To clarify the safety profile of paracetamol for home-care patients with COVID-19: a real-world cohort study, with nested case–control analysis, in primary care
Lapi et al.
, To clarify the safety profile of paracetamol for home-care patients with COVID-19: a real-world cohort study,..
, Internal and Emergency Medicine, doi:10.1007/s11739-022-03054-1
Retrospective paracetamol use with a primary care database in Italy, showing no significant difference in hospitalization/death for use 0-3 and 4-7 days from diagnosis, and significantly higher risk for use >7 days from diagnosis. Confounding by indication
may have a greater effect on late usage.
risk of death/hospitalization, 15.0% higher, OR 1.15, p = 0.22, adjusted per study, early use, RR approximated with OR.
risk of death/hospitalization, 29.0% higher, OR 1.29, p = 0.52, adjusted per study, mid-term use, RR approximated with OR.
risk of death/hospitalization, 75.0% higher, OR 1.75, p < 0.001, adjusted per study, late use, RR approximated with OR, late treatment result, excluded in exclusion analyses:
substantial unadjusted confounding by indication likely.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Lapi et al., 30 Jul 2022, retrospective, Italy, peer-reviewed, 8 authors.
Abstract: Internal and Emergency Medicine
To clarify the safety profile of paracetamol for home‑care patients
with COVID‑19: a real‑world cohort study, with nested case–control
analysis, in primary care
Francesco Lapi1 · Ettore Marconi1 · Ignazio Grattagliano2 · Alessandro Rossi2 · Diego Fornasari3 · Alberto Magni2 ·
Pierangelo Lora Aprile2 · Claudio Cricelli2
Received: 3 June 2022 / Accepted: 11 July 2022
© The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI) 2022
Background and objective This study aimed to compare the prescribing patterns of paracetamol in COVID-19 with
those for similar respiratory conditions and investigated the association between paracetamol use and COVID-19-related
Methods Using a primary care data source, we conducted a cohort study to calculate the incidence rate of paracetamol use
in COVID-19 and for similar respiratory conditions in 2020 and 2019 (i.e. pre-pandemic phase), respectively. In the study
cohort, we nested a case–control analyses to investigate the association between paracetamol use and COVID-19-related
Results Overall, 1554 (33.4 per 1000) and 2566 patients (78.3 per 1000) were newly prescribed with paracetamol to treat
COVID-19 or other respiratory conditions, respectively. Those aged 35–44 showed the highest prevalence rate (44.7 or 99.0
per 1000), while the oldest category reported the lowest value (17.8 or 39.8 per 1000). There was no association for early
(OR = 1.15; 95% CI: 0.92–1.43) or mid-term (OR = 1.29; 95% CI: 0.61–2.73) users of paracetamol vs. non-users. Instead,
the late users of paracetamol showed a statistically significant increased risk of hospitalization/death (OR = 1.75; 95% CI:
Conclusions Our findings provide reassuring evidence on the use and safety profile of paracetamol to treat early symptoms
of COVID-19 as in other respiratory infections.
Keywords Paracetamol · Prescribing pattern · Safety profile · Home-care · COVID-19
The SARS-CoV-2 pandemic is still burdening the healthcare
system of several Western countries. Patients with mild-tomoderate COVID-19, for whom home-care treatment is
requested, generally present flu-like symptoms such as fever,
* Francesco Lapi
Health Search, Italian College of General Practitioners
and Primary Care, Via del Sansovino 179, 50142 Florence,
Italian College of General Practitioners and Primary Care,
Department Medical Biotechnology and Translational
Medicine, Università Degli Studi Di Milano, Milan, Italy
pharyngitis, cough, rhinitis, headache, and myalgia [1, 2].
Among the available medications, paracetamol is recommended by the World Health Organization (WHO) , the
National Institute for Health and Care Excellence (NICE)
 as well as other regulatory agencies [5, 6] and scientific
societies  among the mainstays to manage coronavirusrelated early symptoms.
Nevertheless, there was conflicting and misleading communication [8, 9] on the pharmacotherapy for the home
care of COVID-19. Some clinicians and researchers raised
concerns on the safety profile of paracetamol when used
in SARS-CoV-2 infections [10, 11]. They underlined that
the potential depletion of glutathione (GSH) induced by
paracetamol may even favour the pulmonary endothelium
damages by SARS-CoV-2 [10, 12]. The authors therefore
recommended to avoid the..
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