The featured content is presented in order to show the iter translating into the publication of an article on a scientific journal. The most important ones in the scientific community examine its contents through the analysis of two experts of that particular area (Peer Review process).

Thus, they come to a sentence: rejected or accepted. No third possibility allowed. In most cases, modifications or integrations can be requested, as a necessary condition for a publishing. The Peer Reviewed publication on a scientific journal means that the article has stood the test of plausibility for the featured contents.

Here’s the article, together with the comment by one of the Reviewers.

Comments from the editors and reviewers

This brief letter to the editor from Giulio and Giuseppe Scigliano at the National Neurological Institute in Milan describes the potential role of free radicals in mediating the cytokine storm of COVID-19 pneumonia.

The role of free radicals in exacerbating inflammation in COVID-19 pneumonitis deserves serious consideration.

There is substantial research regarding the role of free radicals in SARS infections (Tse 2004 (5)), in RSV infections (Wang, 2018 (6)), and in viral pneumonias in general (Khomich, 2018 (2)), including changes to redox homeostasis induced by various respiratory viruses. Tian’s (February 2020, (4)) description of microscopic pathology in the lungs of two patients with early COVID-19 pneumonia reveals protein exudates with intra-alveolar fibrin, similar to the hyaline membranes in respiratory distress syndrome of the newborn, together with mixed mononuclear inflammatory cells and Type II pneumocyte hyperplasia, suggesting particular damage to surfactant producing Type II cells, which are known to be sensitive to inspired oxygen toxicity mediated by oxygen centered free radicals.Hence, one can easily imagine a scenario in which the viral infection activates mononuclear cells and also perhaps pulmonary capillary endothelial cells, both of which are known producers of superoxide. Especially in the presence of free (low molecular weight chelate) iron, Fenton chemistry could happen sufficiently to damage and cause early reactive hyperplasia of Type II surfactant producing cells, leading to pulmonary edema with hyaline membranes.

Further local destruction to alveolar epithelial and endothelial cells could accelerate lung flooding and protein accumulation. Hence, there is good reason to propose the involvement of free radicals in COVID-19 pneumonitis and the potential of antioxidant therapy. Under the present circumstances this paper surely deserves expedited review.

In their letter Scigliano and Scigliano emphasize the potential use of methylene blue in low doses as antioxidant therapy. In addition, it is worth mentioning the potential therapeutic roles of other relatively safe drugs, such as deferoxamine to chelate catalytic free iron, vitamin E as a lipid soluble chain-breaking antioxidant, and water-soluble vitamin E analogues (Trolox; see Sagach et al., 2002 (3)). There is also water-soluble glutathione, which can be administered either by inhalation or injection. Interestingly, Achudume (2009 (1)) shows that chloroquine, which is being studied (Solidarity clinical trial) as a treatment for COVID-19 pneumonia, increases glutathione levels several fold in rats.

If the authors are willing, this short letter to the editor could be expanded into a full-length hypothesis paper. To allow for rapid dissemination, the authors might well consider posting this letter to the World Health Organization’s International Clinical Trials Registry Platform (WHO ICTRP). It might encourage front-line clinicians to give antioxidants a try in abbreviated case series.