2.3. Data Collection and Outcomes
death, tumor necrosis, fungal infections, viral infection, leucopenia
TUMOR NECROSIS, THROMBOCYTOPENIA, VIRAL INFECTION, FUNGAL INFECTIONS, SECONDARY, LEUCOPENIA, EVENTS
The primary outcome was survival and discharge from the hospital without the need for intubation/mechanical ventilation. The secondary outcomes included (1) no increase in oxygen requirement or oxygen delivery measures to maintain oxygen saturation > 90% from Day 2 (48 h) to Day 10 (120 h); (2) at least a 25% decrease in serum ferritin, LDH, CRP, and D-dimer at 48 h; (3) normalization or ≥ 75% improvement by Day 10 (120 h) in each of the following laboratory CSS attributes if elevated beyond the normal range at randomization: ferritin, fibrinogen, AST, ALT, leucopenia, thrombocytopenia, D-dimer, CRP, triglycerides; (4) decreased time from the initial dosing of anakinra or placebo to the achievement of ≥ 93% oxygen saturation on room air for 24 h; and (5) no increased prevalence of nosocomial bacterial, fungal, or non-COVID-19-related viral infection through the time of hospital discharge until Day 28. As an exploratory outcome, we also collected blood for the assessment of a panel of cytokines that included interleukin-2 (IL-2), soluble IL-2 receptor-alpha (sCD25), IL-12, IL-4, IL-5, IL-10, IL-13, IL-17, IL-6, IL-8, interferon gamma (IFN-γ), IL-1β, tumor necrosis factor, CXCL9, and sCD163 (soluble haptoglobin receptor), collected at Day 0 and Day 10. IL-18 levels were assayed at Day 0.Until the date of hospital discharge (prior to or subsequent to Day 10), the occurrence of the following events was recorded according to a time-to-event analysis: requirement for mechanical ventilation, withdrawal of oxygen therapy due to lack of requirement to maintain RA oxygen saturation ≥ 93%, and/or death of the study subject. The patients were reassessed at Day 28 and again at Day 60 and by electronic health record review at Day 90. At both Day 28 and Day 60, any new viral, bacterial, or fungal infections were recorded. The current oxygen support or the last day of needed oxygen support subsequent to hospital discharge, and any need for re-hospitalization were recorded. The data from patients who were event-free at the end of the follow-up were censored at 90 days for the primary and secondary outcomes. 