The Clinical Efficacy and Safety of Anti-Viral Agents for Non-Hospitalized Patients with COVID-19: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

This network meta-analysis compared the clinical efficacy and safety of anti-viral agents for the prevention of disease progression among non-hospitalized patients with COVID-19. PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov and the WHO International Clinical Trials Registry P...

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Main Authors: Chih-Cheng Lai, Ya-Hui Wang, Kuang-Hung Chen, Chao-Hsien Chen, Cheng-Yi Wang
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/14/8/1706
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author Chih-Cheng Lai
Ya-Hui Wang
Kuang-Hung Chen
Chao-Hsien Chen
Cheng-Yi Wang
author_facet Chih-Cheng Lai
Ya-Hui Wang
Kuang-Hung Chen
Chao-Hsien Chen
Cheng-Yi Wang
author_sort Chih-Cheng Lai
collection DOAJ
description This network meta-analysis compared the clinical efficacy and safety of anti-viral agents for the prevention of disease progression among non-hospitalized patients with COVID-19. PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched from their inception to 28 May 2022. Only randomized controlled trials (RCTs) that investigated the clinical efficacy of anti-viral agents for non-hospitalized patients with COVID-19 were included. Three RCTs involving 4241 patients were included. Overall, anti-viral agents were associated with a significantly lower risk of COVID-19 related hospitalization or death compared with the placebo (OR, 0.23; 95% CI: 0.06–0.96; <i>p</i> = 0.04). Compared with the placebo, patients receiving nirmatrelvir plus ritonavir had the lowest risk of hospitalization or death (OR, 0.12; 95% CI: 0.06–0.24), followed by remdesivir (OR, 0.13; 95% CI: 0.03–0.57) and then molnupiravir (OR, 0.67; 95% CI: 0.46–0.99). The rank probability for each treatment calculated using the P-score revealed that nirmatrelvir plus ritonavir was the best anti-viral treatment, followed by remdesivir and then molnupiravir. Finally, anti-viral agents were not associated with an increased risk of adverse events compared with the placebo. For non-hospitalized patients with COVID-19 who are at risk of disease progression, the currently recommended three anti-viral agents, nirmatrelvir plus ritonavir, molnupiravir and remdesivir, should continue to be recommended for the prevention of disease progression. Among them, oral nirmatrelvir plus ritonavir and intravenous remdesivir seem to be the better choice, followed by molnupiravir, as determined by this network meta-analysis. Additionally, these three anti-viral agents were shown to be as tolerable as the placebo in this clinical setting.
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spelling doaj.art-41a2f15b88d440cbb7bc91b03e22291f2023-11-30T22:38:59ZengMDPI AGViruses1999-49152022-08-01148170610.3390/v14081706The Clinical Efficacy and Safety of Anti-Viral Agents for Non-Hospitalized Patients with COVID-19: A Systematic Review and Network Meta-Analysis of Randomized Controlled TrialsChih-Cheng Lai0Ya-Hui Wang1Kuang-Hung Chen2Chao-Hsien Chen3Cheng-Yi Wang4Division of Hospital Medicine, Department of Internal Medicine, Chi Mei Medical Center, Tainan 710, TaiwanMedical Research Center, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 231, TaiwanDepartment of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100, TaiwanDivision of Pulmonary, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 104, TaiwanDepartment of Internal Medicine, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 231, TaiwanThis network meta-analysis compared the clinical efficacy and safety of anti-viral agents for the prevention of disease progression among non-hospitalized patients with COVID-19. PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched from their inception to 28 May 2022. Only randomized controlled trials (RCTs) that investigated the clinical efficacy of anti-viral agents for non-hospitalized patients with COVID-19 were included. Three RCTs involving 4241 patients were included. Overall, anti-viral agents were associated with a significantly lower risk of COVID-19 related hospitalization or death compared with the placebo (OR, 0.23; 95% CI: 0.06–0.96; <i>p</i> = 0.04). Compared with the placebo, patients receiving nirmatrelvir plus ritonavir had the lowest risk of hospitalization or death (OR, 0.12; 95% CI: 0.06–0.24), followed by remdesivir (OR, 0.13; 95% CI: 0.03–0.57) and then molnupiravir (OR, 0.67; 95% CI: 0.46–0.99). The rank probability for each treatment calculated using the P-score revealed that nirmatrelvir plus ritonavir was the best anti-viral treatment, followed by remdesivir and then molnupiravir. Finally, anti-viral agents were not associated with an increased risk of adverse events compared with the placebo. For non-hospitalized patients with COVID-19 who are at risk of disease progression, the currently recommended three anti-viral agents, nirmatrelvir plus ritonavir, molnupiravir and remdesivir, should continue to be recommended for the prevention of disease progression. Among them, oral nirmatrelvir plus ritonavir and intravenous remdesivir seem to be the better choice, followed by molnupiravir, as determined by this network meta-analysis. Additionally, these three anti-viral agents were shown to be as tolerable as the placebo in this clinical setting.https://www.mdpi.com/1999-4915/14/8/1706COVID-19nirmatrelvir plus ritonavirremdesivirmolnupiravir
spellingShingle Chih-Cheng Lai
Ya-Hui Wang
Kuang-Hung Chen
Chao-Hsien Chen
Cheng-Yi Wang
The Clinical Efficacy and Safety of Anti-Viral Agents for Non-Hospitalized Patients with COVID-19: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
Viruses
COVID-19
nirmatrelvir plus ritonavir
remdesivir
molnupiravir
title The Clinical Efficacy and Safety of Anti-Viral Agents for Non-Hospitalized Patients with COVID-19: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
title_full The Clinical Efficacy and Safety of Anti-Viral Agents for Non-Hospitalized Patients with COVID-19: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
title_fullStr The Clinical Efficacy and Safety of Anti-Viral Agents for Non-Hospitalized Patients with COVID-19: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
title_full_unstemmed The Clinical Efficacy and Safety of Anti-Viral Agents for Non-Hospitalized Patients with COVID-19: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
title_short The Clinical Efficacy and Safety of Anti-Viral Agents for Non-Hospitalized Patients with COVID-19: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
title_sort clinical efficacy and safety of anti viral agents for non hospitalized patients with covid 19 a systematic review and network meta analysis of randomized controlled trials
topic COVID-19
nirmatrelvir plus ritonavir
remdesivir
molnupiravir
url https://www.mdpi.com/1999-4915/14/8/1706
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