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Template for COVID-19 management in a rural health system - News-Medical.Net
As the COVID-19 pandemic continues to challenge existing health networks, a new study published on the preprint server medRxiv in October 2020 reports on a strategy to address existing health care disparities in rural and urban areas of the USA. This should d…
As the COVID-19 pandemic continues to challenge existing health networks, a new study published on the preprint server medRxiv* in October 2020 reports on a strategy to address existing health care disparities in rural and urban areas of the USA. This should draw attention to the need for more such systems to ensure proper rural healthcare in the current and future pandemics. Issues in Rural COVID-19 Management Rural areas in the US have a higher prevalence of elderly patients with COVID-19 as well as those with chronic disease. With the long-standing lack of many medical specialties in such areas, deficits in hospital inpatient and ICU capacity and the increasing inability of rural hospitals to cope with COVID ensure that many rural USA patients will not receive adequate healthcare. Another significant issue facing rural healthcare facilities is their lack of infrastructure and clinical experience, which denies them the opportunity to participate in clinical trials. As a result, the physicians in these areas either do not treat patients with COVID-19 or use medications off-label despite society's recommendations to reserve them for clinical trials. How healthcare for this infection may be better delivered in one such area is the current study's focus. This is served by the St. Lawrence Health System (SLHS), a model with treats inpatients with a small team of specialists competent to deal broadly with many areas in their respective disciplines. It also serves as one of the spokes serving its hub hospital, Canton Potsdam Hospital (CPH). Characteristics of Patients This study notes the 20 inpatients' characteristics in the CPH over the first two months following the outbreak. Patients had a median age of 63, about 60% being female. Half were obese, while a fifth each had cardiovascular disease, lung disease/asthma, or obstructive sleep apnea. A tenth had diabetes mellitus. Almost a third were smokers or had a history of smoking. The mean Charlson Comorbidity Index (CCI) was 3.2. Patients had been symptomatic for ~6 days, on average, prior to admission. 70% gave a history of contact with a known case before admission. The most common symptoms were cough, shortness of breath, and fever, all reported in half or more of patients. Admission temperatures were elevated in a third, while a sixth had tachycardia. About 60% had fast breathing, and almost half had oxygen saturation below 93%. At the time of admission, over a third were on oxygen, while saturation was being measured. Radiologic and Laboratory Findings The researchers found that 93% of patients had positive radiological evidence of COVID-19 pneumonia on chest X-ray or CT. Markers of inflammation (LDH and ferritin) were high, with a low lymphocyte count. The latter declined still more over their hospital stay, while ferritin levels rose. A sixth of patients had high troponin at or after admission. Varying Clinical Course and Treatments The researchers found that the median hospital stay duration was six days, with a fifth being admitted to the ICU. Of the latter four patients, two were shifted out after one day, while the others remained hospitalized for 19 and 27 days, respectively. About half and over a third of patients met NIH criteria for severe and critical COVID-19. Among the seven patients in the latter category, all had respiratory failure, a little below half of the patients developed septic shock, and over 70% had multi-organ dysfunction. Over 85% had renal impairment, and many had liver inflammation. Cardiac manifestations were observed in a sixth of patients, while 40% required supplemental oxygen, and a quarter was on ventilation. Various drugs were used as therapy, including hydroxychloroquine, azithromycin, systemic corticosteroids, tocilizumab, and convalescent plasma, besides inhaled bronchodilators and vasopressors. The standard of care underwent numerous changes in accordance with ongoing research worldwide, accounting for the temporal shift in the type of medication used, the dosage, and the use of combinations. Regarding the use of tocilizumab, a costly drug and one for which third-party insurance is frequently unavailable, the researchers worked out arrangements to include this in a clinical trial initiated at the end of the current study period. This shows how rural hospitals can be incorporated into ongoing research in order to broaden their access to expensive resources and to allow clinical decisions to be made based on the need rather than cost alone. Only one patient died as a result of the previously made decision not to use invasive ventilation, while all others survived, with the mean WHO ordinal score of 4.3 on admission and the lowest score over hospitalization being 3.8, on average. Implications and Recommendations This is the first template study for the care of rural patients hospitalized with COVID-19. It illustrates the relevance of a spoke-and-hub design and the high efficiency that may be brought into play by rapidly setting up a small team of medical specialists who are generalists within their areas of expertise. Such teams can cover inpatient care over a broad range of needs, including infectious disease, rheumatology, and pharmacy. The multidisciplinary approach to care allows the optimal use of limited resources to offer current care for COVID-19. It also allowed the efficient and effective treatment of COVID-19 with multiple complications, achieving a low mortality rate without outside transfer, even without the use of remdesivir, dialysis services, and extracorporeal membrane oxygenation (ECMO) in this health system. The researchers point out the significant difficulties they faced in gaining access to medications and convalescent plasma, with delays of up to 2 weeks in the latter's procurement from the date of request. This should stimulate efforts to upgrade infrastructure and clinical experience to the level that is essential for a clinical trial, thus improving access to novel drugs and treatments. Again, the investigators say that adequate healthcare networks are always fundamental to crisis management, whether connecting staff at hub hospitals to those at the spoke, setting up better facilities and training opportunities, or streamlining available resources with centralized management. Moreover, rural practitioners should be in touch with academic professionals in their field in order to bring about improvement in both practice and research settings. The authors suggest, “An improved version of this model would include a backup COVID-19 consultation team at a regional academic center, the incorporation of patient engagement and machine learning tools into care delivery, and research alliances that connect hub and spoke hospitals with larger academic partners.” This will help rural areas cope with their own share of future crises, and the current model may guide the development of such systems. *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.
SARS-CoV-2 can survive for 4 weeks on glass, money and metal - News-Medical.net
Published in the Virology Journal, the study shows that the virus can stay infectious for more extended periods on surfaces such as phone screens, stainless steel, and banknotes than previously thought.
Ten months into the coronavirus disease (COVID-19) pandemic, scientists learn more about the virus on a daily basis. Previously, studies have pointed out that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can persist on surfaces for days. Now, a new study provides an alarming finding that the virus can persist on surfaces for up to 28 days. Published in the Virology Journal, the study shows that the virus can stay infectious for more extended periods on surfaces such as phone screens, stainless steel, and banknotes than previously thought. The study A team of researchers at the Australian Centre for Disease Preparedness aimed to determine the role of fomite transmission in the spread of the SARS-CoV-2 virus across the globe, which has now infected more than 37.68 million people worldwide, according to the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). In the study, the team measured the survival rates of infections SARS-CoV-2, suspended in a standard ASTM E2197 matrix, on many common types of surfaces. The team carried out the experiments in the dark to negate the effects of ultraviolet light. Further, the researchers incubated the inoculated surfaces at 20 °C, 30 °C and 40 °C. The team obtained the virus isolate used in the study by the Peter Doherty Institute on behalf of the South Australian Health. All the experiments with the infectious virus isolate were performed in the high containment laboratory (Biosafety level 4) at the Australian Centre for Disease Preparedness. The team used commonly touched surfaces and items to see how long the infectious virus particles could survive. They used Australian polymer banknotes, de-monetized paper banknotes, and common surfaces, including glass, cotton cloth, and brushed stainless steel. Paper and polymer banknotes were also included to determine the role of note-based currency for the potential for fomite transmission. Also, stainless steel is commonly used in kitchen areas and other public facilities. At the same time, glass was chosen due to its prevalence in public areas, and it is used as a screen for mobile phones, ATMs, and other public items, such as tables, public transport windows, and hospital waiting rooms, among others. The team also used vinyl since it is also a widely used material used in grab handles on public transport, tables, and flooring. Meanwhile, cotton was tested since it is used in clothing, household fabrics, and beddings. What the study found The researchers determined the survival rates of SARS-CoV-2 at different temperatures. They obtained half-lives of between 1.7 and 2.7 days at 20 °C, decreasing to a few hours when the temperature was increased to 40 °C. The virus also persisted on most surfaces for about six to seven days before starting to lose its potency. After two weeks, the team still found many live and infectious virus particles, which could still infect people. The team also found that a viable virus was isolated for up to 28 days at 20°C from common surfaces like stainless steel, glass, and both paper and polymer banknotes. However, the infectious virus survived less than 24 hours at 40 °C on some surfaces. “These findings demonstrate SARS-CoV-2 can remain infectious for significantly longer periods than generally considered possible. These results could be used to inform improved risk mitigation procedures to prevent the fomite spread of COVID-19,” the team concluded. The team added that while the primary spread of SARS-CoV-2 appears to be through aerosols and respiratory droplets, fomites may also play a pivotal role in virus transmission. Fomite transmission has been shown as an important factor in the spread of other coronaviruses, such as the porcine epidemic diarrhea virus, the Middle East Respiratory Syndrome (MERS) coronavirus, human coronavirus 229E and OC43, and the current SARS-CoV-2. “Increasing the temperature while maintaining humidity drastically reduced the survivability of the virus to as little as 24 h at 40 °C,” the researchers explained. “The persistence of SARS-CoV-2 demonstrated in this study is pertinent to the public health and transport sectors. This data should be considered in strategies designed to mitigate the risk of fomite transmission during the current pandemic response,” they added. Health experts and agencies reiterate the importance of regular handwashing, wearing masks, and social distancing to reduce the spread of the coronavirus. It is essential to practice proper hand hygiene, especially after touching common items and surfaces to reduce the risk of being infected with COVID-19, which has now killed more than a million people globally.
- Riddell, S., Goldie, S., Hill, A., Eagles, D., and Drew, T. (2020). The effect of temperature on the persistence of SARS CoV 2 on common surfaces. Virology Journal. https://link.springer.com/epdf/10.1186/s12985-020-01418-7?sharing_token=gZeWNzpBqGqMWWlYBszijm_BpE1tBhCbnbw3BuzI2RPH7jdqQjm4GSWc627bmRViN0gdjUUXa4XmNsLCVxARS5fW6_H-pdK1v6GxwHmr02IpeWQaQhWfdiZqkh8IAAPswG5OMBeJlMvLtQ_xpm3V7AzNehvYyja-6O3X0Zs6-M4%3D
A special issue on the emerging COVID-19 infection - News-Medical.Net
Acta Pharmaceutica Sinica B publishes special issue on 'Research on Emerging COVID-19 (Target, Mechanism, and Therapeutics)' edited by Hai-Bin Luo, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; Shilin Chen, Institute of Chinese …
Reviewed by Emily Henderson, B.Sc.Sep 29 2020 Acta Pharmaceutica Sinica B publishes special issue on 'Research on Emerging COVID-19 (Target, Mechanism, and Therapeutics)' edited by Hai-Bin Luo, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; Shilin Chen, Institute of Chinese Materia Medica, Beijing, China and Peiqing Liu, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. In recent months, due to its high infectivity and pathogenicity, SARS-CoV-2 has gradually spread to more than 200 countries and regions, resulting in more than 500,000 deaths globally. There is an urgent need for effective prevention and treatment (drugs and vaccines) against this highly pathogenic coronavirus. This special issue includes original five research articles, three review articles, and two letters to the editor covering topics around the identification of readily available drugs or natural products as a rapid way to provide clinical treatment in COVID-19 therapy. Featured papers in this issue are: Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19 by authors Xiaoyan Liu, Zhe Li, Shuai Liu, Jing Sun and Hai-Bin Luo. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, the authors found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, the authors identified an anticoagulation agent dipyridamole (DIP) in silico, which suppressed SARS-CoV-2 replication in vitro. Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites by authors Sisi Kang, Mei Yang, Zhongsi Hong, Liping Zhang and Shoudeng Chen . The structural information of SARS-CoV-2 nucleocapsid protein remains unclear. The authors have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein and revealed potential unique drug targeting sites, which can help guide the design of novel antiviral agents targeting SARS-CoV-2. D3Targets-2019-nCoV: a webserver for predicting drug targets and for multi-target and multi-site based virtual screening against COVID-19 by authors Yulong Shi, Xinben Zhang, Kaijie Mu, Cheng Peng and Weiliang Zhu. The authors have developed a molecular docking-based web server D3Targets-2019-nCoV to accelerate drug discovery against COVID-19. The server has two functions; one, to predict targets for active compounds, and two, to identify potent compounds via virtual screening. The webserver is useful to medical chemists, pharmacologists and clinicians for efficiently discovering or developing effective drugs against SARS-CoV-2. Other articles published in the issue include: Review articles Combating COVID-19 with integrated traditional Chinese and Western medicine in China Liqiang Ni, Lili Chen, Xia Huang, Chouping Han, Hongzhuan Chen. Bioactive natural compounds against human coronaviruses: a review and perspective Yanfang Xian, Juan Zhang, Zhaoxiang Bian, Hua Zhou, Hongxi Xu. Highly pathogenic coronaviruses: thrusting vaccine development in the spotlight Chunting He, Ming Qin, Xun Sun. Compuscript Ltd Chen, S., et al. (2020) Special Column: Research on Emerging COVID-19 (Target, Mechanism, and Therapeutics). Acta Pharmaceutica Sinica B.
Rheumatoid arthritis is associated with increased risk of developing diabetes - News-Medical.Net
A new study presented at this year's annual meeting of the European Association for the Study of Diabetes (EASD), held online this year, shows that rheumatoid arthritis (RA) is associated with a 23% increased risk of type 2 diabetes (T2D), and may indicate th…
Reviewed by Emily Henderson, B.Sc.Sep 21 2020 A new study presented at this year's annual meeting of the European Association for the Study of Diabetes (EASD), held online this year, shows that rheumatoid arthritis (RA) is associated with a 23% increased risk of type 2 diabetes (T2D), and may indicate that both diseases are linked to the body's inflammatory response. The research was conducted by Zixing Tian and Dr Adrian Heald, University of Manchester, UK, and colleagues. Inflammation has emerged as a key factor in the onset and progression of T2D, and RA is an autoimmune and inflammatory disease. The team suggest that the systemic inflammation associated with RA might therefore contribute to the risk of an individual developing diabetes in the future. The team conducted a comprehensive search of a range of medical and scientific databases up to 10 March 2020, for cohort studies comparing the incidence of T2D among people with RA to the diabetes risk within the general population. Statistical analyses were performed to calculate the relative risks, as well as to test for possible publication bias (in which the outcome of research influences the decision whether to publish it or not). The eligible studies identified comprised a total of 1,629,854 participants. Most of the studies were population-based and one was hospital-based, while no evidence was found for publication bias in any of them. The authors found that having RA was associated with a 23% higher chance of developing T2D, compared to the diabetes risk within the general population. They conclude that: "This finding supports the notion that inflammatory pathways are involved in the pathogenesis of diabetes." We suggest that more intensive screening and management of diabetes risk factors should be considered in people with rheumatoid arthritis. Agents that reduce systemic inflammatory marker levels may have a role in preventing type 2 diabetes. This may involve focussing on more than one pathway at a time." Researchers
COVID-19 ‘long-haulers’ experience lingering health effects - News-Medical.Net
Called “long-haulers” or “long-termers,” some people report lingering symptoms of the illness for months. These people experience symptoms ranging from fatigue and weakness to chest pains and difficulty breathing.
The coronavirus disease (COVID-19) pandemic is actively spreading, adding more infections to the 29.27 million cases across the globe. Though a majority of these people only experience mild to moderate symptoms, there is a group of COVID-19 survivors who have never recovered. A news feature on nature.com discusses their plight. Called “long-haulers” or “long-termers,” some people report lingering symptoms of the illness for months. These people experience symptoms ranging from fatigue and weakness to chest pains and difficulty breathing. Persistent symptoms A team of scientists at the University of Southern California in Los Angeles (UCLA) began tracking COVID-19 patients in January using computed tomography (CT) scanning to examine their lungs. They followed 33 patients for a month. The results of their work, which has not yet been published, show that more than a third of the patients had tissue death that appeared as scars in their lungs. The researchers plan to follow these patients for years to determine the long-lasting effects of COVID-19 on the body. According to Ali Gholamrezanezhad, a clinical radiologist and part of the team, most of the cases are mild to moderate and do not end up being admitted to the hospital. He estimates that the rate of intermediate-term lung damage is about less than 10 percent. However, since there are 29 million people who were infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), even a low percentage may imply that thousands of people experience long-lasting and persistent health problems. With many people having lingering symptoms, many doctors are concerned that the number will grow as the cases surge. The disease is novel, and no one has any idea of its long-term effects on the body. Doctors worry that organ damage may be permanent or may linger for months, or even years. They are also unsure if the damage is likely due to intensive treatments such as intubation, or caused by the virus itself. Yet, as the pandemic evolves, many new studies show that the virus attacks many organs, not just the lungs. Lung damage One of the most affected organs in the body is the lungs since COVID-19 is mainly a respiratory disease. In the first few months of the pandemic, many countries crammed to contain the spread of the virus, implementing lockdowns. The focus of hospitals and clinicians were to cope with the skyrocketing cases, while research was focused on finding the source and treatment for the infection. Recently, amid the sudden increase of health consequences of the illness, doctors are now looking for answers on why many patients do not fully recover from the illness. In another study out of Austria, researchers discovered that lung damage reduced over time. About 88 percent of the study participants had visible lung damage six weeks after being discharged from the hospital. By 12 weeks, the number fell to 56 percent. In the current UCLA research, the team led by Gholamrezanezhad analyzed the lung images from the CT scan of more than 900 patients from published studies. They found that the most affected part of the lungs is the lower lobes. The CT scan images were packed with whitish and opaque patches that imply inflammation, making it hard for people to breathe during sustained exercise. The team said that the damage seemed to improve after two weeks. Further, the team noted that some symptoms might take longer to subside. Another study of 152 post-discharge patients published in the preprint source, medRxiv* showed that among people who have been hospitalized due to COVID-19, more than 70 percent of patients report shortness of breath and 13.5 percent needed oxygen at home after a month of being discharged. Meanwhile, the U.S. Centers for Disease Control and Prevention (CDC) says that COVID-19 can result in prolonged illness, even among young people without underlying health conditions. In a study cited by the CDC, a survey of symptomatic adults who had been diagnosed with COVID-19 showed that 35 percent had not returned to their normal state of health when they were interviewed two to three weeks after diagnosis. Among young adults with no underlying medical illness, one in five had not fully recovered. “These findings have important implications for understanding the full effects of COVID-19, even in persons with milder outpatient illness,” the health agency said.
Detecting SARS-CoV-2 in 30 seconds with cheap and sensitive nanotubes - News-Medical.Net
In a fascinating new medRxiv preprint paper, researchers from the University of Nevada, Reno demonstrate the power of cobalt-functionalized titanium dioxide nanotubes by selectively detecting the spike glycoprotein of the severe acute respiratory syndrome cor…
In a fascinating new medRxiv* preprint paper, researchers from the University of Nevada, Reno demonstrate the power of cobalt-functionalized titanium dioxide nanotubes by selectively detecting the spike glycoprotein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in less than 30 seconds. The relentless pandemic of coronavirus disease (COVID-19), caused by SARS-COV-2, resulted in a disruption to society not experienced since the 1918 influenza pandemic. One of the reasons for such rapid spread of the virus is the asymptomatic clinical presentation in many infected individuals, which contributes to involuntary transmission. Consequently, consistent surveillance and quarantining of not only infected individuals but also asymptomatic ones could provide a somewhat effective measure to curtail further spread of SARS-CoV-2. Nonetheless, methods that are currently being used for SARS-CoV-2 diagnosis are time-consuming, expensive, and require trained personnel – albeit certain inexpensive solutions are obtaining approvals for emergency usage. The promise of electrochemical biosensors Electrochemical biosensors are a favorable choice for sensing biomolecules due to their propensity to detect biomarkers with adequate accuracy, high sensitivity, and specificity. As a result, they have been used to detect influenza viruses, enteroviruses, and Middle East respiratory syndrome coronavirus (MERS-CoV). The functionality of such electrochemical biosensors can be additionally improved by nano-structuring the electrode since this step increases the electrochemical reaction rate by increasing the electrode surface area to analyte fluid volume. This is why researchers from the University of Nevada in Reno, hypothesized that SARS-CoV-2 could be detected through complexing of functionalized nanoparticles with characteristic viral proteins. Synthesizing titanium dioxide nanotubes This group of researchers, led by Dr. Bhaskar Sravan Vadlamani, developed a cobalt-metal functionalized titanium dioxide nanotubes (Co-TNT) as a sensing material for electrochemical detection of SARS-CoV-2 by detecting the receptor-binding domain (RBD) of spike glycoprotein. More specifically, titanium dioxide nanotubes (TNTs) were synthesized by electrochemical anodization of titanium sheet. The annealed TNTs acquired from the furnace were functionalized with cobalt by employing an incipient wetting method, i.e., a wet ion exchange process. The morphology of the TNTs and Co-TNT was then examined with the use of Dual Beam Scanning Electron Microscopy. Moreover, the spike-RBD protein, the aforementioned biomarker for SARS-CoV-2 detection, has been characterized via sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under denaturizing conditions. The ability of Co-TNT to sense spike-RBD protein of SARS-CoV-2 was determined by carrying out an amperometry experiment at -0.8 volts. Finally, the electrochemical sensing was performed with the use of a custom-built Co-TNT packaged and printed circuit board setup. SARS-CoV-2 concentration and detection time The study has shown that the sensor detected the spike-RBD protein of SARS-CoV-2 even at very low concentrations (ranging from 14 nM to 1400 nM). Furthermore, a linear response in the detection of viral protein with concentration has been demonstrated. Importantly, the time needed for detection was very short (approximately 30 seconds), confirming the possibility of using this technology to develop a rapid diagnostic assay that can be exploited as a point of care diagnostics for rapid SARS-CoV-2 detection. Also, the average sensor response time (defined as the time needed to reach the peak current) was found to be approximately 2 seconds. This is very short in comparison with earlier studies from the same authors on the sensor for colorectal cancer, as sensor response time there was 100-fold higher. Scalable diagnostic platform "Our report demonstrates the development of a simple, inexpensive, rapid, and non-invasive diagnostic platform that has the potential of detecting SARS-CoV-2 on clinical specimens including nasal, nasopharyngeal swabs or saliva" study authors summarize their findings. "Moreover, the developed approach has the potential for diagnosis of other respiratory viral diseases by identifying appropriate metallic elements to functionalize TNTs," they add in this medRxiv preprint paper. Advantageously, the sensor readout is an electrochemical signal gathered through a potentiostat or galvanostat, which can be adopted for smartphone applications and point of care diagnostics for COVID-19. Finally, the sensor sensitivity may also be improved by using longer Co-TNT, since higher surface area provides a better reaction rate. As a result, higher sensor response current can be reached even at lower protein concentrations. All of this makes this technology a potentially useful addition to our diagnostic armamentarium. *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.
Metabolite signature reveals signs of multi-organ damage in COVID-19 patients - News-Medical.Net
SARS-CoV-2, the virus responsible for COVID-19, can cause a wide range of symptoms, from none at all to severe respiratory stress, multi-organ failure and death.
Reviewed by Emily Henderson, B.Sc.Sep 9 2020 SARS-CoV-2, the virus responsible for COVID-19, can cause a wide range of symptoms, from none at all to severe respiratory stress, multi-organ failure and death. The virus notably targets the lungs, but many patients also experience non-respiratory symptoms. Now, researchers reporting in ACS' Journal of Proteome Research compared lipoproteins and metabolites in the blood of COVID-19 patients and healthy subjects, revealing signs of multi-organ damage in patients that could someday help diagnose and treat COVID-19. Current diagnostic tests for COVID-19 rely on the detection of viral RNA or antibodies against the virus. Both types of tests are prone to false-negative results, as well as having other limitations. Another possible way of detecting SARS-CoV-2 infection could involve analyzing metabolic changes the virus causes in an infected person. Jeremy Nicholson, Elaine Holmes and colleagues wanted to analyze the systemic effects of the disease and determine whether there is a general metabolic signature of COVID-19. The researchers collected blood samples from 17 patients who tested positive for COVID-19 with current assays and from 25 healthy age-, sex- and body mass index-matched controls who were proven negative for current or prior SARS-CoV-2 infection with an antibody test. Then, the team analyzed the plasma lipoprotein, metabolite and amino acid levels in blood plasma with nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. Through multivariate statistical analyses that detected differences between patients and controls, the researchers revealed a metabolic signature of SARS-CoV-2 infection involving signs of acute inflammation, liver dysfunction, diabetes and cardiovascular disease risk. The team is now validating the data in a much larger group of patients. In addition to possibly being used to develop a metabolite-based diagnostic test, these results suggest that recovered COVID-19 patients should be evaluated for increased risks for other conditions, the researchers say. American Chemical Society Kimhofer, T., et al. (2020) Integrative Modelling of Quantitative Plasma Lipoprotein, Metabolic and Amino Acid Data Reveals a Multi-organ Pathological Signature of SARS-CoV-2 Infection. Journal of Proteome Research.doi.org/10.1021/acs.jproteome.0c00519.
'Molecular brake' on the immune system could be potential treatment target for severe COVID-19 - News-Medical.Net
Older people and people with underlying medical conditions are at particular risk of severe COVID-19. A group of researchers from Charité - Universitätsmedizin Berlin have discovered one possible reason for this vulnerability.
Older people and people with underlying medical conditions are at particular risk of severe COVID-19. A group of researchers from Charité - Universitätsmedizin Berlin have discovered one possible reason for this vulnerability. While these risk groups produce greater quantities of an important type of immune cell known as 'T-helper cells', their T-helper cells show impaired function. This 'molecular brake' on the immune system could serve as a potential new treatment target in patients with severe COVID-19. The researchers' findings have been published in the Journal of Clinical Investigation. Soon after the emergence of COVID-19, medical experts from across the globe reported the same phenomenon. They found that older people and people with underlying medical conditions (such as cardiovascular disease and diabetes) were more likely to develop severe disease. There is likely an array of medical reasons why advancing age or health problems should make it more difficult for our bodies to fight an infection with SARS-CoV-2. One of the factors suspected of playing a major role in this regard was the immune system. An interdisciplinary team of researchers from Charité has collated findings which support this hypothesis. As part of their study, the researchers collected blood samples from 39 COVID-19 patients who had been admitted to Charité for treatment. The researchers used these blood samples to isolate immune cells which they then stimulated with specially synthesized fragments of the SARS-CoV-2 virus. Using specific dyes to make them visible, the researchers then counted T-helper cells which had reacted to the viral fragments. As a last step, the researchers tested whether there might be a link between the number of activated T-helper cells and the patients' risk factors. The researchers were able to show a positive correlation between the frequency of virus-specific T-helper cells and the patients' age. The same positive correlation was found to exist in relation to the 'Comorbidity Index', a compound measure expressing the severity of 19 different underlying medical conditions: the higher the patient's Comorbidity Index, the higher the number of SARS-CoV-2-specific T-helper cells in their blood. However, the team also found that advancing age and overall comorbidity scores were linked to a decrease in the proportion of cells producing the messenger substance 'interferon gamma' (IFN?). Cells normally release this molecule when they have recognized a virus; it is used to stimulate other components of the body's immune response which are needed to fight the pathogen. "Some of the SARS-CoV-2-specific T cells which we found in the blood of COVID-19 patients with risk factors no longer function properly," explains leading co-first author Dr. Arne Sattler, a researcher in the Translational Immunology Research Group at Charité's Department of General, Visceral and Vascular Surgery. Summing up the study's findings, Dr. Sattler says: "One might say that these T-helper cells are being slowed down in people with risk factors. We believe this has the potential to hamper the body's ability to mount an effective response against the pathogen." One substance known to act as a molecular 'brake' on the immune system is the protein PD-1. Found on the surface of T cells, this protein normally ensures an appropriate immune response and prevents the immune system attacking the body. Notably, the Charité researchers were able to show that the virus-specific T-helper cells produced significantly more PD-1 in patients with acute infection than in patients who had recovered from relatively mild symptoms. "Seen in combination with the findings from other researchers, our data suggest that PD-1 could be partly responsible for the fact that, in some people with COVID-19, the immune system produces insufficient quantities of messenger substances to be able to fight the pathogen," says Dr. Sattler. He adds: "COVID-19 patients may therefore benefit from treatments which aim to release this type of 'immune system brake'. However, many more studies will be needed in order to clarify this matter." Charité - Universitätsmedizin Berlin Sattler, A., et al. (2020) SARS-CoV-2 specific T-cell responses and correlations with COVID-19 patient predisposition. Journal of Clinical Investigation. doi.org/10.1172/JCI140965.
Scientists describe various dynamic structures of the SARS-CoV-2 spike protein - News-Medical.Net
Early in the pandemic, scientists uncovered the role of the ACE2 receptor in SARS-CoV-2, the virus that causes the coronavirus disease (COVID-19). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the angiotensin-converting en…
Early in the pandemic, scientists uncovered the role of the ACE2 receptor in SARS-CoV-2, the virus that causes the coronavirus disease (COVID-19). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the angiotensin-converting enzyme 2 (ACE2) receptors act as a lock and key for cell infection. Now, a team of researchers at the Indian Institute of Science Education and Research (IISER) Kolkata has explained the different dynamic structures of the SARS-CoV-2 spike protein, which acts as the molecular machine that permits the entry of the novel coronavirus into cells. The study, published in the Journal of Physical Chemistry Letters, highlights show their findings can help in formulating and developing effective vaccines against the virus, which has now infected more than 27.24 million people across the globe. What is the spike protein? One of the describing features of SARS-CoV-2 is the protein spikes that cover the surface, which the virus uses to bind with and enter human cells. Analyzing the structure of these spikes could provide clues about the virus’ evolution, and they can act as the key to the development of effective vaccines. Most of the vaccines being developed across the globe, where some are now in the last phase of clinical evaluation, work in a basic code – revealing the body to the spike protein, which acts as protrusions seen on the outer surface of the virus, to trick the body into believing that it has been attacked by a pathogen, hence, inducing an immune response. Since then, scientists study the three-dimensional structure of the spike protein, and they are learning about the spike protein and how they can target this part of the virus, which is the key to infecting cells. Dynamic asymmetry The spike protein of SARS-CoV-2 is a smart molecular machine that initiates the entry of the coronavirus into the cell, causing COVID-19. The researchers used a symmetry-information-loaded structure-based Hamiltonian, using recent Cryo-EM structural data to determine the conformational energy landscape of the perfusion spike protein. “The study finds the 2019-nCoV prefusion spike to adopt a unique strategy by undertaking a dynamic conformational asymmetry that results in two prevalent asymmetric structures of spike where one or two spike heads rotate up to provide better exposure to the host-cell receptor,” the researchers wrote in the paper. The team also explained that the stability of every biomolecular structure is controlled by a “free energy” parameter, which is essential in understanding how the molecule responds to its surroundings. The scientists described the free energy profile for the various structures of the SARS-CoV-2 spike protein. The constancy of every biomolecular structure is controlled by a parameter called ‘free energy,’ which is fundamental in understanding how the molecule will react with its surroundings. The spike protein contains three combined chains of amino acids, which are considered the building blocks of proteins. When these amino acids interact with each other, they create a set of dynamics within spike proteins, which the scientist described as the “dance of the spike protein.” In the study, the researchers defined the states wherein these spike proteins are most likely to help the virus bind to the ACE2 receptor sites. The three states induce the immune response, so having a better understanding of these dynamics can help in developing effective vaccines for protection against the infectious disease. “The dynamic asymmetry induced by the identified unique interchain interactions in this study highlights a different mechanism for SARS-CoV-2 S stabilizing more up conformation,” the authors wrote. “Although in the current situation developing diagnostics and antiviral therapies are of utmost priority, we believe the present structure-based-model-derived information at the microscopic interaction level might provide deep insight into design effective decoys or vaccine to fight 2019-nCoV infection,” they added.
Research provides a map of coronavirus entry factors across the human body - News-Medical.net
An infection with the coronavirus SARS-CoV-2 can affect multiple organs. With this in mind, researchers of the German Center for Neurodegenerative Diseases and Cornell University in the US have investigated cellular factors that could be significant for an in…
Reviewed by Emily Henderson, B.Sc.Sep 3 2020 An infection with the coronavirus SARS-CoV-2 can affect multiple organs. With this in mind, researchers of the German Center for Neurodegenerative Diseases (DZNE) and Cornell University in the US have investigated cellular factors that could be significant for an infection. To this end, they analyzed the activity of 28 specific genes in a wide range of human tissues. Their findings, which provide a map of potentially disease-relevant factors across the human body, are published in the journal Cell Reports. SARS-CoV-2 not just infects the respiratory system, it has the potential to affect many other organs in the body. Even if the virus infects the respiratory system first, it is essential to be able to predict where it might go next. This aids to develop therapies. Our goal was thus to learn more about what makes the different organs susceptible to infection. Therefore, we looked at different tissues to see which components of the cellular machinery might be relevant for infection and also which cell types appear to be particularly susceptible." Dr. Vikas Bansal, data scientist at the DZNE's Tuebingen site Bansal co-authored the current paper with Manvendra Singh, a Cornell presidential fellow, and with Cedric Feschotte, professor in the Department of Molecular Biology and Genetics at the Cornell University. Searching candidates In cooperation with his US colleagues, Bansal started by identifying 28 human genes, respectively cellular factors, that enable the virus to enter human cells or that might otherwise be important for an infection. In addition to receptors on the cell surface, these included, for example, proteins that the pathogen presumably needs in order to multiply within a cell. Importantly, the list of studied factors also contains enzymes that block the penetration of pathogens into cells - known as "restrictors factors". In summary, the 28 analysed cellular features are dubbed "SCARFs" for "SARS-CoV-2 and coronavirus associated receptors and factors". "The virus is known to misuse the so-called ACE2 receptor, which occurs on the surface of human cells, to dock and infiltrate them. A lot of attention is therefore paid to this receptor and other factors associated with it. They are potential starting points for therapies," said Bansal. However, related corona viruses are known to use a broad range of possibilities to infect cells. According to the researcher, evidence suggests that this also applies to SARS-CoV-2. "Therefore, we have extended our analysis to cellular factors that have been found to be relevant in other corona viruses and may therefore also be important for SARS-CoV-2." Whether this is actually the case, future experiments will have to show, explained Bansal. For such investigations, he said, the aim was to identify promising candidates. "Our study is only a snapshot, however. Research is developing rapidly. We are constantly learning new facts about this virus." Profiles of gene activity Using information from scientific databases, the researchers analyzed gene activity - also known as "expression patterns" - in around 400,000 human cells from various types of tissue. These included nasal mucosa, lungs, gut, kidneys, heart, brain and reproductive organs. Analysis was done on a single-cell level and using sophisticated bioinformatics methods. "This enabled us to investigate in which cells the SCARFs are expressed and also what percentage of cells within a given tissue express these factors," said Bansal. "Our results are certainly limited by the fact that expression patterns can change in the course of an infection and that such activity profiles do not directly reflect the abundance of proteins such as cell receptors. However, expression patterns are good indicators." Battlegrounds and hotspots In line with the known fact that SARS-CoV-2 attacks in particular the respiratory tract, the expression patterns identify the nasal mucosa as a "battleground". Accordingly, cells of the nasal mucosa contain both factors that facilitate infection like the ACE2 receptor as well as factors that inhibit viral entry, like IFITM3 and LY6E. "IFITM3 is a protein known to prevent other coronaviruses from crossing the cell membrane. Same might also apply to SARS-CoV-2. LY6E also acts as a defensive mechanism", said Bansal. "It thus seems that contact of the virus with the nasal mucosa leads to a tug-of-war. The question therefore is, who will emerge as the winner. Interestingly, our data suggest that the expression level of entry factors in the human nasal tissue shift with age. This could be a reason why the elderly are more susceptible to infection by SARS-CoV-2." According to the current study, the intestine, kidneys, testes and placenta are potential hotspots, that is, these areas seem to be characterized by significant co-expression of ACE2 with TMPRSS2, an enzyme involved in viral entry in combination with ACE2. "We were also able to identify a number of cellular factors that, as alternatives to the ACE2 receptor, could contribute to SARS-CoV-2 entering the lungs, heart and central nervous system," said Bansal. "SARS-CoV-2 is by now known to be able to trigger neurological disorders. Although the virus has not yet been detected in neurons, the nervous system includes other cells such as astrocytes and pericytes that are for example involved in the regulation of the blood-brain barrier, which is the interface between the brain and the bloodstream. According to our study these cells might well be susceptible to infection. This could possibly involve a receptor called BSG. All in all, our study therefore provides a wealth of data and specific clues for future studies on the coronavirus." DZNE - German Center for Neurodegenerative Diseases Singh, M., et al. (2020) A single-cell RNA expression map of human coronavirus entry factors. Cell Reports.doi.org/10.1016/j.celrep.2020.108175.