Pharmacological intervention Sample size and criteria Treatment protocol Key findings Conclusion Reference
• Tocilizumab for IL-6 cytokine release syndrome • Multicenter Randomized controlled trial (RCT)
• Severe COVID-19 infections
• 18–85 years of age
• Elevated serum IL-6
•  N = 94 standard therapy + tocilizumab
•  N = 94 standard therapy • 4–8 mg/kg tocilizumab i.v. once
• Additional dose if fever persists in 24 h after first dose • First phase showed normalization of fever within 24 h of tocilizumab
• Improved respiratory function, oxygenation, and pulmonary lesions • Phase 4 study completed in May 2020
• Results pending
• Tocilizumab may be a promising investigative therapy to reduce cytokine release syndrome and associated multi-organ damage (ChiCTR2000029765, 2020)
• Tocilizumab to mitigate cytokine storm and associated complications • Retrospective cohort study
• >18 years of age
• Intensive care unit (ICU) COVID-19 hospitalization
• Primary endpoint of hospital-related mortality
•  N = 210 standard care + tocilizumab
•  N = 420 standard care • 400 mg single dose or 8 mg/kg tocilizumab
• 88% required 1 infusion, 12% received a second infusion • Hazard ratio (HR) 0.71 for hospital related mortality (95% confidence interval (CI) 0.56–0.89)
• Treatment was more effective in patients with C-reactive protein (CRP) >15 mg/dL
• HR 0.48 (95% CI 0.30–0.77) than those with CRP <15 mg/dL HR 0.92 (95% CI 0.57–1.48) • Tocilizumab treatment is associated with a lower rate of mortality, particularly in those with enhanced inflammatory state
• Double blind RCT recently completed with results pending NCT04320615 (Biran et al., 2020)
• Tocilizumab to mitigate cytokine storm • Prospective observational study
• Severe or critical COVID-19 infection
• 25 to 88 years of age
•  N = 21 tocilizumab + standard therapy
• 42.9% had CVD • 4–8 mg/kg or 400 mg tocilizumab i.v. once
• 85.7% received single dose of tocilizumab, 14.3% required second dose within 12 h of first dose • Fever normalized within 24 h
• Reduced O2 therapy requirements
• Minimal improvement in IL-6 levels
• CT lung lesion improvement
• All patients discharged • Limited sample size and no control group
• Tocilizumab treatment in severe COVID-19 cases may improve clinical symptoms in hyperinflammatory state (Xu et al., 2020)
• Intensive methylprednisolone regimen +/− tocilizumab for management of cytokine storm • Prospective observational study
• O2 sat ≤ 94% OR tachypnea, elevated CRP, high D-dimer
• Primary outcome of hospital discharge or clinical improvement
•  N = 86 methylprednisolone +/− tocilizumab
• N = 86 standard care • Stage 1: Immediate methylprednisolone 250 mg i.v. on day 1, then 80 mg on days 2–5
• Stage 2 (lack of clinical improvement or worsening respiratory status): Add tocilizumab 8 mg/kg i.v. once between days 2–5 • Improvement in respiratory status HR 1.79 (95% CI 1.20–2.67)
• Improvement reached in a shorter time vs. control
• Reduced hospital mortality and need for mechanical ventilation • Short duration of intensive immunosuppressive therapy is associated with improved clinical outcomes in patients with hyperinflammaory state (Ramiro et al., 2020)
• Ruxolitinib treatment for elevated cytokine levels and inflammatory response • Prospective RCT
• 18 to 75 years of age with severe infection
• Primary outcome of time to clinical improvement
•  N = 20 ruxolitinib + standard care
•  N = 21 placebo + standard care • Ruxolitinib 5 mg twice daily
• Placebo vitamin C 100 mg twice daily • No difference in primary endpoint HR 1.669 (95% CI 0.836–3.335)
• Improvement in lung computerized tomography (CT) scans
• Significantly reduced cytokine levels and CRP by day 3 • Ruxolitinib may hasten time of chest CT scan improvement and mitigate systemic inflammation (Cao et al., 2020)
• Anakinra for targeting the cytokine inflammatory cascade through IL-1 blockade • Open label case series
• Elevated CRP N = 9
• 6/9 with CVD risk factors (diabetes, obesity)
• 3/9 with hypertension • Anakinra 100 mg every 12 h s.c. on days 1–3
• Anakinra 100 mg once daily s.c. on days 4–10 • Fever subsided by day 3
• CRP normalized in 5 patients by day 11
• Halted progression of CT lung lesions
• 100% survival • Small case series, potential for confounding factors
• Potential therapy to target inflammatory cascade
• Positive results in patients with hypertension and other CVD risk factors (Aouba et al., 2020)
• Ana-COVID study
• Anakinra for COVID-19 hyperinflammatory state • Prospective/retrospective cohort study
• Hospitalized adults with critical lung function
• Cohort with CVD (hypertension, stroke, cardiopathy)
• Primary outcome of ICU admission with mechanical ventilation or death
•  N = 52 anakinra + standard care
•  N = 44 standard care • Anakinra 100 mg s.c. twice daily for 3 days
• Then anakinra 100 mg s.c. once daily for 7 days • Significantly reduced need for mechanical ventilation or death HR 0.22 (0.11–0.41) • Anakinra may be associated with improved outcomes in patients with severe COVID-19 infection, including those with CVD and history of cardiovascular events
• May be due to mitigation of inflammatory cascade (Huet et al., 2020)