{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:12:48Z","timestamp":1783930368673,"version":"3.55.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Clin Pharmacol"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1007\/s00228-026-04126-3","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T07:01:34Z","timestamp":1782716494000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of Ensitrelvir in COVID-19 patients: a systematic review and meta-analysis with focus on viral clearance and RNA change"],"prefix":"10.1007","volume":"82","author":[{"given":"Shahd","family":"Nofal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama","family":"Al-said","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Alnimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jood Mudar","family":"Sarah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tala Abu","family":"Alam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dua","family":"Abuquteish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"4126_CR1","doi-asserted-by":"publisher","unstructured":"Radiography (2020) Effectiveness of COVID-19 diagnosis and management tools: a review. Radiography. https:\/\/doi.org\/10.1016\/j.radi.2020.09.010","DOI":"10.1016\/j.radi.2020.09.010"},{"key":"4126_CR2","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1007\/s12016-022-08921-5","volume":"64","author":"JJ Zhang","year":"2023","unstructured":"Zhang JJ, Dong X, Liu GH, Gao YD (2023) Risk and protective factors for COVID-19 morbidity, severity, and mortality. Clin Rev Allergy Immunol 64:90\u2013107. https:\/\/doi.org\/10.1007\/s12016-022-08921-5","journal-title":"Clin Rev Allergy Immunol"},{"key":"4126_CR3","doi-asserted-by":"publisher","first-page":"100042","DOI":"10.1016\/j.sintl.2020.100042","volume":"1","author":"NP Mishra","year":"2020","unstructured":"Mishra NP, Das SS, Yadav S, Khan W, Afzal M, Alarifi A et al (2020) RETRACTED: Global impacts of pre- and post-COVID-19 pandemic: focus on socio-economic consequences. Sens Int 1:100042. https:\/\/doi.org\/10.1016\/j.sintl.2020.100042","journal-title":"Sens Int"},{"key":"4126_CR4","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciag272","author":"JV Baker","year":"2026","unstructured":"Baker JV, Siegel L, Losso M et al (2026) Ensitrelvir for the treatment of hospitalized adults with COVID-19: an international phase 3 randomized placebo-controlled trial. Clin Infect Dis. https:\/\/doi.org\/10.1093\/cid\/ciag272","journal-title":"Clin Infect Dis"},{"key":"4126_CR5","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1039\/d3md00493g","volume":"15","author":"YL Janin","year":"2023","unstructured":"Janin YL (2023) On the origins of SARS-CoV-2 main protease inhibitors. RSC Med Chem 15:81\u2013118. https:\/\/doi.org\/10.1039\/d3md00493g","journal-title":"RSC Med Chem"},{"key":"4126_CR6","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/s40005-021-00520-4","volume":"51","author":"DA Ghareeb","year":"2021","unstructured":"Ghareeb DA, Saleh SR, Nofal MS, Kaddah MMY, Hassan SF, Seif IK et al (2021) Potential therapeutic and pharmacological strategies for SARS-CoV2. J Pharm Investig 51:281\u2013296. https:\/\/doi.org\/10.1007\/s40005-021-00520-4","journal-title":"J Pharm Investig"},{"key":"4126_CR7","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00632-22","author":"Antimicrobial Agents and Chemotherapy","year":"2022","unstructured":"Antimicrobial Agents and Chemotherapy (2022) safety, tolerability, and pharmacokinetics of the novel antiviral agent ensitrelvir fumaric Acid, a SARS-CoV-2 3CL protease inhibitor. Healthy Adults Antimicrob Agents Chemother. https:\/\/doi.org\/10.1128\/aac.00632-22","journal-title":"Healthy Adults Antimicrob Agents Chemother"},{"key":"4126_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-05071-y","author":"C Biology","year":"2023","unstructured":"Biology C (2023) Molecular mechanism of ensitrelvir inhibiting SARS-CoV-2 main protease and its variants. Commun Biol. https:\/\/doi.org\/10.1038\/s42003-023-05071-y","journal-title":"Commun Biol"},{"key":"4126_CR9","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","volume":"372","author":"BMJ The","year":"2021","unstructured":"The BMJ (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71. https:\/\/doi.org\/10.1136\/bmj.n71","journal-title":"BMJ"},{"key":"4126_CR10","unstructured":"Rayyan. https:\/\/rayyan.ai\/users\/sign_in."},{"key":"4126_CR11","doi-asserted-by":"publisher","first-page":"l4898","DOI":"10.1136\/bmj.l4898","volume":"366","author":"BMJ The","year":"2019","unstructured":"The BMJ (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 366:l4898. https:\/\/doi.org\/10.1136\/bmj.l4898","journal-title":"BMJ"},{"key":"4126_CR12","unstructured":"GRADEpro. https:\/\/www.gradepro.org\/."},{"key":"4126_CR13","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/1471-2288-14-135","volume":"14","author":"X Wan","year":"2014","unstructured":"Wan X, Wang W, Liu J et al (2014) Estimating the sample mean and standard deviation from the sample size, median, range and\/or interquartile range. BMC Med Res Methodol 14:135. https:\/\/doi.org\/10.1186\/1471-2288-14-135","journal-title":"BMC Med Res Methodol"},{"key":"4126_CR14","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.4401","author":"H Mukae","year":"2022","unstructured":"Mukae H et al (2022) Efficacy and Safety of Ensitrelvir in patients with mild-to-moderate coronavirus disease 2019: the phase 2b part of a randomized, placebo-controlled, phase 2\/3 study. JAMA Netw Open. https:\/\/doi.org\/10.1001\/jamanetworkopen.2022.4401","journal-title":"JAMA Netw Open"},{"key":"4126_CR15","doi-asserted-by":"publisher","first-page":"e13338","DOI":"10.1111\/irv.13338","volume":"18","author":"N Ohmagari","year":"2024","unstructured":"Ohmagari N, Yotsuyanagi H, Doi Y, Yamato M, Imamura T, Sakaguchi H et al (2024) Efficacy and safety of ensitrelvir for asymptomatic or mild COVID-19: an exploratory analysis of a multicenter, randomized, phase 2b\/3 clinical trial. Influenza Other Respir Viruses 18:e13338. https:\/\/doi.org\/10.1111\/irv.13338","journal-title":"Influenza Other Respir Viruses"},{"key":"4126_CR16","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.0001","author":"H Yotsuyanagi","year":"2024","unstructured":"Yotsuyanagi H et al (2024) Efficacy and safety of 5-day oral ensitrelvir for patients with mild to moderate COVID-19: the SCORPIO-SR randomized clinical trial; development of a tool to measure student perceptions of equity and inclusion in medical schools. JAMA Netw Open. https:\/\/doi.org\/10.1001\/jamanetworkopen.2024.0001","journal-title":"JAMA Netw Open"},{"key":"4126_CR17","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00697-22","author":"H Mukae","year":"2022","unstructured":"Mukae H et al (2022) A randomized phase 2\/3 study of ensitrelvir, a novel oral SARS-CoV-2 3C-like protease inhibitor, in Japanese patients with mild-to-moderate COVID-19 or asymptomatic SARS-CoV-2 infection: results of the phase 2a part. Antimicrob Agents Chemother. https:\/\/doi.org\/10.1128\/aac.00697-22","journal-title":"Antimicrob Agents Chemother"},{"key":"4126_CR18","doi-asserted-by":"publisher","first-page":"2984","DOI":"10.1093\/jac\/dkac257","volume":"77","author":"H Nobori","year":"2022","unstructured":"Nobori H, Fukao K, Kuroda T, Anan N, Tashima R, Nakashima M et al (2022) Efficacy of ensitrelvir against SARS-CoV-2 in a delayed-treatment mouse model. J Antimicrob Chemother 77:2984\u20132991. https:\/\/doi.org\/10.1093\/jac\/dkac257","journal-title":"J Antimicrob Chemother"},{"key":"4126_CR19","doi-asserted-by":"publisher","first-page":"105969","DOI":"10.1016\/j.antiviral.2024.105969","volume":"231","author":"S Rauch","year":"2024","unstructured":"Rauch S, Costacurta F, Sch\u00f6ppe H, Peng JY, Bante D, Erisoez EE et al (2024) Highly specific SARS-CoV-2 main protease (Mpro) mutations against the clinical antiviral ensitrelvir selected in a safe, VSV-based system. Antiviral Res 231:105969. https:\/\/doi.org\/10.1016\/j.antiviral.2024.105969","journal-title":"Antiviral Res"},{"key":"4126_CR20","doi-asserted-by":"publisher","first-page":"6499","DOI":"10.1021\/acs.jmedchem.2c00117","volume":"65","author":"Y Unoh","year":"2022","unstructured":"Unoh Y, Uehara S, Nakahara K et al (2022) Discovery of S-217622, a noncovalent oral SARS-CoV-2 3CL protease inhibitor clinical candidate for treating COVID-19. J Med Chem 65:6499\u20136512. https:\/\/doi.org\/10.1021\/acs.jmedchem.2c00117","journal-title":"J Med Chem"},{"key":"4126_CR21","doi-asserted-by":"publisher","DOI":"10.7883\/yoken.JJID.2024.372","author":"S Khorramnia","year":"2025","unstructured":"Khorramnia S, Pakzad Moghadam SH, Sarkoohi A et al (2025) Ensitrelvir for the treatment of COVID-19: a systematic review of evidence. Jpn J Infect Dis. https:\/\/doi.org\/10.7883\/yoken.JJID.2024.372","journal-title":"Jpn J Infect Dis"}],"container-title":["European Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00228-026-04126-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00228-026-04126-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00228-026-04126-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T07:57:20Z","timestamp":1783929440000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00228-026-04126-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,29]]},"references-count":21,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["4126"],"URL":"https:\/\/doi.org\/10.1007\/s00228-026-04126-3","relation":{},"ISSN":["0031-6970","1432-1041"],"issn-type":[{"value":"0031-6970","type":"print"},{"value":"1432-1041","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,29]]},"assertion":[{"value":"10 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethical approval was not required for this study as it is a systematic review and meta-analysis of previously published studies. No primary data were collected, and no human participants were directly involved.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Clinical trial number: Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Clinical trial registration"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human ethics and consent to participate"}},{"value":"The authors declare no competing interests.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"192"}}