Is Antioxidant Therapy a Useful Complementary Measure for Covid-19 Treatment? An Algorithm for Its Application

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes the corona virus disease-19 which is accompanied by severe pneumonia, pulmonary alveolar collapses and which stops oxygen exchange. Viral transmissibility and pathogenesis depend on recognition by a receptor in the host, protease cleavage of the host membrane and fusion. SARS-CoV-2 binds to the angiotensin converting enzyme 2 receptor. Here, we discuss the general characteristics of the virus, its mechanism of action and the way in which the mechanism correlates with the comorbidities that increase the death rate. We also discuss the currently proposed therapeutic measures and propose the use of antioxidant drugs to help patients infected with the SARS-CoV-2. Oxidizing agents come from phagocytic leukocytes such as neutrophils, monocytes, macrophages and eosinophils that invade tissue. Free radicals promote cytotoxicity thus injuring cells. They also trigger the mechanism of inflammation by mediating the activation of NFkB and inducing the transcription of cytokine production genes. Release of cytokines enhances the inflammatory response. Oxidative stress is elevated during critical illnesses and contributes to organ failure. In corona virus disease-19 there is an intense inflammatory response known as a cytokine storm that could be mediated by oxidative stress. Although antioxidant therapy has not been tested in corona virus disease-19, the consequences of antioxidant therapy in sepsis, acute respiratory distress syndrome and acute lung injury are known. It improves oxygenation rates, glutathione levels and strengthens the immune response. It reduces mechanical ventilation time, the length of stay in the intensive care unit, multiple organ dysfunctions and the length of stay in the hospital and mortality rates in acute lung injury/acute respiratory distress syndrome and could thus help patients with corona virus disease-19.

Open Clinical Trial of the Use of Antioxidants and Pentoxifylline as Coadjuvant Measures to Standard Therapy to Improve Prognosis of Patients with Pneumonia and Septic Shock due to Covid-19

“…Here we evaluated the clinical anti-inflammatory status and the OS deregulation, and our results are promising. Therefore, our results and others shown in the literature suggest that NAC could contribute to the deceleration of the aggressive and lethal development of COVID-19 with the use of moderate doses [1,70].…”

“…Meropenem. In all patients, the use of hydroxychloroquine or antivirals was not considered, since they received individualized management according to the algorithm proposed [1].…”

The kidnapping of mitochondrial function associated to the SARS-CoV-2 infection

“…Regarding the damage to proteins, it might be caused by the virus S-nitrosylation resulting from an excess in the production of ONOO − . This molecule is a secondary metabolite of the oxidation of nitric oxide, and its presence is associated with overproduction by the inducible nitric oxide synthase in a state of the chronic in ammation such as is present in COVID-19 (Pérez-Torres et al, 2020;Soto et al, 2020). ONOO − may inactivate different mitochondrial proteins, including ETC components and citric acid cycle dehydrogenases and this may contribute to inactivation decreasing the ATP levels (Pérez-Torres et al, 2020).…”

“…The cytokine storm can block mitochondrial oxidative phosphorylation and it is associated with a low production of ATP (Paumard et al, 2002). Although this cytokine storm is the host's response to eliminate the virus, it is counterproductive for the host and can result in multi-organ failure (Soto et al, 2020). Some of the structural and non-structural proteins that are encoded by the RNA genome of SARS-CoV-2 may interact with mitochondrial components.…”

G6PD deficiency, redox homeostasis, and viral infections: implications for SARS-CoV-2 (COVID-19)

“…The redox milieu can modulate viral replication, including HIV, influenza, and respiratory syncytial viruses [44][45][46]. Antioxidant therapy may prove effective in the prevention of viral infection through redox control [47][48][49][50], while insufficient antioxidant capacity is conducive to viral production and virulence [51,52]. For instance, glutathione can inactivate dengue and chikungunya viruses in the blood [53,54].…”