{ "abstract": "Real-world evidence for leritrelvir, a single-component 3C-like protease inhibitor, in adults with mild-to-moderate coronavirus disease 2019 (COVID-19) remains limited. We evaluated the association of early leritrelvir use with symptom resolution, negative viral-test conversion, and adverse events in routine clinical practice. This prospective, multicenter, nonrandomized, open-label observational cohort study was conducted at 141 sites in China (mainland ). Among 1,527 adults with mild-to-moderate COVID-19, 1,388 received leritrelvir (400 mg three times daily for 5 days) plus standard care and 139 received standard care alone. The primary endpoint was time to sustained resolution of 11 predefined symptoms. The key secondary endpoint was time to negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test (NAT) conversion. All participants contributed a primary time-to-event record. We estimated unadjusted and multivariable-adjusted Cox models and performed 1:1 propensity score (PS) matching (136 participants per group). For sustained symptom resolution, the unadjusted hazard ratio (HR) was 1.41 [95% confidence interval (CI): 1.18-1.68; P<0.001], the multivariable-adjusted HR was 1.66 (95% CI: 1.38-1.99; P<0.001), and the PS-matched HR was 1.81 (robust 95% CI: 1.43-2.29; P<0.001). In the matched cohort, median time to symptom resolution was 6 days with leritrelvir and 8 days with standard care alone. For negative NAT conversion, the corresponding HRs were 1.20 (95% CI: 1.01-1.43; P=0.04), 1.22 (95% CI: 1.01-1.47; P=0.04), and 1.47 (robust 95% CI: 1.21-1.79; P<0.001); matched medians were 3 and 4 days. Adverse events occurred in 22.41% and 19.42% of the unmatched groups, respectively. In this prospective, multicenter, nonrandomized cohort, leritrelvir use was associated with earlier sustained symptom resolution and negative SARS-CoV-2 NAT conversion than standard care alone. Although the direction of association was consistent across multivariable-adjusted and PS-matched analyses, residual confounding, open-label symptom assessment, nonproportional hazards, incomplete follow-up, and the absence of severe-outcome events preclude causal, subgroup-specific, or severe-outcome conclusions.", "abstract_shown": true, "affiliations": [ "State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.", "Guangzhou National Laboratory, Guangzhou, China.", "Emergency Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China.", "Teaching Hospital of Fujian Medical University, Xiamen, China.", "Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, China.", "Zhejiang Institute of Traditional Chinese Medicine, Hangzhou, China.", "Division of Infectious Disease, The First Affiliated Hospital of Jinan University, Guangzhou, China.", "Key Laboratory of Hematopoietic Malignancies, The First Affiliated Hospital of Zhejiang University, Hangzhou, China.", "Department of Severe Tuberculosis Medicine, Guangzhou Chest Hospital, Guangzhou, China.", "Zhengzhou Third People's Hospital, Zhengzhou, China.", "Dongguan Binhai Bay Central Hospital, Dongguan, China.", "Department of Infectious Diseases, The Second Affiliated Hospital Guangzhou Medical University, Guangzhou, China.", "Baoding First Hospital, Baoding, China.", "Luoyang First People's Hospital, Luoyang, China.", "Tangshan Central Hospital, Tangshan, China.", "The Second Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.", "Chizhou People's Hospital, Chizhou, China.", "Zhengzhou Sixth People's Hospital, Zhengzhou, China.", "Zhengzhou Central Hospital, Zhengzhou, China.", "The Fourth People's Hospital of Chenzhou, Chenzhou, China.", "Hebei University of Engineering Affiliated Hospital, Handan, China.", "Henan Provincial Traditional Chinese Medicine Hospital, Zhengzhou, China.", "Yibin Second People's Hospital, Yibin, China.", "Julu County Hospital, Xingtai, China.", "Huainan Oriental Hospital Group Cancer Hospital, Huainan, China.", "Pengzhou People's Hospital, Pengzhou, China.", "Hebei Provincial Chest Hospital, Shijiazhuang, China.", "Yiyang Central Hospital, Yiyang, China.", "Shanghai First People's Hospital, Shanghai, China.", "Shanghai Sixth People's Hospital, Shanghai, China." ], "article_type": "research article", "arxiv": null, "author_total": 34, "authors": [ { "affs": [ 0, 1 ], "name": "Lin-Ling Cheng" }, { "affs": [ 0, 1 ], "name": "Ming-Qing Lu" }, { "affs": [ 2 ], "name": "Bang-Han Ding" }, { "affs": [ 3 ], "name": "Hui-Qing Zeng" }, { "affs": [ 4 ], "name": "Tian-Xin Xiang" }, { "affs": [ 5 ], "name": "Wei-Dong Weng" }, { "affs": [ 6 ], "name": "Xu-Jing Liang" }, { "affs": [ 7 ], "name": "Jie Jin" }, { "affs": [ 0 ], "name": "Zi-Hao Liu" }, { "affs": [ 8 ], "name": "Hai-Ping Dong" }, { "affs": [ 9 ], "name": "Hui-Lin Wang" }, { "affs": [ 10 ], "name": "Chen-Li Xie" }, { "affs": [ 11 ], "name": "Run-Qi Luo" }, { "affs": [ 12 ], "name": "Xue-Bing Rong" }, { "affs": [ 13 ], "name": "Li-Li Yue" }, { "affs": [ 14 ], "name": "Jun-Rui Li" }, { "affs": [ 15 ], "name": "Feng Li" }, { "affs": [ 16 ], "name": "Yu-Ping Wei" }, { "affs": [ 17 ], "name": "San-Jing Li" }, { "affs": [ 18 ], "name": "Chao Xu" }, { "affs": [ 19 ], "name": "Chi-Guan Li" }, { "affs": [ 20 ], "name": "Hong-Yan Yu" }, { "affs": [ 21 ], "name": "Fei Wei" }, { "affs": [ 22 ], "name": "Wen-Quan Li" }, { "affs": [ 23 ], "name": "Hui-Feng Wang" }, { "affs": [ 24 ], "name": "Chuan-Liu Yang" }, { "affs": [ 25 ], "name": "Bang-Qiong Weng" }, { "affs": [ 26 ], "name": "Liang Wang" }, { "affs": [ 27 ], "name": "De-Qiang Wang" }, { "affs": [ 28 ], "name": "Peng-Yu Zhang" }, { "affs": [ 29 ], "name": "Zheng-Hao Tang" }, { "affs": [ 0, 1 ], "name": "Zi-Feng Yang" }, { "affs": [ 0, 1 ], "name": "Jian-Xing He" }, { "affs": [ 0, 1 ], "name": "Nan-Shan Zhong" } ], "bibtex": "https://research.draconitic.com/paper/f6na8qsy4q2mv.bib", "cited_by": 0, "doi": "10.21037/jtd-2026-2569", "fulltext_url": "https://europepmc.org/articles/PMC13740802", "id": "f6na8qsy4q2mv", "issns": [ "2072-1439", "2077-6624" ], "landing_url": "https://europepmc.org/article/MED/42996986", "language": "eng", "licence": "CC-BY-NC-ND", "licence_label": "CC BY-NC-ND", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2725|COVID-19 Clinical Research Studies" ] ], "openalex": "W7224121883", "pdf_url": "https://europepmc.org/articles/PMC13740802?pdf=render", "pmcid": "PMC13740802", "pmid": "42996986", "published": "2026-10-27", "publisher": null, "ris": "https://research.draconitic.com/paper/f6na8qsy4q2mv.ris", "sources": [ { "first_seen": "2026-11-09T15:20:34Z", "native_id": "MED:42996986", "source": "europepmc", "url": "https://europepmc.org/article/MED/42996986" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2725|COVID-19 Clinical Research Studies", "subfield": "infectious-disease" } ], "title": "Effects of leritrelvir for adults with mild-to-moderate coronavirus disease 2019: a multicenter real-world study.", "title_text": "Effects of leritrelvir for adults with mild-to-moderate coronavirus disease 2019: a multicenter real-world study.", "type": "peer-reviewed", "updated_at": "2026-11-10T03:20:49Z", "url": "https://research.draconitic.com/paper/f6na8qsy4q2mv", "venue": "Journal of thoracic disease", "versions": [] }