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

Sergio Pandolfi; Vincenzo Simonetti; Giovanni Ricevuti; Salvatore Chirumbolo

Abstract: DOI: 10.1002/jmv.27158 LETTER TO THE EDITOR Paracetamol in the home treatment of early COVID‐19 symptoms: A possible foe rather than a friend for elderly patients? To the Editor, development and prevent crowding in hospitalization.9 In Italy, a civil On October 2020, Sestili and Fimognari reported that acet- outcry from some physicians, practitioners, and family doctors, is aminophen (N‐aetyl‐para‐aminophenol), commonly known as para- expanding the debate, even in politics, about how best to treat cetamol, induces or worsens glutathione (GSH) consumption in COVID‐19 at home. The civil legacy of these professionals was ar- elderly patients affected by early or mild coronavirus disease 2019 ranged to prevent the huge concern of elderly people treated with (COVID‐19), thus greatly enhancing the risk of COVID‐19 exacer- simple paracetamol, counseled to wait under paracetamol therapy bation in these patients.1 By early COVID‐19, we mean the typical or for reduced symptoms, yet then often undergoing rapid exacerbation commonly acknowledged symptomatology associated with the early and in many cases even death while being hospitalized. phases of COVID‐19, occurring usually when a patient stays at home, Suter and colleagues recently created an algorithm of the best that is, fever and dyspnea, besides weakness and pain,2 despite the and simplest home therapy for mild symptoms in early COVID‐19, to COVID‐19 symptoms being particularly variable and complex andl prevent hospitalization.10 In their retrospective observational study, only 50% of patients infected with severe acute respiratory syn- the control cohort (45 patients on 77; 58.44%) received paracetamol drome coronavirus 2 (SARS‐CoV‐2) developing a forthright symp- as home therapy, whereas in the cohort of patients following a re- tomatology.2 In any case, fever is one of the most common symptoms commended protocol only 6 of 86 (6.98%) used paracetamol as the during the early stages of COVID‐19, where people use paracetamol leading therapy. The rate of hospitalization was 1.2% for patients quite exclusively. undergoing the recommended protocol and 13.1% (p = .007) for pa- Reduction of GSH is a condition particularly severe for the in- tients using predominantly paracetamol, that is, 44 cumulative days dividual's antioxidant and anti‐inflammatory response and it is com- of hospitalization (recommended) versus 481 (controls).10 This evi- prehensible that its depletion is crucial for COVID‐19 worsening. dence shows that using paracetamol at home to treat mild COVID‐ Moreover, Zhang and colleagues, recently showed that SARS‐CoV‐2 19 symptoms, particularly in older adults with comorbidity, greatly hijacks folate and one‐carbon metabolism in the infected cell, by re- enhanced the risk of hospitalization for dyspnea from interstitial modeling their biochemical turnover at the posttranscriptional level pneumonia, so increasing the huge concern of crowding the intensive and going ahead with the de novo synthesis of purines.3 Figure 1 care units. Possible causes of this exacerbation might be the acti- shows the fundamental role of GSH in one‐carbon metabolism. vation of prothrombotic mechanisms, currently reported as the SARS‐CoV‐2 uses the cytosolic serine hydroxymethyltransferase‐1 to leading pathogenetic cause of COVID‐19, alongside endothelial activate the one‐carbon metabolism for de novo synthesis of purines2 dysfunction.11 Actually, GSH..

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