A Novel Protein Drug, Novaferon, as the Potential Antiviral Drug for COVID-19

Zheng, Fang; Zhou, Yi; Zhou, Zhiguo; Ye, Fei; Huang, Baoying; Huang, Yaxiong; Ma, Jing; Zuo, Qi; Tan, Xiaojuan; Xie, Jun; Niu, Peihua; Wang, Wenlong; Xu, Yun; Peng, Feng; Zhou, Ning; Cai, Chunlin; Tang, Wei; Xiao, Xuewen; Li, Yang; Zhou, Zhiguang; Jiang, Yongfang; Xie, Yuanlin; Tan, Wenjie; Gong, Guozhong

doi:10.1101/2020.04.24.20077735

Cited by 13 publications

(26 citation statements)

References 16 publications

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“…After screening 7285 titles and abstracts and 122 full texts, 32 unique randomised controlled trials were identified that evaluated drug treatments as of 20 July 2020 (fig 1). 30313233343536373839404142434445464748495051 Searches of living evidence retrieval services identified one additional eligible randomised controlled trial 52. Eighteen randomised controlled trials have been published in peer reviewed journals, and 14 only as preprints.…”

Section: Resultsmentioning

confidence: 99%

“…Of the 32 included drug trials, six evaluated treatment against active comparators, 18 evaluated treatment against standard care or placebo, and two evaluated different durations or doses of the same treatment. Our analyses were performed on 26 June 2020 and include 20 randomised controlled trials 3134353637383941424344454647484950Table 1. presents the characteristics of the included studies.…”

Section: Resultsmentioning

confidence: 99%

“…Eleven randomised controlled trials including 1875 participants3138394143444546475072 reported adverse effects leading to discontinuation of the study drug. The treatment nodes included in the network meta-analysis were hydroxychloroquine, remdesivir, and standard care.…”

Section: Resultsmentioning

confidence: 99%

“…All 10 randomised controlled trials that cumulatively enrolled 856 participants34374244454647505272 measured viral clearance with polymerase chain reaction cut-off points. The treatment nodes included in the network meta-analysis were hydroxychloroquine, lopinavir-ritonavir, remdesivir, and standard care.…”

Section: Resultsmentioning

confidence: 99%

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Drug treatments for covid-19: living systematic review and network meta-analysis

Siemieniuk

Bartoszko

Zeraatkar

et al. 2020

BMJ

677

659

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ObjectiveTo compare the effects of treatments for coronavirus disease 2019 (covid-19).DesignLiving systematic review and network meta-analysis.Data sourcesUS Centers for Disease Control and Prevention COVID-19 Research Articles Downloadable Database, which includes 25 electronic databases and six additional Chinese databases to 20 July 2020.Study selectionRandomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.MethodsAfter duplicate data abstraction, a bayesian random effects network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.Results23 randomised controlled trials were included in the analysis performed on 26 June 2020. The certainty of the evidence for most comparisons was very low because of risk of bias (lack of blinding) and serious imprecision. Glucocorticoids were the only intervention with evidence for a reduction in death compared with standard care (risk difference 37 fewer per 1000 patients, 95% credible interval 63 fewer to 11 fewer, moderate certainty) and mechanical ventilation (31 fewer per 1000 patients, 47 fewer to 9 fewer, moderate certainty). These estimates are based on direct evidence; network estimates for glucocorticoids compared with standard care were less precise because of network heterogeneity. Three drugs might reduce symptom duration compared with standard care: hydroxychloroquine (mean difference −4.5 days, low certainty), remdesivir (−2.6 days, moderate certainty), and lopinavir-ritonavir (−1.2 days, low certainty). Hydroxychloroquine might increase the risk of adverse events compared with the other interventions, and remdesivir probably does not substantially increase the risk of adverse effects leading to drug discontinuation. No other interventions included enough patients to meaningfully interpret adverse effects leading to drug discontinuation.ConclusionGlucocorticoids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care. The effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important study limitations.Systematic review registrationThis review was not registered. The protocol is included as a supplement.Readers’ noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Drug treatments for covid-19: living systematic review and network meta-analysis

Siemieniuk

Bartoszko

Zeraatkar

et al. 2020

BMJ

677

659

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“…Two trials compared convalescent plasma added to standard care versus standard care alone [ 40 , 52 ]. The remaining trials and comparisons included hydroxychloroquine with and without azithromycin added to standard care versus standard care alone [ 55 ], hydroxychloroquine versus placebo [ 54 , 68 ], hydroxychloroquine and chloroquine added to standard care versus standard care alone [ 49 ], methylprednisolone added to standard care versus standard care alone [ 57 ], lopinavir–ritonavir versus umifenovir and versus standard care [ 41 ], favipravir versus umifenovir [ 34 ], high-flow nasal oxygenation versus standard mask oxygenation prior to fibreotic tracheal intubation [ 45 ], α-lipoic acid versus placebo [ 47 ], the combination of novaferon plus lopinavir–ritonavir versus novaferon and versus lopinavir–ritonavir [ 46 ], baloxavir marboxil versus favipiravir and versus standard care [ 42 ], 5 versus 10 days of remdesivir [ 38 ], interferon β-1a added to standard care versus standard care alone [ 37 ], colchicine added to standard care versus standard care alone [ 50 ], high-dosage with low-dosage chloroquine diphosphate [ 51 ], intravenous immunoglobulin added to standard care versus standard care alone [ 58 ], ribavirin plus interferon alpha versus lopinavir/ritonavir plus interferon alpha versis ribavirin plus lopinavir/ritonavir plus interferon alpha [ 62 ], darunavir/cobicistat plus interferon alpha-2b versus interferon alpha-2b alone [ 61 ], lincomycin HCl versus azitromycin [ 63 ], 99mTc-methyl diphosphonate (99mTc-MDP) injection added to standard care versus standard care alone [ 64 ], and interferon alpha-2b plus gamma versus interferon alpha-2b alone [ 65 ].…”

Section: Resultsmentioning

confidence: 99%

Interventions for treatment of COVID-19: A living systematic review with meta-analyses and trial sequential analyses (The LIVING Project)

et al. 2020

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Background Coronavirus disease 2019 (COVID-19) is a rapidly spreading disease that has caused extensive burden to individuals, families, countries, and the world. Effective treatments of COVID-19 are urgently needed. Methods and findings This is the first edition of a living systematic review of randomized clinical trials comparing the effects of all treatment interventions for participants in all age groups with COVID-19. We planned to conduct aggregate data meta-analyses, trial sequential analyses, network meta-analysis, and individual patient data meta-analyses. Our systematic review is based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Cochrane guidelines, and our 8-step procedure for better validation of clinical significance of meta-analysis results. We performed both fixed-effect and random-effects meta-analyses. Primary outcomes were all-cause mortality and serious adverse events. Secondary outcomes were admission to intensive care, mechanical ventilation, renal replacement therapy, quality of life, and nonserious adverse events. We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence. We searched relevant databases and websites for published and unpublished trials until August 7, 2020. Two reviewers independently extracted data and assessed trial methodology. We included 33 randomized clinical trials enrolling a total of 13,312 participants. All trials were at overall high risk of bias. We identified one trial randomizing 6,425 participants to dexamethasone versus standard care. This trial showed evidence of a beneficial effect of dexamethasone on all-cause mortality (rate ratio 0.83; 95% confidence interval [CI] 0.75–0.93; p < 0.001; low certainty) and on mechanical ventilation (risk ratio [RR] 0.77; 95% CI 0.62–0.95; p = 0.021; low certainty). It was possible to perform meta-analysis of 10 comparisons. Meta-analysis showed no evidence of a difference between remdesivir versus placebo on all-cause mortality (RR 0.74; 95% CI 0.40–1.37; p = 0.34, I 2 = 58%; 2 trials; very low certainty) or nonserious adverse events (RR 0.94; 95% CI 0.80–1.11; p = 0.48, I 2 = 29%; 2 trials; low certainty). Meta-analysis showed evidence of a beneficial effect of remdesivir versus placebo on serious adverse events (RR 0.77; 95% CI 0.63–0.94; p = 0.009, I 2 = 0%; 2 trials; very low certainty) mainly driven by respiratory failure in one trial. Meta-analyses and trial sequential analyses showed that we could exclude the possibility that hydroxychloroquine versus standard care reduced the risk of all-cause mortality (RR 1.07; 95% CI 0.97–1.19; p = 0.17; I 2 = 0%; 7 trials; low certainty) and ...

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