Conv. Plasma
Nigella Sativa
Peg.. Lambda

All acetaminophen studies
Meta analysis
study COVID-19 treatment researchAcetaminophenAcetaminophen (more..)
Melatonin Meta
Bromhexine Meta Metformin Meta
Budesonide Meta
Cannabidiol Meta Molnupiravir Meta
Colchicine Meta
Conv. Plasma Meta
Curcumin Meta Nigella Sativa Meta
Ensovibep Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Peg.. Lambda Meta
Fluvoxamine Meta Quercetin Meta
Hydroxychlor.. Meta Remdesivir Meta
Ivermectin Meta
Lactoferrin Meta

All Studies   Meta Analysis   Recent:  
0 0.5 1 1.5 2+ Mortality -61% Improvement Relative Risk Severe case -816% Acetaminophen for COVID-19  Reese et al.  Prophylaxis Is prophylaxis with acetaminophen beneficial for COVID-19? PSM retrospective 41,652 patients in the USA Higher mortality (p<0.0001) and severe cases (p<0.0001) Reese et al., medRxiv, April 2021 Favors acetaminophen Favors control

Cyclooxygenase inhibitor use is associated with increased COVID-19 severity

Reese et al., medRxiv, doi:10.1101/2021.04.13.21255438
Apr 2021  
  Source   PDF   All Studies   Meta AnalysisMeta
N3C retrospective 250,533 patients showing significantly higher mortality with acetaminophen use. Note that acetaminophen results were not included in the journal version or v2 of this preprint, which focuses on NSAID analysis. Acetaminophen is also known as paracetamol, Tylenol, Panadol, Calpol, Tempra, Calprofen, Doliprane, Efferalgan, Grippostad C, Dolo, Acamol, Fevadol, Crocin, and Perfalgan.
This study includes ibuprofen, aspirin, and acetaminophen.
risk of death, 61.0% higher, HR 1.61, p < 0.001, treatment 20,826, control 20,826, propensity score matching, Cox proportional hazards, Table S58.
risk of severe case, 816.0% higher, OR 9.16, p < 0.001, treatment 20,826, control 20,826, propensity score matching, Table S50, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Reese et al., 20 Apr 2021, retrospective, USA, preprint, 23 authors.
All Studies   Meta Analysis   Submit Updates or Corrections
This PaperAcetaminophenAll
Cyclooxygenase inhibitor use is associated with increased COVID-19 severity
Justin T Reese, Ben Coleman2, Lauren Chan3, Hannah Blau4, Tiffany J Callahan5, Luca Cappelletti7, Tommaso Fontana8, Katie Rebecca Bradwell9, Nomi L Harris1, Elena Casiraghi7, Giorgio Valentini7, Guy Karlebach4, Rachel Deer11, Julie A Mcmurry6, Melissa A Haendel6, Christopher G Chute12, Emily Pfaff13, Richard Moffitt14, Heidi Spratt11, Jasvinder Singh15, Christopher J Mungall1, Andrew E Williams17, Peter N Robinson
BACKGROUND Cyclooxygenase (COX) inhibitors including non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain, fever, and inflammation but have been associated with complications in community acquired pneumonia and other respiratory tract infections (RTIs). Conclusive data are not available about potential beneficial or adverse effects of COX inhibitors on COVID-19 patients. METHODS We conducted a retrospective, multi-center observational study by leveraging the harmonized, high-granularity electronic health record data of the National COVID Cohort Collaborative (N3C). Potential associations of eight COX inhibitors with COVID-19 severity were assessed using ordinal logistic regression (OLR) on treatment with the medication in question after matching by treatment propensity as predicted by age, race, ethnicity, gender, smoking status, comorbidities, and BMI. Cox proportional hazards analysis was used to estimate the correlation of medication use with morbidity for eight subcohorts defined by common indications for COX inhibitors. RESULTS OLR revealed statistically significant associations between use of any of five COX inhibitors and increased severity of COVID-19. For instance, the odds ratio of aspirin use in the osteoarthritis cohort (n=2266 patients) was 3.25 (95% CI 2.76 -3.83). Aspirin and acetaminophen were associated with increased mortality. CONCLUSIONS The association between use of COX inhibitors and COVID-19 severity was consistent across five COX inhibitors and multiple indication subcohorts. Our results align with earlier reports associating NSAID use with complications in RTI patients. Further research is needed to characterize the precise risk of individual COX inhibitors in COVID-19 patients. .
Amici, Caro, Ciucci, Indomethacin has a potent antiviral activity against SARS coronavirus, Antivir Ther
Austin, Wong, Uzzo, Beck, Egleston, Why Summary Comorbidity Measures Such As the Charlson Comorbidity Index and Elixhauser Score Work, Med Care
Bancos, Bernard, Topham, Phipps, Ibuprofen and other widely used nonsteroidal anti-inflammatory drugs inhibit antibody production in human cells, Cell Immunol
Bennett, Moffitt, Hajagos, The National COVID Cohort Collaborative: Clinical Characterization and Early Severity Prediction, doi:10.1101/2021.01.12.21249511
Bruce, Barlow-Pay, Short, Prior Routine Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Important Outcomes in Hospitalised Patients with COVID-19, J Clin Med Res, doi:10.3390/jcm9082586
Cannon, Cannon, Physiology. COX-2 inhibitors and cardiovascular risk, Science
Choi, Ahn, Ryu, Clinical Characteristics and Disease Progression in Early-Stage COVID-19 Patients in South Korea, J Clin Med Res, doi:10.3390/jcm9061959
Chow, Khanna, Kethireddy, Aspirin Use is Associated with Decreased Mechanical Ventilation, ICU Admission, and In-Hospital Mortality in Hospitalized Patients with COVID-19, Anesth Analg, doi:10.1213/ANE.0000000000005292
Christopher, Chute supported by U24 TR002306; Heidi Spratt supported by NIH
Christopher, Mungall Supported, None
Day, Covid-19: ibuprofen should not be used for managing symptoms, say doctors and scientists, BMJ
Fitzgerald, Patrono, The coxibs, selective inhibitors of cyclooxygenase-2, N Engl J Med
Gianfrancesco, Hyrich, Al-Adely, Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry, Ann Rheum Dis
Graham, Burrell, Douglas, Debelle, Davies, Adverse effects of aspirin, acetaminophen, and ibuprofen on immune function, viral shedding, and clinical status in rhinovirus-infected volunteers, J Infect Dis
Grosser, Fries, Fitzgerald, Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities, J Clin Invest
Haendel, Chute, Bennett, The National COVID Cohort Collaborative (N3C): Rationale, design, infrastructure, and deployment, J Am Med Inform Assoc
Hendren, De Lemos, Ayers, Association of Body Mass Index and Age With Morbidity and Mortality in Patients Hospitalized With COVID-19: Results From the American Heart Association COVID-19 Cardiovascular Disease Registry, Circulation
Hinz, Cheremina, Brune, Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man, FASEB J
Hripcsak, Duke, Shah, Observational Health Data Sciences and Informatics (OHDSI): Opportunities for Observational Researchers, Stud Health Technol Inform
Katie ; Chan, Reese, Chute, Christopher, Tiffany et al., Bill and Melinda Gates Foundation grant to Sage Bionetworks • Icahn School of Medicine at Mount Sinai -UL1TR001433
Lund, Reilev, Hallas, Association of Nonsteroidal Anti-inflammatory Drug Use and Adverse Outcomes Among Patients Hospitalized With Influenza, JAMA Netw Open
Maier, Kapsner, Mate, Prokosch, Kraus, Patient Cohort Identification on Time Series Data Using the OMOP Common Data Model, Appl Clin Inform
Micallef, Soeiro, Society, of Pharmacology, Therapeutics (SFPT). Non-steroidal anti-inflammatory drugs, pharmacology, and COVID-19 infection, Therapie
Nomi, Harris supported by Director
Ortiz-Prado, Simbaña-Rivera, Gómez-Barreno, Clinical, molecular, and epidemiological characterization of the SARS-CoV-2 virus and the Coronavirus Disease 2019 (COVID-19), a comprehensive literature review, Diagn Microbiol Infect Dis
Peter, Robinson, Donald, Roux Family Fund at the Jackson Laboratory Conflicts of Interest References
Pirmohamed, James, Meakin, Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients, BMJ
Rinott, Kozer, Shapira, Bar-Haim, Youngster, Ibuprofen use and clinical outcomes in COVID-19 patients, Clin Microbiol Infect
Schönthal, Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy, Br J Cancer
Silverstein, Faich, Goldstein, Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study, JAMA
Suzuki, Eastwood, Bailey, Paracetamol therapy and outcome of critically ill patients: a multicenter retrospective observational study, Crit Care
Torjesen, Ibuprofen can mask symptoms of infection and might worsen outcomes, says European drugs agency, BMJ
Ursu, Holmes, Knockel, DrugCentral: online drug compendium, Nucleic Acids Res
Vaja, Chan, Ferreira, The COVID-19 ibuprofen controversy: A systematic review of NSAIDs in adult acute lower respiratory tract infections, Br J Clin Pharmacol
Vanderweele, Ding, Sensitivity Analysis in Observational Research: Introducing the E-Value, Ann Intern Med
Voiriot, Dury, Parrot, Mayaud, Fartoukh, Nonsteroidal antiinflammatory drugs may affect the presentation and course of community-acquired pneumonia, Chest
Voiriot, Philippot, Elabbadi, Elbim, Chalumeau et al., Risks Related to the Use of Non-Steroidal Anti-Inflammatory Drugs in Community-Acquired Pneumonia in Adult and Pediatric Patients, J Clin Med Res, doi:10.3390/jcm8060786
Voss, Makadia, Matcho, Feasibility and utility of applications of the common data model to multiple, disparate observational health databases, J Am Med Inform Assoc
Weiss, Murdoch, Clinical course and mortality risk of severe COVID-19
Wong, Mackenna, Morton, Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts, Ann Rheum Dis, doi:10.1136/annrheumdis-2020-219517
Wright, Moots, Bucknall, Edwards, Neutrophil function in inflammation and inflammatory diseases, Rheumatology
Yu, Ricciotti, Scalia, Vascular COX-2 modulates blood pressure and thrombosis in mice, Sci Transl Med
Zhang, Propensity score method: a non-parametric technique to reduce model dependence, Ann Transl Med
Please send us corrections, updates, or comments. c19early involves the extraction of over 100,000 datapoints from thousands of papers. Community updates help ensure high accuracy. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop