ABSTRACT
Since December 2019, an outbreak of a new coronavirus, COVID-19, infection has been taking place. At present, COVID-19 has spread to most countries worldwide. The latest evidence suggests that cytokine storm syndrome (CSS) is an important cause of the transition from mild to critical pneumonia and critically ill patients' death. The sudden exacerbation of COVID-19 may be related to a cytokine storm. Therefore, early identification and active treatment of CSS may play very important roles in improving the patients' prognosis, and these tasks are given attention in the current treatment of new Coronavirus pneumonia. However, there is still no specific medicine for this purpose. This article reviews cytokine storms and conducts an exploratory review of pharmacotherapy for cytokine storms to provide a reference for clinical treatment.
Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Myocarditis/immunology , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Monoclonal, Humanized/therapeutic use , Antioxidants/therapeutic use , Apoptosis , Atrial Natriuretic Factor/therapeutic use , Azetidines/therapeutic use , Benzyl Compounds/therapeutic use , Cytokine Release Syndrome/drug therapy , Enzyme Inhibitors/therapeutic use , Glucocorticoids/therapeutic use , Glycoproteins/therapeutic use , Humans , Hypoxia/metabolism , Hypoxia/therapy , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Myocardial Ischemia/metabolism , Myocarditis/metabolism , Myocarditis/therapy , Myocytes, Cardiac/metabolism , Oxidative Stress , Oxygen Inhalation Therapy , Respiration, Artificial , SARS-CoV-2 , Sphingosine 1 Phosphate Receptor Modulators/therapeutic use , Trypsin Inhibitors/therapeutic use , Tumor Necrosis Factor Inhibitors/therapeutic use , alpha-Methyltyrosine/therapeutic use , COVID-19 Drug TreatmentABSTRACT
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.