Paracetamol-Induced Glutathione Consumption: Is There a Link With Severe COVID-19 Illness?

Abstract

COVID-19 pandemic is posing an unprecedented sanitary threat: antiviral and hostdirected 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.

Inflammatory Response Leads to Neuronal Death in Human Post-Mortem Cerebral Cortex in Patients with COVID-19

“… 36 , 37 In fact, both a cytokine storm and ARDS have been known to be involved in severe stages of COVID-19. 1 , 38 Similarly, the use of antioxidant agents can decrease the cytokine storm, which is caused by viral infection. 39 In fact, antioxidative-related treatments have been shown to repair damages caused by COVID-19 in infected patients.…”

“…In December of 2019, a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, causing the coronavirus disease of 2019 (COVID-19). 1 Although COVID-19 is primarily a respiratory virus, it may spread to nonrespiratory sites like the brain with associated neurological manifestations including smell and taste disturbances, headaches, vision impairment, and stroke. 2 The presence of COVID-19 in the brain has been shown by the detection of COVID-19 RNA in the cerebrospinal fluid (CSF) in patients with COVID-19.…”

A simple, home-therapy algorithm to prevent hospitalisation for COVID-19 patients: A retrospective observational matched-cohort study

“…Paracetamol is suggested as a safe and recommendable alternative for the early management of pain and fever in COVID-19 patients. However, it should be taken into account that besides being a negligible anti-inflammatory drug, paracetamol reduces plasma and tissue gluthatione levels when given at relatively low doses, which might exacerbate COVID-19, as recently hypothesised [29]. Although more selective inhibition of COX-2 is desirable to limit the gastrointestinal toxicity seen with less selective COX-2 inhibitors, physicians may be aware of the finding that the use of NSAIDs has been associated with higher rates of cardiovascular events [30].…”

A Simple, Home-Therapy Algorithm to Prevent Hospitalization for COVID-19 Patients:A Retrospective Observational Matched-Cohort Study

“…However, it should be taken into account that besides being a negligible anti-inflammatory drug, paracetamol reduces plasma and tissue gluthatione levels when given at relatively low doses, which might exacerbate COVID-19 illness, as recently hypothesised. 28 Although more selective inhibition of COX-2 is desirable to limit the gastrointestinal toxicity seen with less selective COX-2 inhibitors, physicians may be aware of the finding that the use of NSAIDs has been associated with higher rates of cardiovascular events. 29 Moreover, nimesulide can associate with a risk of hepatotoxicity, very low when the drug is administered at recommended time of exposure and daily dosage.…”