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Authors: Horowitz, Richard I. et al

Link to paper: https://www.sciencedirect.com/science/article/pii/S2213007120301350

[NB: Unable to access supplementary data. Data may prove more insightful in future]

Journal/ Pre-Print: Respiratory Medicine Case Reports

Tags: Immunology/Immunity, Inflammation, Therapeutics

Research Highlights 

1. Trial administration of 2g of PO or IV glutathione (GSH) in the treatment of 2 patients with dyspnea 10 days after symptom onset during peak stage of illness.

2. Both patients were started on combination therapy of hydroxychloroquine and antibiotics and experienced gradual improvement.

3. Dyspnea improved within 1 h of use, repeated use further relieved respiratory symptoms. However, uncertain whether GSH had a direct impact in improvement of clinical symptoms due to complex combination therapy

Summary

Observational case study evaluating the effects of using high dose oral and/or IV glutathione in the treatment of 2 patients (54 year old male and 48 year old female both with a history of Lyme and tick-bourne co-infections) with dyspnea secondary to COVID-19 pneumonia. Both patients were on combination therapy including hydroxychloroquine and antibiotics. Respiratory distress improved within 1 hour of administration of GSH and repeated use further improved dyspnea. Authors conclude that glutathione therapy may represent a novel treatment approach for addressing cytokine storm syndrome and respiratory distress in patients with COVID-19 pneumonia, however no evidence is provided.

Impact for SARS-CoV2/COVID19 research efforts

Treat of SARS-CoV2/COVID19 positive individuals

Study Type

· Patient Case study

Strengths and limitations of the paper

Novelty: Antioxidants may represent potential strategy to block NF-kb and reduce cytokine storm to improved respiratory distress in patients suffering with COVI9-19 pneumonia.

Standing in the field:

Precursors of glutathione (NAC) have been used in several randomised clinical trials (RCT) for ARDs treatment. Meta-analysis of eight RCTs comparing the effects of NAC on patients with ARDs concluded that NAC is ineffective in reducing mortality but reduced length of ICU stay (https://journals.sagepub.com/doi/10.1177/1024907918794559).

A review of NAC therapy for COVID19 by Oxford’s Centre for Evidence-Based Medicine modelled use of therapy in acute respiratory disorders, including that secondary to influenza, but had inconclusive findings for use on COVID19 from available literature. (https://www.cebm.net/covid-19/n-acetylcysteine-a-rapid-review-of-the-evidence-for-effectiveness-in-treating-covid-19/)

To date, no clinical trials involving antioxidants for COVID-19 dyspnea, pneumonia or ARDS.

Appropriate statistics: n/a (observational case study)

Viral model used: SARS-COV2

(1 patient tested positive for SARS-COV2 by Ab test, other patient suspected with SARS-COV2 but not confirmed)

Translatability: Authors suggest that a randomised control study of GSH administration should be carried out in the future.

Main limitations:

· Only 2 patients in the study

· Observational case study and not mechanistic

· Unknown if one of the patients had COVID19

· Both patients clinically improved prior to GSH administration

· Both patients already at peak of the illness and symptoms may have improved on their own or due to other drugs given as part of combination therapy. Difficult to draw out any conclusions.