Cyclosporine therapy in cytokine storm due to coronavirus disease 2019 (COVID-19)

Cüre, Erkan; Küçük, Adem; Cüre, Medine Cumhur

doi:10.1007/s00296-020-04603-7

Cited by 34 publications

(40 citation statements)

References 17 publications

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“…Overall, the over-activation of NLRP3 inflammasomes amplifies the innate immune response and contributes to cell death by pyroptosis and virus propagation. HCQ, hydroxychloroquine 6.1.4 | Immunosuppressants Three clinical trials are recruiting COVID-19 patients to test the efficacy of the immunosuppressant sirolimus (NCT04341675, NCT04371640, and NCT04374903), whereas no clinical study on the calcineurin inhibitor cyclosporine in COVID-19 has been recorded, although it has been suggested as a potential treatment for SARS-CoV-2 infection (Cure, Kucuk, & Cumhur Cure, 2020). Both these immunosuppressants can interfere with NLRP3 inflammasome.…”

Section: Azithromycinmentioning

confidence: 99%

The hidden role of NLRP3 inflammasome in obesity‐related COVID‐19 exacerbations: Lessons for drug repurposing

Bertocchi

Foglietta

Collotta

et al. 2020

British J Pharmacology

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COVID-19, the illness caused by SARS-CoV-2, has a wide-ranging clinical spectrum that, in the worst-case scenario, involves a rapid progression to severe acute respiratory syndrome and death. Epidemiological data show that obesity and diabetes are among the main risk factors associated with high morbidity and mortality. The increased susceptibility to SARS-CoV-2 infection documented in obesity-related metabolic derangements argues for initial defects in defence mechanisms, most likely due to an elevated systemic metabolic inflammation ("metaflammation"). The NLRP3 inflammasome is a master regulator of metaflammation and has a pivotal role in the pathophysiology of either obesity or diabetes. Here, we discuss the most recent findings suggesting contribution of NLRP3 inflammasome to the increase in complications in COVID-19 patients with diabesity. We also review current pharmacological strategies for COVID-19, focusing on treatments whose efficacy could be due, at least in part, to interference with the activation of the NLRP3 inflammasome.

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Section: Azithromycinmentioning

confidence: 99%

The hidden role of NLRP3 inflammasome in obesity‐related COVID‐19 exacerbations: Lessons for drug repurposing

Bertocchi

Foglietta

Collotta

et al. 2020

British J Pharmacology

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“…Experimental data, hydroxychloroquine was demonstrated to inhibit the viral reproduction, and the drug was employed alone or in association with antivirals [27]. Similarly, as anti-calcineurin immunosuppressants cyclosporin A, and alisporivir (an analogue of cyclosporin) were detected to exert antiviral action, some authors suggested their use [28,29]. Second, since the more severe clinical manifestations were found to be mainly related to massive cytokine outbreak from immune cells, thus resembling an autoinflammatory condition [30], anti-cytokine agents, including anti-IL-6 tocilizumab, sarilumab, and siltuximab, anti-IL-1 anakinra, Janus kinase (JAK) inhibitors ruxolitinib, and baricitinib, anti-granulocyte-macrophage colony-stimulating factor receptor-alpha monoclonal antibody (anti-GM-CSF) mavrilimumab, and anti-CD6 itolizumab were used [31,32].…”

Section: Introductionmentioning

confidence: 99%

Immune Therapy, or Antiviral Therapy, or Both for COVID-19: A Systematic Review

Cantini

Goletti

Petrone

et al. 2020

Drugs

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Background Based on current evidence, recent guidelines of the National Institute of Health, USA indicated the use of remdesivir and dexamethasone for the treatment of COVID-19 patients with mild-moderate disease, not requiring highflow oxygen. No therapeutic agent directed against the immunologic pathogenic mechanisms related to the cytokine release syndrome complicating the disease was indicated. Objectives The purpose of this review was to assess the clinical impact of different therapies for COVID-19; thus, helping to identify the optimal management of the disease. To explain the rationale for the different therapeutic approaches, the characteristics of SARS-CoV-2, the pathogenesis of COVID-19, and the immune response triggered by SARS-CoV-2 infection were reported. Methods The efficacy assessment of the different treatments was performed by a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Available English language published articles including randomised controlled trials, open-label trials of antivirals and immune therapies extracted from Medline, Google Scholar, and MedRxiv databases were analysed. For inclusion, the primary end point of the trials had to be the efficacy as measured by the improvement of clinical features, or mortality, or the Intensive Care Unit Admission rate, or the discharge number. Case reports, paediatric studies, and studies without control group were excluded. The literature search was extended up to August 15, 2020. Results After the removal of duplicate articles, and the exclusion of studies not meeting the eligibility criteria, 2 trials of lopinavir/ritonavir, 1 of favipiravir, 3 of remdesivir, 1 of dexamethasone, 3 of hydroxychloroquine, 2 of colchicine, 6 of tocilizumab, 1 of sarilumab, 1 of siltuximab, 2 of anakinra, 3 of baricitinib, 1 of ruxolitinib, 1 of mavrilimumab, and 1 of itolizumab were suitable for the review. Among antivirals, only remdesivir significantly reduced the time to recovery, and mortality. Data for chloroquine and hydroxychloroquine were largely inconclusive. In a large trial, dexamethasone 6 mg/ day reduced mortality by one-third. Trials of tocilizumab and sarilumab did not definitively demonstrate efficacy. Anakinra significantly reduced the mortality in 2 trials. Three retrospective trials on a cumulative number of 145 patients, reported the efficacy of baricitinib, with significant reduction of intensive care unit admission, and deaths. These results were recently confirmed by the ACTT-2 trial. Due to paucity of studies and to the small size clinical series, the results of other immune therapies were not conclusive. Conclusions Beyond the supportive therapy, up to now the best therapeutic approach for COVID-19 may be a three-step combination therapy, including remdesivir 100 mg/day (200 mg loading dose on first day) in the first stage of the disease, and combined dexamethasone 6 mg/day plus baricitinib 4 mg/day to target the immune dysregulation triggered by the SARS-CoV-2 infection. ...

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“…On the other hand, there are concerns regarding the capacity of CsA to increase ACE2 shedding and, consequently, to augment SARS-CoV-2 infection by increment the ACE2 upregulation. 200 Furthermore, the CsA has serious side effects, which can cause hyperlipidaemia, gingival hyperplasia, nausea, vomiting, abdominal pain, headache, susceptibility to infections, triggering of cancer development, blood pressure increase, nephrotoxicity, and immune suppression. Its nephrotoxic effect is dose and duration dependent.…”

Section: Drug Repurposing For Covid-19mentioning

confidence: 99%

“… 201 Therefore, it is not clear whether CsA may mitigate or aggravate the SARS-CoV-2 infection, since there is no CsA clinical studies published up to now, even has been suggested that low-dose CsA can be useful for patients presenting SARS-CoV-2-induced cytokine storm. 200 …”

Section: Drug Repurposing For Covid-19mentioning

confidence: 99%