Small-molecule antivirals treatment for COVID-19: A systematic review and network meta-analysis
Bei Zheng, Qinqin Zhao, Wenjuan Yang, Pinpin Feng, Chuanwei Xin, Yin Ying, Bo Yang, Bing Han, Jun Zhu, Meiling Zhang, Gonghua Li
International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2024.107096
Highlights Systematic review and network meta-analysis assessing the efficacy and safety of small-molecule antivirals treatment for COVID-19. Proxalutamide, nirmatrelvir/ritonavir, triazavirin, azvudine, molnupiravir, and VV116 were ranked as the most effective drugs overall in both mild-to-moderate and unstratified groups. In both mild-to-moderate and unstratified groups, leritrelvir ranked first in virus clearance on days 7; however, no significant statistical difference was observed between leritrelvir and the subsequent medications Simnotrelvir/ritonavir and leritrelvir need further clinical data to confirm their efficacy and safety profiles. In terms of safety, the incidence of serious adverse events did not demonstrate an increase across all small-molecule antivirals, thereby confirming their favorable tolerability.
Competing Interests: The authors declare no competing interests. Ethical Approval: Not required.
Sequence Information: Not applicable
References
Ac Siemieniuk, Bartoszko, Zeraatkar, Drug treatments for covid-19: living systematic review and network meta-analysis, BMJ,
doi:10.1136/bmj.m2980Amani, Zareei, Amani, Rapid review and meta-analysis of adverse events associated with molnupiravir in patients with COVID-19, Br J Clin Pharmacol,
doi:10.1111/bcp.15449Behnam Amani, Amani, Efficacy and safety of nirmatrelvir/ritonavir (Paxlovid) for COVID-19: A rapid review and meta-analysis, Review J Med Virol,
doi:10.1002/jmv.28441Cheng, Chen, Jia, Efficacy and safety of current medications for treating severe and non-severe COVID-19 patients: an updated network meta-analysis of randomized placebo-controlled trials, Aging,
doi:10.18632/aging.203522Fariz, Zamzam Zein, Setiya Sulistiyana, Matthew Raffaello, Sofosbuvir with daclatasvir and the outcomes of patients with COVID-19: a systematic review and meta-analysis with GRADE assessment, Postgrad Med J,
doi:10.1136/postgradmedj-2021-140287Freeman, Fisher, White, Identifying inconsistency in network meta-analysis: is the net heat plot a reliable method?, Stat Med,
doi:10.1002/sim.8383Gao, Liu, Li, Molnupiravir for treatment of adults with mild or moderate COVID-19: a systematic review and meta-analysis of randomized controlled trials, Clin Microbiol Infect,
doi:10.1016/j.cmi.2023.04.014Gregori, Giacovelli, Minto, Association of Pharmacological Treatments With Long-term Pain Control in Patients With Knee Osteoarthritis A Systematic Review and Meta-analysis, JAMA,
doi:10.1001/jama.2018.19319Higgins, Savović, Page, Chapter 8: Assessing risk of bias in a randomized trial In Cochrane Handbook for Systematic Reviews of Interventions Version 6.1
Hsu, Chen, Chen, Effect of sofosbuvir-based treatment on clinical outcomes of patients with COVID-19: a systematic review and meta-analysis of randomised controlled trials, Int J Antimicrob Agents,
doi:10.1016/j.ijantimicag.2022.106545Huzaifa A Cheema, Jafar, Sohail, Nirmatrelvir-ritonavir for the treatment of COVID-19 patients: A systematic review and meta-analysis, J Med Virol,
doi:10.1002/jmv.28471Javier, Sánchez, Martínez-Sellés, María Molero, García, Insights for COVID-19 in 2023, Rev Esp Quimioter,
doi:10.37201/req/122.2022Li, He, Comparative efficacy and safety of current drugs against COVID-19: A systematic review and network meta-analysis, medRxiv,
doi:10.1101/2020.11.16.20232884Lo, Mertz, Loeb, Newcastle-Ottawa Scale: comparing reviewers' to authors' assessments, BMC Med Res Methodol,
doi:10.1186/1471-2288-14-45Page, Mckenzie, Bossuyt, The PRISMA 2020 statement: An updated guideline for reporting systematic reviews, Syst. Rev,
doi:10.1136/bmj.n71Peters, Sutton, Jones, Contouren hanced meta analysis funnel plots help distinguish publication bias from other causes of asymmetry, J Clin Epidemiol,
doi:10.1016/j.jclinepi.2007.11.010Pitre, Van Alstine, Chick, Antiviral drug treatment for nonsevere COVID-19: a systematic review and network meta-analysis, CMAJ,
doi:10.1503/cmaj.220471Polatoğlu, Oncu-Oner, Dalman, COVID-19 in early 2023: Structure, replication mechanism, variants of SARS-CoV-2, diagnostic tests, and vaccine & drug development studies, MedComm,
doi:10.1002/mco2.228Salanti, Ades, Ioannidis, Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial, J Clin Epidemiol,
doi:10.1016/j.jclinepi.2010.03.016Schandelmaier, Briel, Varadhan, Development of the Instrument to assess the Credibility of Effect Modification Analyses (ICEMAN) in randomized controlled trials and meta-analyses, CMAJ,
doi:10.1503/cmaj.200077Siang Kow, Javed, Ramachandram, Clinical outcomes of sofosbuvir-based antivirals in patients with COVID-19: a systematic review and meta-analysis of randomized trials, Expert Rev Anti Infect Ther,
doi:10.1080/14787210.2022.2000861Unoh, Uehara, Nakahara, Discovery of S-217622, a noncovalent oral SARS-CoV-2 3CL protease inhibitor clinical candidate for treating COVID-19, J. Med. Chem,
doi:10.1021/acs.jmedchem.2c00117Van Valkenhoef, Dias, Ades, Automated generation of node-splitting models for assessment of inconsistency in network meta-analysis, Res Synth Methods,
doi:10.1002/jrsm.1167Veroniki, Straus, Fyraridis, The rank-heat plot is a novel way to present the results from a network meta-analysis including multiple outcomes, J Clin Epidemiol,
doi:10.1016/j.jclinepi.2016.02.016Veroniki, Vasiliadis, Higgins, Evaluation of inconsistency in networks of interventions, Int J Epidemiol,
doi:10.1093/ije/dys222Vivek P Chavda 1, Aayushi, Patel 2, Darsh, Vaghasiya, SARS-CoV-2 variants and vulnerability at the global level, J Med Virol,
doi:10.1002/jmv.27717Vivek P Chavda, Raval, Sheta, Blood filtering system for COVID-19 management: novel modality of the cytokine storm therapeutics, Front Immunol,
doi:10.3389/fimmu.2023.1064459Who, Coronavirus disease COVID-19
DOI record:
{
"DOI": "10.1016/j.ijantimicag.2024.107096",
"ISSN": [
"0924-8579"
],
"URL": "http://dx.doi.org/10.1016/j.ijantimicag.2024.107096",
"alternative-id": [
"S0924857924000141"
],
"article-number": "107096",
"assertion": [
{
"label": "This article is maintained by",
"name": "publisher",
"value": "Elsevier"
},
{
"label": "Article Title",
"name": "articletitle",
"value": "Small-molecule antivirals treatment for COVID-19: A systematic review and network meta-analysis"
},
{
"label": "Journal Title",
"name": "journaltitle",
"value": "International Journal of Antimicrobial Agents"
},
{
"label": "CrossRef DOI link to publisher maintained version",
"name": "articlelink",
"value": "https://doi.org/10.1016/j.ijantimicag.2024.107096"
},
{
"label": "Content Type",
"name": "content_type",
"value": "article"
},
{
"label": "Copyright",
"name": "copyright",
"value": "© 2024 The Author(s). Published by Elsevier Ltd."
}
],
"author": [
{
"ORCID": "http://orcid.org/0000-0003-0575-1607",
"affiliation": [],
"authenticated-orcid": false,
"family": "Zheng",
"given": "Bei",
"sequence": "first"
},
{
"affiliation": [],
"family": "Zhao",
"given": "Qinqin",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Yang",
"given": "Wenjuan",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Feng",
"given": "Pinpin",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Xin",
"given": "Chuanwei",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0003-4767-0602",
"affiliation": [],
"authenticated-orcid": false,
"family": "Ying",
"given": "Yin",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-1572-9764",
"affiliation": [],
"authenticated-orcid": false,
"family": "Yang",
"given": "Bo",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Han",
"given": "Bing",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Zhu",
"given": "Jun",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-1023-8827",
"affiliation": [],
"authenticated-orcid": false,
"family": "Zhang",
"given": "Meiling",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Li",
"given": "Gonghua",
"sequence": "additional"
}
],
"container-title": "International Journal of Antimicrobial Agents",
"container-title-short": "International Journal of Antimicrobial Agents",
"content-domain": {
"crossmark-restriction": true,
"domain": [
"clinicalkey.fr",
"clinicalkey.jp",
"clinicalkey.es",
"clinicalkey.com.au",
"clinicalkey.com",
"elsevier.com",
"sciencedirect.com"
]
},
"created": {
"date-parts": [
[
2024,
1,
18
]
],
"date-time": "2024-01-18T17:06:20Z",
"timestamp": 1705597580000
},
"deposited": {
"date-parts": [
[
2024,
1,
19
]
],
"date-time": "2024-01-19T23:15:17Z",
"timestamp": 1705706117000
},
"funder": [
{
"DOI": "10.13039/501100020777",
"award": [
"2022ZYJ08",
"2022ZYJ20"
],
"doi-asserted-by": "publisher",
"name": "Zhejiang Pharmaceutical Association"
},
{
"DOI": "10.13039/501100004731",
"award": [
"LGF20G030004",
"LYQ20H310003"
],
"doi-asserted-by": "publisher",
"name": "Natural Science Foundation of Zhejiang Province"
}
],
"indexed": {
"date-parts": [
[
2024,
1,
20
]
],
"date-time": "2024-01-20T23:11:56Z",
"timestamp": 1705792316721
},
"is-referenced-by-count": 0,
"issued": {
"date-parts": [
[
2024,
1
]
]
},
"language": "en",
"license": [
{
"URL": "https://www.elsevier.com/tdm/userlicense/1.0/",
"content-version": "tdm",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2024,
1,
1
]
],
"date-time": "2024-01-01T00:00:00Z",
"timestamp": 1704067200000
}
},
{
"URL": "http://creativecommons.org/licenses/by-nc-nd/4.0/",
"content-version": "vor",
"delay-in-days": 16,
"start": {
"date-parts": [
[
2024,
1,
17
]
],
"date-time": "2024-01-17T00:00:00Z",
"timestamp": 1705449600000
}
}
],
"link": [
{
"URL": "https://api.elsevier.com/content/article/PII:S0924857924000141?httpAccept=text/xml",
"content-type": "text/xml",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "https://api.elsevier.com/content/article/PII:S0924857924000141?httpAccept=text/plain",
"content-type": "text/plain",
"content-version": "vor",
"intended-application": "text-mining"
}
],
"member": "78",
"original-title": [],
"page": "107096",
"prefix": "10.1016",
"published": {
"date-parts": [
[
2024,
1
]
]
},
"published-print": {
"date-parts": [
[
2024,
1
]
]
},
"publisher": "Elsevier BV",
"reference-count": 0,
"references-count": 0,
"relation": {},
"resource": {
"primary": {
"URL": "https://linkinghub.elsevier.com/retrieve/pii/S0924857924000141"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [
"Pharmacology (medical)",
"Infectious Diseases",
"Microbiology (medical)",
"General Medicine"
],
"subtitle": [],
"title": "Small-molecule antivirals treatment for COVID-19: A systematic review and network meta-analysis",
"type": "journal-article",
"update-policy": "http://dx.doi.org/10.1016/elsevier_cm_policy"
}
