AbstractNirmatrelvir plus ritonavir received Emergency Use Authorization for treating mild to moderate COVID-19 in high-risk patients. Its efficacy against the Omicron variant of SARS-CoV-2 remains uncertain. This retrospective cohort study assessed the effect of nirmatrelvir–ritonavir in preventing severe disease progression and long COVID symptoms after acute COVID-19 in non-hospitalized adults.

摘要尼马曲韦联合利托那韦获得紧急使用授权，用于治疗高危患者的轻度至中度COVID-19。其对SARS-CoV-2的Omicron变体的功效仍不确定。这项回顾性队列研究评估了尼马曲韦-利托那韦在非住院成人急性新型冠状病毒肺炎后预防严重疾病进展和长期新型冠状病毒症状的效果。

SALAMA medical records from Dubai’s COVID-19 healthcare centers between May 22, 2022, and April 30, 2023, were used to identify 7290 eligible patients, 9.6% of whom received nirmatrelvir–ritonavir. Treatment was associated with a notable reduction in COVID-19-related hospitalizations (adjusted hazard ratio [HR] of 0.39; 95% CI, 0.18–0.85) by day 28 of symptom onset.

2022年5月22日至2023年4月30日期间，迪拜新型冠状病毒肺炎医疗中心的萨拉马医疗记录被用于确定7290名符合条件的患者，其中9.6%接受了尼马曲韦-利托那韦治疗。到症状出现的第28天，治疗与新型冠状病毒相关的住院率显着降低（调整后的危险比[HR]为0.39；95%CI为0.18-0.85）相关。

Moreover, nirmatrelvir–ritonavir was associated with fewer long COVID symptoms (adjusted HR of 0.42; 95% CI, 0.19–0.95). This suggests the significant effectiveness of nirmatrelvir–ritonavir against the Omicron variant, reducing both severe and long-term COVID-19 symptoms..

此外，尼马曲韦-利托那韦与较少的长COVID症状相关（调整后的HR为0.42；95%CI为0.19-0.95）。这表明尼马曲韦-利托那韦对Omicron变体具有显着的有效性，可减少严重和长期的COVID-19症状。。

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated coronavirus disease 2019 (COVID-19) continue to threaten global health. Patients with underlying clinical conditions such as diabetes, cardiovascular disease, and obesity are at increased risk for severe COVID-19 and associated adverse outcomes1.

引言严重急性呼吸综合征冠状病毒2（SARS-CoV-2）和2019年相关冠状病毒病（COVID-19）继续威胁全球健康。患有糖尿病，心血管疾病和肥胖等潜在临床疾病的患者患严重新型冠状病毒肺炎和相关不良后果的风险增加1。

These patients are more likely to progress to severe COVID-19, develop long-term COVID symptoms, and die from COVID-192,3.Effective oral COVID-19 treatments are needed to prevent progression to severe disease. In December 2021, the Food and Drug Administration (FDA) granted an Emergency Use Authorization (EUA) for nirmatrelvir plus ritonavir to treat mild to moderate COVID-19 in adults and children aged 12 and older who are at increased risk of progressing to severe COVID-194.

这些患者更有可能发展为严重的新型冠状病毒肺炎，发展为长期的新型冠状病毒肺炎症状，并死于新型冠状病毒肺炎。3.需要有效的口服新型冠状病毒肺炎治疗来预防严重疾病的进展。2021年12月，美国食品和药物管理局（FDA）批准尼马曲韦联合利托那韦紧急使用授权（EUA），用于治疗12岁及以上成人和儿童中轻度至中度COVID-19，这些儿童发展为严重COVID-194的风险增加。

Currently, the COVID-19 treatment guidelines provided by the National Institutes of Health (NIH) widely recommend that patients with mild to moderate COVID-19 who are at high risk of progressing to severe disease be treated with either oral nirmatrelvir-ritonavir or intravenous remdesivir5. Although oral molnupiravir has been shown to reduce the risk of progression to severe COVID-196, it is listed as an alternative therapy to these options.Nirmatrelvir is an oral antiviral agent that inhibits the 3-chymotrypsin–like cysteine protease enzyme (Mpro) of SARS-CoV-2, which is essential for the viral replication cycle7.

目前，美国国立卫生研究院（NIH）提供的新型冠状病毒肺炎（COVID-19）治疗指南广泛建议轻度至中度新型冠状病毒肺炎（COVID-19）患者进展为严重疾病的高风险患者接受口服尼马曲韦-利托那韦或静脉注射雷米地韦5治疗。尽管口服莫那韦已被证明可以降低进展为严重COVID-196的风险，但它被列为这些选择的替代疗法。尼马曲韦是一种口服抗病毒药物，可抑制SARS-CoV-2的3-胰凝乳蛋白酶样半胱氨酸蛋白酶（Mpro），这对病毒复制周期至关重要7。

Nirmatrelvir inhibits Mpro activity and virus replication across a broad spectrum of coronaviruses in vitro and in mouse infection models. Oral administration of nirmatrelvir resulted in significantly lower lung titers of SARS-CoV-2 compared to mice treated with a placebo7. Moreover, nirmatrelvir is metabolized mainly by CYP3A4; and therefore, its co-adm.

尼马曲韦在体外和小鼠感染模型中抑制Mpro活性和病毒在广谱冠状病毒中的复制。与用安慰剂治疗的小鼠相比，口服尼马曲韦导致SARS-CoV-2的肺滴度显着降低7。此外，尼马曲韦主要由CYP3A4代谢；因此，它的联合adm。

Data availability

数据可用性

All data analyzed during this study are deposited in Supplementary File.

本研究期间分析的所有数据均保存在补充文件中。

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Download referencesAuthor informationAuthor notesFatemeh Saheb Sharif-Askari and Hawra Ali Hussain Alsayed contributed equally to this work.Authors and AffiliationsResearch Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab EmiratesFatemeh Saheb Sharif-Askari, Hawra Ali Hussain Alsayed, Narjes Saheb Sharif-Askari & Rabih HalwaniDepartment of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah, United Arab EmiratesFatemeh Saheb Sharif-AskariDepartment of Pharmacy, Rashid Hospital, Dubai Academic Health Corporation, Dubai, United Arab EmiratesHawra Ali Hussain AlsayedDepartment of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesNarjes Saheb Sharif-Askari & Rabih HalwaniDepartment of Pharmacy, Dubai Health Authority, Dubai, United Arab EmiratesAli Al Sayed HussainImmunology Research Laboratory, Department of Pediatrics, College of Medicine and King Saud University Medical City, King Saud University, Riyadh, Saudi ArabiaSaleh Al-MuhsenDepartment of Pediatrics, Faculty of Medicine, Prince Abdullah Ben Khaled Celiac Disease Chair, King Saud University, Riyadh, Saudi ArabiaRabih HalwaniAuthorsFatemeh Saheb Sharif-AskariView author publicationsYou can also search for this author in.

下载参考文献作者信息作者注释Fatemeh Saheb Sharif Askari和Hawra Ali Hussain Alsayed对这项工作做出了同样的贡献。作者和附属机构沙迦大学医学与健康科学研究所，沙迦，阿拉伯联合酋长国Fatemeh Saheb Sharif Askari，Hawra Ali Hussain Alsayed，Narjes Saheb Sharif Askari＆Rabih HalwaniDepartment of Pharmaceutical Practice and Pharmaceuticals，College of Pharmaceutical，沙迦，沙迦，阿拉伯联合酋长国沙迦，阿拉伯联合酋长国沙迦大学药学院，拉希德医院，迪拜学术健康公司迪拜，阿拉伯联合酋长国Shawra Ali Hussain Alsayed沙迦大学医学院临床科学系，沙迦，阿拉伯联合酋长国Snarjes Saheb Sharif Askari＆Rabih HalwaniDepartment of Pharmacy，迪拜卫生局，迪拜，阿拉伯联合酋长国萨利·赛义德·侯赛因免疫学研究实验室，医学院和沙特国王大学医学城儿科，沙特利雅得沙特国王大学医学院儿科，阿卜杜拉·本·哈立德亲王乳糜泻主席，沙特利雅得沙特国王大学HalwaniAuthorsFatemeh Saheb Sharif AskariView作者出版物您也可以在中搜索这位作者。

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PubMed Google ScholarContributionsF.S.S.A., H.A.H.A., N.S.S.A., A.A.S.H., S.A.M. and R.H., wrote the manuscript; F.S.S.A., H.A.H.A., N.S.S.A., and R.H., designed the research; F.S.S.A., H.A.H.A., A.A.S.H., and N.S.S.A., performed the research; F.S.S.A. analyzed the data; R.H., contributed new reagents/analytical tools.Corresponding authorCorrespondence to.

PubMed谷歌学术贡献。S、 S.A.，H.A.H.A.，N.S.S.A.，A.A.S.H.，S.A.M.和R.H.撰写了手稿；F、 S.S.A.，H.A.H.A.，N.S.S.A。和R.H.设计了这项研究；F、 S.S.A.，H.A.H.A.，A.A.S.H。和N.S.S.A.进行了这项研究；F、 S.S.A.分析了数据；R、 H.，贡献了新的试剂/分析工具。对应作者对应。

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Reprints and permissionsAbout this articleCite this articleSaheb Sharif-Askari, F., Ali Hussain Alsayed, H., Saheb Sharif-Askari, N. et al. Nirmatrelvir plus ritonavir reduces COVID-19 hospitalization and prevents long COVID in adult outpatients.

转载和许可本文引用本文Saheb Sharif Askari，F.，Ali Hussain Alsayed，H.，Saheb Sharif Askari，N。等人。尼马曲韦加利托那韦可减少COVID-19住院治疗，并预防成人门诊患者的长时间COVID。

Sci Rep 14, 25901 (2024). https://doi.org/10.1038/s41598-024-76472-0Download citationReceived: 25 January 2024Accepted: 14 October 2024Published: 29 October 2024DOI: https://doi.org/10.1038/s41598-024-76472-0Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

《科学报告》1425901（2024）。https://doi.org/10.1038/s41598-024-76472-0Download引文接收日期：2024年1月25日接受日期：2024年10月14日发布日期：2024年10月29日OI：https://doi.org/10.1038/s41598-024-76472-0Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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KeywordsNirmatrelvir–ritonavirOmicron variantCOVID-19Long COVIDHospitalization

关键词Nirmatrevir ritonavir奥密克戎变异株新冠肺炎-19长期新冠肺炎住院