Leal et al. Acetaminophen for COVID-19 Prophylaxis
Paracetamol Is Associated with a Lower Risk of COVID-19 Infection and Decreased ACE2 Protein Expression: A Retrospective Analysis
et al., COVID,
Paracetamol Is Associated with a Lower Risk of COVID-19 Infection and Decreased ACE2 Protein Expression: A..
UK Biobank retrospective showing lower cases with acetaminophen use.
risk of case, , RR approximated with OR.
7.0% lower, OR 0.93, p = 0.004
Effect extraction follows
pre-specified rules prioritizing more serious outcomes. Submit updates
Leal et al., 16 Aug 2021, retrospective, United Kingdom, peer-reviewed, 5 authors, study period 16 March, 2020 - 1 February, 2021.
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Paracetamol Is Associated with a Lower Risk of COVID-19
Infection and Decreased ACE2 Protein Expression:
A Retrospective Analysis
Nuno Santos Leal † , Yizhou Yu † , Yuwen Chen
, Giorgio Fedele and Luís Miguel Martins *
MRC Toxicology Unit, Gleeson Building, Tennis Court Road, University of Cambridge, Cambridge CB2 1QR, UK;
email@example.com (N.S.L.); firstname.lastname@example.org (Y.Y.); email@example.com (Y.C.);
* Correspondence: firstname.lastname@example.org
† These authors contributed equally to this work.
Citation: Leal, N.S.; Yu, Y.; Chen, Y.;
Fedele, G.; Martins, L.M. Paracetamol
Is Associated with a Lower Risk of
COVID-19 Infection and Decreased
ACE2 Protein Expression: A
Abstract: Ibuprofen is a common over-the-counter drug taken for pain relief. However, recent studies
have raised concerns about its potential toxic effect with coronavirus disease 2019 (COVID-19), which
is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has been proposed
that ibuprofen may increase levels of angiotensin-converting enzyme 2 (ACE2), the human receptor
for SARS-CoV-2 infection. Therefore, paracetamol is suggested as an alternative to ibuprofen for
treating COVID-19 symptoms. Nevertheless, the relationship between intake of paracetamol or
ibuprofen and either susceptibility to infection by SARS-CoV-2 or modulation of cellular ACE2 levels
remains unclear. In this study, we combined data from human medical records and cells in culture
to explore the role of the intake of these drugs in COVID-19. Although ibuprofen did not influence
COVID-19 infectivity or ACE2 levels, paracetamol intake was associated with a lower occurrence of
COVID-19 in our cohort. We also found that paracetamol led to decreased ACE2 protein levels in
cultured cells. Our work identifies a putative protective effect of paracetamol against SARS-CoV2 infection. Future work should explore the molecular mechanisms underlying the relationship
between paracetamol and COVID-19.
Retrospective Analysis. COVID 2021,
1, 218–229. https://doi.org/10.3390/
Keywords: paracetamol; acetaminophen; ibuprofen; ACE2; COVID-19; SARS-CoV-2; UK Biobank
Received: 7 July 2021
Accepted: 10 August 2021
Published: 16 August 2021
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