Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults

Nature Medicine, Год журнала: 2022, Номер 28(5), С. 1031 - 1041

Опубликована: Март 31, 2022

Язык: Английский

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Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses

The Lancet, Год журнала: 2022, Номер 399(10339), С. 1941 - 1953

Опубликована: Май 1, 2022

BackgroundThe Solidarity trial among COVID-19 inpatients has previously reported interim mortality analyses for four repurposed antiviral drugs. Lopinavir, hydroxychloroquine, and interferon (IFN)-β1a were discontinued futility but randomisation to remdesivir continued. Here, we report the final results of meta-analyses in all relevant trials date.MethodsSolidarity enrolled consenting adults (aged ≥18 years) recently hospitalised with, view their doctor, definite no contraindication any study drugs, regardless other patient characteristics. Participants randomly allocated, equal proportions between locally available options, receive whichever drugs (lopinavir, IFN-β1a, or remdesivir) at that time drug (controls). All patients also received local standard care. No placebos given. The protocol-specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints progression ventilation if not already ventilated, time-to-discharge from hospital. Final log-rank Kaplan-Meier are presented remdesivir, appended Meta-analyses give weighted averages findings this randomised these hospital inpatients. is registered with ISRCTN, ISRCTN83971151, ClinicalTrials.gov, NCT04315948.FindingsBetween March 22, 2020, Jan 29, 2021, 14 304 potentially eligible recruited 454 hospitals 35 countries six WHO regions. After exclusion 83 (0·6%) a refuted diagnosis encrypted consent entered into database, 221 patients, including 8275 allocated (1:1) either (ten daily infusions, unless discharged earlier) its control (allocated although available). Compliance high both groups. Overall, 602 (14·5%) 4146 assigned died versus 643 (15·6%) 4129 (mortality rate ratio [RR] 0·91 [95% CI 0·82–1·02], p=0·12). Of those 151 (42·1%) 359 134 (38·6%) 347 (RR 1·13 [0·89–1·42], p=0·32). ventilated on oxygen, 14·6% 16·3% 0·87 [0·76–0·99], p=0·03). 1730 oxygen initially, 2·9% 3·8% 0·76 [0·46–1·28], p=0·30). Combining 11·9% 13·5% 0·86 [0·76–0·98], p=0·02) 14·1% 15·7% progressed 0·88 [0·77–1·00], p=0·04). non-prespecified composite outcome death occurred 19·6% 22·5% 0·84 [0·75–0·93], p=0·001). Allocation infusions (vs open-label control) delayed discharge about 1 day during 10-day treatment period. A meta-analysis yielded similar findings.InterpretationRemdesivir significant effect who being ventilated. Among it small against (or both).FundingWHO.

Язык: Английский

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Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial

The Lancet Infectious Diseases, Год журнала: 2021, Номер 22(2), С. 209 - 221

Опубликована: Сен. 14, 2021

Язык: Английский

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Efficacy of antiviral therapies for COVID-19: a systematic review of randomized controlled trials

BMC Infectious Diseases, Год журнала: 2022, Номер 22(1)

Опубликована: Янв. 31, 2022

Abstract Background Coronavirus disease 2019 (COVID-19) continues to pose a significant threat public health worldwide. The purpose of this study was review current evidence obtained from randomized clinical trials on the efficacy antivirals for COVID-19 treatment. Methods A systematic literature search performed using PubMed identify controlled published up September 4, 2021 that examined Studies were not or did include treatment with approved excluded. Risk bias assessed Scottish Intercollegiate Guidelines Network (SIGN) method. Due heterogeneity, inferential statistics and data expressed as descriptive statistics. Results Of 2,284 articles retrieved, 31 (12,440 patients) included. Overall, more effective when administered early in course. No antiviral demonstrated at reducing mortality. Sofosbuvir/daclatasvir results suggested improvement, although statistical power low. Remdesivir exhibited time recovery, but inconsistent across trials. Conclusions Although select have improve outcomes patients, none Larger RCTs are needed conclusively establish efficacy.

Язык: Английский

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Effects of remdesivir in patients hospitalised with COVID-19: a systematic review and individual patient data meta-analysis of randomised controlled trials

The Lancet Respiratory Medicine, Год журнала: 2023, Номер 11(5), С. 453 - 464

Опубликована: Фев. 22, 2023

Язык: Английский

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Remdesivir for the treatment of COVID-19

Cochrane library, Год журнала: 2023, Номер 2023(1)

Опубликована: Янв. 25, 2023

Язык: Английский

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Remdesivir for the treatment of COVID-19: a systematic review and meta-analysis

Clinical Microbiology and Infection, Год журнала: 2022, Номер 28(9), С. 1203 - 1210

Опубликована: Май 19, 2022

Язык: Английский

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Pharmacological treatment of COVID-19: an opinion paper

Revista Española de Quimioterapia, Год журнала: 2021, Номер 35(2), С. 115 - 130

Опубликована: Дек. 11, 2021

The precocity and efficacy of the vaccines developed so far against COVID-19 has been most significant saving advance pandemic. development not prevented, during whole period pandemic, constant search for therapeutic medicines, both among existing drugs with different indications in new drugs. Scientific Committee Illustrious College Physicians Madrid wanted to offer an early, simplified critical approach these drugs, developments immunotherapy what learned from immune response modulators already known which have proven effective virus, order help understand current situation.

Язык: Английский

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Respiratory dysfunction three months after severe COVID‐19 is associated with gut microbiota alterations

Journal of Internal Medicine, Год журнала: 2022, Номер 291(6), С. 801 - 812

Опубликована: Фев. 25, 2022

Although coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, mounting evidence suggests that the gastrointestinal tract involved in disease, with gut barrier dysfunction and microbiota alterations being related to severity. Whether these persist are long-term remains unknown.Plasma was collected during hospital admission after 3 months from NOR-Solidarity trial (n = 181) analyzed for markers of inflammation. At 3-month follow-up, pulmonary function assessed by measuring diffusing capacity lungs carbon monoxide (DLCO ). Rectal swabs analyses were 97) sequencing 16S rRNA gene.Gut diversity reduced COVID-19 patients dysfunction, defined as DLCO below lower limit normal hospitalization. These also had an altered global composition, relative abundance 20 bacterial taxa increased five taxa, including Veillonella, potentially linked fibrosis. During hospitalization, plasma levels lipopolysaccharide-binding protein (LBP) strongly associated failure, pO2 /fiO2 (P/F ratio) <26.6 kPa. LBP remained elevated hospitalization low-grade inflammation months.Respiratory persistently levels. Our results should be regarded hypothesis generating, pointing potential gut-lung axis further investigated relation long COVID.

Язык: Английский

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Antiviral drug treatment for nonsevere COVID-19: a systematic review and network meta-analysis

Canadian Medical Association Journal, Год журнала: 2022, Номер 194(28), С. E969 - E980

Опубликована: Июль 24, 2022

Background:

Randomized trial evidence suggests that some antiviral drugs are effective in patients with COVID-19. However, the comparative effectiveness of nonsevere COVID-19 is unclear.

Methods:

We searched Epistemonikos L·OVE (Living Overview Evidence) database for randomized trials comparing treatments, standard care or placebo adult up to Apr. 25, 2022. Reviewers extracted data and assessed risk bias. performed a frequentist network meta-analysis certainty using Grading Recommendations, Assessment, Development Evaluation (GRADE) approach.

Results:

identified 41 trials, which included 18 568 patients. Compared placebo, molnupiravir nirmatrelvir–ritonavir each reduced death moderate (10.9 fewer deaths per 1000, 95% confidence interval [CI] 12.6 4.5 molnupiravir; 11.7 CI 13.1 2.6 more). molnupiravir, probably hospital admission (27.8 admissions 32.8 18.3 fewer; certainty). Remdesivir has no effect on death, but may reduce (39.1 48.7 13.7 low

Interpretation:

Molnupiravir among Nirmatrelvir–ritonavir more than reducing admissions. Most were conducted unvaccinated patients, before emergence Omicron variant; these must thus be tested vaccinated against newer variants.

Язык: Английский

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