Impact of Treatment with Antioxidants as an Adjuvant to Standard Therapy in Patients with Septic Shock: Analysis of the Correlation between Cytokine Storm and Oxidative Stress and Therapeutic Effects.

Cellular homeostasis is lost or becomes dysfunctional during septic shock due to the activation of the inflammatory response and the deregulation of oxidative stress. Antioxidant therapy administered alongside standard treatment could restore this lost homeostasis. We included 131 patients with septic shock who were treated with standard treatment and vitamin C (Vit C), vitamin E (Vit E), N-acetylcysteine (NAC), or melatonin (MT), in a randomized trial. Organ damage quantified by Sequential Organ Failure Assessment (SOFA) score, and we determined levels of Interleukins (IL) IL1ß, Tumor necrosis factor alpha (TNFα), IL-6, monocyte chemoattractant protein-1 (MCP-1), Transforming growth factor B (TGFß), IL-4, IL-10, IL-12, and Interferon-γ (IFNγ). The SOFA score decreased in patients treated with Vit C, NAC, and MT. Patients treated with MT had statistically significantly reduced of IL-6, IL-8, MCP-1, and IL-10 levels. Lipid peroxidation, Nitrates and nitrites (NO3- and NO2-), glutathione reductase, and superoxide dismutase decreased after treatment with Vit C, Vit E, NAC, and MT. The levels of thiols recovered with the use of Vit E, and all patients treated with antioxidants maintained their selenium levels, in contrast with controls (p = 0.04). The findings regarding oxidative stress markers and cytokines after treatment with antioxidants allow us to consider to future the combined use of antioxidants in a randomized clinical trial with a larger sample to demonstrate the reproducibility of these beneficial effects.

Alteration in the Lipid Profile and the Desaturases Activity in Patients With Severe Pneumonia by SARS-CoV-2.

The kidnapping of the lipid metabolism of the host's cells by severe acute respiratory syndrome (SARS-CoV-2) allows the virus to transform the cells into optimal machines for its assembly and replication. Here we evaluated changes in the fatty acid (FA) profile and the participation of the activity of the desaturases, in plasma of patients with severe pneumonia by SARS-CoV-2. We found that SARS-CoV-2 alters the FA metabolism in the cells of the host. Changes are characterized by variations in the desaturases that lead to a decrease in total fatty acid (TFA), phospholipids (PL) and non-esterified fatty acids (NEFAs). These alterations include a decrease in palmitic and stearic acids (p ≤ 0.009) which could be used for the formation of the viral membranes and for the reparation of the host's own membrane. There is also an increase in oleic acid (OA; p = 0.001) which could modulate the inflammatory process, the cytokine release, apoptosis, necrosis, oxidative stress (OS). An increase in linoleic acid (LA) in TFA (p = 0.03) and a decreased in PL (p = 0.001) was also present. They result from damage of the internal mitochondrial membrane. The arachidonic acid (AA) percentage was elevated (p = 0.02) in the TFA and this can be participated in the inflammatory process. EPA was decreased (p = 0.001) and this may decrease of pro-resolving mediators with increase in the inflammatory process. The total of NEFAs (p = 0.03), PL (p = 0.001), cholesterol, HDL and LDL were decreased, and triglycerides were increased in plasma of the COVID-19 patients. Therefore, SARS-CoV-2 alters the FA metabolism, the changes are characterized by alterations in the desaturases that lead to variations in the TFA, PL, and NEFAs profiles. These changes may favor the replication of the virus but, at the same time, they are part of the defense system provided by the host cell metabolism in its eagerness to repair damage caused by the virus to cell membranes.

Antioxidants and pentoxifylline as coadjuvant measures to standard therapy to improve prognosis of patients with pneumonia by COVID-19.

The type 2 coronavirus causes severe acute respiratory syndrome (SARS-CoV-2) and produces pneumonia with pulmonary alveolar collapse. In some cases it also causes sepsis and septic shock. There is no specific treatment for coronavirus disease 2019 (COVID-19). Vitamin C (Vit C), Vitamin E (Vit E), N-acetylcysteine (NAC) and Melatonin (MT) increase the intracellular content of GSH, kidnap free radicals and protect DNA, proteins in the cytosol and lipids in cell membranes. Pentoxifylline (Px) has anti-inflammatory activities. Here we evaluate the effect of Vit C, Vit E, NAC, and MT plus Px in COVID-19 patients with moderate and severe pneumonia. 110 patients of either sex were included. They were divided into five groups with 22 patients each. Group 1 received Vit C + Px, group 2 Vit E + Px, group 3 NAC + Px, group 4 MT + Px, and group 5 only Px. Oxidative stress (OS) markers such as lipid peroxidation (LPO) levels, total antioxidant capacity (TAC) and nitrites (NO2 -) were evaluated in plasma. The antioxidant therapy improved the survival scores including the Sequential Organ Failure Assessment (SOFA), the Acute Physiology and chronic Health Evaluation II (Apache II), the Simplified Acute Physiology Score II (SAPS II), the Critical Illness Risk Score, Launched during COVID-19 crisis (COVIDGRAM) and the Glasgow Coma Scale (GCS). We found that LPO (p≤0.04) and inflammation markers such as interleukin-6 (IL-6, p≤ 0.01), C reactive protein (CRP, p ≤ 0.01) and procalcitonin (PCT, p ≤ 0.05) were elevated. TAC (p ≤ 0.03) and NO2 - (p ≤ 0.04) found themselves diminished in diminished in COVID-19 patients upon admission to the hospital. The different antioxidants reversed this alteration at the end of the treatment. The treatment with antioxidant supplements such as Vit C, E, NAC, and MT plus Px could decelerate the aggressive and lethal development of COVID-19. Antioxidant therapy can be effective in this pandemia since it improves the survival scores including SOFA, Apache II, SAPS II, COVIDGRAM, GCS by lowering the LPO, IL-6, CRP, PCT and increasing systemic TAC and NO2 -.