Background: Growth arrest-specific factor 6 (GAS6) and the Tyro3, AXL, and MERTK (TAM) receptors counterbalance pro-inflammatory responses. AXL is a candidate receptor for SARS-CoV-2, particularly in the respiratory system, and the GAS6/AXL axis is targeted in current clinical trials against COVID-19. However, GAS6 and TAMs have not been evaluated in COVID-19 patients at emergency admission. Methods: Plasma GAS6, AXL, and MERTK were analyzed in 132 patients consecutively admitted to the emergency ward during the first peak of COVID-19. Results: GAS6 levels were higher in the SARS-CoV-2-positive patients, increasing progressively with the severity of the disease. Patients with initial GAS6 at the highest quartile had the worst outcome, with a 3-month survival of 65%, compared to a 90% survival for the rest. Soluble AXL exhibited higher plasma concentration in deceased patients, without significant differences in MERTK among SARS-CoV-2-positive groups. GAS6 mRNA was mainly expressed in alveolar cells and AXL in airway macrophages. Remarkably, THP-1 human macrophage differentiation neatly induces AXL, and its inhibition (bemcentinib) reduced cytokine production in human macrophages after LPS challenge. Conclusions: Plasma GAS6 and AXL levels reflect COVID-19 severity and could be early markers of disease prognosis, supporting a relevant role of the GAS6/AXL system in the immune response in COVID-19.
【저자키워드】 COVID-19, viral infection, immune response, immunothrombosis, vitamin K, AXL, GAS6, MERTK, 【초록키워드】 SARS-CoV-2, clinical trial, macrophages, Prognosis, severity, COVID-19 severity, outcome, airway, survival, mRNA, Patient, Respiratory system, receptor, human macrophage, disease, Admission, patients, cytokine production, LPS, marker, Deceased, COVID-19 patient, plasma concentration, significant difference, pro-inflammatory responses, SARS-CoV-2-positive patients, macrophage differentiation, quartile, emergency ward, THP-1, TAM, initial, highest, analyzed, the disease, evaluated, reduced, exhibited, expressed, alveolar cell, induce, groups, 【제목키워드】 clinical, Factor, Increased,