Interventions for treatment of COVID-19: Second edition of a living systematic review with meta-analyses and trial sequential analyses (The LIVING Project).
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SUBMITTER: Juul S
PROVIDER: S-EPMC7954033 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
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Interventions for treatment of COVID-19: Second edition of a living systematic review with meta-analyses and trial sequential analyses (The LIVING Project).
Juul Sophie S Nielsen Emil Eik EE Feinberg Joshua J Siddiqui Faiza F Jørgensen Caroline Kamp CK Barot Emily E Holgersson Johan J Nielsen Niklas N Bentzer Peter P Veroniki Areti Angeliki AA Thabane Lehana L Bu Fanlong F Klingenberg Sarah S Gluud Christian C Jakobsen Janus Christian JC
PloS one 20210311 3
<h4>Background</h4>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. This is the second edition of a living systematic review of randomized clinical trials assessing the effects of all treatment interventions for participants in all age groups with COVID-19.<h4>Methods and findings</h4>We planned to conduct aggregate data meta-analyses, trial sequential analyses, netwo ...[more]
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| S-EPMC7498193 | biostudies-literature
Project description:ObjectivesTo assess the effects of interventions authorised by the European Medicines Agency (EMA) or the US Food and Drug Administration (FDA) for prevention of COVID-19 progression to severe disease in outpatients.SettingOutpatient treatment.ParticipantsParticipants with a diagnosis of COVID-19 and the associated SARS-CoV-2 virus irrespective of age, sex and comorbidities.InterventionsDrug interventions authorised by EMA or FDA.Primary outcome measuresPrimary outcomes were all-cause mortality and serious adverse events.ResultsWe included 17 clinical trials randomising 16 257 participants to 8 different interventions authorised by EMA or FDA. 15/17 of the included trials (88.2%) were assessed at high risk of bias. Only molnupiravir and ritonavir-boosted nirmatrelvir seemed to improve both our primary outcomes. Meta-analyses showed that molnupiravir reduced the risk of death (relative risk (RR) 0.11, 95% CI 0.02 to 0.64; p=0.0145, 2 trials; very low certainty of evidence) and serious adverse events (RR 0.63, 95% CI 0.47 to 0.84; p=0.0018, 5 trials; very low certainty of evidence). Fisher's exact test showed that ritonavir-boosted nirmatrelvir reduced the risk of death (p=0.0002, 1 trial; very low certainty of evidence) and serious adverse events (p<0.0001, 1 trial; very low certainty of evidence) in 1 trial including 2246 patients, while another trial including 1140 patients reported 0 deaths in both groups.ConclusionsThe certainty of the evidence was very low, but, from the results of this study, molnupiravir showed the most consistent benefit and ranked highest among the approved interventions for prevention of COVID-19 progression to severe disease in outpatients. The lack of certain evidence should be considered when treating patients with COVID-19 for prevention of disease progression.Prospero registration numberCRD42020178787.
| S-EPMC10314423 | biostudies-literature
Project description:BackgroundCOVID-19 is a rapidly spreading virus infection that has quickly caused extensive burden to individual, families, countries, and the globe. No intervention has yet been proven effective for the treatment of COVID-19. Some randomized clinical trials assessing the effects of different drugs have been published, and more are currently underway. There is an urgent need for a living, dynamic systematic review that continuously evaluates the beneficial and harmful effects of all available interventions for COVID-19.Methods/designWe will conduct a living systematic review based on searches of major medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify relevant randomized clinical trials. We will update the literature search once a week to continuously assess if new evidence is available. Two review authors will independently extract data and perform risk of bias assessment. We will include randomized clinical trials comparing any intervention for the treatment of COVID-19 (e.g., pharmacological interventions, fluid therapy, invasive or noninvasive ventilation, or similar interventions) with any comparator (e.g., an "active" comparator, standard care, placebo, no intervention, or "active placebo") for participants in all age groups with a diagnosis of COVID-19. Primary outcomes will be all-cause mortality and serious adverse events. Secondary outcomes will be admission to intensive care, mechanical ventilation, renal replacement therapy, quality of life, and non-serious adverse events. The living systematic review will include aggregate data meta-analyses, Trial Sequential Analyses, network meta-analysis, and individual patient data meta-analyses. Risk of bias will be assessed with domains, an eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations (GRADE).DiscussionCOVID-19 has become a pandemic with substantial mortality. A living systematic review evaluating the beneficial and harmful effects of pharmacological and other interventions is urgently needed. This review will continuously inform best practice in treatment and clinical research of this highly prevalent disease.Systematic review registrationPROSPERO CRD42020178787.
| S-EPMC7210799 | biostudies-literature
Project description:SummaryThe web platform 3DBionotes-WS integrates multiple Web Services and an interactive Web Viewer to provide a unified environment in which biological annotations can be analyzed in their structural context. Since the COVID-19 outbreak, new structural data from many viral proteins have been provided at a very fast pace. This effort includes many cryogenic Electron Microscopy (cryo-EM) studies, together with more traditional ones (X-rays, NMR), using several modeling approaches and complemented with structural predictions. At the same time, a plethora of new genomics and interactomics information (including fragment screening and structure-based virtual screening efforts) have been made available from different servers. In this context we have developed 3DBionotes-COVID-19 as an answer to: (1) The need to explore multi-omics data in a unified context with a special focus on structural information and (2) the drive to incorporate quality measurements, especially in the form of advanced validation metrics for cryogenic Electron Microscopy.Availabilityhttps://3dbionotes.cnb.csic.es/ws/covid19.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC8241415 | biostudies-literature
Project description:Background: The coronavirus disease 2019 (COVID-19) pandemic has created a great burden on governments and the medical fraternity globally. Many clinical studies from the Indian system of Traditional Medicines [Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homoeopathy (AYUSH)] have been carried out to find appropriate solutions. Through a living systematic review and meta-analysis, this study aims to determine the effectiveness of the Traditional System of Indian Medicine (AYUSH system) in lowering the incidence, duration, and severity of COVID-19. Methods: We will search the following databases: Pubmed; the Cochrane central register of controlled trials (CENTRAL); the Clinical Trials Registry - India (CTRI); Digital Helpline for Ayurveda Research Articles (DHARA); AYUSH research portal; Google scholar and World Health Organization (WHO) COVID-19 database. Clinical improvement, WHO ordinal scale, viral clearance, incidences of COVID-19 infection, and mortality will be considered as primary outcomes. Secondary outcomes will be use of O2 therapy or mechanical ventilator, admission to high dependency unit or emergency unit, duration of hospitalization, the time to symptom resolution, and adverse events. Data will be synthesized, with RevMan 5.4 tool and the risk of bias will be assessed with RoB 2 (for RCTs) and ROBINS I (for NRSIs). Certainty of evidence will be assessed through the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) tool. The review will be updated bi-monthly with two updates. Conclusion: This living systematic review will be the first to address AYUSH interventions in COVID-19, synthesizing the full spectrum of Indian Traditional System of Medicine against COVID-19. It will facilitate professionals, guideline developers, and authorities with up to date synthesis on interventions periodically to make health-care decisions on AYUSH therapies in the management of COVID-19.
| S-EPMC8822137 | biostudies-literature
Project description:BackgroundCoronavirus disease 2019 (COVID-19) has rapidly spread worldwide, but safe and effective treatment options remain unavailable. Numerous systematic reviews of varying qualities have tried to summarize the evidence on the available therapeutic interventions for COVID-19. This overview of reviews aims to provide a succinct summary of the findings of systematic reviews on different pharmacological and non-pharmacological therapeutic interventions for COVID-19.MethodsWe searched PubMed, Embase, Google Scholar, Cochrane Database of Systematic Reviews, and WHO database of publications on COVID-19 from 1 December 2019 through to 11 June 2020 for peer-reviewed systematic review studies that reported on potential pharmacological or non-pharmacological therapies for COVID-19. Quality assessment was completed using A MeaSurement Tool to Assess systematic Reviews-2 (AMSTAR-2) measure.ResultsOut of 816 non-duplicate studies, 45 were included in the overview. Antiviral and antibiotic agents, corticosteroids, and anti-malarial agents were the most common drug classes used to treat COVID-19; however, there was no direct or strong evidence to support their efficacy. Oxygen therapy and ventilatory support was the most common non-pharmacological supportive care. The quality of most of the included reviews was rated as low or critically low.ConclusionThis overview of reviews demonstrates that although some therapeutic interventions may be beneficial to specific subgroups of COVID-19 patients, the available data are insufficient to strongly recommend any particular treatment option to be used at a population level. Future systematic reviews on COVID-19 treatments should adhere to the recommended systematic review methodologies and ensure that promptness and comprehensiveness are balanced.The reviews of this paper are available via the supplemental material section.
| S-EPMC7747112 | biostudies-literature
Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) which has rapidly spread worldwide. Several human randomized clinical trials assessing potential vaccines are currently underway. There is an urgent need for a living systematic review that continuously assesses the beneficial and harmful effects of all available vaccines for COVID-19.Methods/designWe will conduct a living systematic review based on searches of major medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify relevant randomized clinical trials. We will update the literature search once a week to continuously assess if new evidence is available. Two review authors will independently extract data and conduct risk of bias assessments. We will include randomized clinical trials comparing any vaccine aiming to prevent COVID-19 (including but not limited to messenger RNA; DNA; non-replicating viral vector; replicating viral vector; inactivated virus; protein subunit; dendritic cell; other vaccines) with any comparator (placebo; "active placebo;" no intervention; standard care; an "active" intervention; another vaccine for COVID-19) for participants in all age groups. Primary outcomes will be all-cause mortality; a diagnosis of COVID-19; and serious adverse events. Secondary outcomes will be quality of life and non-serious adverse events. The living systematic review will include aggregate data meta-analyses, trial sequential analyses, network meta-analyses, and individual patient data meta-analyses. Within-study bias will be assessed using Cochrane risk of bias tool. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) and Confidence in Network Meta-Analysis (CINeMA) approaches will be used to assess certainty of evidence. Observational studies describing harms identified during the search for trials will also be included and described and analyzed separately.DiscussionCOVID-19 has become a pandemic with substantial mortality. A living systematic review assessing the beneficial and harmful effects of different vaccines is urgently needed. This living systematic review will regularly inform best practice in vaccine prevention and clinical research of this highly prevalent disease.Systematic review registrationPROSPERO CRD42020196492.
| S-EPMC7678579 | biostudies-literature
Project description:BackgroundUp to 15% of survivors of COVID-19 infection experience long-term health effects, including fatigue, myalgia and impaired cognitive function, termed post-COVID-19 condition or long COVID. Several trials that study the benefits and harms of various interventions to manage long COVID have been published and hundreds more are planned or are ongoing. Trustworthy systematic reviews that clarify the benefits and harms of interventions are critical to promote evidence-based practice.ObjectiveTo create and maintain a living systematic review and network meta-analysis addressing the benefits and harms of pharmacologic and non-pharmacologic interventions for the treatment and management of long COVID.MethodsEligible trials will randomise adults with long COVID to pharmacologic or non-pharmacologic interventions, placebo, sham or usual care. We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, PsycINFO, AMED and CENTRAL from inception, without language restrictions.Reviewers will work independently and in duplicate to screen search records, collect data from eligible trials, including trial and patient characteristics and outcomes of interest and assess risk of bias. Our outcomes of interest will include patient-reported fatigue, pain, postexertional malaise, changes in education or employment status, cognitive function, mental health, dyspnoea, quality of life, physical function, recovery and serious adverse events.For each outcome, when possible, we will perform a frequentist random-effects network meta-analysis. When there are compelling reasons to suspect that certain interventions are only applicable or effective for a subtype of long COVID, we will perform separate network meta-analyses. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach will guide our assessment of the certainty of evidence.We will update our living review biannually, on the publication of a seminal trial, or when new evidence emerges that may change clinical practice.ConclusionThis living systematic review and network meta-analysis will provide comprehensive, trustworthy and up-to-date summaries of the evidence addressing the benefits and harms of interventions for the treatment and management of long COVID. We will make our findings available publicly and work with guideline-producing organisations to inform their recommendations.Ethics and disseminationThe study describes the protocol for a systematic review that uses data from published trial reports. Therefore, the study is exempt from ethics review. We intend to deposit all data in a public repository and publish each iteration of the living review online.
| S-EPMC11808878 | biostudies-literature
Project description:BackgroundCOVID-19 is rapidly spreading causing extensive burdens across the world. Effective vaccines to prevent COVID-19 are urgently needed.Methods and findingsOur objective was to assess the effectiveness and safety of COVID-19 vaccines through analyses of all currently available randomized clinical trials. We searched the databases CENTRAL, MEDLINE, Embase, and other sources from inception to June 17, 2021 for randomized clinical trials assessing vaccines for COVID-19. At least two independent reviewers screened studies, extracted data, and assessed risks of bias. We conducted meta-analyses, network meta-analyses, and Trial Sequential Analyses (TSA). Our primary outcomes included all-cause mortality, vaccine efficacy, and serious adverse events. We assessed the certainty of evidence with GRADE. We identified 46 trials; 35 trials randomizing 219 864 participants could be included in our analyses. Our meta-analyses showed that mRNA vaccines (efficacy, 95% [95% confidence interval (CI), 92% to 97%]; 71 514 participants; 3 trials; moderate certainty); inactivated vaccines (efficacy, 61% [95% CI, 52% to 68%]; 48 029 participants; 3 trials; moderate certainty); protein subunit vaccines (efficacy, 77% [95% CI, -5% to 95%]; 17 737 participants; 2 trials; low certainty); and viral vector vaccines (efficacy 68% [95% CI, 61% to 74%]; 71 401 participants; 5 trials; low certainty) prevented COVID-19. Viral vector vaccines decreased mortality (risk ratio, 0.25 [95% CI 0.09 to 0.67]; 67 563 participants; 3 trials, low certainty), but comparable data on inactivated, mRNA, and protein subunit vaccines were imprecise. None of the vaccines showed evidence of a difference on serious adverse events, but observational evidence suggested rare serious adverse events. All the vaccines increased the risk of non-serious adverse events.ConclusionsThe evidence suggests that all the included vaccines are effective in preventing COVID-19. The mRNA vaccines seem most effective in preventing COVID-19, but viral vector vaccines seem most effective in reducing mortality. Further trials and longer follow-up are necessary to provide better insight into the safety profile of these vaccines.
| S-EPMC8782520 | biostudies-literature
Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies, particularly those preventing interaction between the viral spike receptor-binding domain and the host angiotensin-converting enzyme 2 receptor, may prevent viral entry into host cells and disease progression.MethodsWe performed a systematic review, meta-analysis, trial sequential analysis (TSA), and meta-regression of RCTs to evaluate the benefit of convalescent plasma for COVID-19. The primary outcome was 28-30 day mortality. Secondary outcomes included need for mechanical ventilation and ICU admission. Data sources were PubMed, Embase, MedRxiv, and the Cochrane library on July 2, 2021.ResultsWe identified 17 RCTs that recruited 15 587 patients with 8027 (51.5%) allocated to receive convalescent plasma. Convalescent plasma use was not associated with a mortality benefit (24.7% vs 25.5%; odds ratio [OR]=0.94 [0.85-1.04]; P=0.23; I2=4%; TSA adjusted confidence interval [CI], 0.84-1.05), or reduction in need for mechanical ventilation (15.7% vs 15.4%; OR=1.01 [0.92-1.11]; P=0.82; I2=0%; TSA adjusted CI, 0.91-1.13), or ICU admission (22.4% vs 16.7%; OR=0.80 [0.21-3.09]; P=0.75; I2=63%; TSA adjusted CI, 0.0-196.05). Meta-regression did not reveal association with titre of convalescent plasma, timing of administration, or risk of death and treatment effect (P>0.05). Risk of bias was high in most studies.ConclusionsIn patients with COVID-19, there was no clear mortality benefit associated with convalescent plasma treatment. In patients with mild disease, convalescent plasma did not prevent either the need for mechanical ventilation or ICU admission.Clinical trial registrationCRD42021234201 (PROSPERO).
| S-EPMC8403663 | biostudies-literature