Interleukin-6 blocking agents for treating COVID-19: a living systematic review.
Ontology highlight
ABSTRACT:
SUBMITTER: Ghosn L
PROVIDER: S-EPMC8406988 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
Publications
Interleukin-6 blocking agents for treating COVID-19: a living systematic review.
Ghosn Lina L Chaimani Anna A Evrenoglou Theodoros T Davidson Mauricia M Graña Carolina C Schmucker Christine C Bollig Claudia C Henschke Nicholas N Sguassero Yanina Y Nejstgaard Camilla Hansen CH Menon Sonia S Nguyen Thu Van TV Ferrand Gabriel G Kapp Philipp P Riveros Carolina C Ávila Camila C Devane Declan D Meerpohl Joerg J JJ Rada Gabriel G Hróbjartsson Asbjørn A Grasselli Giacomo G Tovey David D Ravaud Philippe P Boutron Isabelle I
The Cochrane database of systematic reviews 20210318
<h4>Background</h4>Interleukin 6 (IL-6) blocking agents have been used for treating severe coronavirus disease 2019 (COVID-19). Their immunosuppressive effect might be valuable in patients with COVID-19 characterised by substantial immune system dysfunction by controlling inflammation and promoting disease tolerance.<h4>Objectives</h4>To assess the effect of IL-6 blocking agents compared to standard care alone or with placebo on efficacy and safety outcomes in COVID-19. We will update this asses ...[more]
Similar Datasets
Project description: Not available
| S-EPMC8791232 | biostudies-literature
Project description:IL-1 is a master cytokine of local and systemic inflammation. With the availability of specific IL-1 targeting therapies, a broadening list of diseases has revealed the pathologic role of IL-1-mediated inflammation. Although IL-1, either IL-1? or IL-1?, was administered to patients in order to improve bone marrow function or increase host immune responses to cancer, these patients experienced unacceptable toxicity with fever, anorexia, myalgias, arthralgias, fatigue, gastrointestinal upset and sleep disturbances; frank hypotension occurred. Thus it was not unexpected that specific pharmacological blockade of IL-1 activity in inflammatory diseases would be beneficial. Monotherapy blocking IL-1 activity in a broad spectrum of inflammatory syndromes results in a rapid and sustained reduction in disease severity. In common conditions such as heart failure and gout arthritis, IL-1 blockade can be effective therapy. Three IL-1blockers have been approved: the IL-1 receptor antagonist, anakinra, blocks the IL-1 receptor and therefore reduces the activity of IL-1? and IL-1?. A soluble decoy receptor, rilonacept, and a neutralizing monoclonal anti-interleukin-1? antibody, canakinumab, are also approved. A monoclonal antibody directed against the IL-1 receptor and a neutralizing anti-IL-1? are in clinical trials. By specifically blocking IL-1, we have learned a great deal about the role of this cytokine in inflammation but equally important, reducing IL-1 activity has lifted the burden of disease for many patients.
| S-EPMC3953875 | biostudies-other
Project description:This systematic review summarizes the evidence on the earliest patients with COVID-19-HIV co-infection. We searched PubMed, Scopus, Web of Science, Embase, preprint databases, and Google Scholar from December 01, 2019, to June 1, 2020. From an initial 547 publications and 75 reports, 25 studies provided specific information on COVID-19 patients living with HIV. Studies described 252 patients, 80.9% were male, the mean age was 52.7 years, and 98% were on antiretroviral treatment (ART). Co-morbidities in addition to HIV and COVID-19 (multimorbidity) included hypertension (39.3%), obesity or hyperlipidemia (19.3%), chronic obstructive pulmonary disease (18.0%), and diabetes (17.2%). Two-thirds (66.5%) had mild to moderate symptoms, the most common being fever (74.0%) and cough (58.3%). Among patients who died, the majority (90.5%) were over 50 years old, male (85.7%), and had multimorbidity (64.3%). Our findings highlight the importance of identifying co-infections, addressing co-morbidities, and ensuring a secure supply of ART for PLHIV during the COVID-19 pandemic.
| S-EPMC7391049 | biostudies-literature
Project description:Coronaviruses may activate dysregulated host immune responses. As exploratory studies have suggested that interleukin-6 (IL-6) levels are elevated in cases of complicated Covid-19, we undertook a systematic review and meta-analysis to assess the evidence in this field. We systematically searched MEDLINE and EMBASE for studies investigating the immunological response in Covid-19; additional grey literature searches were undertaken. Study selection and data abstraction was undertaken independently by two authors. Meta-analysis was undertaken using random effects models to compute ratios of means with 95% confidence intervals (95%CIs). Eight published studies and two preprints (n = 1798) were eligible for inclusion. Meta-analysis of mean IL-6 concentrations demonstrated 2.9-fold higher levels in patients with complicated Covid-19 compared with patients with noncomplicated disease (six studies; n = 1302; 95%CI, 1.17-7.19; I2 = 100%). Consistent results were found in sensitivity analyses exclusively restricted to studies comparing patients requiring ICU admission vs no ICU admission (two studies; n = 540; ratio of means = 3.24; 95%CI, 2.54-4.14; P < .001; I2 = 87%). Nine of ten studies were assessed to have at least moderate risk of bias. In patients with Covid-19, IL-6 levels are significantly elevated and associated with adverse clinical outcomes. Inhibition of IL-6 may be a novel target for therapeutics for the management of dysregulated host responses in patients with Covid-19 and high-quality studies of intervention in this field are urgently required.
| S-EPMC7460877 | biostudies-literature
Project description: Not available
| S-EPMC9891348 | biostudies-literature
Project description:Since the coronavirus disease 2019 (COVID-19) outbreak was identified in December 2019 in Wuhan, China, a strong response from the research community has been observed with the proliferation of independent clinical trials assessing diagnostic methods, therapeutic and prophylactic strategies. While there is no intervention for the prevention or treatment of COVID-19 with proven clinical efficacy to date, tools to distil the current research landscape by intervention, level of evidence and those studies likely powered to address future research questions is essential. This living systematic review aims to provide an open, accessible and frequently updated resource summarising the characteristics of COVID-19 clinical trial registrations. Weekly search updates of the WHO International Clinical Trials Registry Platform (ICTRP) and source registries will be conducted. Data extraction by two independent reviewers of trial characteristic variables including categorisation of trial design, geographic location, intervention type and targets, level of evidence and intervention adaptability to low resource settings will be completed. Descriptive and thematic synthesis will be conducted. A searchable and interactive visualisation of the results database will be created, and made openly available online. Weekly results from the continued search updates will be published and made available on the Infectious Diseases Data Observatory (IDDO) website ( COVID-19 website). This living systematic review will provide a useful resource of COVID-19 clinical trial registrations for researchers in a rapidly evolving context. In the future, this sustained review will allow prioritisation of research targets for individual patient data meta-analysis.
| S-EPMC7141164 | biostudies-literature
Project description:UpdatesThis is the second version (first update) of the living systematic review, replacing the previous version (available as a data supplement). When citing this paper please consider adding the version number and date of access for clarity.ObjectiveTo determine and compare the effects of drug prophylaxis on severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (covid-19).DesignLiving systematic review and network meta-analysis (NMA).Data sourcesWorld Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 4 March 2022.Study selectionRandomised trials in which people at risk of covid-19 were allocated to prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles.MethodsAfter duplicate data abstraction, we conducted random-effects bayesian network meta-analysis. We assessed risk of bias of the included studies using a modification of the Cochrane risk of bias 2.0 tool and assessed the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach.ResultsThe second iteration of this living NMA includes 32 randomised trials which enrolled 25 147 participants and addressed 21 different prophylactic drugs; adding 21 trials (66%), 18 162 participants (75%) and 16 (76%) prophylactic drugs. Of the 16 prophylactic drugs analysed, none provided convincing evidence of a reduction in the risk of laboratory confirmed SARS-CoV-2 infection. For admission to hospital and mortality outcomes, no prophylactic drug proved different than standard care or placebo. Hydroxychloroquine and vitamin C combined with zinc probably increase the risk of adverse effects leading to drug discontinuation—risk difference for hydroxychloroquine (RD) 6 more per 1000 (95% credible interval (CrI) 2 more to 10 more); for vitamin C combined with zinc, RD 69 more per 1000 (47 more to 90 more), moderate certainty evidence.ConclusionsMuch of the evidence remains very low certainty and we therefore anticipate future studies evaluating drugs for prophylaxis may change the results for SARS-CoV-2 infection, admission to hospital and mortality outcomes. Both hydroxychloroquine and vitamin C combined with zinc probably increase adverse effects.Systematic review registrationThis review was not registered. The protocol established a priori is included as a supplement.FundingThis study was supported by the Canadian Institutes of Health Research (grant CIHR-IRSC:0579001321).
| S-EPMC8073806 | biostudies-literature
Project description:The inflammatory cytokines IL-1α and IL-1β orchestrate local and systemic inflammatory responses underlying a broad spectrum of diseases. Three agents for reducing IL-1 activities are currently available. Anakinra is a recombinant form of the naturally occurring IL-1 receptor antagonist. Anakinra binds to the IL-1 receptor and prevents the activity of IL-1α and IL-1β. The soluble decoy receptor rilonacept and the neutralizing mAb canakinumab block IL-1β. A mAb directed against the IL-1 receptor and a neutralizing anti-human IL-1α are in clinical trials. The availability of therapies specifically targeting IL-1 unveiled the pathological role of IL-1-mediated inflammation in a broadening list of diseases. Conditions effectively treated with agents blocking IL-1 range from classic rheumatic diseases, such as RA and gout, to autoinflammatory syndromes, such as systemic JIA and FMF. However, IL-1 antagonism is also effective against highly prevalent inflammatory diseases, namely cardiovascular diseases and type 2 diabetes, conditions that are frequently encountered as co-morbidities in patients with rheumatic diseases. Thereby, IL-1 inhibition has the potential to lift the burden of disease for patients with rheumatic conditions, but also to provide clinical benefits beyond the efficacy on osteoarticular manifestations.
| S-EPMC5009422 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) had caused huge health losses worldwide. Several drugs had been applied to treat patients with COVID-19, and repurposing colchicine had been proposed for its anti-inflammatory properties via several pathways. In this systematic review, we evaluated the effects of colchicine treatment. From inception to May 31, 2021, databases, including PubMed, EMbase, medRxiv, and Research Square were searched, and 11 studies were enrolled. A total of 17,205 COVID-19 patients with male predominance (62.9%) were analyzed. Patients with colchicine treatment had a significantly lower risk of mortality (odds ratio (OR): 0.57, 95% confidence interval (CI): 0.38-0.87, I2: 72%; p < 0.01) and a non-significantly lower rate of mechanical ventilation (OR: 0.67, 95%CI: 0.39-1.15). The side effects were mild and not significantly different (OR: 2.03, 95%CI: 0.51-8.09). Subgroup analysis with randomized controlled trials showed no statistically significant difference in the mortality (OR: 0.80, 95%CI: 0.44-1.46, I2: 33%; p = 0.22). In conclusion, our meta-analysis found that colchicine treatment was associated with a significantly lower risk of mortality in patients with COVID-19. However, this benefit was not observed in the subgroup analysis of randomized controlled trials. Further randomized controlled studies are required to confirm the potential benefits of colchicine treatment.
| S-EPMC8398430 | biostudies-literature
Project description:ObjectiveTo compare the effects of treatments for coronavirus disease 2019 (covid-19).DesignLiving systematic review and network meta-analysis.Data sourcesWHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 1 December 2021 were included in the analysis.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 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.Results463 trials enrolling 166 581 patients were included; 267 (57.7%) trials and 89 814 (53.9%) patients are new from the previous iteration; 265 (57.2%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, three drugs reduced mortality in patients with mostly severe disease with at least moderate certainty: systemic corticosteroids (risk difference 23 fewer per 1000 patients, 95% credible interval 40 fewer to 7 fewer, moderate certainty), interleukin-6 receptor antagonists when given with corticosteroids (23 fewer per 1000, 36 fewer to 7 fewer, moderate certainty), and Janus kinase inhibitors (44 fewer per 1000, 64 fewer to 20 fewer, high certainty). Compared with standard care, two drugs probably reduce hospital admission in patients with non-severe disease: nirmatrelvir/ritonavir (36 fewer per 1000, 41 fewer to 26 fewer, moderate certainty) and molnupiravir (19 fewer per 1000, 29 fewer to 5 fewer, moderate certainty). Remdesivir may reduce hospital admission (29 fewer per 1000, 40 fewer to 6 fewer, low certainty). Only molnupiravir had at least moderate quality evidence of a reduction in time to symptom resolution (3.3 days fewer, 4.8 fewer to 1.6 fewer, moderate certainty); several others showed a possible benefit. Several drugs may increase the risk of adverse effects leading to drug discontinuation; hydroxychloroquine probably increases the risk of mechanical ventilation (moderate certainty).ConclusionCorticosteroids, interleukin-6 receptor antagonists, and Janus kinase inhibitors probably reduce mortality and confer other important benefits in patients with severe covid-19. Molnupiravir and nirmatrelvir/ritonavir probably reduce admission to hospital in patients with non-severe covid-19.Systematic review registrationThis review was not registered. The protocol is publicly available in the supplementary material.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. This is the fifth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.
| S-EPMC7390912 | biostudies-literature