Current evidence on the use of anakinra in COVID-19

Khani, Elnaz; Shahrabi, Marzieh; Rezaei, Haleh; Pourkarim, Fariba; Afsharirad, Hoda; Solduzian, Mohammad

doi:10.1016/j.intimp.2022.109075

Cited by 38 publications

(32 citation statements)

References 67 publications

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“…A study concluded that early anakinra treatment is associated with significantly lower ICU admissions and mortality in patients with moderate/severe COVID-19[ 117 ]. Successful anakinra therapy includes treatment duration ≥ 10 d, dose ≥ 100 mg, intravenous administration, and early initiation of therapy[ 118 ]. Canakinumab is a human monoclonal anti-IL-1β specific antibody.…”

Section: Management Of Liver Injury In Patients With Covid-19mentioning

confidence: 99%

Liver injury in COVID-19: Clinical features, potential mechanisms, risk factors and clinical treatments

Zhao¹,

Li²,

Li³

et al. 2023

World J Gastroenterol

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The coronavirus disease 2019 (COVID-19) pandemic has been a serious threat to global health for nearly 3 years. In addition to pulmonary complications, liver injury is not uncommon in patients with novel COVID-19. Although the prevalence of liver injury varies widely among COVID-19 patients, its incidence is significantly increased in severe cases. Hence, there is an urgent need to understand liver injury caused by COVID-19. Clinical features of liver injury include detectable liver function abnormalities and liver imaging changes. Liver function tests, computed tomography scans, and ultrasound can help evaluate liver injury. Risk factors for liver injury in patients with COVID-19 include male sex, preexisting liver disease including liver transplantation and chronic liver disease, diabetes, obesity, and hypertension. To date, the mechanism of COVID-19-related liver injury is not fully understood. Its pathophysiological basis can generally be explained by systemic inflammatory response, hypoxic damage, ischemia-reperfusion injury, and drug side effects. In this review, we systematically summarize the existing literature on liver injury caused by COVID-19, including clinical features, underlying mechanisms, and potential risk factors. Finally, we discuss clinical management and provide recommendations for the care of patients with liver injury.

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Section: Management Of Liver Injury In Patients With Covid-19mentioning

confidence: 99%

Liver injury in COVID-19: Clinical features, potential mechanisms, risk factors and clinical treatments

Zhao¹,

Li²,

Li³

et al. 2023

World J Gastroenterol

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“…Furthermore, there are potential contributary factors that should be taken into consideration. From the review of the role of anakinra during the management of patients with COVID-19 disease, there are no clear evidence of the optimal timing of intervention, route of administration, exact relevant biomarkers or ideal dose or duration ( Khani et al, 2022 ) . From previous studies, there is increased awareness of the concept of the possible narrow therapeutic window to treat cytokine storms with cytokine inhibitors as well as the right time to initiate IL-1 inhibitors ( Cavalli and Dagna, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

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

Elmekaty

Maklad²,

Abouelhassan³

et al. 2023

Front. Microbiol.

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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.

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“…This has important implications for the hypothesis that the S1 spike protein may contribute to pathogenicity in both COVID-19 and PASC because IL-1β is a primary cytokine candidate to drive the COVID-19 cytokine storm and downstream cytokine production [ 11 , 57 ]. Treatments that target IL-1β production early in COVID-19 infection block the cytokine storm [ 58 , 59 ]. No other cytokines in our ten-cytokine panel were stimulated by the S1 spike in A549+ lung cells.…”

Section: Discussionmentioning

confidence: 99%

The SARS-CoV-2 S1 Spike Protein Promotes MAPK and NF-kB Activation in Human Lung Cells and Inflammatory Cytokine Production in Human Lung and Intestinal Epithelial Cells

et al. 2022

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The coronavirus disease 2019 (COVID-19) pandemic began in January 2020 in Wuhan, China, with a new coronavirus designated SARS-CoV-2. The principal cause of death from COVID-19 disease quickly emerged as acute respiratory distress syndrome (ARDS). A key ARDS pathogenic mechanism is the “Cytokine Storm”, which is a dramatic increase in inflammatory cytokines in the blood. In the last two years of the pandemic, a new pathology has emerged in some COVID-19 survivors, in which a variety of long-term symptoms occur, a condition called post-acute sequelae of COVID-19 (PASC) or “Long COVID”. Therefore, there is an urgent need to better understand the mechanisms of the virus. The spike protein on the surface of the virus is composed of joined S1–S2 subunits. Upon S1 binding to the ACE2 receptor on human cells, the S1 subunit is cleaved and the S2 subunit mediates the entry of the virus. The S1 protein is then released into the blood, which might be one of the pivotal triggers for the initiation and/or perpetuation of the cytokine storm. In this study, we tested the hypothesis that the S1 spike protein is sufficient to activate inflammatory signaling and cytokine production, independent of the virus. Our data support a possible role for the S1 spike protein in the activation of inflammatory signaling and cytokine production in human lung and intestinal epithelial cells in culture. These data support a potential role for the SARS-CoV-2 S1 spike protein in COVID-19 pathogenesis and PASC.

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Current evidence on the use of anakinra in COVID-19

Cited by 38 publications

References 67 publications

Liver injury in COVID-19: Clinical features, potential mechanisms, risk factors and clinical treatments

Liver injury in COVID-19: Clinical features, potential mechanisms, risk factors and clinical treatments

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

The SARS-CoV-2 S1 Spike Protein Promotes MAPK and NF-kB Activation in Human Lung Cells and Inflammatory Cytokine Production in Human Lung and Intestinal Epithelial Cells

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