Paracetamol in the home treatment of early COVID-19 symptoms: A possible foe rather than a friend for elderly patients?

On October 2020, Sestili and Fimognari reported that acetaminophen (N-aetyl-para-aminophenol), commonly known as paracetamol, induces or worsens glutathione (GSH) consumption in elderly patients affected by early or mild coronavirus disease 2019 (COVID-19), thus greatly enhancing the risk of COVID-19 exacerbation in these patients.1 By early COVID-19, we mean the typical or commonly acknowledged symptomatology associated with the early phases of COVID-19, occurring usually when a patient stays at home, that is, fever and dyspnea, besides weakness and pain,2 despite the COVID-19 symptoms being particularly variable and complex andl only 50% of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) developing a forthright symptomatology.2 In any case, fever is one of the most common symptoms during the early stages of COVID-19, where people use paracetamol quite exclusively.

Reduction of GSH is a condition particularly severe for the individual’s antioxidant and anti-inflammatory response and it is comprehensible that its depletion is crucial for COVID-19 worsening. Moreover, Zhang and colleagues, recently showed that SARS-CoV-2 hijacks folate and one-carbon metabolism in the infected cell, by remodeling their biochemical turnover at the posttranscriptional level and going ahead with the de novo synthesis of purines.3 Figure 1 shows the fundamental role of GSH in one-carbon metabolism. SARS-CoV-2 uses the cytosolic serine hydroxymethyltransferase-1 to activate the one-carbon metabolism for de novo synthesis of purines2 and subtracting serine, and its precursor folic acid hijacks serine from producing cystathionine and therefore GSH (Figure 1). Reduction in plasma and intracellular GSH levels is typical in elderly patients,4 particularly if affected by metabolic syndrome,5 therefore if Sestili and Fimognari are right, elderly patients with prodromic COVID-19 symptomatology should not be treated with N-acetyl-para-aminophenol…

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