL) role in lung involvement and mortality of COVID-19 patients. In this case-control study, mild (outpatient), moderate (hospitalized), and severe (ICU) COVID-19 patients and healthy subjects were investigated. RNA isolated from PBMCs for cDNA synthesis and expression of mFas/mFasL mRNA was evaluated by RT-PCR. Serum sFas/sFasL protein by ELISA and severity of lung involvement by CT-scan were evaluated. Also, we docked Fas and FasL via Bioinformatics software (in silico) to predict the best-fit Fas/FasL complex and performed molecular dynamics simulation (MDS) in hyponatremia and fever (COVID-19 patients), and healthy conditions. mFasL expression was increased in moderate and severe COVID-19 patients compared to the control group. Moreover, mFas expression showed an inverse correlation with myalgia symptom in COVID-19 patients. Elevation of sFasL protein in serum was associated with reduced lung injury and mortality. Bioinformatics analysis confirmed that blood profile alterations of COVID-19 patients, such as fever and hyponatremia could affect Fas/FasL complex interactions. Our translational findings showed that decreased sFasL is associated with lung involvement; severity and mortality in COVID-19 patients. We think that sFasL is a mediator of neutrophilia and lymphopenia in COVID-19. However, additional investigation is suggested. This is the first report describing that the serum sFasL protein is a severity and mortality prognostic marker for the clinical management of COVID-19 patients.

Identification of Clinical Response Predictors of Tocilizumab Treatment in Patients with Severe COVID-19 Based on Single-Center Experience

“…Deepening the knowledge of established biomarkers’ utility is needed, such as the optimization of IL-6 cut-offs in patient selection for immunomodulatory treatment. Novel biomarkers in COVID-19 reflecting endothelial damage (i.e., intercellular adhesion molecule 1, ICAM1), inflammation (i.e., interleukin-1 and -6 receptors, IL-1R and IL-6R; interleukin-8 and -18, IL-8 and IL-18; soluble Fas ligand, sFasL; granulocyte–macrophage colony-stimulating factor, GM-CSF; and soluble urokinase plasminogen activator receptor, suPAR), immune dysregulation (autoantibodies against tissues, cytokines, and chemokines, including autoantibodies against type I interferon, antiphospholipid antibodies, antinuclear antibodies), or genetic risk ( TYK2 , IFNAR2 , CCR2 , and others) should be studied [ 106 , 107 , 108 ].…”

Mortality in ICU COVID-19 Patients Is Associated with Neutrophil-to-Lymphocyte Ratio (NLR): Utility of NLR as a Promising Immunohematological Marker

“…We recently suggested soluble Fas ligand (sFasL) as a prognostic marker for mortality and severity of COVID-19. Moreover, we indicated that sFasL could be an infammatory marker that mediates the cytokine storm in COVID-19 via afecting infammatory cells, such as neutrophils and lymphocytes [12,13].…”

Matrix metalloproteinase/Fas ligand (MMP/FasL) interaction dynamics in COVID-19: An in silico study and neuroimmune perspective

“…The overall quality score calculated by ProSA for a special input construct is shown in a graph that indicates the scores of every experimentally quantified protein structure accessible in the Protein Data Bank (PDB) [ 22 ]. ERRAT ProCheck is another tool that scores amino acids in 9-residue intervals [ 4 , [23] , [24] , [25] , [26] ]. The quality of the modeled protein was verified by Ramachandran plot, ProSA, and UCLA SAVES 6 analyses ( Supplementary material ).…”

“…Hyponatremia and fever are important findings in COVID-19 patients. For fever and hyponatremia conditions, we chose mild fever that is often found in COVID-19 patients (38.85 °C) and 130 Na + levels, in line with our recent study findings [ 3 , 4 , 29 ]. Finally, four separate MD production runs were performed for 10 ns allowing the system to evolve.…”

“…sFasL was found to be a severity and mortality marker in COVID-19 patients with robust diagnostic performance. Also, sFasL was associated with lung injury in COVID-19 patients [ 4 ]. Another study also showed than attenuated sFasL resulted in TNF-driven neutrophil necroptosis in critical COVID-19 patients [ 5 ].…”