- need for oxygen supplementation >4 l/min via nasal cannula or ≥40% via venturi mask. - need for oxygen supplementation via high-flow nasal cannula. - need for invasive mechanical ventilation. - extent of pulmonary involvement > 50% by ct scan. - chronic renal failure (estimated glomerular filtration rate <30 ml/min/1.73 m2) - history of liver cirrhosis (bilirubins levels > 3mg/dl) - history of heart failure ( ejection fraction <40%) - history of steven-johnson disease - history of stroke in the last 6 months - history of sickle cell disease - chronic use of oral steroid therapy or other immunosuppressive or biologic response modifiers. - prior history of chronic hepatitis b or c infection and known hiv positive. - patient undergoing chemotherapy for cancer - sepsis caused by fungal or multidrug resistant gram-negative bacteria - known allergy to methotrexate. - body mass index(bmi) > 40 or <18.5 - pregnancy or breastfeeding. - patients enrolled in other clinical trials in the last 12 months - patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study.

- need for oxygen supplementation >4 l/min via nasal cannula or ≥40% via venturi mask. - need for oxygen supplementation via high-flow nasal cannula. - need for invasive mechanical ventilation. - extent of pulmonary involvement > 50% by ct scan. - chronic renal failure (estimated glomerular filtration rate <30 ml/min/1.73 m2) - history of liver cirrhosis (bilirubins levels > 3mg/dl) - history of heart failure ( ejection fraction <40%) - history of steven-johnson disease - history of stroke in the last 6 months - history of sickle cell disease - chronic use of oral steroid therapy or other immunosuppressive or biologic response modifiers. - prior history of chronic hepatitis b or c infection and known hiv positive. - patient undergoing chemotherapy for cancer - sepsis caused by fungal or multidrug resistant gram-negative bacteria - known allergy to methotrexate. - body mass index(bmi) > 40 or <18.5 - pregnancy or breastfeeding. - patients enrolled in other clinical trials in the last 12 months - patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study.