ArticleEuropean journal of pharmacology2020
Application of methylene blue -vitamin C -N-acetyl cysteine for treatment of critically ill COVID-19 patients, report of a phase-I clinical trial.
Article in European journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04370288 (The Clinical Trial of Application of Methylene Blue Vial for Treatment of Covid-19 Patients), which is not on this map. Cited by 60 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Clinical Trial of Application of Methylene Blue Vial for Treatment of Covid-19 Patients
Who cites it
60 citing papers in PubMed, 120 citations in OpenAlex.
- Response to Intravenous N-Acetylcysteine Supplementation in Critically Ill Patients with COVID-19.Nutrients · 2023Trial
- A pilot study on intravenous N-Acetylcysteine treatment in patients with mild-to-moderate COVID19-associated acute respiratory distress syndrome.Pharmacological reports : PR · 2021Trial
- Article
- Herbal and Dietary Supplements as Adjunctive Treatment for Mild SARS-CoV-2 Infection in Italy.Nutrients · 2025Review
- TLR2 Activation as a Marker of Severe COVID-19 and a Potential Therapeutic Target.Current medicinal chemistry · 2025Review
- Laboratory Puzzle of Oxidative Stress, Parameters of Hemostasis and Inflammation in Hospitalized Patients with COVID-19.Biomedicines · 2024Article
- Nitrite Attenuates the In Vitro Inflammatory Response of Immune Cells to the SARS-CoV-2 S Protein without Interfering in the Antioxidant Enzyme Activation.International journal of molecular sciences · 2024Article
- Clinical efficacy of N-acetylcysteine for COVID-19: A systematic review and meta-analysis of randomized controlled trials.Heliyon · 2024Article
- N-Acetylcysteine Treats Spinal Cord Injury by Inhibiting Astrocyte Proliferation.Analytical cellular pathology (Amsterdam) · 2024Article
- Application of methylene blue for the prevention and treatment of COVID-19: A narrative review.Iranian journal of basic medical sciences · 2024Review
- Nanotherapy therapy for acute respiratory distress syndrome: a review.Frontiers in medicine · 2024Review
- Microglial Inflammatory Responses to SARS-CoV-2 Infection: A Comprehensive Review.Cellular and molecular neurobiology · 2023Review
- Severity of oxidative stress as a hallmark in COVID-19 patients.European journal of medical research · 2023Article
- Smart stimuli-responsive drug delivery systems in spotlight of COVID-19.Asian journal of pharmaceutical sciences · 2023Review
- Evaluation of the efficacy and safety of oral N-acetylcysteine in patients with COVID-19 receiving the routine antiviral and hydroxychloroquine protocol: A randomized controlled clinical trial.Immunity, inflammation and disease · 2023Article
- Exploring the Anti-Hypoxaemia Effect of Hydromethylthionine: A Prospective Study of Phase 3 Clinical Trial Participants.International journal of molecular sciences · 2023Article
- Effect of educational intervention on knowledge and attitude about the role of vitamins, minerals and nutraceuticals in COVID-19 and other disorders among medical and nursing undergraduates of a tertiary care teaching hospital.Clinical nutrition ESPEN · 2023Article
- [Evolución de marcadores de laboratorio en pacientes con detección persistente de SARS-CoV-2.]Revista espanola de salud publica · 2023Article
- Modifiable contributing factors to COVID-19: A comprehensive review.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2023Review
- The oxygen dissociation curve of blood in COVID-19-An update.Frontiers in medicine · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
COVID-19 is a global catastrophic event that causes severe acute respiratory syndrome. The mechanism of the disease remains unclear, and hypoxia is one of the main complications. There is no currently approved protocol for treatment. The microbial threat as induced by COVID-19 causes the activation of macrophages to produce a huge amount of inflammatory molecules and nitric oxide (NO). Activation of macrophages population into a pro-inflammatory phenotype induces a self-reinforcing cycle. Oxidative stress and NO contribute to this cycle, establishing a cascade inflammatory state that can kill the patient. Interrupting this vicious cycle by a simple remedy may save critical patients' lives. Nitrite, nitrate (the metabolites of NO), methemoglobin, and prooxidant-antioxidant-balance levels were measured in 25 ICU COVID-19 patients and 25 healthy individuals. As the last therapeutic option, five patients were administered methylene blue-vitamin C-N-acetyl Cysteine (MCN). Nitrite, nitrate, methemoglobin, and oxidative stress were significantly increased in patients in comparison to healthy individuals. Four of the five patients responded well to treatment. In conclusion, NO, methemoglobin and oxidative stress may play a central role in the pathogenesis of critical COVID-19 disease. MCN treatment seems to increase the survival rate of these patients. Considering the vicious cycle of macrophage activation leading to deadly NO, oxidative stress, and cytokine cascade syndrome; the therapeutic effect of MCN seems to be reasonable. Accordingly, a wider clinical trial has been designed. It should be noted that the protocol is using the low-cost drugs which the FDA approved for other diseases. TRIAL REGISTRATION NUMBER: NCT04370288.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.