Cytokine release syndrome in severe COVID-19 Moore, John B; June, Carl H
Science (American Association for the Advancement of Science),
05/2020, Letnik:
368, Številka:
6490
Journal Article
Recenzirano
Odprti dostop
Lessons from arthritis and cell therapy in cancer patients point to therapy for severe disease
In December 2019, a new strain of coronavirus, severe acute respiratory syndrome–coronavirus 2 ...(SARS-CoV-2), was recognized to have emerged in Wuhan, China. Along with SARS-CoV and Middle East respiratory syndrome–coronavirus (MERS-CoV), SARS-CoV-2 is the third coronavirus to cause severe respiratory illness in humans, called coronavirus disease 2019 (COVID-19). This was recognized as a pandemic by the World Health Organization (WHO) in March 2020 and has had considerable global economic and health impacts. Although the situation is rapidly evolving, severe disease manifested by fever and pneumonia, leading to acute respiratory distress syndrome (ARDS), has been described in up to 20% of COVID-19 cases. This is reminiscent of cytokine release syndrome (CRS)–induced ARDS and secondary hemophagocytic lymphohistiocytosis (sHLH) observed in patients with SARS-CoV and MERS-CoV as well as in leukemia patients receiving engineered T cell therapy. Given this experience, urgently needed therapeutics based on suppressing CRS, such as tocilizumab, have entered clinical trials to treat COVID-19.
This Viewpoint proposes ways to maximize vaccine efficacy and allocation given the rise of coronavirus variants and authorization of a Johnson & Johnson vaccine, including reserving the latter for ...younger healthier populations, boosting it with a single-dose messenger RNA (mRNA) vaccination, and single mRNA immunization of people with prior documented SARS-CoV-2 infection.
This Viewpoint reviews circulating SARS-CoV-2 genetic variants and mechanisms of immunity by which they might escape coronavirus vaccine-induced protection and proposes 6 measures to address them, ...including enhanced variant isolation and testing procedures and continued adherence to mask-wearing and other established public health measures.
Abstract Cardiovascular disease (CVD) is a leading cause of death and disability in the United States. National quality programs such as the National Cardiovascular Data Registry (NCDR®) permit ...assessments of the quality of care and outcomes for broad populations of patients with CVD. This report provides data from 2014 from four NCDR® hospital quality programs: 1) CathPCI® for coronary angiography and percutaneous coronary intervention (667,424 procedures performed in 1,612 hospitals) ICD™ for implantable cardioverter defibrillators (158,649 procedures performed in 1,715 hospitals); 3) ACTION®-GWTG™ for acute coronary syndromes (182,903 patients admitted to 907 hospitals); and 4) IMPACT® for cardiac catheterization and intervention for pediatric and adult congenital heart disease (20,169 procedures in 76 hospitals). The report provides perspectives on the demographic and clinical characteristics of enrolled patients; characteristics of participating centers; selected measures of processes and outcomes of care.
Global fire regimes are shifting due to climate and land use changes. Understanding the responses of belowground communities to fire is key to predicting changes in the ecosystem processes they ...regulate. We conducted a comprehensive meta‐analysis of 1634 observations from 131 empirical studies to investigate the effect of fire on soil microorganisms and mesofauna. Fire had a strong negative effect on soil biota biomass, abundance, richness, evenness, and diversity. Fire reduced microorganism biomass and abundance by up to 96%. Bacteria were more resistant to fire than fungi. Fire reduced nematode abundance by 88% but had no significant effect on soil arthropods. Fire reduced richness, evenness and diversity of soil microorganisms and mesofauna by up to 99%. We found little evidence of temporal trends towards recovery within 10 years post‐disturbance suggesting little resilience of the soil community to fire. Interactions between biome, fire type, and depth explained few of these negative trends. Future research at the intersection of fire ecology and soil biology should aim to integrate soil community structure with the ecosystem processes they mediate under changing global fire regimes.
Climate change and its social, environmental, economic and ethical consequences are widely recognized as the major set of interconnected problems facing human societies. Its impacts and costs will be ...large, serious, and unevenly spread, globally for decades. The main factor causing climate change and global warming is the increase of global carbon emissions produced by human activities such as deforestation and burning of fossil fuels. In this special volume, the articles mainly focus on investigations of technical innovations and policy interventions for improved energy efficiency and carbon emissions reduction in a wide diversity of industrial, construction and agricultural sectors at different scales, from the smallest scales (firm or household), cities, regional, to national and global scales. Some articles in this special volume assess alternative carbon emissions reduction approaches, such as carbon capture and storage and geoengineering schemes. Given the high cost and internal/external uncertainties of carbon capture and storage and risks and side effects of various geoengineering schemes, improved energy efficiency and widespread implementation of low fossil-carbon renewable-energy based systems are clearly the most direct and effective approaches to reduce carbon emissions. This means that we have to radically transform our societal metabolism towards low/no fossil-carbon economies. However, design and implementation of low/no fossil-carbon production will require fundamental changes in the design, production and use of products and these needed changes are evolving but much more needs to be done. Additionally, the design and timing of suitable climate policy interventions, such as various carbon taxation/trading schemes, must be integral in facilitating the development of low fossil carbon products and accelerating the transition to post-fossil carbon societies.
•Technical innovations are presented for carbon emissions reduction in various industrial, construction and agricultural sectors.•Investigations of widespread implementation of low-fossil carbon energy systems are presented.•Assessments of carbon capture and storage and geoengineering as alternative approaches to reduce carbon emissions are highlighted.•The design, implementation and impacts of carbon emission taxation/trading schemes are explored.
We conducted a model-based assessment of changes in permafrost area and carbon storage for simulations driven by RCP4.5 and RCP8.5 projections between 2010 and 2299 for the northern permafrost ...region. All models simulating carbon represented soil with depth, a critical structural feature needed to represent the permafrost carbon–climate feedback, but that is not a universal feature of all climate models. Between 2010 and 2299, simulations indicated losses of permafrost between 3 and 5 million km² for the RCP4.5 climate and between 6 and 16 million km² for the RCP8.5 climate. For the RCP4.5 projection, cumulative change in soil carbon varied between 66-Pg C (1015-g carbon) loss to 70-Pg C gain. For the RCP8.5 projection, losses in soil carbon varied between 74 and 652 Pg C (mean loss, 341 Pg C). For the RCP4.5 projection, gains in vegetation carbon were largely responsible for the overall projected net gains in ecosystem carbon by 2299 (8- to 244-Pg C gains). In contrast, for the RCP8.5 projection, gains in vegetation carbon were not great enough to compensate for the losses of carbon projected by four of the five models; changes in ecosystem carbon ranged from a 641-Pg C loss to a 167-Pg C gain (mean, 208-Pg C loss). The models indicate that substantial net losses of ecosystem carbon would not occur until after 2100. This assessment suggests that effective mitigation efforts during the remainder of this century could attenuate the negative consequences of the permafrost carbon–climate feedback.
Summary
We describe the development and potential use of various designs of recombinant HIV‐1 envelope glycoprotein trimers that mimic the structure of the virion‐associated spike, which is the ...target for neutralizing antibodies. The goal of trimer development programs is to induce broadly neutralizing antibodies with the potential to intervene against multiple circulating HIV‐1 strains. Among the topics we address are the designs of various constructs; how native‐like trimers can be produced and purified; the properties of such trimers in vitro and their immunogenicity in various animals; and the immunization strategies that may lead to the eventual elicitation of broadly neutralizing antibodies. In summary, native‐like trimers are a now a platform for structure‐ and immunology‐based design improvements that could eventually yield immunogens of practical value for solving the long‐standing HIV‐1 vaccine problem.
All previously characterized broadly neutralizing antibodies to the HIV-1 envelope glycoprotein (Env) target one of four major sites of vulnerability. Here, we define and structurally characterize a ...unique epitope on Env that is recognized by a recently discovered family of human monoclonal antibodies (PGT151–PGT158). The PGT151 epitope is comprised of residues and glycans at the interface of gp41 and gp120 within a single protomer and glycans from both subunits of a second protomer and represents a neutralizing epitope that is dependent on both gp120 and gp41. Because PGT151 binds only to properly formed, cleaved trimers, this distinctive property, and its ability to stabilize Env trimers, has enabled the successful purification of mature, cleaved Env trimers from the cell surface as a complex with PGT151. Here we compare the structural and functional properties of membrane-extracted Env trimers from several clades with those of the soluble, cleaved SOSIP gp140 trimer.
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•PGT151 binds an interprotomer epitope formed by gp41 and gp120 on cleaved Env trimers•The PGT151 epitope does not overlap with any other epitope described so far•PGT151 enables isolation of functional cleaved Env from the cell membrane•Membrane-extracted and soluble SOSIP.664 Env trimers are structurally similar
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