Editor – We read the article ‘Potential role of endothelial cell surface ectopic redox complexes in COVID-19 disease pathogenesis’ with great interest.1 Dr Isabella Panfoli explains the cause of viral damage-induced microvascular inflammation and thrombosis seen in susceptible people with COVID-19. She proposes ectopic expression of electron transport chain (ETC) on the luminal endothelial cell (EC) membrane secondary to viral damage as a cause of luminal oxidative stress priming microvascular thrombosis. She comments that high oxygen input in the presence of impaired ectopic ETC can result in uncontrolled augmented reactive oxygen species (ROS) production that can be prevented by strict fine tuning of oxygen flux during mechanic ventilation. This is concordant with the experimental study by Helmerhorst et al who demonstrated prolonged ventilation with higher oxygen concentrations (hyperoxia) induced immune response in pulmonary compartment in mice.2 In contrast to these, Goyal et al put forward that hypoxia is itself pro-inflammatory and its timely detection and correction by oxygen supplementation likely improves mortality in COVID-19 patients.3 So, titrating fractional inspired oxygen (FiO2) to correct hypoxia but without causing hyperoxia that could result in deleterious ROS production is of paramount importance. But which clinical criteria determines correctly the transition line between harm and therapy by supplemental oxygen? What is the correct timing? Can ROS scavengers (including N-acetyl cysteine, glutathione, alpha-lipoic acid or ascorbic acid), nuclear factor erythroid 2-related factor 2 (nrf-2) agonists, ETC complex I or III inhibitors or angiotensin-II blockers be used to liberally increase FiO2 during mechanical ventilation? Are there other sources of ROS than ECs? It seems that we need further experimental and clinical studies to answer even the optimal dosing of supplemental oxygen in correcting hypoxaemia in patients with COVID-19.
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