Evaluation of anakinra in the management of patients with COVID-19 infection: A randomized clinical trial

Abstract

BackgroundThe global COVID-19 pandemic led to substantial clinical and economic outcomes with catastrophic consequences. While the majority of cases has mild to moderate disease, minority of patients progress into severe disease secondary to the stimulation of the immune response. The hyperinflammatory state contributes towards progression into multi-organ failure which necessitates suppressive therapy with variable outcomes. This study aims to explore the safety and efficacy of anakinra in COVID-19 patients with severe disease leading to cytokine release syndromes.MethodsIn this open-label, multi-center, randomized clinical trial, patients with confirmed COVID-19 infection with evidence of respiratory distress and signs of cytokine release syndrome were randomized in 1:1 ratio to receive either standard of care (SOC) or anakinra (100 mg subcutaneously every 12 h for 3 days then 100 mg subcutaneously once daily for 4 days) in addition to SOC. The primary outcome was treatment success at day 14 as defined by the WHO clinical progression score of ≤3. Primary analysis was based upon intention-to-treat population, with value of p of <0.05.ResultsOut 327 patients screened for eligibility, 80 patients were recruited for the study. The mean age was 49.9 years (SD = 11.7), with male predominance at 82.5% (n = 66). The primary outcome was not statistically different (87.5% (n = 35) in anakinra group vs. 92.5% (n = 37) in SOC group, p = 0.712; OR = 1.762 (95%CI: 0.39–7.93). The majority of reported adverse events were mild in severity and not related to the study treatment. Elevated aspartate aminotransferase was the only significant adverse event which was not associated with discontinuation of therapy.ConclusionIn patients with severe COVID-19 infection, the addition of anakinra to SOC treatment was safe but was not associated with significant improvement according to the WHO clinical progression scale. Further studies are warranted to explore patients’ subgroups characteristics that might benefit from administered therapy.Clinical Trial RegistrationTrial registration at ClinicalTrials.gov, identifier: NCT04643678.

The Potential of Anti-coronavirus Plant Secondary Metabolites in COVID-19 Drug Discovery as an Alternative to Repurposed Drugs: A Review

“…Vein thrombosis [30][31] Paxlovid (Nirmatrelvir-Ritonavir) Inhibition of viral replication Headache, diarrhea, vomiting dysgeusia [32] Molnupiravir (Lagevrio) Inhibition of virus multiplying Dizziness, rash, diarrhea, nausea [33][34] Kineret (anakinra) Inhibition of interleukin-1 (IL-1) receptor Reaction in injection site, enhancement of liver enzymes, hypertension [35][36] Gohibic (Vilobelimab) Vilobelimab as an antagonist od complement component 5a (C5-a) receptor, acts as anti-inflammatory agent Hypertension, pneumonia, pulmonary embolism, delirium, and sepsis [37] Prioritizing Potential Candidates for Anti-SARS-CoV-2 Drug Development and Discovery from Phytochemicals and Plant Secondary Metabolites…”

“…The repurposed antiviral drugs used to treat COVID-19 may provide protection against infection or speed up recovery, but all COVID-19 antiviral drugs currently on the market have drawbacks that may prevent their use by the general public [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. For example, remdesivir administration led to mild to moderate undesirable outcomes, including but not restricted to liver toxicity, queasiness, anemia, kidney impairment, low blood pressure, respiratory collapse, and constipation, among other things [38][39][40][41][42].…”

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“…The repurposed antiviral drugs used to treat COVID-19 may provide protection against infection or speed up recovery, but all COVID-19 antiviral drugs currently on the market have drawbacks that may prevent their use by the general public [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. For example, remdesivir administration led to mild to moderate undesirable outcomes, including but not restricted to liver toxicity, queasiness, anemia, kidney impairment, low blood pressure, respiratory collapse, and constipation, among other things [38][39][40][41][42].…”