{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:07:39Z","timestamp":1791925659250,"version":"4.3.4"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T00:00:00Z","timestamp":1650326400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T00:00:00Z","timestamp":1650326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Kris Gopalakrishnan"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Indomethacin, a non-steroidal anti-inflammatory drug (NSAID), has been presented as a broad-spectrum antiviral agent. This randomised clinical trial in a hospital setting evaluated the efficacy and safety of this drug in RT-PCR-positive coronavirus disease 2019 (COVID-19) patients. A total of 210 RT-PCR-positive COVID-19 patients who provided consent were allotted to the control or case arm, based on block randomisation. The control arm received standard of care comprising paracetamol, ivermectin, and other adjuvant therapies. The patients in the case arm received indomethacin instead of paracetamol, with other medications retained. The primary endpoint was the development of hypoxia\/desaturation with SpO\n                    <jats:sub>2<\/jats:sub>\n                    \u2009\u2264\u200993, while time to become afebrile and time for cough and myalgia resolution were the secondary endpoints. The results of 210 patients were available, with 103 and 107 patients in the indomethacin and paracetamol arms, respectively. We monitored patient profiles along with everyday clinical parameters. In addition, blood chemistry at the time of admission and discharge was assessed. As no one in either of the arms required high-flow oxygen, desaturation with a SpO\n                    <jats:sub>2<\/jats:sub>\n                    level of 93 and below was the vital goal. In the indomethacin group, none of the 103 patients developed desaturation. On the other hand, 20 of the 107 patients in the paracetamol arm developed desaturation. Patients who received indomethacin also experienced more rapid symptomatic relief than those in the paracetamol arm, with most symptoms disappearing in half the time.\u00a0In addition, 56 out of 107 in the paracetamol arm had fever on the seventh day, while no patient in the indomethacin group had fever. Neither arm reported any adverse event. The fourteenth-day follow-up revealed that the paracetamol arm patients had faced several discomforts; indomethacin arm patients mostly complained only of tiredness. Indomethacin is a safe and effective drug for treating patients with mild and moderate covid-19.\n                  <\/jats:p>","DOI":"10.1038\/s41598-022-10370-1","type":"journal-article","created":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T08:08:21Z","timestamp":1650355701000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["An open label randomized clinical trial of Indomethacin for mild and moderate hospitalised Covid-19 patients"],"prefix":"10.1038","volume":"12","author":[{"given":"Rajan","family":"Ravichandran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surapaneni Krishna","family":"Mohan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh Kumar","family":"Sukumaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devakumar","family":"Kamaraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumetha Suga","family":"Daivasuga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samson Oliver Abraham Samuel","family":"Ravi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivakumar","family":"Vijayaraghavalu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramarathnam Krishna","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,19]]},"reference":[{"issue":"3","key":"10370_CR1","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/s41579-020-00468-6","volume":"19","author":"P V\u2019kovski","year":"2021","unstructured":"V\u2019kovski, P., Kratzel, A., Steiner, S., Stalder, H. & Thiel, V. Coronavirus biology and replication: implications for SARS-CoV-2. Nat. Rev. Microbiol. 19(3), 155\u2013170 (2021).","journal-title":"Nat. Rev. Microbiol."},{"issue":"7816","key":"10370_CR2","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1038\/s41586-020-2286-9","volume":"583","author":"DE Gordon","year":"2020","unstructured":"Gordon, D. E. et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 583(7816), 459\u2013468 (2020).","journal-title":"Nature"},{"issue":"1","key":"10370_CR3","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1002\/med.21728","volume":"41","author":"X Wang","year":"2021","unstructured":"Wang, X. & Guan, Y. COVID-19 drug repurposing: A review of computational screening methods, clinical trials, and protein interaction assays. Med. Res. Rev. 41(1), 5\u201328 (2021).","journal-title":"Med. Res. Rev."},{"issue":"1","key":"10370_CR4","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1038\/s41392-021-00558-8","volume":"6","author":"M-M Zhao","year":"2021","unstructured":"Zhao, M.-M. et al. Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development. Signal Transd. Target. Therapy 6(1), 134 (2021).","journal-title":"Signal Transd. Target. Therapy"},{"key":"10370_CR5","first-page":"10","volume":"2020","author":"CP Gomes","year":"2020","unstructured":"Gomes, C. P. et al. Cathepsin L in COVID-19: from pharmacological evidences to genetics. Front. Cell. Infect. Microbiol. 2020, 10 (2020).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"10370_CR6","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.cegh.2020.07.006","volume":"9","author":"A Frediansyah","year":"2021","unstructured":"Frediansyah, A., Tiwari, R., Sharun, K., Dhama, K. & Harapan, H. Antivirals for COVID-19: a critical review. Clin. Epidemiol. Glob. Health 9, 90\u201398 (2021).","journal-title":"Clin. Epidemiol. Glob. Health"},{"issue":"21","key":"10370_CR7","doi-asserted-by":"publisher","first-page":"12359","DOI":"10.1021\/acs.jmedchem.0c00606","volume":"63","author":"C Gil","year":"2020","unstructured":"Gil, C. et al. COVID-19: drug targets and potential treatments. J. Med. Chem. 63(21), 12359\u201312386 (2020).","journal-title":"J. Med. Chem."},{"issue":"7","key":"10370_CR8","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1007\/s10067-020-05190-5","volume":"39","author":"M Soy","year":"2020","unstructured":"Soy, M. et al. Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment. Clin. Rheumatol. 39(7), 2085\u20132094 (2020).","journal-title":"Clin. Rheumatol."},{"issue":"10","key":"10370_CR9","first-page":"1","volume":"9403","author":"DE Gordon","year":"2020","unstructured":"Gordon, D. E. et al. Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science 9403(10), 1\u201338 (2020).","journal-title":"Science"},{"issue":"8","key":"10370_CR10","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1177\/135965350601100803","volume":"11","author":"C Amici","year":"2006","unstructured":"Amici, C. et al. Indomethacin has a potent antiviral activity against SARS coronavirus. Antivir. Ther. 11(8), 1021\u20131030 (2006).","journal-title":"Antivir. Ther."},{"key":"10370_CR11","first-page":"8","volume":"12","author":"T Xu","year":"2020","unstructured":"Xu, T., Gao, X., Wu, Z., Selinger, D. W. & Zhou, Z. Indomethacin has a potent antiviral activity against SARS CoV-2 in vitro and canine coronavirus in vivo. bioRxiv 12, 8 (2020).","journal-title":"bioRxiv"},{"key":"10370_CR12","unstructured":"Napolitano, F., Gambardella, G., Carrella, D., Gao, X., & di Bernardo, D. Computational drug repositioning and elucidation of mechanism of action of compounds against SARS-CoV-2 (2020)"},{"key":"10370_CR13","first-page":"188","volume":"98","author":"N Raghav","year":"1993","unstructured":"Raghav, N., Kamboj, R. C. & Singh, H. Effect of some steroidal and non-steroidal anti-inflammatory drugs on purified goat brain cathepsin L. Indian J. Med. Res. B Biomed. Res. Other Infect. Dis. 98, 188\u2013192 (1993).","journal-title":"Indian J. Med. Res. B Biomed. Res. Other Infect. Dis."},{"issue":"9","key":"10370_CR14","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1111\/cmi.12446","volume":"17","author":"C Amici","year":"2015","unstructured":"Amici, C. et al. Inhibition of viral protein translation by indomethacin in vesicular stomatitis virus infection: role of eIF2\u03b1 kinase PKR. Cell. Microbiol. 17(9), 1391\u20131404 (2015).","journal-title":"Cell. Microbiol."},{"issue":"2","key":"10370_CR15","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1042\/BJ20111236","volume":"443","author":"C Brunelli","year":"2012","unstructured":"Brunelli, C. et al. The non-steroidal anti-inflammatory drug indomethacin activates the eIF2\u03b1kinase PKR, causing a translational block in human colorectal cancer cells. Biochem. J. 443(2), 379\u2013386 (2012).","journal-title":"Biochem. J."},{"key":"10370_CR16","doi-asserted-by":"publisher","first-page":"104370","DOI":"10.1016\/j.jcv.2020.104370","volume":"127","author":"F Liu","year":"2020","unstructured":"Liu, F. et al. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J. Clin. Virol. 127, 104370 (2020).","journal-title":"J. Clin. Virol."},{"key":"10370_CR17","doi-asserted-by":"publisher","first-page":"155151","DOI":"10.1016\/j.cyto.2020.155151","volume":"133","author":"M Mahmudpour","year":"2020","unstructured":"Mahmudpour, M., Roozbeh, J., Keshavarz, M., Farrokhi, S. & Nabipour, I. COVID-19 cytokine storm: the anger of inflammation. Cytokine 133, 155151 (2020).","journal-title":"Cytokine"},{"issue":"8","key":"10370_CR18","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1016\/S0531-5565(00)00128-5","volume":"35","author":"AMJ Bour","year":"2000","unstructured":"Bour, A. M. J., Westendorp, R. G., Laterveer, J., Bollen, E. L. E. & Remarque, E. Interaction of indomethacin with cytokine production in whole blood. Potential mechanism for a brain-protective effect. Exp. Gerontol. 35(8), 1017\u20131024 (2000).","journal-title":"Exp. Gerontol."},{"issue":"1","key":"10370_CR19","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1097\/00007890-199201000-00017","volume":"53","author":"MR First","year":"1992","unstructured":"First, M. R., Schroeder, T. J., Hariharan, S., Alexander, J. W. & Weiskittel, P. The effect of indomethacin on the febrile response following OKT3 therapy1. Transplantation 53(1), 91\u201393 (1992).","journal-title":"Transplantation"},{"issue":"3","key":"10370_CR20","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/S0272-6386(12)80906-1","volume":"24","author":"WJ Gaughan","year":"1994","unstructured":"Gaughan, W. J., Francos, B. B., Dunn, S. R., Francos, G. C. & Burke, J. F. A retrospective analysis of the effect of indomethacin on adverse reactions to orthoclone OKT3 in the therapy of acute renal allograft rejection. Am. J. Kidney Dis. 24(3), 486\u2013490 (1994).","journal-title":"Am. J. Kidney Dis."},{"issue":"7","key":"10370_CR21","first-page":"42","volume":"119","author":"R Ravichandran","year":"2021","unstructured":"Ravichandran, R. et al. Use of indomethacin in COVID-19 patients: experience from two medical centres. J. Indian Med. Assoc. 119(7), 42\u201346 (2021).","journal-title":"J. Indian Med. Assoc."},{"key":"10370_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5455\/IJMRCR.LOW-DOSE-INDOMETHACIN","volume":"2020","author":"R Rajan","year":"2020","unstructured":"Rajan, R., Subramanian, S. & Clark, C. Low dose indomethacin for symptomatic treatment of COVID-19. Int. J. Med. Rev. Case Rep. 2020, 1 (2020).","journal-title":"Int. J. Med. Rev. Case Rep."},{"issue":"10","key":"10370_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4236\/oalib.1106860","volume":"07","author":"A Kanakaraj","year":"2020","unstructured":"Kanakaraj, A. & Ravichandran, R. Low dose indomethacin in the outpatient treatment of COVID-19 in kidney transplant recipients\u2014a case series. OALib. 07(10), 1\u20138 (2020).","journal-title":"OALib."},{"issue":"1","key":"10370_CR24","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/1471-2288-4-26","volume":"4","author":"M Saghaei","year":"2004","unstructured":"Saghaei, M. Random allocation software for parallel group randomized trials. BMC Med. Res. Methodol. 4(1), 26 (2004).","journal-title":"BMC Med. Res. Methodol."},{"issue":"2","key":"10370_CR25","doi-asserted-by":"crossref","first-page":"67","DOI":"10.4103\/2229-3485.71856","volume":"1","author":"T Sakpal","year":"2010","unstructured":"Sakpal, T. Sample size estimation in clinical trial. Perspect. Clin. Res. 1(2), 67 (2010).","journal-title":"Perspect. Clin. Res."},{"issue":"1","key":"10370_CR26","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1080\/13102818.2020.1775118","volume":"34","author":"G Momekov","year":"2020","unstructured":"Momekov, G. & Momekova, D. Ivermectin as a potential COVID-19 treatment from the pharmacokinetic point of view: antiviral levels are not likely attainable with known dosing regimens. Biotechnol. Biotechnol. Equip. 34(1), 469\u2013474 (2020).","journal-title":"Biotechnol. Biotechnol. Equip."},{"issue":"5532","key":"10370_CR27","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1136\/bmj.1.5532.69","volume":"1","author":"P Donnelly","year":"1967","unstructured":"Donnelly, P., Lloyd, K. & Campbell, H. Indomethacin in rheumatoid arthritis: an evaluation of its anti-inflammatory and side effects. BMJ 1(5532), 69\u201375 (1967).","journal-title":"BMJ"},{"key":"10370_CR28","unstructured":"Indomethacin drug usage statistics, United States, 2018 [Internet]. 2018. https:\/\/clincalc.com\/DrugStats\/Drugs\/Indomethacin"},{"issue":"3","key":"10370_CR29","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1007\/s40495-021-00257-6","volume":"7","author":"M Alkotaji","year":"2021","unstructured":"Alkotaji, M. & Al-Zidan, R. N. Indomethacin: can it counteract bradykinin effects in COVID-19 patients?. Curr. Pharmacol. Rep. 7(3), 102\u2013106 (2021).","journal-title":"Curr. Pharmacol. Rep."}],"updated-by":[{"DOI":"10.1038\/s41598-022-15107-8","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T00:00:00Z","timestamp":1655683200000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-10370-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-10370-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-10370-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,22]],"date-time":"2024-09-22T09:00:25Z","timestamp":1726995625000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-10370-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,19]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["10370"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-10370-1","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.07.24.21261007","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,19]]},"assertion":[{"value":"14 December 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 April 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 April 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2022","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41598-022-15107-8","URL":"https:\/\/doi.org\/10.1038\/s41598-022-15107-8","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6413"}}