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Ibuprofen use and clinical outcomes in COVID-19 patients

Rinott et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.06.003
Sep 2020  
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Mortality -473% Improvement Relative Risk Oxygen therapy -534% Acetaminophen  Rinott et al.  EARLY TREATMENT Is early treatment with acetaminophen beneficial for COVID-19? Retrospective 134 patients in Israel (March - April 2020) Study compares with ibuprofen, results vs. placebo may differ Higher mortality (p=0.3) and higher oxygen therapy (p=0.055), not sig. c19early.org Rinott et al., Clinical Microbiology a.., Sep 2020 Favorsacetaminophen Favorsibuprofen 0 0.5 1 1.5 2+
2nd treatment shown to increase risk in November 2020, now with p = 0.00000029 from 27 studies, but still recommended in 64 countries.
5,100+ studies for 109 treatments. c19early.org
Retrospective 89 febrile COVID-19 patients in Israel taking paracetamol and 49 taking ibuprofen, showing higher need for respiratory support with paracetamol. Although not statistically significant, patients in the paracetamol group were older.
Paracetamol is also known as acetaminophen, Tylenol, Panadol, Calpol, Tempra, Calprofen, Doliprane, Efferalgan, Grippostad C, Dolo, Acamol, Fevadol, Crocin, and Perfalgan.
This study is excluded in the after exclusion results of meta analysis: unadjusted differences between groups.
Study covers acetaminophen and ibuprofen.
risk of death, 472.9% higher, RR 5.73, p = 0.30, treatment 3 of 85 (3.5%), control 0 of 49 (0.0%), continuity correction due to zero event (with reciprocal of the contrasting arm).
risk of oxygen therapy, 534.1% higher, RR 6.34, p = 0.06, treatment 11 of 85 (12.9%), control 1 of 49 (2.0%).
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Rinott et al., 30 Sep 2020, retrospective, Israel, peer-reviewed, median age 45.0, 5 authors, study period 15 March, 2020 - 15 April, 2020, this trial compares with another treatment - results may be better when compared to placebo. Contact: youngsteri@shamir.gov.il.
This PaperAcetaminophenAll
Ibuprofen use and clinical outcomes in COVID-19 patients
E Rinott, E Kozer, Y Shapira, A Bar-Haim, I Youngster
Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.06.003
Objective: It was recently suggested that ibuprofen might increase the risk for severe and fatal coronavirus disease 2019 and should therefore be avoided in this patient population. We aimed to evaluate whether ibuprofen use in individuals with COVID-19 was associated with more severe disease, compared with individuals using paracetamol or no antipyretics. Methods: In a retrospective cohort study of patients with COVID-19 from Shamir Medical Centre, Israel, we monitored any use of ibuprofen from a week before diagnosis of COVID-19 throughout the disease. Primary outcomes were mortality and the need for respiratory support, including oxygen administration and mechanical ventilation. Results: The study included 403 confirmed cases of COVID-19, with a median age of 45 years. Of the entire cohort, 44 patients (11%) needed respiratory support and 12 (3%) died. One hundred and seventynine (44%) patients had fever, with 32% using paracetamol and 22% using ibuprofen, for symptom-relief. In the ibuprofen group, 3 (3.4%) patients died, whereas in the non-ibuprofen group, 9 (2.8%) patients died (p 0.95). Nine (10.3%) patients from the ibuprofen group needed respiratory support, compared with 35 (11%) from the non-ibuprofen group (p 1). When compared with exclusive paracetamol users, no differences were observed in mortality rates or the need for respiratory support among patients using ibuprofen. Conclusions: In this cohort of COVID-19 patients, ibuprofen use was not associated with worse clinical outcomes, compared with paracetamol or no antipyretic.
Authors' contributions EK and IY conceptualized the study, IY, YS and ABH collected the data, IY and ER conducted the data analyses, ER wrote the first draft of the manuscript, IY and EK revised the manuscript, all authors approved the final version.
References
Day, Covid-19: ibuprofen should not be used for managing symptoms, say doctors and scientists, BMJ, doi:10.1136/bmj.m1086
Fang, Karakiulakis, Roth, Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?, Lancet Respir Med, doi:10.1016/S2213-2600(20)30116-8
Little, Non-steroidal anti-inflammatory drugs and covid-19, BMJ, doi:10.1136/bmj.m1185
Shang, Ye, Shi, Wan, Luo et al., Structural basis of receptor recognition by SARS-CoV-2, Nature, doi:10.1038/s41586-020-2179-y
Wan, Shang, Graham, Baric, Li, Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus, J Virol, doi:10.1128/JVI.00127-20
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