IL-6 blockade for COVID-19: a global scientific call to arms.
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ABSTRACT:
SUBMITTER: Murthy S
PROVIDER: S-EPMC8078876 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
Publications
IL-6 blockade for COVID-19: a global scientific call to arms.
Murthy Srinivas S Lee Todd C TC
The Lancet. Respiratory medicine 20210304 5
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Project description: Not available
| S-EPMC7529519 | biostudies-literature
Project description:In this review article, it is highlighted the implications of pleiotropic functions of interleukin-6 (IL-6) for one of the therapeutic options targeting for COVID-19. Moreover, it is discussed how real-world data and trials with IL-6 signaling blockade will be crucial in informing the development of new treatment for COVID-19 pneumonia. Given physiological roles of IL-6 in inflammatory conditions and the data from real world, IL-6 signal inhibitors, along with standard of care (SOC) treatment, might provide efficacy, offering the potential to treat COVID-19 in hospitalized populations more effectively than current SOC alone. Therefore, on-going and planned randomized placebo-controlled studies in combination with SOC and other therapeutics to assess safety and efficacy of IL-6 signal inhibitors in hospitalized patients with severe COVID-19 pneumonia will be warranted to address the high unmet need and burden of disease in this severely ill population.
| S-EPMC7533147 | biostudies-literature
Project description:Nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale and warrants urgent investigation of its therapeutic potential, for COVID-19-induced acute respiratory distress syndrome (ARDS). COVID-19 ARDS displays the typical features of diffuse alveolar damage with extensive pulmonary coagulation activation resulting in fibrin deposition in the microvasculature and formation of hyaline membranes in the air sacs. Patients infected with SARS-CoV-2 who manifest severe disease have high levels of inflammatory cytokines in plasma and bronchoalveolar lavage fluid and significant coagulopathy. There is a strong association between the extent of the coagulopathy and poor clinical outcomes.The anti-coagulant actions of nebulised UFH limit fibrin deposition and microvascular thrombosis. Trials in patients with acute lung injury and related conditions found inhaled UFH reduced pulmonary dead space, coagulation activation, microvascular thrombosis and clinical deterioration, resulting in increased time free of ventilatory support. In addition, UFH has anti-inflammatory, mucolytic and anti-viral properties and, specifically, has been shown to inactivate the SARS-CoV-2 virus and prevent its entry into mammalian cells, thereby inhibiting pulmonary infection by SARS-CoV-2. Furthermore, clinical studies have shown that inhaled UFH safely improves outcomes in other inflammatory respiratory diseases and also acts as an effective mucolytic in sputum-producing respiratory patients. UFH is widely available and inexpensive, which may make this treatment also accessible for low- and middle-income countries.These potentially important therapeutic properties of nebulised UFH underline the need for expedited large-scale clinical trials to test its potential to reduce mortality in COVID-19 patients.
| S-EPMC7374660 | biostudies-literature
Project description:BackgroundMicrosatellite (MS) markers have become an important tool for studying the population diversity, evolutionary history and multiplicity of infection (MOI) of malaria parasite infections. MS are typically selected on the basis of being highly polymorphic. However, it is known that the polymorphic potential (mutability) of each marker can vary as much as two orders of magnitude, which radically changes how diversity is represented in the genome from one marker to the next. Over the past decade, approximately 240 Plasmodium vivax MS have been published, comprising nine major panels of markers. Inconsistent usage of each panel has resulted in a surfeit of descriptive genetic diversity data that are largely incomparable between populations. The objective of this study was to statistically evaluate the quality of individual MS markers in order to validate a refined panel of markers that will provide a balanced picture of P. vivax population diversity.MethodsAll previously published data, including genetic diversity indices, MS parameters, and population parameters, were assembled from 18 different global studies into a flat file to facilitate statistical analysis and modelling using JMP® Genomics 6.0 (SAS Institute Inc, Cary, NC, USA). Statistical modeling was employed to down-select markers with extreme variation among the mean number of alleles, expected heterozygosity, maximum repeat length and/or chromosomal location of the repeat. Individual MS were analysed by step-down whole model linear regression and standard least squares fit models, both stratified by annual parasite incidence to identify MS markers with values significantly different from the mean.ResultsOf the 42 MS under evaluation in this study, 18 (nine high priority) were identified as ideal candidates for measuring population diversity between global regions, while five (two high priority) additional markers were identified as candidates for MOI studies.ConclusionsMS diversity was found to be a function of endemicity and motif structure. Evaluation of individual MS permitted the assembly of a refined panel of markers that can be reliably utilized in the field to compare population structures between global regions.
| S-EPMC3878832 | biostudies-literature
Project description:BackgroundPrevious studies on COVID-19 scholarly articles have primarily focused on bibliometric characteristics, neglecting the identification of institutional actors that cite recent scientific contributions related to COVID-19 in the policy domain, and their locations.ObjectiveThe purpose of this study was to assess the online citation network and knowledge structure of COVID-19 research across policy domains over 2 years from January 2020 to January 2022, with a particular emphasis on geographical frequency. Two research questions were addressed. The first question was related to who has been the most active in policy engagement with science and research information sharing during the COVID-19 pandemic, particularly in terms of countries and organization types. The second question was related to whether there are significant differences in the types of coronavirus research shared among countries and continents.MethodsThe Altmetric database was used to collect policy report citations of scientific articles for 3 topic terms (COVID-19, COVID-19 vaccine, and COVID-19 variants). Altmetric provides the URLs of policy agencies that have cited COVID-19 research. The scientific articles used for Altmetric citations are extracted from journals indexed by PubMed. The numbers of COVID-19, COVID-19 vaccine, and COVID-19 variant research outputs between January 1, 2020, and January 31, 2022, were 216,787, 16,748, and 2777, respectively. The study examined the frequency of citations based on policy institutional domains, such as intergovernmental organizations, national and domestic governmental organizations, and nongovernmental organizations (think tanks and academic institutions).ResultsThe World Health Organization (WHO) stood out as the most notable institution citing COVID-19-related research outputs. The WHO actively sought and disseminated information regarding the COVID-19 pandemic. The COVID-19 vaccine citation network exhibited the most extensive connections in terms of degree centrality, 2-local eigenvector centrality, and eigenvector centrality among the 3 key terms. The Netherlands, the United States, the United Kingdom, and Australia were the countries that sought and shared the most information on COVID-19 vaccines, likely due to their high numbers of COVID-19 cases. Developing nations, although gaining quicker access to COVID-19 vaccine information, appeared to be relatively isolated from the enriched COVID-19 pandemic content in the global network.ConclusionsThe global scientific network ecology during the COVID-19 pandemic revealed distinct types of links primarily centered around the WHO. Western countries demonstrated effective networking practices in constructing these networks. The prominent position of the key term "COVID-19 vaccine" demonstrates that nation-states align with global authority regardless of their national contexts. In summary, the citation networking practices of policy agencies have the potential to uncover the global knowledge distribution structure as a proxy for the networking strategy employed during a pandemic.
| S-EPMC10365591 | biostudies-literature
Project description: Not available
| S-EPMC8055918 | biostudies-literature
Project description:The novel coronavirus disease, affecting ~9 million people in the past five months and causing >460,000 deaths worldwide, is completely new to mankind. More than 2,000 research projects registered at ClinTrials.gov are aiming at finding effective treatments for rapid transfer to clinical practice. Unfortunately, just few studies have a sufficiently valid design to provide reliable information for clinical practice.
| S-EPMC7321654 | biostudies-literature
Project description:Around the tenth day after diagnosis, ∼20% of patients with coronavirus disease 2019 (COVID-19)-associated pneumonia evolve toward severe oxygen dependence (stage 2b) and acute respiratory distress syndrome (stage 3) associated with systemic inflammation often termed a "cytokine storm." Because interleukin-1 (IL-1) blocks the production of IL-6 and other proinflammatory cytokines, we treated COVID-19 patients early in the disease with the IL-1 receptor antagonist, anakinra. We retrospectively compared 22 patients from three different centers in France with stages 2b and 3 COVID-19-associated pneumonia presenting with acute severe respiratory failure and systemic inflammation who received either standard-of-care treatment alone (10 patients) or combined with intravenous anakinra (12 patients). Treatment started at 300 mg⋅d-1 for 5 d, then tapered with lower dosing over 3 d. Both populations were comparable for age, comorbidities, clinical stage, and elevated biomarkers of systemic inflammation. All of the patients treated with anakinra improved clinically (P < 0.01), with no deaths, significant decreases in oxygen requirements (P < 0.05), and more days without invasive mechanical ventilation (P < 0.06), compared with the control group. The effect of anakinra was rapid, as judged by significant decrease of fever and C-reactive protein at day 3. A mean total dose of 1,950 mg was infused with no adverse side effects or bacterial infection. We conclude that early blockade of the IL-1 receptor is therapeutic in acute hyperinflammatory respiratory failure in COVID-19 patients.
| S-EPMC7430998 | biostudies-literature
Project description:Susceptibility to viral infection, development of immunity, response to treatment and patient clinical outcomes are all under the control of heritable factors in the host. In the context of the current SARS-Cov-2 pandemic, this review considers existing immunogenetic knowledge of virus-immune system interactions. A major focus is to highlight areas in which work is required in order to improve understanding of antiviral immune responses and to move towards improved patient management.
| S-EPMC7405410 | biostudies-literature
Project description:ObjectiveTo identify the issues needing to be resolved to design, implement, and complete a definitive randomized controlled trial of adjunctive corticosteroid use in children with septic shock.DesignPediatric studies from MEDLINE (1946 to January 2015) and Embase (1947 to January 2015) that addressed adrenal function or steroid use in critically ill children with systemic inflammatory response syndrome, sepsis, or septic shock were reviewed and their relevant points discussed.ResultsThere is considerable interest in the field of corticosteroids in pediatric septic shock, which has not as yet translated into a much needed randomized controlled trial. We found that the issues that need to be resolved include identification of the target population, achievement of individual and community equipoise, selection of a patient centered, clinically meaningful primary outcome measure, and consideration of the adverse effects of corticosteroids.ConclusionsWe strongly believe that the time has come to conduct a trial on the use of corticosteroids in pediatric septic shock and that the question to be answered is Will corticosteroids given to children with septic shock result in a benefit to some patients without resulting in harm to others? Answering this question will require a collaborative and committed effort on the parts of ethics boards, families, clinicians, and researchers to actually make it happen once and for all, and we propose an international planning meeting of interested parties to achieve agreement on these identified issues.
| S-EPMC4592399 | biostudies-literature