key: cord-0780910-s4zt7ttp
authors: Kassi, Eva N.; Papavassiliou, Kostas A.; Papavassiliou, Athanasios G.
title: Defective Anti-oxidant System: An Aggravating Factor for COVID-19 Patients Outcome?
date: 2020-05-22
journal: Arch Med Res
DOI: 10.1016/j.arcmed.2020.05.017
sha: e302973bef67aeddcd7ac7c86b2bc21081c20822
doc_id: 780910
cord_uid: s4zt7ttp

nan

Several comorbidities have been reported as risk factors for unfavorable prognosis in patients with COVID-19. The most common comorbidities that influence the outcome of COVID-19 patients are cardiovascular disease (CVD), diabetes mellitus type 2 (DMT2), hypertension, malignancy and chronic obstructive pulmonary disease (COPD) among others. Smoking has also emerged as a risk factor associated with a worse outcome. It has been shown that oxidative stress, a condition of imbalance between the release of reactive oxygen species (ROS) and the endogenous antioxidant capacity, is causally involved in the same diseases that increase the risk of a severe outcome from COVID-19, including CVD and DMT2 (1) . It is also well-known that smoking can induce cellular oxidative stress while it depletes anti-oxidants through various mechanisms (2) . Emerging evidence on COVID-19 indicates a male preponderance in both vulnerability and mortality. Based on data from China, the much higher smoking rate in men might explain the observation that COVID-19 poses a greater risk to men than women (3).

In terms of oxidative stress, dysregulation of glucose 6-phosphate dehydrogenase (G6PD) leads to increased oxidative stress and damage as this enzyme is responsible for generating NADPH, a key cellular reducing agent. Studies have shown that G6PD deficiency leads to increased sensitivity to even mild oxidative stress, while altered activity and levels of G6PD have been recognized as a marker of inflammation. Apart from the elevated oxidative stress, G6PD-deficient cells are at a Arch Med Res E20_727 2 greater risk for protein glycosylation (4), a process that plays an essential role in viral pathogenesisincluding COVID-19-by promoting folding, trafficking and viral spread, whilst host cell and viral glycans are known to act as attachment factors (5,6) . Notably, a previous study has shown that nicotine significantly inhibited G6PD activity in the rat lung, while the potent anti-oxidant vitamin E was able to restore this effect (7).

Could an intrinsically defective anti-oxidant system, such as G6PD deficiency or other causes, predispose to COVID-19 infection and poorer prognosis? To this end, Wu YH, et al. (8) demonstrated that human lung epithelial A549 cells with lower G6PD activity (via RNA interference) had a 12 fold higher viral production when infected with human coronavirus 229E, which shares a sequence similarity with COVID-19 and clinically resembles it, compared to control cells (8, 9) . This work received no funding from any source.

The authors declare that there are no conflicts of interest.

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