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.

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We have previously reported a new receptor (NC‐2) for natural cytotoxicity (NC) on murine leucocytes, identified by monoclonal antibody D9 (mAb D9). Pretreatment of mouse spleen cells with different concentrations of mAb D9 in vitro blocked NC against WEHI‐164, whereas natural killing (NK) activity against YAC‐1 was unaffected. This paper reports the immune surveillance against the growth of WEHI‐164 tumour cells in mice by NC‐2+ Cells. The kinetics of in vivo reduction in NC activity were investigated by treating BALB/c and (CBA × C57BL/6) F1 mice with a single injection of 40 μg of mAb D9 and monitoring splenic NC activity by 51Cr‐release assay at intervals from 24 h to 3 weeks. Control mice were injected with OKT8 irrelevant antibody. Results showed a significant (P < 0.05) reduction in splenic NC activity within 24 h which persisted for up to 1 week. Similar results were also obtained when (CBA × C57BL/6) F1 mice were employed (P < 0.001). In vivo tumour studies were undertaken to investigate the role of NC‐2+ cells in surveillance against tumour growth and metastasis of the WEHI‐164 fibrosarcoma. When syngeneic BALB/c mice were injected with 40 μg of mAb D9 and then challenged with 5 × 105 WEHI‐164 cells, results showed significantly increased growth rate of the transplanted WEHI‐164 fibrosarcoma and tumour nodules in the lungs of animals, when compared to control mice with normal NC activity. Our data support an innate surveillance in metastasis and growth of WEHI‐164 fibrosarcoma in mice.