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Open AccessJournal ArticleDOI

Repurposing Treatment of Wernicke-Korsakoff Syndrome for Th-17 Cell Immune Storm Syndrome and Neurological Symptoms in COVID-19: Thiamine Efficacy and Safety, In-Vitro Evidence and Pharmacokinetic Profile

TLDR
In this article, Thiamine can effectively lower the Th17 response in a clinical study [Proinflammatory state in alcohol use disorder patients termed as disease controls (DC)] and corroborated the results using an in vitro study.
Abstract
Coronavirus disease identified in 2019 (COVID-19) can be complicated by the Th17 cell-mediated IL-17 proinflammatory response We tested if thiamine can effectively lower the Th17 response in a clinical study [Proinflammatory state in alcohol use disorder patients termed as disease controls (DC)] and corroborated the results using an in vitro study We developed an effective dose range and model for key pharmacokinetic measures with the potential of targeting the cytokine storm and neurological symptoms of COVID-19 Three-week 200 mg dose of thiamine was administered to sixteen DC patients Eight healthy volunteers (HV) were also included in this investigation A subsequent in vitro study was performed to validate the effectiveness of thiamine [100 mg/day equivalent (0 01 mug/ml)] treatment in lowering the Th17 proinflammatory response in a mouse macrophage cell line (RAW264 7) treated with ethanol Based on recent publications, we compared the results of the IL-17 response from our clinical and in vitro study to those found in other proinflammatory disease conditions (metabolic conditions, septic shock, viral infections and COVID-19) and effective and safe dose ranges of thiamine We developed a pharmacokinetic profile for thiamine dose range as a novel intervention strategy in COVID-19 DC group showed significantly elevated proinflammatory cytokines compared to HV Thiamine-treated DC patients showed significant lowering in IL-17 and increase in the IL-22 levels In humans, a range of 79-474 mg daily of thiamine was estimated to be effective and safe as an intervention for the COVID-19 cytokine storm A literature review showed that several neurological symptoms of COVID-19 (~45 5% of the severe cases) occur in other viral infections and neuroinflammatory states that may also respond to thiamine treatment Thiamine, a very safe drug even at very high doses, could be repurposed for treating the Th17 mediated IL-17 immune storm, and the subsequent neurological symptoms observed in COVID-19 Further studies using thiamine as an intervention/prevention strategy in COVID-19 patients could identify its precise anti-inflammatory role

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Citations
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The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections

TL;DR: This study focuses on cytokine secretions of innate and adaptive immune responses against COVID-19, including interleukins, interferons, tumor necrosis factor-alpha, and other chemokines, and discusses potential immunotherapeutic approaches based on relevant pathophysiological features.
Journal ArticleDOI

Neuropsychiatric manifestations of COVID-19, potential neurotropic mechanisms, and therapeutic interventions.

TL;DR: In this paper, the authors summarize recent animal and human studies for neurotrophic properties of severe acute respiratory syndrome coronavirus (SARS-CoV-2) and elucidate potential neuropathogenic mechanisms involved in the viral invasion of the central nervous system as a cause for brain damage and neurological impairments.
Journal ArticleDOI

Metabolic Profiling from an Asymptomatic Ferret Model of SARS-CoV-2 Infection

TL;DR: The utility of metabolomics applied to ferrets for further CO VID-19 research that advances early diagnosis of asymptomatic and mild clinical COVID-19 infections, in addition to assessing the effectiveness of new or re-purposed drug therapies is indicated.
References
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Journal ArticleDOI

COVID-19: consider cytokine storm syndromes and immunosuppression

TL;DR: Re-analysis of data from a phase 3 randomised controlled trial of IL-1 blockade (anakinra) in sepsis, showed significant survival benefit in patients with hyperinflammation, without increased adverse events.
Journal ArticleDOI

The trinity of COVID-19: immunity, inflammation and intervention.

TL;DR: The interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression is described and the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation are highlighted.
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