High-dose intravenous anakinra treatment is safe and effective in severe and critical COVID-19 patients: a propensity score-matched study in a single center

Bektaş, Murat; Yüce, Servet; Ay, Mustafa; Uyar, Muhammed Hamdi; Önder, Mustafa Erkut; Kılıç, Muhammed İkbal

doi:10.1007/s10787-023-01138-8

Cited by 7 publications

(8 citation statements)

References 36 publications

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“…Corona Virus Disease 2019 (COVID-19) refers to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing pneumonia, first discovered in 2019 ( 5 ). The COVID-19 pandemic poses serious challenges to the global economy and development ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of 3 key genes as novel diagnostic and therapeutic targets for OA and COVID-19

et al. 2023

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BackgroundCorona Virus Disease 2019 (COVID-19) and Osteoarthritis (OA) are diseases that seriously affect the physical and mental health and life quality of patients, particularly elderly patients. However, the association between COVID-19 and osteoarthritis at the genetic level has not been investigated. This study is intended to analyze the pathogenesis shared by OA and COVID-19 and to identify drugs that could be used to treat SARS-CoV-2-infected OA patients.MethodsThe four datasets of OA and COVID-19 (GSE114007, GSE55235, GSE147507, and GSE17111) used for the analysis in this paper were obtained from the GEO database. Common genes of OA and COVID-19 were identified through Weighted Gene Co-Expression Network Analysis (WGCNA) and differential gene expression analysis. The least absolute shrinkage and selection operator (LASSO) algorithm was used to screen key genes, which were analyzed for expression patterns by single-cell analysis. Finally, drug prediction and molecular docking were carried out using the Drug Signatures Database (DSigDB) and AutoDockToolsResultsFirstly, WGCNA identified a total of 26 genes common between OA and COVID-19, and functional analysis of the common genes revealed the common pathological processes and molecular changes between OA and COVID-19 are mainly related to immune dysfunction. In addition, we screened 3 key genes, DDIT3, MAFF, and PNRC1, and uncovered that key genes are possibly involved in the pathogenesis of OA and COVID-19 through high expression in neutrophils. Finally, we established a regulatory network of common genes between OA and COVID-19, and the free energy of binding estimation was used to identify suitable medicines for the treatment of OA patients infected with SARS-CoV-2.ConclusionIn the present study, we succeeded in identifying 3 key genes, DDIT3, MAFF, and PNRC1, which are possibly involved in the development of both OA and COVID-19 and have high diagnostic value for OA and COVID-19. In addition, niclosamide, ciclopirox, and ticlopidine were found to be potentially useful for the treatment of OA patients infected with SARS-CoV-2.

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Section: Introductionmentioning

confidence: 99%

Identification of 3 key genes as novel diagnostic and therapeutic targets for OA and COVID-19

et al. 2023

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“…The treatment was discontinued for one child due to infection and one adult due to neutropenia. There was no clear relationship between dose and adverse events in this small compiled cohort, as previously described in patients with COVID‐19 49 . Thirty‐four patients (74%) had functional outcomes reported during follow‐up, with 21 of those 34 (62%) being moderately to severely disabled.…”

Section: Acute Phasementioning

confidence: 52%

“…There was no clear relationship between dose and adverse events in this small compiled cohort, as previously described in patients with COVID-19. 49 Thirty-four patients (74%) had functional outcomes reported during follow-up, with 21 of those 34 (62%) being moderately to severely disabled. Post-NORSE seizure persistence was reported in 88% (29/33) of patients with available follow-up data, and the timing of initiating anakinra did not seem to correlate with long-term outcomes.…”

Section: Anakinramentioning

confidence: 99%

Second‐line immunotherapy in new onset refractory status epilepticus

Hanin,

Muscal,

Hirsch

2024

Epilepsia

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Several pieces of evidence suggest immune dysregulation could trigger the onset and modulate sequelae of new onset refractory status epilepticus (NORSE), including its subtype with prior fever known as febrile infection‐related epilepsy syndrome (FIRES). Consensus‐driven recommendations have been established to guide the initiation of first‐ and second‐line immunotherapies in these patients. Here, we review the literature to date on second‐line immunotherapy for NORSE/FIRES, presenting results from 28 case reports and series describing the use of anakinra, tocilizumab, or intrathecal dexamethasone in 75 patients with NORSE. Among them, 52 patients were managed with anakinra, 21 with tocilizumab, and eight with intrathecal dexamethasone. Most had elevated serum or cerebrospinal fluid cytokine levels at treatment initiation. Treatments were predominantly initiated during the acute phase of the disease (92%) and resulted, within the first 2 weeks, in seizure control for up to 73% of patients with anakinra, 70% with tocilizumab, and 50% with intrathecal dexamethasone. Cytokine levels decreased after treatment for most patients. Anakinra and intrathecal dexamethasone were mainly initiated in children with FIRES, whereas tocilizumab was more frequently prescribed for adults, with or without a prior febrile infection. There was no clear correlation between the response to treatment and the time to initiate the treatment. Most patients experienced long‐term disability and drug‐resistant post‐NORSE epilepsy. Initiation of second‐line immunotherapies during status epilepticus (SE) had no clear effect on the emergence of post‐NORSE epilepsy or long‐term functional outcomes. In a small number of cases, the initiation of anakinra or tocilizumab several years after SE onset resulted in a reduction of seizure frequency for 67% of patients. These data highlight the potential utility of anakinra, tocilizumab, and intrathecal dexamethasone in patients with NORSE. There continues to be interest in the utilization of early cytokine measurements to guide treatment selection and response. Prospective studies are necessary to understand the role of early immunomodulation and its associations with epilepsy and functional outcomes.

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“…This observational retrospective study is a secondary analysis of our previous study ( 7 ) carried out at a tertiary referral center between September 01, 2021, and February 01, 2022, in Turkey. All patients had positive polymerase chain reaction (PCR), typical computer tomography (CT) findings, and clinical signs and symptoms attributed to COVID-19.…”

Section: Methodsmentioning

confidence: 99%

Individualized High Dose Intravenous Anakinra Treatment in Cancer Patients with COVID-19 Associated Cytokine Storm: A Retrospective Controlled Study

Cakmak,

Bektas

2024

Infect Dis Clin Microbiol

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Objective Patients with COVID-19 accompanying cancer have been reported to have higher morbidity and mortality. In this study, we aimed to evaluate the high-dose high intravenous anakinra treatment response and outcome in patients with COVID-19-associated cytokine storm accompanying cancer. Materials and Methods This retrospective observational study was carried out at a tertiary referral center between September 01, 2021, and February 01, 2022, in Turkey. The study population consisted of two groups: patients receiving high-dose intravenous anakinra and patients treated with standard care. Results Data from 146 patients in the anakinra group and 114 patients in the control group were analyzed. Malignancy frequency was 11% (n=16) in the anakinra group and 7% (n=8) in the control group. In survival analysis, a significantly lower survival rate was observed in patients with malignancy than those without in the control group (log-rank: p =0.002) and patients with malignancy in the control group compared to the anakinra group (log-rank: p =0.013). However, it did not differ between patients with and without malignancy in the anakinra group (log-rank: p =0.9). Conclusion In the control group, mortality was higher in patients with malignancy compared to those without malignancy, but not in the anakinra group. Also, mortality was higher in patients receiving SoC compared to anakinra. Intravenous high-dose anakinra treatment is safe and effective in patients with COVID-19 accompanying cancer.

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High-dose intravenous anakinra treatment is safe and effective in severe and critical COVID-19 patients: a propensity score-matched study in a single center

Cited by 7 publications

References 36 publications

Identification of 3 key genes as novel diagnostic and therapeutic targets for OA and COVID-19

Identification of 3 key genes as novel diagnostic and therapeutic targets for OA and COVID-19

Second‐line immunotherapy in new onset refractory status epilepticus

Individualized High Dose Intravenous Anakinra Treatment in Cancer Patients with COVID-19 Associated Cytokine Storm: A Retrospective Controlled Study

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