Abstract
COVID-19 pandemic is posing an unprecedented sanitary threat: antiviral and host-directed medications to treat the disease are urgently needed. A great effort has been paid to find drugs and treatments for hospitalized, severely ill patients. However, medications used for the domiciliary management of early symptoms, notwithstanding their importance, have not been and are not presently regarded with the same attention and seriousness. In analogy with other airways viral infections, COVID-19 patients in the early phase require specific antivirals (still lacking) and non-etiotropic drugs to lower pain, fever, and control inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol (PAC) are widely used as non-etiotropic agents in common airways viral infections and hence are both theoretically repurposable for COVID-19. However, a warning from some research reports and National Authorities raised NSAIDs safety concerns because of the supposed induction of angiotensin-converting enzyme 2 (ACE2) levels (the receptor used by SARS-CoV2 to enter host airways cells), the increased risk of bacterial superinfections and masking of disease symptoms. As a consequence, the use of NSAIDs was, and is still, discouraged while the alternative adoption of paracetamol is still preferred. On the basis of novel data and hypothesis on the possible role of scarce glutathione (GSH) levels in the exacerbation of COVID-19 and of the GSH depleting activity of PAC, this commentary raises the question of whether PAC may be the better choice.
Highlights
COVID-19 pandemic is posing an unprecedented sanitary threat
It is important noting that the major risk factors for severe COVID-19 illness are aging, comorbidities, smoking habit, all characterized by intrinsically low antioxidant capacity and high Reactive oxygen species (ROS)/GSH ratios (Polonikov, 2020)
No answer can be given to the above open questions because PAC efficacy/adverse effects, unlike most of the drugs repositioned for COVID-19 therapy, have not yet been evaluated in controlled clinical trials or analyzed through retrospective analyses. These trials, as well as studies aimed at determining the levels of GSH in the plasma of PAC-treated vs -untreated COVID-19 patients should be encouraged
Summary
COVID-19 pandemic is posing an unprecedented sanitary threat. In the absence of specific vaccines and anti-SARS-CoV-2 drugs, medicines that may reduce the severity of the disease and limit the high number of fatalities are urgently needed. These three independent reports— referring to only fifteen cases—reciprocally strengthen each other in highlighting the relevance of poor GSH levels in COVID-19 clinical progression as well as the importance of maintaining/repleting GSH pools as a countermeasure against SARS-CoV2 virulence To this end, it is important noting that the major risk factors for severe COVID-19 illness are aging, comorbidities, smoking habit, all characterized by intrinsically low antioxidant capacity and high ROS/GSH ratios (Polonikov, 2020) (see Figure 1). These trials, as well as studies aimed at determining the levels of GSH in the plasma of PAC-treated vs -untreated COVID-19 patients should be encouraged
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