Could glutathione depletion be the Trojan horse of COVID-19 mortality?

Eur Rev Med Pharmacol Sci. 2020 Dec;24(23):12500-12509. doi: 10.26355/eurrev_202012_24046.


Objective: Since the emergence of coronavirus disease (COVID-19), the death toll has been increasing daily. Many risk factors are associated with a high mortality rate in COVID-19. Establishment of a common pathway among these risk factors could improve our understanding of COVID-19 severity and mortality. This review aims at establishing this common pathway and its possible effect on COVID-19 mortality.

Materials and methods: The current review was executed in five consecutive stages starting from determining the risk factors of COVID-19 mortality and trying to find a common pathway among them depending on the available literature. This was followed by proposing a mechanism explaining how this common pathway could increase the mortality. Finally, its potential role in managing COVID-19 was proposed.

Results: This review identified this common pathway to be a low baseline of reduced glutathione (i.e., GSH) level. In particular, this review provided an in-depth discussion regarding the pathophysiology by which COVID-19 leads to GSH depletion, tissue damage, and acute respiratory distress syndrome. In addition, the current review demonstrated how GSH depletion could result in failure of the immune system and rendering the end organs vulnerable to damage from the oxidative stress.

Conclusions: This preclinical study shows that GSH depletion may have a central role in COVID-19 mortality and pathophysiology. Therefore, elevating the GSH level in tissues may decrease the severity and mortality rates of COVID-19.

Publication types

  • Review

MeSH terms

  • Acute Lung Injury / metabolism
  • Age Factors
  • Antioxidants / metabolism
  • Apoptosis
  • COVID-19 / immunology
  • COVID-19 / metabolism
  • COVID-19 / mortality*
  • Cytokine Release Syndrome / immunology*
  • Cytokine Release Syndrome / metabolism
  • Diabetes Mellitus / epidemiology
  • Diabetes Mellitus / metabolism
  • Glutathione / immunology
  • Glutathione / metabolism*
  • Humans
  • Hypertension / epidemiology
  • Hypertension / metabolism
  • Macrophages / immunology
  • Myocardial Ischemia / epidemiology
  • Myocardial Ischemia / metabolism
  • Obesity / epidemiology
  • Obesity / metabolism
  • Reactive Oxygen Species / metabolism
  • Respiratory Distress Syndrome / metabolism
  • Risk Factors
  • SARS-CoV-2
  • Smoking / epidemiology
  • Smoking / metabolism


  • Antioxidants
  • Reactive Oxygen Species
  • Glutathione