Decreased Plasma HO Levels Are Associated with the Pathogenesis Leading to COVID-19 Worsening and Mortality

Oxidative Stress (OS) is involved in the pathogenesis of COVID-19 and in the mechanisms by which SARS-CoV-2 causes injuries to tissues, leading to cytopathic hypoxia and ultimately multiple organ failure. The measurement of blood glutathione (GSH), HO, and catalase activity may help clarify the pathophysiology pathways of this disease. We developed and standardized a sensitive and specific chemiluminescence technique for HO and GSH measurement in plasma and red blood cells of COVID-19 patients admitted to the intensive care unit (ICU). Contrary to what was expected, the plasma concentration of HO was substantially reduced (10-fold) in COVID-19 patients compared to the healthy control group. From the cohort of patients discharged from the hospital and those who were deceased, the former showed a 3.6-fold and the later 16-fold HO reduction compared to the healthy control. There was a 4.4 reduction of HO concentration in the deceased group compared to the discharged group. Interestingly, there was no variation in GSH levels between groups, and reduced catalase activity was found in discharged and deceased patients compared to control. These data represent strong evidence that HO is converted into highly reactive oxygen species (ROS), leading to the worst prognosis and death outcome in COVID-19 patients admitted to ICU. Considering the difference in the levels of HO between the control group and the deceased patients, it is proposed the quantification of plasma HO as a marker of disease progression and the induction of the synthesis of antioxidant enzymes as a strategy to reduce the production of oxidative stress during severe COVID-19.HighlightsHO plasma levels is dramatically reduced in patients who deceased compared to those discharged and to the control group.Plasmatic quantification of HO can be possibly used as a predictor of disease progression.Catalase activity is reduced in COVID-19.GSH levels remain unchanged in COVID-19 compared to the control group.