Early Treatment of Cytokine Storm Syndrome in Covid-19

The first aim of this project is to determine whether rapidly assayed early clinical laboratory markers of CSS (eCSS: leucopenia, lymphopenia, and elevated ferritin, d-dimer, LDH, CRP, and AST/ALT) in patients admitted to the hospital with respiratory compromise in the setting of Covid-19 infection can accurately identify patients with CSS as defined by validated CSS case definitions (H-Score, aHLH-2004). Confirmation of eCSS predictive of evolving CSS will identify patients at risk for rapid deterioration of lung function and inform early initiation of treatment for CSS. Genotyping studies will also be performed on patients with confirmed CSS to determine whether perforin pathway mutations commonly present in CSS associated with other disorders are present. The second aim is to determine whether early treatment with rhIL-1Ra (anakinra) in patients admitted to the hospital with markers of CSS improves or prevents deterioration of respiratory dysfunction and prevents the development of respiratory failure requiring mechanical ventilation.

Inclusion criteria

• 18 years old or older
• Molecular (pcRNA) diagnosis of SARS-CoV-2 infection
• Chest imaging studies consistent with Covid-19 pneumonia
• Hyperferritinemia (>700 ng/ml)
• History of fever >38 degrees C
• Any three of the following:

• Elevated d-dimer (> 500 ng/ml)
• thrombocytopenia (< 130,000/mm3)
• leucopenia (WBC <3500/mm3) or lymphopenia (<1000/mm3)
• elevated AST or ALT (> 2X ULN)
• elevated LDH (> 2X ULN)
• CRP > 100 mg/L

Exclusion criteria

• Participation in other investigational treatment protocols for Covid-19 infection
• Culture confirmed active bacterial infection requiring antibiotic therapy
• On mechanical ventilation
• Previous known hypersensitivity reaction to anakinra
• Previous known hypersensitivity reaction to E Coli derived proteins
• Pregnant or breast-feeding females