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0 0.5 1 1.5 2+ Case 3% Improvement Relative Risk Ibuprofen for COVID-19  Leal et al.  Prophylaxis Does ibuprofen reduce COVID-19 infections? Retrospective study in the United Kingdom (March 2020 - February 2021) No significant difference in cases c19early.org Leal et al., COVID, August 2021 Favors ibuprofen Favors control

Paracetamol Is Associated with a Lower Risk of COVID-19 Infection and Decreased ACE2 Protein Expression: A Retrospective Analysis

Leal et al., COVID, doi:10.3390/covid1010018
Aug 2021  
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UK Biobank retrospective showing no significant difference in cases with ibuprofen use.
Study covers ibuprofen and acetaminophen.
risk of case, 3.0% lower, OR 0.97, p = 0.29, RR approximated with OR.
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. Contact: martins.lmiguel@gmail.com (corresponding author), njs76@mrc-tox.cam.ac.uk, yzy21@cam.ac.uk, yc487@cam.ac.uk, gf334@mrc-tox.cam.ac.uk.
This PaperIbuprofenAll
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, Luís Miguel Martins
COVID, doi:10.3390/covid1010018
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-CoV-2 infection. Future work should explore the molecular mechanisms underlying the relationship between paracetamol and COVID-19.
Conflicts of Interest: The authors declare no competing interests nor conflict of interest. Abbreviations
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