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Non-steroidal anti-inflammatory agent use may not be associated with mortality of coronavirus disease 19

Park et al., Scientific Reports, doi:10.1038/s41598-021-84539-5
Mar 2021  
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Mortality 25% Improvement Relative Risk Ventilation 38% Acetaminophen for COVID-19  Park et al.  Prophylaxis Is prophylaxis with acetaminophen beneficial for COVID-19? PSM retrospective 794 patients in South Korea Study compares with NSAIDs, results vs. placebo may differ Lower mortality (p=0.46) and ventilation (p=0.42), not sig. c19early.org Park et al., Scientific Reports, March 2021 Favorsacetaminophen FavorsNSAIDs 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.
5,000+ studies for 109 treatments. c19early.org
Retrospective 2,365 patients prescribed acetaminophen and 398 prescribed NSAIDs in South Korea, showing no significant differences.
Acetaminophen is also known as paracetamol, Tylenol, Panadol, Calpol, Tempra, Calprofen, Doliprane, Efferalgan, Grippostad C, Dolo, Acamol, Fevadol, Crocin, and Perfalgan.
risk of death, 24.8% lower, HR 0.75, p = 0.46, treatment 12 of 397 (3.0%), control 16 of 397 (4.0%), NNT 99, inverted to make HR<1 favor treatment, propensity score matching.
risk of mechanical ventilation, 37.5% lower, HR 0.62, p = 0.42, treatment 5 of 397 (1.3%), control 8 of 397 (2.0%), NNT 132, inverted to make HR<1 favor treatment, propensity score matching.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Park et al., 3 Mar 2021, retrospective, South Korea, peer-reviewed, 5 authors, this trial compares with another treatment - results may be better when compared to placebo. Contact: shuaaa.lee@samsung.com, kmhi.yang@samsung.com.
This PaperAcetaminophenAll
Non-steroidal anti-inflammatory agent use may not be associated with mortality of coronavirus disease 19
Jungchan Park, Seung-Hwa Lee, Seng Chan You, Jinseob Kim, Kwangmo Yang
Scientific Reports, doi:10.1038/s41598-021-84539-5
Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used in patients with respiratory infection, but their safety in coronavirus disease 19 (Covid-19) patients has not been fully investigated. We evaluated an association between NSAID use and outcomes of Covid-19. This study was a retrospective observational cohort study based on insurance benefit claims sent to the Health Insurance Review and Assessment Service of Korea by May 15, 2020. These claims comprised all Covid-19-tested cases and history of medical service use for the past 3 years in these patients. The primary outcome was all-cause mortality, and the secondary outcome was need for ventilator care. Among 7590 patients diagnosed with Covid-19, two distinct cohorts were generated based on NSAID or acetaminophen prescription within 2 weeks before Covid-19 diagnosis. A total of 398 patients was prescribed NSAIDs, and 2365 patients were prescribed acetaminophen. After propensity score matching, 397 pairs of data set were generated, and all-cause mortality of the NSAIDs group showed no significant difference compared with the acetaminophen group (4.0% vs. 3.0%; hazard ratio [HR], 1.33; 95% confidence interval [CI], 0.63-2.88; P = 0.46). The rate of ventilator care also did not show significantly different results between the two groups (2.0% vs. 1.3%; HR, 1.60; 95% CI 0.53-5.30; P = 0.42). Use of NSAIDs was not associated with mortality or ventilator care in Covid-19 patients. NSAIDs may be safely used to relieve symptoms in patients with suspicion of Covid-19. In December 2019, a major outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) in Wuhan City, China, was first reported. It was later characterized as coronavirus disease 19 (Covid-19) and has become a global threatening disease with more than 6,000,000 confirmed cases worldwide as of June 2020 1 . By then, more than 11,629 cases of Covid-19 had been diagnosed, and 273 deaths had been reported throughout Korea. Based on this, the government of Korea decided to share the world's first de-identified Covid-19 nationwide patient data collected from the Korean National Health Insurance System for the purpose of investigation. The primary site of infection in Covid-19 is the respiratory system. However, epidemiologic reports indicated that mortality of Covid-19 was much higher in patients with cardiovascular disease 2 , and the most serious complications of Covid-19 are those involving cardiovascular and respiratory systems, as well as sepsis 3, 4 . Non-steroidal anti-inflammatory drugs (NSAIDs) have long been widely used for symptomatic relief of infected patients by controlling pain, fever, and inflammation, although safety concerns remain regarding harmful effects on the cardiovascular system 5 . Moreover, NSAID treatment was associated with pulmonary complication in patients with pneumonia 6 . The association between NSAID use and adverse outcome of Covid-19 has been previously evaluated, but limited..
Author contributions Conceptualization: S.-H.L. Data curation: S.C.Y. and J.K. Formal analysis: J.K. Methodology: J.P., K.Y. Software: J.K. Validation: J.P., K.Y., S.C.Y., and S.-H.L. Investigation: J.P., K.Y., S.-H.L. Writing-original draft: J.P. and S.-H.L. Writing-review and editing: S.C.Y., J.K. and K.Y. Competing interests The authors declare no competing interests.
References
Basille, Nonsteroidal antiinflammatory drug use and clinical outcomes of community-acquired pneumonia, Am. J. Respir. Crit. Care Med, doi:10.1164/rccm.201802-0229LE
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Guan, Clinical characteristics of coronavirus disease 2019 in China, N. Engl. J. Med, doi:10.1056/NEJMoa2002032
Huang, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet, doi:10.1016/S0140-6736(20)30183-5
Little, Non-steroidal anti-inflammatory drugs and covid-19, BMJ, doi:10.1136/bmj.m1185
Overhage, Ryan, Reich, Hartzema, Stang, Validation of a common data model for active safety surveillance research, J. Am. Med. Inform. Assoc, doi:10.1136/amiajnl-2011-000376
Rinott, Kozer, Shapira, Bar-Haim, Youngster, Ibuprofen use and clinical outcomes in COVID-19 patients, Clin. Microbiol. Infect, doi:10.1016/j.cmi.2020.06.003
Russell, Moss, Rigg, Van Hemelrijck, COVID-19 and treatment with NSAIDs and corticosteroids: Should we be limiting their use in the clinical setting?, Ecancermedicalscience, doi:10.3332/ecancer.2020.1023
Schjerning, Mcgettigan, Gislason, Cardiovascular effects and safety of (non-aspirin) NSAIDs, Nat. Rev. Cardiol, doi:10.1038/s41569-020-0366-z
Suchard, Simpson, Zorych, Ryan, Madigan, Massive parallelization of serial inference algorithms for a complex generalized linear model, ACM Trans. Model. Comput. Simul, doi:10.1145/2414416.2414791
Szeto, Non-steroidal anti-inflammatory drug (NSAID) therapy in patients with hypertension, cardiovascular, renal or gastrointestinal comorbidities: Joint APAGE/APLAR/APSDE/APSH/APSN/PoA recommendations, Gut, doi:10.1136/gutjnl-2019-319300
Wen, Acute respiratory infection and use of nonsteroidal anti-inflammatory drugs on risk of acute myocardial infarction: A nationwide case-crossover study, J. Infect. Dis, doi:10.1093/infdis/jiw603
You, Precision Healthcare Through Informatics
Zheng, Ma, Zhang, Xie, COVID-19 and the cardiovascular system, Nat. Rev. Cardiol, doi:10.1038/s41569-020-0360-5
Zhou, Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study, Lancet, doi:10.1016/S0140-6736(20)30566-3
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