A Multiple-Hit Hypothesis Involving Reactive Oxygen Species and Myeloperoxidase Explains Clinical Deterioration and Fatality in COVID-19
| Autor: | Husam M. Abu-Soud, Pravin T. Goud, David Bai |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Heme binding
myeloperoxidase HOCl medicine.medical_treatment Coronavirus. COVID-19 Inflammation Vasodilation Oxidative phosphorylation Review Applied Microbiology and Biotechnology Catalysis Nitric oxide 03 medical and health sciences chemistry.chemical_compound medicine Humans Molecular Biology Ecology Evolution Behavior and Systematics 030304 developmental biology Peroxidase chemistry.chemical_classification 0303 health sciences Reactive oxygen species biology Clinical Deterioration business.industry SARS-CoV-2 COVID-19 Cell Biology Hypochlorous Acid Cytokine chemistry free iron Myeloperoxidase Immunology biology.protein medicine.symptom business Reactive Oxygen Species Oxidation-Reduction Developmental Biology |
| Zdroj: | International Journal of Biological Sciences |
| ISSN: | 1449-2288 |
| Popis: | Multi-system involvement and rapid clinical deterioration are hallmarks of coronavirus disease 2019 (COVID-19) related mortality. The unique clinical phenomena in severe COVID-19 can be perplexing, and they include disproportionately severe hypoxemia relative to lung alveolar-parenchymal pathology and rapid clinical deterioration, with poor response to O2 supplementation, despite preserved lung mechanics. Factors such as microvascular injury, thromboembolism, pulmonary hypertension, and alteration in hemoglobin structure and function could play important roles. Overwhelming immune response associated with "cytokine storms" could activate reactive oxygen species (ROS), which may result in consumption of nitric oxide (NO), a critical vasodilation regulator. In other inflammatory infections, activated neutrophils are known to release myeloperoxidase (MPO) in a natural immune response, which contributes to production of hypochlorous acid (HOCl). However, during overwhelming inflammation, HOCl competes with O2 at heme binding sites, decreasing O2 saturation. Moreover, HOCl contributes to several oxidative reactions, including hemoglobin-heme iron oxidation, heme destruction, and subsequent release of free iron, which mediates toxic tissue injury through additional generation of ROS and NO consumption. Connecting these reactions in a multi-hit model can explain generalized tissue damage, vasoconstriction, severe hypoxia, and precipitous clinical deterioration in critically ill COVID-19 patients. Understanding these mechanisms is critical to develop therapeutic strategies to combat COVID-19. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|