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Precision epidemiology could help explain variability in COVID-19 symptoms - News-Medical.Net
Researchers from National Taiwan University have presented a multi-omics view of how mutations in angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) affect infection with severe acute respiratory syndrome coronavirus 2 (SARS-…
Researchers from National Taiwan University have presented a multi-omics view of how mutations in angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) affect infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and progression of coronaviruses disease 2019 (COVID-19). ACE2 is the human receptor that COVID-19's causative agent - SARS-COV-2 - uses to bind to host cells, and TMPRSS2 is the enzyme that activates the viral spike protein for membrane fusion. For both the ACE2 and TMPRS22 genes, Eric Chuang and colleagues report on findings from a comparative analysis of the single nucleotide polymorphisms (SNPs) that may contribute to variability in COVID-19 symptoms among sub-populations. They also report on calculations of the prevalence of structural variations amongst populations and a study of expression patterns across all human tissues. "This work is a good first step to be followed by additional studies and functional assays towards informed treatment decisions and improved control of the infection rate," writes the team. A pre-print version of the paper is available on the server bioRxiv*, while the article undergoes peer review. COVID-19 disease course is highly variable Precision epidemiology using genomic technologies enables a targeted approach towards infectious disease control. It includes genome-based approaches to provide information on molecular diagnosis and treatment regimens at both the population and individual level. The disease course in cases of COVID-19 is highly variable, ranging from mild or asymptomatic to severe and potentially fatal. Aside from known risk factors associated with severe disease such as older age and co-existing comorbidity, such variability in symptoms and outcomes may be explained by genetic architecture differences, suggest Chuang and colleagues. "It is necessary to identify variants of the ACE2 and TMPRSS2 genes that confer higher susceptibility to fatality and symptoms," say the researchers. However, the team says a susceptibility gene may likely have low penetrance, meaning not all carriers will develop COVID-19. Furthermore, specific environmental factors may affect the degree of transmission and severity of infections. Therefore, the team has presented multiple lines of supporting evidence from multi-omics data, including information on SNPs, structural variations such as copy number variations (CNVs), and gene expression patterns, to show how such approaches can help identify COVID-19 risk factors. The SNP analysis The researchers used an online database they developed called VariED, which provides annotation and expression profiles for variants related to human diseases, to obtain allele frequencies for all SNP variants from both ACE2 and TMPRSS2 for different global sub-populations. They identified SNPs in both ACE2 and TMPRSS2 that had higher allele frequencies among Africans and East Asian populations than among Europeans and Americans. Chuang and the team say that Africans exhibited particularly significant variation for most SNPs, which may indicate differential susceptibility towards coronavirus in the respective populations. Analysis of structural variations The team used a web-based system they developed called CNVIntegrate to study the candidate genes' CNV frequencies in the control cohort ExAC, which consists of healthy individuals from global sub-populations, and the control cohort TWCNV, which consists of healthy Taiwanese individuals. The researchers calculated the duplications and deletions frequencies for both ACE2 and TMPRSS2 among the two cohorts. For ACE2, no duplications or deletions were observed among either population. For TMPRSS2, duplication was observed in 0.06% of samples from TWCNV and in 0.014% of samples from ExAC. TMPRSS2 deletion was also observed in 1.08% of TWCNV samples. Chuang and colleagues say this suggests that these variations are rare among healthy cohorts and provides evidence that they could be pathogenic. The gene expression analysis The team used a database tool they developed called CellExpress to study ACE2 and TMPRSS2 gene expression patterns across all human tissues, stratified by gender and age. The gene expression data for baseline healthy populations did not show any significant difference in gene expression levels between males and females, with the exception of the pituitary gland. Similarly, no significant difference was observed when gene expression was stratified by age. However, a search for both genes across all tissues in cancer datasets did reveal high expression levels of both ACE2 and TMPRS22 across all tissues, with no effect of gender and age. "A good first step" towards identifying high-risk patients "This study conducts genetic probing with the intention of explaining the variability in symptoms and diverse outcomes of COVID-19. It provides some significant findings (SNP, CNV, and gene expression) from ACE2 and TMPRSS2, as evidence, for a plausible place to start looking into them," said Chuang and colleagues. "The work is a good first step to be followed by additional studies and functional assays that could potentially evaluate the findings to identify patients who may be at a higher risk of COVID-19-related mortality or infection, towards informed decisions for treatment and cure," concludes the team. *Important Notice bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Higher physical activity, lower sitting time linked with better physical and mental health in older adults - News-Medical.Net
Older adults with higher physical activity and lower sitting time have better overall physical and mental health, according to a new study from the American Cancer Society.
Reviewed by Emily Henderson, B.Sc.Oct 20 2020 Older adults with higher physical activity and lower sitting time have better overall physical and mental health, according to a new study from the American Cancer Society (ACS). The study, appearing in the journal, CANCER, suggests that higher amounts of regular moderate- to vigorous-intensity physical activity (MVPA) and lower duration of sedentary time is associated with higher global mental and physical health for older cancer survivors and older adults, in general. With a rapidly aging population and nearly 16.9 million cancer survivors in the United States today, there is a need to identify strategies associated with healthy aging and improving quality of life for aging cancer survivors. Being physically active is related to several health benefits, and in this study, ACS investigators led by Dr. Erika Rees-Punia analyzed self-reported aerobic and muscle-strengthening physical activities, sitting time, and mental and physical health among nearly 78,000 participants in the ACS's Cancer Prevention Study II Nutrition Cohort. Participants (average age 78 years) included older cancer survivors up to 10 years post-diagnosis, and cancer-free adults. The investigators found that regardless of cancer history, the differences in global mental and physical health between the most and least active, and the least and most sedentary, were clinically meaningful. These findings provide evidence for the importance of engaging in regular MVPA and decreasing sitting time as a reasonable non-pharmacologic strategy to improve quality of life in older men and women, with or without a prior cancer diagnosis. In fact, the recently published ACS physical activity guidelines recommend that adults get 150-300 minutes of moderate-intensity activity or 75-150 minutes of vigorous-intensity activity through the week, and to limit sedentary behaviors such as screen-based entertainment. The findings reinforce the importance of moving more and sitting less for both physical and mental health, no matter your age or history of cancer. This is especially relevant now as so many of us, particularly cancer survivors, may be staying home to avoid COVID-19 exposure, and may be feeling a little isolated or down. A simple walk or other physical activity that you enjoy may be good for your mind and body." Dr. Erika Rees-Punia, ACS Investigator American Cancer Society Rees‐Punia, E., et al. (2020) Self‐reported physical activity, sitting time, and mental and physical health among older cancer survivors compared with adults without a history of cancer. Cancer.doi.org/10.1002/cncr.33257.
Fever and cough best indicators for COVID-19 in children and adolescents - News-Medical.Net
Most testing is driven by fever, persistent cough of recent onset, and abnormalities in smell. Such symptoms are considered indicative of continuing SARS-CoV-2 infection, requiring quarantine of all such individuals until they test negative for the virus. Thi…
In most places around the world today, testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is initially based on common symptoms. The assumption is that testing symptomatic individuals and tracing, testing, and isolating their positive contacts is the most efficient way of using limited testing resources. In the UK, the criteria for testing individuals for SARS-CoV-2 are the presence of fever, a new persistent cough, and loss or change in the sense of smell. Similar symptom-based case definitions are operating in other countries. A recent study published on the preprint server medRxiv* in October 2020 examines the kind of symptoms that should drive such testing. Case Definitions Most testing is driven by fever, persistent cough of recent onset, and abnormalities in smell. Such symptoms are considered indicative of continuing SARS-CoV-2 infection, requiring quarantine of all such individuals until they test negative for the virus. This approach is justifiable in adults since fever and cough from other causes are rare in healthy adults. On the other hand, these are insensitive indicators in children and young people (CYP), who are liable to as many as ten upper respiratory infections (URI) per year, more commonly during colder weather. Increasing Symptomatic Testing Follows Reopening UK in-person schooling began in September 2020 and has been followed by a ten-fold rise in the number of individuals with suspected COVID-19 symptoms who are 18 years old or less. While many of these are probably due to seasonal viral infections, they led to a high increase in the frequency of testing and quarantine recommendations in CYP. Fever and Cough Most Prevalent in COVID-19 Among CYP The current study aims to provide evidence on which symptoms are most likely to be associated with a positive COVID-19 test and those that are probably not. The researchers performed a systematic review of 18 studies, mostly of CYP, who were COVID-19 in-patients. They found that ~15% to 42% of CYP with COVID-19 were asymptomatic. The most common symptoms continued to be fever and cough, found in up to two-thirds and well over half of all patients, respectively. All other symptoms and signs were found in less than a fifth of the patients. Tiredness and muscle pain were present in 8% and 14% in one review, while gastrointestinal symptoms were present in ~7% to ~18% in different studies. Among older children, fever was present in over two-thirds, compared to less than half of infants. Contrasting age profiles were found with respect to gut symptoms. One study reported that 20% of CYP were asymptomatic compared to 5% of adults. The researchers concluded that fever and cough continued to be the most frequently reported symptoms in this condition, among CYP, at 40% to 60% of all COVID-19-positive individuals. Both fever and cough, in combination, were far more prevalent than either alone. URI Should Not be Mistaken for COVID-19 Though commonly found in URI, runny nose and sore throats are relatively rare in COVID-19, along with headache, tiredness and fatigue, diarrhea, and vomiting. Strangely, alterations in the sense of smell were not represented in any of the papers. The reviewers were unable to identify definitive differences in symptom profiles between age groups in CYP. These findings agree with recent studies in the UK and other parts of Europe, which show that fever is found in two-thirds of children hospitalized with COVID-19. A UK study of over 650 hospitalized CYP also found a low prevalence of symptoms, excluding fever and cough. Limitations The study was limited by the fact that most researchers used data from hospitalized CYP, which may cover a broad spectrum of clinical severity. While many countries practiced universal hospitalization of children once diagnosed, whatever the clinical severity, the inclusion of only this group has very probably raised the odds significantly that its findings will apply only to children with symptoms and more severe disease. The real prevalence of symptoms among COVID-19-positive CYP is likely to be much lower when this is taken into account. In other studies, only 20% to 50% of this group has been shown to be symptomatic. This agrees with the high percentage of asymptomatic infection. Duplication of studies is also likely, which prevented meta-analysis of these studies. Again, there was a lot of variation in quality and the possibility of bias, as well as the time period of data collection. The reviews were dominated by Chinese data and severe cases among CYP. Implications and Future Directions The researchers conclude, based on this limited data, that the most common symptoms of COVID-19 in CYP are fever and cough, and these may be used to define potential cases that require testing. When other symptoms are included, specificity may be lost due to their unusual nature. Moreover, symptoms like sore throat and a runny nose are frequent in young children but infrequent as COVID-19 symptoms, which indicates their non-relevance as features of potential COVID-19. In fact, their use may lead to misclassification of young children as potentially infected with SARS-CoV-2, requiring unnecessary testing and quarantine. The researchers say, “Symptoms in community samples including in schools are urgently needed to inform pragmatic identification and testing programs for CYP and reduce misclassification of CYP as potential COVID-19 cases requiring isolation of peers and families." *Important Notice medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Researchers apply deep learning algorithm to CT to produce spectral images - News-Medical.Net
Bioimaging technologies are the eyes that allow doctors to see inside the body in order to diagnose, treat, and monitor disease.
Reviewed by Emily Henderson, B.Sc.Oct 20 2020 Bioimaging technologies are the eyes that allow doctors to see inside the body in order to diagnose, treat, and monitor disease. Ge Wang, an endowed professor of biomedical engineering at Rensselaer Polytechnic Institute, has received significant recognition for devoting his research to coupling those imaging technologies with artificial intelligence in order to improve physicians' "vision." In research published today in Patterns, a team of engineers led by Wang demonstrated how a deep learning algorithm can be applied to a conventional computerized tomography (CT) scan in order to produce images that would typically require a higher level of imaging technology known as dual-energy CT. Wenxiang Cong, a research scientist at Rensselaer, is first author on this paper. Wang and Cong were also joined by coauthors from Shanghai First-Imaging Tech, and researchers from GE Research. We hope that this technique will help extract more information from a regular single-spectrum X-ray CT scan, make it more quantitative, and improve diagnosis." Wenxiang Cong, Research Scientist, Rensselaer Polytechnic Institute Wang is also the director of the Biomedical Imaging Center within the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselaer. Conventional CT scans produce images that show the shape of tissues within the body, but they don't give doctors sufficient information about the composition of those tissues. Even with iodine and other contrast agents, which are used to help doctors differentiate between soft tissue and vasculature, it's hard to distinguish between subtle structures. A higher-level technology called dual-energy CT gathers two datasets in order to produce images that reveal both tissue shape and information about tissue composition. However, this imaging approach often requires a higher dose of radiation and is more expensive due to needed additional hardware. "With traditional CT, you take a grayscale image, but with dual-energy CT you take an image with two colors," Wang said. "With deep learning, we try to use the standard machine to do the job of dual-energy CT imaging." In this research, Wang and his team demonstrated how their neural network was able to produce those more complex images using single-spectrum CT data. The researchers used images produced by dual-energy CT to train their model and found that it was able to produce high-quality approximations with a relative error of less than 2%. "Professor Wang and his team's expertise in bioimaging is giving physicians and surgeons 'new eyes' in diagnosing and treating disease," said Deepak Vashishth, director of CBIS. "This research effort is a prime example of the partnership needed to personalize and solve persistent human health challenges." Rensselaer Polytechnic Institute Cong, W., et al. (2020) Virtual Monoenergetic CT Imaging via Deep Learning. Patterns. doi.org/10.1016/j.patter.2020.100128.
FDA proposes new regulatory framework on artificial intelligence, machine learning technologies - News-Medical.Net
The findings come from a cross-sectional study, published in BMJ Open, of the comments submitted to the US Food and Drug Administration (FDA) 'Proposed Regulatory Framework for Modifications to Artificial Intelligence/Machine Learning (AI/ML)-Based Software a…
Reviewed by Emily Henderson, B.Sc.Oct 16 2020 The findings come from a cross-sectional study, published in BMJ Open, of the comments submitted to the US Food and Drug Administration (FDA) 'Proposed Regulatory Framework for Modifications to Artificial Intelligence/Machine Learning (AI/ML)-Based Software as a Medical Device (SaMD)--Discussion Paper and Request for Feedback'. Artificial intelligence (AI) and machine learning (ML) technologies have the potential to transform health care, continually incorporating insights from the vast amount of data generated every day during the delivery of health care. Many such devices must have regulatory approval or clearance before being available for clinical practice, and in the US that regulation falls to the FDA. The suitability of traditional medical device regulatory pathways for AI/ML have been called into question because the nature of the technology means it is continually evolving and adapting to improve performance. Under the current framework it would mean that as devices evolved they would require further review and approval, which could be time consuming and may affect patient safety and interests. The FDA has therefore proposed a new regulatory framework for modifications to AI/ML and has asked for feedback from the public to refine the regulations. The process for developing regulations is, roughly, to get feedback from the public on its initial proposal, make changes and draft regulations or guidance, get more feedback, and eventually finalise," James Smith, Study Lead Author and Postdoctoral Scientist, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford "Anyone can comment but at present there is no requirement, or even recommendation, to disclose any conflicts of interest. Also, the FDA states that it looks for 'good science' in comments but it is not a requirement to incorporate it. Our goal was to look at the extent and disclosure of financial ties to industry and the use of scientific evidence." The team analysed all 125 publicly available comments on the FDA proposal between 2 April 2019 to 8 August 2019 and found that 79 (63%) comments came from parties with financial ties to industry in the sector. For a further 29% of comments the presence or absence of financial ties could not be confirmed. The vast majority of submitted comments (86%) did not cite any scientific literature, with only 4% citing a systematic review or meta-analysis. James said: "What concerns us about these findings is that we don't have a good idea of the impact of these ties and whether they might lead to bias in this specific context. Whether these observations about prevalence of ties hold true in the development of other regulations, we don't yet know, but there is a growing body of evidence showing the influence of industry throughout the medical research enterprise, and this paper adds to that. I hope it will highlight the need for greater transparency." Gary Collins, Professor of Medical Statistics and a co-author of the study, added: "We were also concerned by the lack of scientific evidence used in comments, and the dominance of industry over academic commenters, despite AI/ML being a very active area of research. But we hope our findings will bring the FDA proposal to the attention of academics and encourage more of them to participate in the next round of feedback on the framework, and other regulatory frameworks, where academic input could be valuable." University of Oxford Smith, J. A., et al. (2020) Industry ties and evidence in public comments on the FDA framework for modifications to artificial intelligence/machine learning-based medical devices: a cross sectional study. BMJ Open. doi.org/10.1136/bmjopen-2020-039969.
Rapid development of functionally diverse SARS-COV-2 mouse monoclonal antibodies - News-Medical.Net
Now, a recent study published on the preprint server bioRxiv in October 2020 reports the development of a rapid process for generating high-affinity mouse mAbs, and their functional attributes.
With the resurgence of the COVID-19 pandemic looming large in many parts of the world, the need for immunological tools such as monoclonal antibodies (mAbs) is more urgent, whether for diagnosis, treatment, or research on the virus. Now, a recent study published on the preprint server bioRxiv* in October 2020 reports the development of a rapid process for generating high-affinity mouse mAbs, and their functional attributes. The RBD in SARS-CoV-2 Immunology The focus of most antibody development efforts is the receptor-binding domain (RBD), a region in the S1 subunit of the SARS-CoV-2 spike protein, about 300 residues in length. This spike protein is thought to be the viral element that mediates its attachment to the host cell through the human angiotensin-converting enzyme 2 (hACE2) receptor. This is found on a variety of cell types in the human host, particularly the lung epithelium. The RBD contains five residues that come into contact with the ACE2 receptor. In order to exploit this viral element, the researchers used a commercially available S1 domain tagged with a C-terminal histidine (His-S1), a commercial RBD with a mouse C-terminal IgG1 Fc domain (mFc-RBD), and mFc-RBD fused with the PP7 bacteriophage virus-like particle (VLP), called PP7zz. The latter is modified such that two sequential Z-domains are displayed with each binding to Fc at 120 places on the surface of the VLP. It has a large display of RBDs that enable binding multiple receptors on immune cells, thus allowing the cell affinity to mature. Any antigen with an Fc tag promotes enhanced antigen uptake and processing. The VLPs have an adjuvant effect, but another adjuvant also enhanced the recombinant S1 and RBD proteins' immunogenicity. Accelerated Immunization and mAb Production The researchers used accelerated immunization schedules using either the His-S1, a combination of mFc-RBD and PP7zz immunogens, and mFc-RBD expressed on VLPs boosted finally by His-S1. The aim was to find which immunogen displayed the maximum response. Spleen cells were then harvested on day 30 from immunization, and cells that secreted high IgG levels were chosen. SARS-CoV-2 Spike protein subunit vaccine strategy and humoral immune response in mice. a, Recombinant spike subunit 1 protein (His-S1, residues 1-681) or S1 Receptor Binding Domain (mouse Fc-RBD, residues 319-541, ACE2 contact residues in purple; PDBID: 6vxx) antigens. b, VLP display of Fc-tagged antigens using the PP7 particle bearing 120 ZZ-domains; a 1:1 mass ratio of mFc-RBD and VLP provides a Fc:ZZ molar ratio of approximately 0.8. Rh = hydrodynamic radius measured by dynamic light scattering in phosphate buffer. c, Vaccine schedule and strategy. Six-week old female BALB/c mice (n = 3 per group) were immunized with primary antigen and adjuvant on day 0 followed by boosts on days 14 and 27. Blood was collected for ELISA on days 0, 14, 21 and 30. d, ELISA responses for serum dilutions against plated His-S1 protein from the sacrificed mice at day 30. e, Titer values from ELISA analysis as in panel d, against plated His-S1 or spike ectodomain protein. Immunization series defined in panel c; a and b designate different mice within that series. Experimental error represents standard deviation. Characterization of Antibodies by Function The antibody titer was then assayed by ELISA, using either recombinant His-S1 or engineered SARS-CoV-2 spike protein, the first being a monomer and the second a trimer. This showed the high immunogenicity of the mFc-RBD antigen, which generated spike-binding mAbs. These were sorted, and the selected mAbs were characterized for binding strength, the avidity of binding, and affinity. The researchers found 33 selected avidly binding light chain IgG1 molecules, irrespective of the spike target protein's storage or incubation under various conditions. The mAbs were then clustered according to the differential expression of various gene sets. The researchers found that neutralizing capacity differentiated the mAbs into three groups, 1-3, which were related to the presence of IGHV1 and 8, and IGKV1, 3, and 6. Group 3 is a large group of non-neutralizing antibodies, all of which are associated with the IGHV14-1 gene and, in 50% of mAbs, IGKV6-32. Evaluating Epitopes Recognized by the mAbs Competitive binding measurements are important in evaluating the epitopes involved in spike binding by the antibodies. Low competitive binding values showed the antibodies were competing for adjacent or the same residues, or residues which were allosterically related. On the other hand, high values showed antibody association to different epitopes. This assay showed six major binding groups related to heavy chain sequences and specific combinations of IGHV and IGKV genes. Impact on RBD-ACE2 Binding They also measured the effect of these mAbs on RBD-ACE2 binding, both directly and indirectly. They found 10 mAbs, three of which had identical sequences, which showed strong RBD binding inhibition with both the full-length ACE2 and a truncated receptor version that does not present the dimerization domain of the ACE2 molecule. They observed potent neutralization with 8 of these 10 antibodies, as well as another two with a different mechanism of inhibition of RBD-ACE2 binding. However, of the mAbs, 21 caused antibody-dependent enhancement (ADE) with the truncated ACE2 but not the full-length ACE2, in 17/21 antibodies. These, therefore, have different recognition epitopes and belong to a different functional class than the first 10. Binding to Denatured RBD Using a luciferase assay, they found some variations in binding patterns, which indicate that these ten antibodies bind to four or more RBD epitopes. Four of them bind specifically to a small peptide on the RBD that contains four of five contact residues. However, none of these were found to have potent neutralizing ability, which may mean that this peptide in linear form does not resemble that present in the infectious viral particle, but only on degraded virions, as shown by the binding of two of these mAbs to spike protein in lung tissue sections. The same pattern was seen following gamma-irradiation of the virions, where mAbs with similar avidity of binding for the spike protein showed comparable neutralizing power in vitro. Still, one had a limit of detection of inactivated virions, which was an order of magnitude larger than the other. Implications This study shows that the use of Fc- and VLP-assisted RBD antigens for immunization combined with rapid hybridoma production of the mAbs in parallel can present a range of binding antibodies that have different but useful functional characteristics for binding and inhibiting the virus. This agrees and fills out earlier studies where B cells from COVID-19 patients were used to produce a large array of mAbs targeting SARS-CoV-2. As in the prior studies, the current approach successfully elicited a number of mAbs with affinities in the low nanomolar range for the spike protein. This confirms many earlier observations that the RBD is a useful target for immunological therapeutic agents. Overall, the study shows at least five functional groups of antibodies. Three groups comprise neutralizing antibodies that recognize distinct epitopes on the RBD. A fourth represents the large group of non-neutralizing mAbs, and the fifth includes mAbs that bind to denatured or inactivated RBD in infected lung tissue samples. Each functional class seems to have distinct neutralizing potency, different epitope recognition sites, and sequence and varying RBD-ACE2 binding effects. *Important Notice bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Experts review contribution of Task Force in prevention and control of non-communicable diseases - News-Medical.Net
On 24 September 2020, the Friends of the Task Force met in the margins of the high-level segment of the 75thsession of the United Nations General Assembly. Participants included Member States, UN agencies and non-State actors.
Reviewed by Emily Henderson, B.Sc.Oct 15 2020 On 24 September 2020, the Friends of the Task Force met in the margins of the high-level segment of the 75th session of the United Nations General Assembly. Participants included Member States, UN agencies and non-State actors. The meeting was co-hosted by the Government of the Russian Federation and the World Health Organization, and co-sponsored by the United Nations Development Programme, the International Development Law Organization, and the Secretariat of the WHO Framework Convention on Tobacco Control. The meeting provided an opportunity to review the contribution of the Task Force to global efforts to scale up prevention and control NCDs, with a special focus on NCDs during the COVID-19 pandemic. The WHO Director-General also announced the fifteen winners of the 2020 UNIATF Awards. The Task Force Secretariat provided a brief overview of Task Force activities over the last year. Mikhail Murashko, Minister of Health of the Russian Federation, highlighted the importance of a systematic approach to combating NCDs and expressed his appreciation of the work done by the Task Force in promoting multi-sectoral collaboration in the area of NCDs, including through the development of the national NCD investment cases under the WHO-UNDP joint programme. The Russian Federation is now providing an additional $ 5 million over the next five years to build on this work. Minister Murashko welcomed contributions from Italy, the European Commission and the Gulf Health Council for the work of the Task Force. Dr Tedros Adhanom Ghebreyesus, WHO Director-General, emphasized the importance of strengthening NCD response during and beyond COVID-19. He highlighted the impact of the pandemic on NCDs and mental health and that strong action on NCDs must be an integral part of the COVID-19 response and recovery. The Director-General reminded participants that he had recently launched a joint WHO, UNDP and Task Force publication, Responding to NCDs during and beyond the COVID-19 pandemic. Dr Tedros described WHO's commitment to work with Task Force members to establish the NCD and Mental Health Multi-Partner Trust Fund. Once established, Dr Tedros said that he would be calling on partners to mobilize additional resources beyond WHO's budget to scale up support to countries for their response to NCDs. There's no doubt that COVID-19 is a setback to our efforts to beat NCDs, but we cannot allow it to become an excuse for failing to deliver on our commitments. On contrary, we must use it as motivation to work all the harder!" Dr Tedros Adhanom Ghebreyesus, Director-General, WHO Aksel Jacobsen, State Secretary of International Development for the Norwegian Ministry of Foreign Affairs, described Norway's NCD Development Policy (2020-2024), which will support low-income countries in their efforts to address NCDs. He underscored the high burden of NCD and COVID-19 comorbidity. The State Secretary called upon countries to ensure that NCD prevention, detection, and treatment is included in their COVID-19 response plans, highlighting the importance of political commitment to achieve equality and equity in access to health protection. "The long-time global underinvestment in NCD prevention and control is part of the reason behind this tragic development." Hon Jakobsen. Dr Osagie Ehanire, Minister of Health of Nigeria, thanked the Task Force for its mission to Nigeria earlier this year, indicating that the mission's recommendations have been approved by the President, and an implementation unit to implement the recommendations has been established. Dr Jennifer Harries, Deputy Chief Medical Officer of the United Kingdom, spoke about the UK's experience in fighting major NCD risk factors, as well as obesity, and the UK's efforts to support people to stay mentally well during the pandemic. Dr Harries emphasized the importance of multilateral approaches to address NCDs, highlighting national WHO Framework Convention on Tobacco Control (FCTC) investment cases that the UK has been supporting. "The UK would support further joint programming across multilaterals through the Multi-Partner Trust Fund to catalyse action on NCDs in low- and middle-income countries at such a critical time." Dr Harries. Mr Rafael Mariano Grossi, Director General of the International Atomic Energy Agency described IAEA's collaboration with WHO over many years, especially with regards the Human Health Programme to address NCD challenges across a range of medical issues. Mr Grossi highlighted IAEA's work in building capacity for NCD and COVID-19 detection, which has involved the provision of thousands of health professionals with resources on the use of radiology for diagnosis and treatment. "Medical imaging has had a significant impact on our understanding of COVID-19-related signs and symptoms." Mr Grossi. Emanuela Del Re, Deputy Minister of Foreign Affairs of Italy, shared the experience of Italy in dealing with NCDs though promotion of healthy diets and food quality assurance. "Healthy lifestyles and balanced diet not only prevent NCDs, but also have a positive impact on people's general health, especially children in the first years of life." Hon Del Re. Ahmed Mohammed Obaid Al Saidi, Minister of Health of the Sultanate of Oman, highlighted the increased use of innovative digital technology solutions for NCD care which emerged from the constraints imposed by COVID-19. "In Oman service pathways for those seeking NCD care have been rearranged to ensure safety for patients and safe delivery of services and medications. This had undoubtedly invited innovation and the introduction of new measures that rely on technology." Hon Al Saidi. Ms Jan Beagle, Director General of the International Development Law Organization, stressed the importance of the rule of law and functioning of legal and regulatory frameworks for adequate and equitable NCD and COVID-19 care for all. "Now, more than ever, COVID-19 has exposed and is being aggravated by the entrenched injustices and equalities under which too many people still live and from which no nation can claim to be exempt." Ms. Beagle. Ms Katie Dain, Chief Executive Officer of the NCD Alliance welcomed the Task Force's recent attention on NCD treatment and management as well as the development of the Multi-Partner Trust Fund. "COVID-19 must be a wake-up call for governments and political leaders to value, prioritize, and invest in health, NCDs, and prevention. We simply won't be prepared for the next pandemic, or any other health threat unless we really get to grips with the burden of NCDs." Ms. Dain. Dr Adriana Blanco Marquizo, Head of Secretariat of the FCTC spoke about the threat posed by tobacco industry in the context of COVID-19 and NCDs, and the important role that the WHO FCTC plays in directing national and international effort at reducing global tobacco prevalence. Dr Blanco highlighted the urgent need to support tobacco users who want to quit, pointing to sensitization of population about importance of health that occurred due to COVID-19. Ms Lena Nanushyan, from the Ministry of Health in Armenia, highlighted the experience of Armenia in working with the Task Force on development and implementation of a national NCD investment case. Ms Nanushyan underscored that the results of the investment case were used to argue for the adoption of a stricter tobacco control law earlier this year. Dr Douglas Webb, Cluster Leader, HIV Health and Development Group at the United Nations Development Programme,spoke about the opportunity to address NCDs through national COVID-19 response and recovery plans, which increasingly reveal synergies with NCD-related action within and beyond the health sector. Dr Webb endorsed the Multi-Partner Trust Fund, noting the significant funding gap in responding to NCDs. "The Multi-Partner Trust Fund is a critical technical tool to allow member states to advance on strengthening their NCD response." Dr Webb. Mr Yahya Alfasi, from the Gulf Health Council, informed the participants about the ongoing work to develop NCD investment cases for six countries across the region through the WHO-UNDP joint programme under the Task Force. Mr William Twomey, from Johnson and Johnson, praised the Access Initiative for Quitting Tobacco (AIQT) to improve global access to tobacco cessation support, stating that it was an important step to curbing the very high economic and social costs that tobacco imposes on our society.
Cloud-based tool can rapidly detect and track emerging pathogens - News-Medical.Net
Published today in the journal GigaScience is a new open source, cloud-based tool called IDseq that makes it possible to rapidly detect, identify, and track emerging pathogens such as SARS-CoV-2.
Reviewed by Emily Henderson, B.Sc.Oct 15 2020 Published today in the journal GigaScience is a new open source, cloud-based tool called IDseq that makes it possible to rapidly detect, identify, and track emerging pathogens such as SARS-CoV-2. This tool can identify pathogens before there is an available complete genome sequence; thus, it can be used for current infectious disease outbreaks and also for emerging ones. This will substantially aid in preventing future pandemics. The coronavirus pandemic demonstrates the importance of global infectious disease monitoring. Finding the cause of an infectious disease outbreak is challenging, especially if it stems from a previously unknown pathogen. IDseq, an open source, cloud-based metagenomic analysis platform, identifies both novel and existing disease-causing pathogens from a given sample -- be it a human, animal, or parasite -- to provide an actionable report of what is happening on the ground in labs and clinics anywhere in the world. "IDseq can be thought of as an early warning radar for emerging or novel infectious agents," said Joe DeRisi, PhD, Co-President of the Chan Zuckerberg Biohub, who contributed to the identification of the SARS coronavirus in 2003 and whose research lab at the University of California, San Francisco initiated the IDseq tool. It is designed to enable the global health community to leverage the ever-decreasing cost of sequencing for tracking and identifying infectious disease in essentially any sample. "At the beginning of the coronavirus pandemic, researchers in Cambodia used IDseq to help confirm and sequence the whole genome of the country's first case of COVID-19 in a matter of days, and in California, we're providing critical SARS-CoV-2 genomic data to public health officials to inform contact tracing and intervention strategies." In a study published in GigaScience, scientists use various approaches to demonstrate that the IDseq tool is indeed able to reliably identify emerging pathogens, among them, as proof of principle, a nasal swab from a COVID-19 patient in Cambodia. A partnership between the Chan Zuckerberg Biohub, the Chan Zuckerberg Initiative (CZI), and the Bill and Melinda Gates Foundation enabled these researchers to sequence and confirm the country's first case of COVID-19 in a matter of days -- not the weeks it could typically take. The results demonstrate that IDseq can detect the presence of an emerging pathogen prior to the existence of a full reference genome. IDseq also now contains a new workflow for building SARS-CoV-2 consensus genomes. Metagenomic sequencing (mNGS) is an incredibly useful tool for pathogen detection because of its highly sensitive and hypothesis-free nature. We've seen labs that are using IDseq for existing mNGS studies rapidly pivot their focus to more targeted sequencing of SARS-CoV-2, which has helped researchers better understand coronavirus transmission patterns." Katrina Kalantar, Computational Biologist, CZI In Cambodia, researchers uploaded the genome sequence to open source pathogen data repository GISAID (Global Initiative on Sharing All Influenza Data) and to Nextstrain, so scientists anywhere can see the full genome sequence of the SARS-CoV-2 coronavirus and study it within the broader context of SARS-CoV-2 coronavirus sequences uploaded globally. Researchers at the Cambodian National Center for Parasitology, Entomology and Malaria Control (CNM) and the National Institute of Allergy and Infectious Diseases (NIAID) partnered with the Institut Pasteur Cambodia to complete this research. These researchers are one of several teams around the world receiving molecular biology and bioinformatics training from the infectious disease team at the Biohub; free access, training, and compute on the IDseq platform from CZI; and the necessary equipment and supplies to begin work in their own countries through the Grand Challenges Explorations Grants. Unlike tests that are specific for a known agent, such as the SARS-CoV-2 PCR test, mNGS is a universal method that can detect novel disease-causing pathogens, which can be especially useful in cases where researchers may not know what is causing an infection, or what pathogens are circulating in a particular area. A mNGS experiment starts with mass-amplifying DNA traces of pathogens from a patient's sample, resulting in millions of small bits of DNA sequences, or reads. This enormous dataset must then be analysed and interpreted using bioinformatic techniques. The aim is to assign individual DNA fragments from the clinical sample to specific pathogens by leveraging knowledge from sequence databases. Analyzing the massive amount of data from a typical mNGS experiment often requires a battery of specialized bioinformatic tools, including highly specialized expertise and expensive commercially licenced software -- making mNGS a hard-to-access method. The new user-friendly IDseq software is open source and freely available to the global health community, reducing the barrier of entry to metagenomics. Researchers can reuse and build upon the code, which works via a cloud-based service and a web application designed for collaboration and data sharing. The pipeline starts with raw sequencing data as the input, and then goes through steps of filtering, quality control, alignment, and reporting and visualization
Common kidney tests can help estimate risk of cardiovascular disease - News-Medical.Net
Taking into account two common kidney disease tests may greatly enhance doctors' abilities to estimate patients' cardiovascular disease risks, enabling millions of patients to have better preventive cardiovascular care, according to a large international stud…
Reviewed by Emily Henderson, B.Sc.Oct 15 2020 Taking into account two common kidney disease tests may greatly enhance doctors' abilities to estimate patients' cardiovascular disease risks, enabling millions of patients to have better preventive cardiovascular care, according to a large international study co-led by researchers at the Johns Hopkins Bloomberg School of Public Health. The researchers used data from more than nine million individuals around the world to develop and validate a risk-scoring calculation that adds blood and urine measures of kidney disease to the current standard method in the United States for assessing cardiovascular disease risk. The two measures--estimated glomerular filtration rate and urine albumin--are commonly used to reveal chronic kidney disease. CKD, as it's called, has long been considered a risk factor for cardiovascular disease, although until now CKD-related measures have not been included in standard algorithms for quantifying cardiovascular disease risk. The researchers showed that the use of their "CKD patch"--a computer-program update--can result in large increases in cardiovascular disease-risk estimates among patients with severe CKD. The investigators also developed a similar patch to enhance the standard risk-assessment tool used in Europe. The study appears October 14 in EClinicalMedicine, a new online open-access journal published by The Lancet. Adding these two measures of kidney disease, which are frequently available from blood and urine tests at checkups, allows potentially big improvements in the accuracy of a patient's risk estimates--improvements that should in turn enable doctors to optimize patient care." Kunihiro Matsushita, MD,Study Co-first Author and Associate Professor, Department of Epidemiology, Bloomberg School "This is a big deal--an estimated ten percent of the United States adult population has kidney disease and potentially would benefit from improved care if this new tool is adopted," says co-last author Josef Coresh, MD, George W. Comstock Professor in the Department of Epidemiology at the Bloomberg School. The other co-first author was Simerjot Jassal, MD, of the University of California, San Diego, and the other co-last author was Elke Schaeffner, MD, of Charité University Hospital Berlin. Shoshana Ballew, PhD, assistant scientist in the Bloomberg School's Department of Epidemiology, helped coordinate the data-gathering. In all, the study included more than 50 researchers. The reduction of kidney function in CKD can lead to higher blood pressure as well as hormonal and other chemical imbalances, and these in turn promote the narrowing of arteries that supply the heart muscle--conditions known as atherosclerosis and arteriolosclerosis. The American Heart Association and the American College of Cardiology, in their guidelines for physicians, already list CKD as a "risk enhancer" for atherosclerotic cardiovascular disease, but without a specific tool that quantifies the added risk as part of the standard risk calculator. Since 2009, Coresh, Matsushita, and colleagues have been assembling a large, international database of CKD patients and healthy adults, under a collaboration known as the CKD Prognosis Consortium. For the new study, they analyzed a portion of this database, covering 4.1 million adults around the world, to develop algorithms that estimate cardiovascular disease risk using standard measures plus the two kidney-disease measures. They then validated the accuracy of their algorithms using further samples covering 4.9 million adults. The two kidney disease measures, estimated glomerular filtration rate and urine albumin, respectively, indicate the kidneys' blood-filtering efficiency and the level of an essential protein called albumin that the kidneys normally would filter out of the urine. The researchers incorporated these measures in a "CKD patch" to the standard cardiovascular disease-risk estimation algorithm developed by the American Heart Association and the American College of Cardiology. They found that for adults who had results on these kidney- disease tests indicating CKD, the addition of these measures via the CKD patch significantly improved the estimated 10-year risks of atherosclerotic cardiovascular disease. For example, for patients with "very high-risk" CKD, the estimated 10-year chances of developing atherosclerotic cardiovascular disease were a median of 1.55 times higher than estimates without the CKD patch, while the figures were a median of 1.24 times higher for "high-risk" CKD patients. The researchers' CKD patch for the standard European 10-year cardiovascular disease mortality risk estimator also boosted estimated risks, by a median of 2.64 times in very high-risk CKD patients, and 1.86 times in high-risk CKD patients. "These results suggest that doctors have tended to underestimate cardiovascular disease risks in kidney disease patients," Matsushita says. The researchers hope that their CKD patches will be adopted widely, enabling more accurate assessments of cardiovascular disease and related mortality risks--which in turn should result in better preventive care including the use of statins and other interventions to ward off cardiovascular disease. "We also hope that the availability and value of these new algorithms will encourage doctors to order estimated glomerular filtration rate and urine albumin tests for their patients more often," Coresh says. Johns Hopkins University Bloomberg School of Public Health Matsushita, K., et al. (2020) Incorporating kidney disease measures into cardiovascular risk prediction: Development and validation in 9 million adults from 72 datasets. EClinicalMedicine. doi.org/10.1016/j.eclinm.2020.100552.
SARS-CoV-2 may become endemic if reinfection proves commonplace, say researchers - News-Medical.Net
To date, a few verified repeat SARS-CoV-2 infections have been documented around the world. "Should reinfection [with SARS-CoV-2] prove commonplace, and barring a highly effective vaccine delivered to most of the world's population, SARS-CoV-2 will likely bec…
Reviewed by Emily Henderson, B.Sc.Oct 15 2020 To date, a few verified repeat SARS-CoV-2 infections have been documented around the world. Should reinfection [with SARS-CoV-2] prove commonplace, and barring a highly effective vaccine delivered to most of the world's population, SARS-CoV-2 will likely become endemic." Jeffrey Shaman & Marta Galanti, Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University For many viruses, a number of processes - particularly insufficient adaptive immune response, waning immunity, and immune escape - can allow subsequent reinfection. In the case of SARS-CoV-2, many questions remain about the nature of these immune responses and trajectories, though, say the authors, insight from other respiratory viruses points to the possibility of reinfection with SARS-CoV-2. If this does happen, the pattern of endemicity that results will depend on the typical time scale at which individuals experience reinfection, seasonal differences in transmissibility, vaccine availability and efficacy, and social, immune, and innate factors that modulate virus transmissibility, say the authors. In addition, the cyclic persistence of SARS-CoV-2 in human populations may be affected by ongoing opportunities for interaction with other respiratory pathogens, say the authors; it is possible infection with a different virus could provide some short-lived protection to SARS-CoV-2. Greater monitoring of the clinical and population-scale interactions of SARS-CoV-2 with other respiratory viruses, particularly influenza viruses, is needed, they write. At the population scale, a possible overlap between influenza and SARS-CoV-2 outbreaks poses a serious threat to public health systems. Conversely, the nonpharmaceutical interventions adopted to mitigate SARS-CoV-2 transmission (personal protective equipment, social distancing, increased hygiene, limited indoor gatherings) may reduce the magnitude of seasonal influenza outbreaks, note Shaman and Galanti. Based on modeling of post-pandemic scenarios for SARS-CoV-2 to date, a duration of immunity similar to that of the other betacoronaviruses (~40 weeks) could lead to yearly outbreaks of SARS-CoV-2, the authors note, whereas a longer immunity profile, coupled with a small degree of protective cross-immunity from other betacoronaviruses, could lead to apparent elimination of the virus followed by resurgence after a few years. "Other scenarios are, of course, possible, because there are many processes at play and much that remains unresolved," say the authors. American Association for the Advancement of Science Shaman, J & Galanti, M (2020) Will SARS-CoV-2 become endemic?. Science. doi.org/10.1126/science.abe5960.