A living WHO guideline on drugs for covid-19

BMJ, Journal Year: 2020, Volume and Issue: unknown, P. m3379 - m3379

Published: Sept. 4, 2020

Abstract Updates This is the fourteenth version (thirteenth update) of living guideline, replacing earlier versions (available as data supplements). New recommendations will be published updates to this guideline. Clinical question What role drugs in treatment patients with covid-19? Context The evidence base for therapeutics covid-19 evolving numerous randomised controlled trials (RCTs) recently completed and underway. Emerging SARS-CoV-2 variants subvariants are changing therapeutics. new? guideline development group (GDG) defined 1.5% a new threshold an important reduction risk hospitalisation non-severe covid-19. Combined updated baseline estimates, resulted stratification into at low, moderate, high hospitalisation. were added moderate nirmatrelvir/ritonavir, low molnupiravir remdesivir. pharmacokinetic was included nirmatrelvir/ritonavir molnupiravir, supporting existing recommendation ivermectin illness light additional trial which reduced degree uncertainty informing previous guidance. A made against antiviral agent VV116 severe or critical outside clinical based on one RCT comparing drug nirmatrelvir/ritonavir. structure publication has also been changed; now ordered by severity About from World Health Organization (WHO) incorporates dynamically update GDG typically evaluates therapy when WHO judges sufficient available make recommendation. While takes individual patient perspective making recommendations, it considers resource implications, acceptability, feasibility, equity, human rights. developed according standards methods trustworthy guidelines, use innovative process achieve efficiency dynamic updating recommendations. aligned Handbook Guideline Development pre-approved protocol (planning proposal) Review Committee (GRC). box end article outlines key methodological aspects process. MAGIC Evidence Ecosystem Foundation provides support, including coordination systematic reviews network meta-analyses inform full online MAGICapp PDF website, summary here BMJ . These formats should facilitate adaptation, strongly encouraged contextualise healthcare system maximise impact. Future Recommendations anticoagulation planned next Updated regarding systemic corticosteroids, azithromycin, favipiravir umefenovir illness, convalescent plasma statin review upcoming iterations.

Language: Английский

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Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19

JAMA, Journal Year: 2020, Volume and Issue: 324(13), P. 1317 - 1317

Published: Sept. 2, 2020

Importance

Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.

Objective

To determine whether hydrocortisone improves outcome patients with COVID-19.

Design, Setting, and Participants

An ongoing adaptive platform trial testing multiple interventions within therapeutic domains, example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 June 17, 2020, 614 adult suspected confirmed COVID-19 were enrolled randomized at least 1 domain following admission to an intensive care unit (ICU) respiratory cardiovascular organ support 121 sites in 8 countries. Of these, 403 open-label the domain. The was halted after results from another released. Follow-up ended August 12, 2020.

Interventions

participants a fixed 7-day course of intravenous (50 mg 100 every 6 hours) (n = 143), shock-dependent hours when shock clinically evident) 152), no 108).

Main Outcomes Measures

primary end point support–free days (days alive free ICU-based support) 21 days, where who died assigned –1 day. analysis bayesian cumulative logistic model that included all COVID-19, adjusting age, sex, site, region, time, assignment other intervention eligibility. Superiority defined as posterior probability odds ratio greater than (threshold conclusion superiority >99%).

Results

After excluding 19 withdrew consent, there 384 (mean 60 years; 29% female) fixed-dose 137), 146), 101) groups; 379 (99%) completed study analysis. mean age 3 groups ranged between 59.5 60.4 most male (range, 70.6%-71.5%); body mass index 29.7 30.9; receiving mechanical ventilation 50.0% 63.5%. For fixed-dose, shock-dependent, groups, respectively, median 0 (IQR, 15), 13), (–1 11) (composed 30%, 26%, 33% mortality rates 11.5, 9.5, among survivors). adjusted 1.43 (95% credible interval, 0.91-2.27) 93% hydrocortisone, 1.22 0.76-1.94) 80% compared hydrocortisone. Serious adverse events reported 4 (3%), 5 (1%) respectively.

Conclusions Relevance

Among treatment dosing resulted probabilities regard improvement days. However, stopped early strategy met prespecified criteria statistical superiority, precluding definitive conclusions.

Trial Registration

ClinicalTrials.gov Identifier:NCT02735707

Language: Английский

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COVID-19-neutralizing antibodies predict disease severity and survival

Cell, Journal Year: 2020, Volume and Issue: 184(2), P. 476 - 488.e11

Published: Dec. 16, 2020

Language: Английский

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Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial

The Lancet Global Health, Journal Year: 2021, Volume and Issue: 10(1), P. e42 - e51

Published: Oct. 28, 2021

BackgroundRecent evidence indicates a potential therapeutic role of fluvoxamine for COVID-19. In the TOGETHER trial acutely symptomatic patients with COVID-19, we aimed to assess efficacy versus placebo in preventing hospitalisation defined as either retention COVID-19 emergency setting or transfer tertiary hospital due COVID-19.MethodsThis placebo-controlled, randomised, adaptive platform done among high-risk Brazilian adults confirmed positive SARS-CoV-2 included eligible from 11 clinical sites Brazil known risk factor progression severe disease. Patients were randomly assigned (1:1) (100 mg twice daily 10 days) (or other treatment groups not reported here). The team, site staff, and masked allocation. Our primary outcome was composite endpoint up 28 days post-random assignment on basis intention treat. Modified treat explored receiving at least 24 h before event per-protocol analysis high level adherence (>80%). We used Bayesian analytic framework establish effects along probability success intervention compared placebo. is registered ClinicalTrials.gov (NCT04727424) ongoing.FindingsThe study team screened 9803 participants this trial. initiated June 2, 2020, current protocol reporting randomisation Jan 20 Aug 5, 2021, when arms stopped superiority. 741 allocated 756 average age 50 years (range 18–102 years); 58% female. proportion observed more than 6 transferred teritary lower group (79 [11%] vs 119 [16%] 756); relative [RR] 0·68; 95% credible interval [95% BCI]: 0·52–0·88), superiority 99·8% surpassing prespecified threshold 97·6% (risk difference 5·0%). Of events, 87% hospitalisations. Findings similar modified intention-to-treat (RR 0·69, BCI 0·53–0·90) larger 0·34, BCI, 0·21–0·54). There 17 deaths 25 (odds ratio [OR] 0·68, CI: 0·36–1·27). one death 12 population (OR 0·09; CI 0·01–0·47). found no significant differences number emergent adverse events groups.InterpretationTreatment outpatients early diagnosed reduced need hospital.FundingFastGrants Rainwater Charitable Foundation.TranslationFor Portuguese translation abstract see Supplementary Materials section.

Language: Английский

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Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial

The Lancet, Journal Year: 2022, Volume and Issue: 401(10373), P. 281 - 293

Published: Dec. 22, 2022

Language: Английский

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Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A

Science, Journal Year: 2021, Volume and Issue: 371(6532), P. 926 - 931

Published: Feb. 25, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins interact with the eukaryotic translation machinery, and inhibitors of have potent antiviral effects. We found that drug plitidepsin (aplidin), which has limited clinical approval, possesses activity (90% inhibitory concentration = 0.88 nM) is more than remdesivir against SARS-CoV-2 in vitro by a factor 27.5, toxicity cell culture. Through use drug-resistant mutant, we show mediated through inhibition known target eEF1A (eukaryotic elongation 1A). demonstrate vivo efficacy treatment two mouse models infection reduction replication lungs orders magnitude using prophylactic treatment. Our results indicate promising therapeutic candidate for COVID-19.

Language: Английский

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COVID-19: breaking down a global health crisis

Annals of Clinical Microbiology and Antimicrobials, Journal Year: 2021, Volume and Issue: 20(1)

Published: May 18, 2021

Abstract Coronavirus disease 2019 (COVID-19) is the second pandemic of twenty-first century, with over one-hundred million infections and two deaths to date. It a novel strain from Coronaviridae family, named Severe Acute Respiratory Distress Syndrome Coronavirus-2 (SARS-CoV-2); 7th known member coronavirus family cause in humans, notably following Middle East syndrome (MERS), (SARS). The most characteristic feature this single-stranded RNA molecule includes spike glycoprotein on its surface. Most patients COVID-19, which elderly immunocompromised are at risk, complain flu-like symptoms, including dry cough headache. common complications include pneumonia, acute respiratory distress syndrome, septic shock, cardiovascular manifestations. Transmission SARS-CoV-2 mainly via droplets, either directly air when an infected patient coughs or sneezes, form fomites surfaces. Maintaining hand-hygiene, social distancing, personal protective equipment (i.e., masks) remain effective precautions. Patient management supportive care anticoagulative measures, focus maintaining function. Therapy dexamethasone, remdesivir, tocilizumab appear be promising date, hydroxychloroquine, lopinavir, ritonavir, interferons falling out favour. Additionally, accelerated vaccination efforts have taken place internationally, several vaccinations being mass deployed. In response COVID-19 pandemic, countries stakeholders varying precautions combat contain spread virus dampen collateral economic damage. This review paper aims synthesize impact global, micro macro scale.

Language: Английский

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COVID-19 Transmission, Current Treatment, and Future Therapeutic Strategies

Molecular Pharmaceutics, Journal Year: 2021, Volume and Issue: 18(3), P. 754 - 771

Published: Jan. 19, 2021

At the stroke of New Year 2020, COVID-19, a zoonotic disease that would turn into global pandemic, was identified in Chinese city Wuhan. Although unique its transmission and virulence, COVID-19 is similar to diseases, including other SARS variants (e.g., SARS-CoV) MERS, exhibiting severe flu-like symptoms acute respiratory distress. Even at molecular level, many parallels have been between so much virus has named SARS-CoV-2. These similarities provided several opportunities treat patients using clinical approaches were proven be effective against SARS. Importantly, identification how SARS-CoV SARS-CoV-2 access host, replicate, trigger life-threatening pathological conditions revealed repurpose drugs In this article, we first an overview etiology vis-à-vis particularly MERS. Then, summarized characteristics droplets/aerosols emitted by they aid among people. Moreover, discussed mechanisms enable host become more contagious than betacoronaviruses such as SARS-CoV. Further, outlined various are currently being employed diagnose symptomatically clinic. Finally, reviewed technologies develop vaccines attempts classes novel therapeutic approaches.

Language: Английский

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Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: April 15, 2021

Abstract Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim estimate the effects of hydroxychloroquine and chloroquine survival in from all available RCT evidence, published unpublished. present a rapid meta-analysis ongoing, completed, discontinued RCTs treatment for any patients (protocol: https://osf.io/QESV4/ ). systematically identified unpublished (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up June 11, 2020), (PubMed, medRxiv bioRxiv October 16, 2020). All-cause mortality extracted (publications/preprints) requested investigators combined random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, publication status. Sixty-three were potentially eligible. included 14 (1308 patients) publications/preprints (9011 patients). Results are dominated by RECOVERY SOLIDARITY, two highly pragmatic trials, employed relatively high doses 4716 1853 patients, respectively (67% total sample size). The OR all-cause is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 1.77 (95%CI: 0.15, 21.13, 4 307 no effects. found that associated increased there benefit Findings have unclear generalizability outpatients, children, pregnant women, people comorbidities.

Language: Английский

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The efficacy and safety of Favipiravir in treatment of COVID-19: a systematic review and meta-analysis of clinical trials

Scientific Reports, Journal Year: 2021, Volume and Issue: 11(1)

Published: May 26, 2021

Abstract The novel coronavirus outbreak began in late December 2019 and rapidly spread worldwide, critically impacting public health systems. A number of already approved marketed drugs are being tested for repurposing, including Favipiravir. We aim to investigate the efficacy safety Favipiravir treatment COVID-19 patients through a systematic review meta-analysis. This meta-analysis were reported accordance with PRISMA statement. registered protocol PROSPERO (CRD42020180032). All clinical trials which addressed comparison other control groups confirmed infection SARS-CoV2 included. searched electronic databases LitCovid/PubMed, Scopus, Web Sciences, Cochrane, Scientific Information Database up 31 2020. assessed risk bias included studies using Cochrane Collaboration criteria. analyses performed Comprehensive Meta-Analysis software version 2, ratio index was calculated. Egger Begg test used assessing publication bias. Nine our results revealed significant improvement group versus during seven days after hospitalization (RR = 1.24, 95% CI: 1.09–1.41; P 0.001). Viral clearance more 14 than group, but this finding marginally not 1.11, 0.98–1.25; 0.094). Requiring supplemental oxygen therapy 7% less 0.93, 0.67–1.28; 0.664). Transferred ICU adverse events statistically different between two groups. mortality rate approximately 30% significant. possibly exerted no beneficial effect term general mild moderate COVID-19. should consider that perhaps use antiviral once patient has symptoms is too would explain their low setting.

Language: Английский

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