This proposal addresses the problem of preventing the very high mortality and morbidity associated with the development of Cytokine Storm Syndrome (CSS) associated respiratory failure in Covid-19 infection.
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.
Drug: Anakinra
The active treatment group will receive anakinra 100 mg subcutaneously every 6-12 hours for a period of 10 days
Other Name: recombinant human IL-ra (rhIL-1ra)
Drug: Normal saline
The control group will receive normal saline placebo subcutaneously every 6-12 hours for period of 10 days
Other Name: NS
Inclusion Criteria:
1. 18 years old or older
2. Molecular (pcRNA) diagnosis of SARS-CoV-2 infection
3. Chest imaging studies consistent with Covid-19 pneumonia
4. Hyperferritinemia (>700 ng/ml)
5. History of fever >38 degrees C
6. Any three of the following:
1. Elevated d-dimer (> 500 ng/ml)
2. thrombocytopenia (< 130,000/mm3)
3. leucopenia (WBC <3500/mm3) or lymphopenia (<1000/mm3)
4. elevated AST or ALT (> 2X ULN)
5. elevated LDH (> 2X ULN)
6. CRP > 100 mg/L
Exclusion Criteria:
1. Participation in other investigational treatment protocols for Covid-19 infection
2. Culture confirmed active bacterial infection requiring antibiotic therapy
3. On mechanical ventilation
4. Previous known hypersensitivity reaction to anakinra
5. Previous known hypersensitivity reaction to E Coli derived proteins
6. Pregnant or breast-feeding females
University of Alabama at Birmingham
Birmingham, Alabama, United States
Walter W Chatham, MD, Principal Investigator
University of Alabama at Birmingham