دورية أكاديمية
Viral clearance as a surrogate of clinical efficacy for COVID-19 therapies in outpatients: a systematic review and meta-analysis.
| العنوان: | Viral clearance as a surrogate of clinical efficacy for COVID-19 therapies in outpatients: a systematic review and meta-analysis. |
|---|---|
| المؤلفون: | Elias KM; Kirby Institute, University of New South Wales, Sydney, NSW, Australia., Khan SR; Kirby Institute, University of New South Wales, Sydney, NSW, Australia., Stadler E; Kirby Institute, University of New South Wales, Sydney, NSW, Australia., Schlub TE; Kirby Institute, University of New South Wales, Sydney, NSW, Australia; Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia., Cromer D; Kirby Institute, University of New South Wales, Sydney, NSW, Australia., Polizzotto MN; Clinical Hub for Interventional Research and John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Canberra, ACT, Australia; Canberra Regional Cancer Centre, The Canberra Hospital, Canberra, ACT, Australia., Kent SJ; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia; Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, VIC, Australia., Turner T; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia., Davenport MP; Kirby Institute, University of New South Wales, Sydney, NSW, Australia., Khoury DS; Kirby Institute, University of New South Wales, Sydney, NSW, Australia. Electronic address: dkhoury@kirby.unsw.edu.au. |
| المصدر: | The Lancet. Microbe [Lancet Microbe] 2024 May; Vol. 5 (5), pp. e459-e467. Date of Electronic Publication: 2024 Apr 04. |
| نوع المنشور: | Journal Article; Systematic Review; Meta-Analysis; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Ltd Country of Publication: England NLM ID: 101769019 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-5247 (Electronic) Linking ISSN: 26665247 NLM ISO Abbreviation: Lancet Microbe Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Oxford] : Elsevier Ltd., [2020]- |
| مواضيع طبية MeSH: | COVID-19*/therapy , COVID-19*/immunology , Antiviral Agents*/therapeutic use , Viral Load*/drug effects , SARS-CoV-2*, Humans ; Treatment Outcome ; COVID-19 Drug Treatment ; Outpatients ; Immunization, Passive ; Randomized Controlled Trials as Topic ; COVID-19 Serotherapy ; Disease Progression ; Hospitalization/statistics & numerical data |
| مستخلص: | Background: Surrogates of antiviral efficacy are needed for COVID-19. We aimed to investigate the relationship between the virological effect of treatment and clinical efficacy as measured by progression to severe disease in outpatients treated for mild-to-moderate COVID-19. Methods: In this systematic review and meta-analysis, we searched PubMed, Scopus, and medRxiv from database inception to Aug 16, 2023, for randomised placebo-controlled trials that tested virus-directed treatments (ie, any monoclonal antibodies, convalescent plasma, or antivirals) in non-hospitalised individuals with COVID-19. We only included studies that reported both clinical outcomes (ie, rate of disease progression to hospitalisation or death) and virological outcomes (ie, viral load within the first 7 days of treatment). We extracted summary data from eligible reports, with discrepancies resolved through discussion. We used an established meta-regression model with random effects to assess the association between clinical efficacy and virological treatment effect, and calculated I 2 to quantify residual study heterogeneity. Findings: We identified 1718 unique studies, of which 22 (with a total of 16 684 participants) met the inclusion criteria, and were in primarily unvaccinated individuals. Risk of bias was assessed as low in 19 of 22 studies for clinical outcomes, whereas for virological outcomes, a high risk of bias was assessed in 11 studies, some risk in ten studies, and a low risk in one study. The unadjusted relative risk of disease progression for each extra log Interpretation: Despite the aggregation of studies with differing designs, and evidence of risk of bias in some virological outcomes, this review provides evidence that treatment-induced acceleration of viral clearance within the first 5 days after treatment is a potential surrogate of clinical efficacy to prevent hospitalisation with COVID-19. This work supports the use of viral clearance as an early phase clinical trial endpoint of therapeutic efficacy. Funding: Australian Government Department of Health, Medical Research Future Fund, and Australian National Health and Medical Research Council. Competing Interests: Declaration of interests MNP declares receiving provision of drugs for clinical trials from CSL Behring, Takeda, Grifols, Emergent Biosciences, and Gilead. DSK has received access to unpublished data via collaboration with employees of Merck & Co for research purposes on an unrelated pharmaceutical product. All other authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.) |
| المشرفين على المادة: | 0 (Antiviral Agents) |
| تواريخ الأحداث: | Date Created: 20240407 Date Completed: 20240510 Latest Revision: 20240510 |
| رمز التحديث: | 20240511 |
| DOI: | 10.1016/S2666-5247(23)00398-1 |
| PMID: | 38583464 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 2666-5247 |
|---|---|
| DOI: | 10.1016/S2666-5247(23)00398-1 |