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8 | 3v80d4ci | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Symptomatic COVID-19 Infection in Eye Professionals in Wuhan China |
13 | mm2sp48e | what are the transmission routes of coronavirus? | Single-cell Analysis of ACE2 Expression in Human Kidneys and Bladders Reveals a Potential Route of 2019-nCoV Infection Since December 2019, a novel coronavirus named 2019 coronavirus (2019-nCoV) has emerged in Wuhan of China and spread to several countries worldwide within just one month. Apart from fever and respiratory complications, acute kidney injury has been observed in some patients with 2019-nCoV. In a short period of time, angiotensin converting enzyme II (ACE2), have been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same for severe acute respiratory syndrome coronavirus (SARS). To investigate the possible cause of kidney damage in 2019-nCoV patients, we used both published kidney and bladder cell atlas data and an independent unpublished kidney single cell RNA-Seq data generated in-house to evaluate ACE2 gene expressions in all cell types in healthy kidneys and bladders. Our results showed the enriched expression of all subtypes of proximal tubule cells of kidney and low but detectable levels of expression in bladder epithelial cells. These results indicated the urinary system is a potential route for 2019-nCoV infection, along with the respiratory system and digestion system. Our findings suggested the kidney abnormalities of SARS and 2019-nCoV patients may be due to proximal tubule cells damage and subsequent systematic inflammatory response induced kidney injury. Beyond that, laboratory tests of viruses and related indicators in urine may be needed in some special patients of 2019-nCoV. |
6 | akriqg0n | what types of rapid testing for Covid-19 have been developed? | Market Trends in Lateral Flow Immunoassays |
16 | cxvnv8dy | how long does coronavirus remain stable on surfaces? | Émergence de virus nouveaux en Asie : les changements climatiques sont-ils en cause ? Résumé L'Afrique tropicale n'est pas la seule région du monde où des virus dangereux pour l'homme aient récemment émergé. L'Asie, en particulier la Chine et le Sud-est asiatique, a également connu l'émergence de viroses humaines graves, telles que la dengue hémorragique (les Philippines, 1954) ou plusieurs pandémies grippales, la grippe asiatique (N2H2) en 1957, la grippe de Hong-Kong (H3N2) en 1968, et la grippe russe (H1N1) en 1977. Mais, c'est surtout au cours des dix dernières années que les émergences virales s'y sont multipliées avec l'apparition de la fièvre hémorragique à virus Alkhurma en Arabie Saoudite (1995), de la grippe aviaire H5N1 à Hong-Kong, en 1997, de l'encéphalite à virus Nipah en Malaisie, en 1998, et surtout du SRAS, en Chine du sud en 2002. Les facteurs climatiques n'ont probablement joué qu'un rôle réduit dans le succès émergentiel de ces viroses, favorisé plutôt par des facteurs humains : le développement d'élevages industriels d'animaux de basse cour augmentant les risques d'épizooties, les habitudes alimentaires, les pressions économiques et démographiques, les négligences dans la surveillance épidémiologique et la déclaration des premiers cas. Abstract Tropical Africa is not the only area where deadly viruses have recently emerged. In South-East Asia severe epidemics of dengue hemorrhagic fever started in 1954 and flu pandemics have originated from China such as the Asian flu (H2N2) in 1957, the Hong-Kong flu (H3N2) in 1968, and the Russian flu (H1N1) in 1977. However, it is especially during the last ten years that very dangerous viruses for mankind have repeatedly developed in Asia, with the occurrence of Alkhurma hemorrhagic fever in Saudi Arabia (1995), avian flu (H5N1) in Hong-Kong (1997), Nipah virus encephalitis in Malaysia (1998,) and, above all, the SARS pandemic fever from Southern China (2002). The evolution of these viral diseases was probably not directly affected by climate change. In fact, their emergential success may be better explained by the development of large industry poultry flocks increasing the risks of epizootics, dietary habits, economic and demographic constraints, and negligence in the surveillance and reporting of the first cases. |
1 | pgtvx6wb | what is the origin of COVID-19 | Delivery of infection from asymptomatic carriers of COVID-19 in a familial cluster Abstract Objectives With the ongoing outbreak of COVID-19 around the world, it has become a worldwide health concern. One previous study reported a family cluster with asymptomatic transmission of COVID-19. Here, we report another series of cases and further demonstrate the repeatability of the transmission of COVID-19 by pre-symptomatic carriers. Methods A familial cluster of five patients associated with COVID-19 was enrolled in the hospital. We collected epidemiological and clinical characteristics, laboratory outcomes from electronic medical records, and also affirmed them with the patients and their families. Results Among them, three family members (Case 3/4/5) had returned from Wuhan. Additionally, two family members, those who had not travelled to Wuhan, also contracted COVID-19 after contacting with the other three family members. Case 1 developed severe pneumonia and was admitted to the ICU. Case 3 and Case 5 presented fever and cough on days 2 through 3 of hospitalization and had ground-glass opacity changes in their lungs. Case 4 presented with diarrhoea and pharyngalgia after admission without radiographic abnormalities. Case 2 presented no clinical or radiographic abnormalities. All the cases had an increasing level of C-reactive protein. Conclusions Our findings indicate that COVID-19 can be transmitted by asymptomatic carriers during the incubation period. |
23 | 5r0ubg5g | what kinds of complications related to COVID-19 are associated with hypertension? | Characterization and Clinical Course of 1000 Patients with COVID-19 in New York: retrospective case series Objective: To characterize patients with coronavirus disease 2019 (COVID-19) in a large New York City (NYC) medical center and describe their clinical course across the emergency department (ED), inpatient floors, and intensive care units (ICUs). Design: Retrospective manual medical record review. Setting: NewYork-Presbyterian/Columbia University Irving Medical Center (NYP/CUIMC), a quaternary care academic medical center in NYC. Participants: The first 1000 consecutive patients with laboratory-confirmed COVID-19. Methods: We identified patients with a positive RT-SARS-CoV-2 PCR receiving care at NYP/CUIMC from March 1 through April 15. Patient data was manually abstracted from the electronic medical record. Main outcome measures: We describe patient characteristics including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, outcomes, and disposition. Results: Among the first 1000 patients with confirmed COVID-19, 151 patients were discharged from or died in the ED, 618 were admitted to the floor, and 231 were admitted or transferred to the ICU; 195 remained hospitalized and 172 had died in the hospital. The most common presenting symptoms were cough (73.2%), fever (72.8%), and dyspnea (62.9%). Compared to Chinese and Italian cohorts, hospitalized patients and ICU patients in particular had more baseline comorbidities including hypertension, diabetes, and obesity and higher rates of acute kidney injury (AKI) and dialysis. ICU patients were older and predominantly male (67.5%); 75.3% developed AKI and 31.2% required dialysis. Notably, of patients who required mechanical ventilation, only 5.9% were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at 3-4 and 9 days. Conclusions: Hospitalized patients with COVID-19 illness at this medical center faced significant morbidity and mortality, with high rates of AKI, dialysis, and a bimodal distribution in time to intubation from symptom onset. Patients in this large sample have more baseline comorbidities and more complications than previous Italian and Chinese cohorts. |
21 | oi0zsdtd | what are the mortality rates overall and in specific populations | COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives The recent outbreak of COVID-19 in Wuhan turned into a public health emergency of international concern. With no antiviral drugs nor vaccines, and the presence of carriers without obvious symptoms, traditional public health intervention measures are significantly less effective. Here, we report the epidemiological and virological characteristics of the COVID-19 outbreak. Originated in bats, 2019-nCoV/ severe acute respiratory syndrome coronavirus (SARS-CoV)-2 likely experienced adaptive evolution in intermediate hosts before transfer to humans at a concentrated source of transmission. Similarities of receptor sequence binding to 2019-nCoV between humans and animals suggest a low species barrier for transmission of the virus to farm animals. We propose, based on the One Health model, that veterinarians and animal specialists should be involved in a cross-disciplinary collaboration in the fight against this epidemic. |
47 | 03odxrgc | what are the health outcomes for children who contract COVID-19? | The relationship between a trusted adult and adolescent outcomes: a protocol of a scoping review. BACKGROUND Although documentation of harm towards children and young people has existed for centuries, it was not until the 1960s that it became a specific focus for health professionals. Since that time, the importance of protective social networks has become better understood. The concept of trusted adults has come into sharper focus, with children being encouraged to develop networks of dependable adults to turn to for support in times of need. While many child protection processes highlight risks to younger children, there has been less emphasis on older children. The role of trusted adults may be particularly important during adolescence, due to burgeoning independence, developing sexuality, relationship formation, and associated vulnerabilities. While important choices relating to health and education are made during this period, there is little formal evidence relating to the impact of trusted adults on such outcomes. This review therefore aims to focus on the role and influence of trusted adults for adolescents. METHODS This study is a scoping review. A broad range of databases will be searched, including MEDLINE, ERIC, Education Abstracts, Web of Science, ASSIA, Sociological Abstracts, and PsycINFO. Predefined inclusion/exclusion criteria will be used, with a focus on outcomes relating to health and education. Two reviewers will blind screen papers independently at all screening stages, with conflicts being resolved by a third reviewer. Quantitative and qualitative studies, as well as unpublished (grey) literature/reports, will be included. We will use the World Health Organization's 'second decade' definition of adolescence. We aim to collate and map evidence in a broad overview and produce meta-analyses of homogenous data. Where this is not possible, a narrative summary will be produced. DISCUSSION There appears to be sparse knowledge regarding the role of trusted adults for adolescents. Potential benefits to health and wellbeing may impact on educational attainment, and vice versa. These areas are of particular relevance during the second decade, when decisions that affect future direction, achievement, and wellbeing are being made. The increased understanding of the role of trusted adults provided by this review may help to inform practice and policy and lead to potential benefits for the health and education of adolescents. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD 42017076739. |
17 | igoz2ei4 | are there any clinical trials available for the coronavirus | Hi Sigma, do I have the Coronavirus?: Call for a New Artificial Intelligence Approach to Support Health Care Professionals Dealing With The COVID-19 Pandemic Just like your phone can detect what song is playing in crowded spaces, we show that Artificial Intelligence transfer learning algorithms trained on cough phone recordings results in diagnostic tests for COVID-19. To gain adoption by the health care community, we plan to validate our results in a clinical trial and three other venues in Mexico, Spain and the USA . However, if we had data from other on-going clinical trials and volunteers, we may do much more. For example, for confirmed stay-at-home COVID-19 patients, a longitudinal audio test could be developed to determine contact-with-hospital recommendations, and for the most critical COVID-19 patients a success ratio forecast test, including patient clinical data, to prioritize ICU allocation. As a challenge to the engineering community and in the context of our clinical trial, the authors suggest distributing cough recordings daily, hoping other trials and crowdsourcing users will contribute more data. Previous approaches to complex AI tasks have either used a static dataset or were private efforts led by large corporations. All existing COVID-19 trials published also follow this paradigm. Instead, we suggest a novel open collective approach to large-scale real-time health care AI. We will be posting updates at https://opensigma.mit.edu. Our personal view is that our approach is the right one for large scale pandemics, and therefore is here to stay - will you join? |
14 | 679qfp2s | what evidence is there related to COVID-19 super spreaders | Lack of Antiviral Activity of Darunavir against SARS-CoV-2 Given the high need and the absence of specific antivirals for treatment of COVID-19 (the disease caused by severe acute respiratory syndrome-associated coronavirus-2 [SARS-CoV-2]), human immunodeficiency virus (HIV) protease inhibitors are being considered as therapeutic alternatives. Prezcobix/Rezolsta is a fixed-dose combination of 800 mg of the HIV protease inhibitor darunavir (DRV) and 150 mg cobicistat, a CYP3A4 inhibitor, which is indicated in combination with other antiretroviral agents for the treatment of HIV infection. There are currently no definitive data on the safety and efficacy of DRV/cobicistat for treatment of COVID-19. The in vitro antiviral activity of darunavir against a clinical isolate from a patient infected with SARS-CoV-2 was assessed. DRV showed no activity against SARS-CoV-2 at clinically relevant concentrations (EC50 >100 μM). Remdesivir, used as a positive control, showed potent antiviral activity (EC50 = 0.38 μM). Overall, the data do not support the use of DRV for treatment of COVID-19. |
15 | od5nnxvg | how long can the coronavirus live outside the body | How can airborne transmission of COVID-19 indoors be minimised? Abstract During the rapid rise in COVID-19 illnesses and deaths globally, and notwithstanding recommended precautions, questions are voiced about routes of transmission for this pandemic disease. Inhaling small airborne droplets is probable as a third route of infection, in addition to more widely recognized transmission via larger respiratory droplets and direct contact with infected people or contaminated surfaces. While uncertainties remain regarding the relative contributions of the different transmission pathways, we argue that existing evidence is sufficiently strong to warrant engineering controls targeting airborne transmission as part of an overall strategy to limit infection risk indoors. Appropriate building engineering controls include sufficient and effective ventilation, possibly enhanced by particle filtration and air disinfection, avoiding air recirculation and avoiding overcrowding. Often, such measures can be easily implemented and without much cost, but if only they are recognised as significant in contributing to infection control goals. We believe that the use of engineering controls in public buildings, including hospitals, shops, offices, schools, kindergartens, libraries, restaurants, cruise ships, elevators, conference rooms or public transport, in parallel with effective application of other controls (including isolation and quarantine, social distancing and hand hygiene), would be an additional important measure globally to reduce the likelihood of transmission and thereby protect healthcare workers, patients and the general public. |
16 | 4vkkkndi | how long does coronavirus remain stable on surfaces? | Transmission risk of SARS-CoV-2 to healthcare workers -observational results of a primary care hospital contact tracing BACKGROUND: The coronavirus disease (COVID)-19 epidemic is evolving rapidly. Healthcare workers are at increased risk for infection, and specific requirements for their protection are advisable to ensure the functioning of the basic healthcare system, including the availability of general practitioners (GPs). Understanding the transmission risk is particularly important for guiding evidence-based protective measures in the primary healthcare setting. METHODS: Healthcare worker contacts of an initially undiagnosed COVID-19 case, who were without personal protective equipment, in particular not wearing facemasks, were screened with nasopharyngeal swabs and polymerase chain reaction tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), irrespective of respiratory symptoms or fever seven days after initial contact. The details of exposure to the index case were obtained during routine contact investigation after unintentional pathogen exposure. RESULTS: Twenty-one healthcare workers reported contacts with the index case. Three healthcare workers reported respiratory symptoms (cough) or low-grade fever within 4 days. None of them tested positive for SARS-CoV-2 at the time of symptom onset. All 21 healthcare workers tested SARS-CoV-2 negative 7 days after initial index case contact, including the three healthcare workers with previous symptoms. Ten of the 21 healthcare workers reported a cumulative exposure time of >15 minutes. Longer cumulative contact times were associated with more individual contacts, reduced contact time per contact and activities with physical patient contact. The closest relative of the index patient tested SARS-CoV-2 positive 2 days after the index case presented at the hospital emergency department. CONCLUSION: We found a low risk of SARS-CoV-2 transmission in a primary care setting. These findings are compatible with previous reports of the highest transmission probability in household settings with prolonged close contacts. The current protective measures for healthcare workers, including strict adherence to basic standard hygiene and facemasks, offer considerable protection during short periods of contact with symptomatic COVID-19 cases by diminishing the risk of direct and indirect transmission. |
20 | g5lanym9 | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | Boosting the arsenal against COVID-19 through computational drug repurposing |
18 | 6wlq7syf | what are the best masks for preventing infection by Covid-19? | Guidelines for TMS/tES Clinical Services and Research through the COVID-19 Pandemic BACKGROUND: The COVID-19 pandemic has broadly disrupted biomedical treatment and research including non-invasive brain stimulation (NIBS). Moreover, the rapid onset of societal disruption and evolving regulatory restrictions may not have allowed for systematic planning of how clinical and research work may continue throughout the pandemic or be restarted as restrictions are abated. The urgency to provide and develop NIBS as an intervention for diverse neurological and mental health indications, and as a catalyst of fundamental brain research, is not dampened by the parallel efforts to address the most life-threatening aspects of COVID-19; rather in many cases the need for NIBS is heightened including the potential to mitigate mental health consequences related to COVID-19. OBJECTIVE: To facilitate the re-establishment of access to NIBS clinical services and research operations during the current COVID-19 pandemic and possible future outbreaks, we develop and discuss a framework for balancing the importance of NIBS operations with safety considerations, while addressing the needs of all stakeholders. We focus on Transcranial Magnetic Stimulation (TMS) and low intensity transcranial Electrical Stimulation (tES) - including transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS). METHODS: The present consensus paper provides guidelines and good practices for managing and reopening NIBS clinics and laboratories through the immediate and ongoing stages of COVID-19. The document reflects the analysis of experts with domain relevant expertise spanning NIBS technology, clinical services, and basic and clinical research – with an international perspective. We outline regulatory aspects, human resources, NIBS optimization, as well as accommodations for specific demographics. RESULTS: A model based on three phases (early COVID-19 impact, current practices, and future preparation) with an 11-step checklist (spanning removing or streamlining in-person protocols, incorporating telemedicine, and addressing COVID-19-associated adverse events) is proposed. Recommendations on implementing social distancing and sterilization of NIBS related equipment, specific considerations of COVID-19 positive populations including mental health comorbidities, as well as considerations regarding regulatory and human resource in the era of COVID-19 are outlined. We discuss COVID-19 considerations specifically for clinical (sub-)populations including pediatric, stroke, addiction, and the elderly. Numerous case-examples across the world are described. CONCLUSION: There is an evident, and in cases urgent, need to maintain NIBS operations through the COVID-19 pandemic, including anticipating future pandemic waves and addressing effects of COVID-19 on brain and mind. The proposed robust and structured strategy aims to address the current and anticipated future challenges while maintaining scientific rigor and managing risk. |
16 | db7stx56 | how long does coronavirus remain stable on surfaces? | Biochemical and Structural Insights into the Mechanisms of SARS Coronavirus RNA Ribose 2′-O-Methylation by nsp16/nsp10 Protein Complex The 5′-cap structure is a distinct feature of eukaryotic mRNAs, and eukaryotic viruses generally modify the 5′-end of viral RNAs to mimic cellular mRNA structure, which is important for RNA stability, protein translation and viral immune escape. SARS coronavirus (SARS-CoV) encodes two S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTase) which sequentially methylate the RNA cap at guanosine-N7 and ribose 2′-O positions, catalyzed by nsp14 N7-MTase and nsp16 2′-O-MTase, respectively. A unique feature for SARS-CoV is that nsp16 requires non-structural protein nsp10 as a stimulatory factor to execute its MTase activity. Here we report the biochemical characterization of SARS-CoV 2′-O-MTase and the crystal structure of nsp16/nsp10 complex bound with methyl donor SAM. We found that SARS-CoV nsp16 MTase methylated m7GpppA-RNA but not m7GpppG-RNA, which is in contrast with nsp14 MTase that functions in a sequence-independent manner. We demonstrated that nsp10 is required for nsp16 to bind both m7GpppA-RNA substrate and SAM cofactor. Structural analysis revealed that nsp16 possesses the canonical scaffold of MTase and associates with nsp10 at 1∶1 ratio. The structure of the nsp16/nsp10 interaction interface shows that nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of nsp16, consistent with the findings in biochemical assays. These results suggest that nsp16/nsp10 interface may represent a better drug target than the viral MTase active site for developing highly specific anti-coronavirus drugs. |
38 | 6gauzzn9 | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | Prevalence of obesity among adult inpatients with COVID-19 in France |
49 | 0phcscz8 | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | Humoral immune response and prolonged PCR positivity in a cohort of 1343 SARS-CoV 2 patients in the New York City region Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The percentage of infected individuals who seroconvert is still an open question. In addition, it has been shown in some individuals that viral genome can still be detected at considerable time post symptom resolution. Here we investigated both seroconversion and PCR-positivity in a large cohort of convalescent serum donors in New York City. Methods: Individuals with confirmed or suspected SARS-CoV-2 infection were screened via PCR for presence of viral genome and via enzyme-linked immunosorbent assay for presence of anti SARS-CoV-2 spike antibodies. Results: All but three confirmed SARS-CoV-2 patients seroconverted to the SARS-CoV-2 spike while only 37.4% of suspected SARS-CoV-2 patients seroconverted. PCR-positivity was detected up to 28 days from symptom resolution. Conclusions: Here we show that the vast majority of confirmed COVID19 patients seroconvert, potentially providing immunity to reinfection. We also report that in a large proportion of individuals, viral genome can be detected via PCR in the upper respiratory tract for weeks post symptom resolution, but it is unclear if this signal represents infectious virus. |
15 | 3xw4qjoy | how long can the coronavirus live outside the body | The Seasonal End of Human Coronavirus Hospital Admissions with Implications for SARS-CoV-2 The seasonality of influenza viruses and endemic human coronaviruses was tracked over an 8-year period to assess key epidemiologic reduction points in disease incidence for an urban area in the northeast United States. Patients admitted to a pediatric hospital with worsening respiratory symptoms were tested using a multiplex PCR assay from nasopharyngeal swabs. The additive seasonal effects of outdoor temperatures and indoor relative humidity (RH) were evaluated. The 8-year average peak activity of human coronaviruses occurred in the first week of January, when droplet and contact transmission was enabled by the low indoor RH of 20-30%. Previous studies have shown that an increase in RH to 50% has been associated with markedly reduced viability and transmission of influenza virus and animal coronaviruses. As disease incidence was reduced by 50% in early March, to 75% in early April, to greater than 99% at the end of April, a relationship was observed from colder temperatures in January with a low indoor RH to a gradual increase in outdoor temperatures in April with an indoor RH of 45-50%. As a lipid-bound, enveloped virus with similar size characteristics to endemic human coronaviruses, SARS-CoV-2 should be subject to the same dynamics of reduced viability and transmission with increased humidity. In addition to the major role of social distancing, the transition from lower to higher indoor RH with increasing outdoor temperatures could have an additive effect on the decrease in SARS-CoV-2 cases in May. Over the 8-year period of this study, human coronavirus activity was either zero or >99% reduction in the months of June through September, and the implication would be that SARS-Cov-2 may follow a similar pattern. |
44 | rol4w9yp | How much impact do masks have on preventing the spread of the COVID-19? | Flattening the curve in COVID-19 using personalised protective equipment: lessons from air pollution |
44 | bp9h52i7 | How much impact do masks have on preventing the spread of the COVID-19? | Universal public mask wear during COVID‐19 pandemic: Rationale, design and acceptability See related Reply See related Reply |
13 | 1nol5brk | what are the transmission routes of coronavirus? | Risk of COVID-19 importation to the Pacific islands through global air travel On 30 January 2020, WHO declared coronavirus (COVID-19) a global public health emergency. As of 12 March 2020, 125 048 confirmed COVID-19 cases in 118 countries had been reported. On 12 March 2020, the first case in the Pacific islands was reported in French Polynesia; no other Pacific island country or territory has reported cases. The purpose of our analysis is to show how travellers may introduce COVID-19 into the Pacific islands and discuss the role robust health systems play in protecting health and reducing transmission risk. We analyse travel and Global Health Security Index data using a scoring tool to produce quantitative estimates of COVID-19 importation risk, by departing and arriving country. Our analysis indicates that, as of 12 March 2020, the highest risk air routes by which COVID-19 may be imported into the Pacific islands are from east Asian countries (specifically, China, Korea and Japan) to north Pacific airports (likely Guam, Commonwealth of the Northern Mariana Islands or, to a less extent, Palau); or from China, Japan, Singapore, the United States of America or France to south Pacific ports (likely, Fiji, Papua New Guinea, French Polynesia or New Caledonia). Other importation routes include from other east Asian countries to Guam, and from Australia, New Zealand and other European countries to the south Pacific. The tool provides a useful method for assessing COVID-19 importation risk and may be useful in other settings. |
24 | 9t73wadp | what kinds of complications related to COVID-19 are associated with diabetes | The legal determinants of health: harnessing the power of law for global health and sustainable development |
12 | od832cia | what are best practices in hospitals and at home in maintaining quarantine? | Quarantäne alleine oder in Kombination mit weiteren Public-Health-Maßnahmen zur Eindämmung der COVID-19 Pandemie: Ein Cochrane Rapid Review./ [Quarantine Alone or in Combination with Other Public Health Measures to Control COVID-19: A Rapid Review (Review)] BACKGROUND: COVID-19 (coronavirus disease 2019) is a new, rapidly emerging zoonotic infectious disease, that was reported to the World Health Organization for the first time on 31 December 2019. Currently, no effective pharmacological interventions or vaccines are available to treat or prevent COVID-19, therefore nonpharmacological public health measures are more in focus. OBJECTIVES: The aim was to assess the effects of quarantine - alone or in combination with other measures - during coronavirus outbreaks. METHODS: Because of the current COVID-19 pandemic, WHO commissioned a rapid review. To save time, the method of systematic reviews was slightly and with caution modified. This publication is a summary of the most important aspects of the rapid review, translated into German by members of the WHO Collaborating Centre at the Danube University Krems (Austria). RESULTS: Overall, 29 studies were included. Ten modeling studies focused on COVID-19, 4 observational studies and 15 modeling studies focused on SARS and MERS. The modeling studies consistently reported a benefit of the simulated quarantine measures. For example, the models estimated that quarantine of people exposed to confirmed or suspected cases of COVID-19 prevented between 44 and 81% of the cases that would otherwise have happened and 31 to 63% of the deaths, when compared to no such measures. In regard to costs, the earlier the quarantine measures are implemented, the greater the cost savings will be. CONCLUSION: Our confidence in the evidence is very limited. This is mainly because the COVID-19 studies based their models on the limited data that have been available in the early weeks of the pandemic and made different assumptions about the virus. The studies of SARS and MERS are not completely generalizable to COVID-19. Despite only having limited evidence, all the studies found quarantine to be important for controlling the spread of severe coronavirus diseases. Looking to the coming months, in order to maintain the best possible balance of measures, decision makers must continue to constantly monitor the outbreak situation and the impact of the measures they implement. |
41 | 6aq29ajy | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | Impact of the COVID-19 Outbreak on the Management of Patients with Cancer The coronavirus SARS-CoV-2 (COVID-19) outbreak is having a profound impact on the management of patients with cancer. In this review, we comprehensively investigate the various aspects of cancer care during the pandemic, taking advantage of data generated in Asia and Europe at the frontline of the COVID-19 pandemic spread. Cancer wards have been subjected to several modifications to protect patients and healthcare professionals from COVID-19 infection, while attempting to maintain cancer diagnosis, therapy, and research. In this setting, the management of COVID-19 infected patients with cancer is particularly challenging. We also discuss the direct and potential remote impacts of the global pandemic on the mortality of patients with cancer. As such, the indirect impact of the pandemic on the global economy and the potential consequences in terms of cancer mortality are discussed. As the infection is spreading worldwide, we are obtaining more knowledge on the COVID-19 pandemic consequences that are currently impacting and may continue to further challenge cancer care in several countries. |
19 | i3mzzxwq | what type of hand sanitizer is needed to destroy Covid-19? | The physiology and pharmacology of singlet oxygen Reactive oxygen species (ROS) are generated by many different cells. Singlet oxygen (1O2) and a reaction product of it, excited carbonyls (CO(*)), are important ROS. 1O2 and CO(*) are nonradicalic and emit light (one photon/molecule) when returning to ground state oxygen. Especially activated polymorphonuclear neutrophil granulocytes (PMN) produce large amounts of 1O2. Via activation of the respiratory burst (NADPH oxidase and myeloperoxidase) they synthesize hypochlorite (NaOCl) and chloramines (in particular N-chlorotaurine). Chloramines are selective and stable chemical generators of 1O2. In the human organism, 1O2 is both a signal and a weapon with therapeutic potency against very different pathogens, such as microbes, virus, cancer cells and thrombi. Chloramines at blood concentrations between 1 and 2 mmol/L inactivate lipid enveloped virus and chloramines at blood concentrations below 0.5 mmol/L, i.e. at oxidant concentrations that do not affect thrombocytes or hemostasis factors, act antithrombotically by activation of the physiologic PMN mediated fibrinolysis; this thrombolysis is of selective nature, i.e. it does not impair the hemostasis system of the patient allowing the antithrombotic treatment in patients where the current risky thrombolytic treatment is contraindicated. The action of 1O2 might be compared to the signaling and destroying gunfire of soldiers directed against bandits at night, resulting in an autorecruitment of the physiological inflammatory response. Chloramines (such as the mild and untoxic oxidant chloramine T(®) (N-chloro-p-toluene-sulfonamide)) and their signaling and destroying reaction product 1O2 might be promising new therapeutic agents against a multitude of up to now refractory diseases. |
37 | 18b2foud | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | First Identification of Human Adenovirus Subtype 21a in China With MinION and Illumina Sequencers Human adenoviruses (HAdVs) have been demonstrated to cause a diversity of diseases among children and adults. The circulation of human adenovirus type 21 (HAdV21) has been mainly documented within closed environments in several countries. Nonetheless, respiratory infections or outbreaks due to HAdV21 have never been reported in China. MinION and Illumina platforms were employed to identify the potential pathogen from a throat swab. Discrepancies between MinION and Illumina sequencing were validated and corrected via polymerase chain reaction (PCR). Genomic characterization and recombinant event detection were then performed. Among the 35,466 high-quality MinION reads, a total of 5,999 reads (16.91%) could be aligned to HAdV21 reference genomes (genome sizes ≈35.3 kb), among which 20 had a length of >30 kb. A genome sequence assembled from MinION reads was further classified as HAdV subtype 21a. Random downsampling revealed as few as 500 nanopore reads could cover ≥96.49% of current genome. Illumina sequencing displayed good consistency (pairwise nucleotide identity = 99.91%) with MinION sequencing but with 31 discrepancies that were further validated and confirmed by PCR coupled with Sanger sequencing. Restriction enzymes such as BamHI and KpnI were able to distinguish the present genome from HAdV21 prototype and HAdV21b. Phylogenetic analysis employing whole-genome sequences placed our genome with members only from subtype 21a. Common features among HAdV21a strains were identified, including polymorphisms discovered in penton and 100 kDa hexon assembly–associated proteins and a recombinant event in the E4 gene. Using MinION and Illumina sequencers, we identified the first HAdV21a strain from China, which could provide key genomic data for disease control and epidemiological investigations. |
35 | oib1ctue | What new public datasets are available related to COVID-19? | Predicting the Growth and Trend of COVID-19 Pandemic using Machine Learning and Cloud Computing The outbreak of COVID-19 Coronavirus, namely SARS-CoV-2, has created a calamitous situation throughout the world. The cumulative incidence of COVID-19 is rapidly increasing day by day. Machine Learning (ML) and Cloud Computing can be deployed very effectively to track the disease, predict growth of the epidemic and design strategies and policy to manage its spread. This study applies an improved mathematical model to analyse and predict the growth of the epidemic. An ML-based improved model has been applied to predict the potential threat of COVID-19 in countries worldwide. We show that using iterative weighting for fitting Generalized Inverse Weibull distribution, a better fit can be obtained to develop a prediction framework. This can be deployed on a cloud computing platform for more accurate and real-time prediction of the growth behavior of the epidemic. A data driven approach with higher accuracy as here can be very useful for a proactive response from the government and citizens. Finally, we propose a set of research opportunities and setup grounds for further practical applications. |
4 | 4sxe7s03 | what causes death from Covid-19? | Liver Chemistries in COVID-19 Patients with Survival or Death: A Meta-Analysis Background and Aims: Although abnormal liver chemistries are linked to higher risk of death related to coronavirus disease (COVID-19), liver manifestations may be diverse and even confused. Thus, we performed a meta-analysis of published liver manifestations and described the liver damage in COVID-19 patients with death or survival. Methods: We searched PubMed, Google Scholar, medRxiv, bioRxiv, Cochrane Library, Embase, and three Chinese electronic databases through April 22, 2020. We analyzed pooled data on liver chemistries stratified by the main clinical outcome of COVID-19 using a fixed or random-effects model. Results: In the meta-analysis of 18 studies, which included a total of 2,862 patients, the pooled mean alanine aminotransferase (ALT) was 30.9 IU/L in the COVID-19 patients with death and 26.3 IU/L in the COVID-19 patients discharged alive (p < 0.0001). The pooled mean aspartate aminotransferase (AST) level was 45.3 IU/L in the COVID-19 patients with death while 30.1 IU/L in the patients discharged alive (p < 0.0001). Compared with the discharged alive cases, the dead cases tended to have lower albumin levels but longer prothrombin time, and international standardized ratio. Conclusions: In this meta-analysis, according to the main clinical outcome of COVID-19, we comprehensively described three patterns of liver impairment related to COVID-19, hepatocellular injury, cholestasis, and hepatocellular disfunction. Patients died from COVID-19 tend to have different liver chemistries from those are discharged alive. Close monitoring of liver chemistries provides an early warning against COVID-19 related death. |
11 | 5hb4f9u8 | what are the guidelines for triaging patients infected with coronavirus? | Risk factors for adverse clinical outcomes with COVID-19 in China: a multicenter, retrospective, observational study Background: The risk factors for adverse events of Coronavirus Disease-19 (COVID-19) have not been well described. We aimed to explore the predictive value of clinical, laboratory and CT imaging characteristics on admission for short-term outcomes of COVID-19 patients. Methods: This multicenter, retrospective, observation study enrolled 703 laboratory-confirmed COVID-19 patients admitted to 16 tertiary hospitals from 8 provinces in China between January 10, 2020 and March 13, 2020. Demographic, clinical, laboratory data, CT imaging findings on admission and clinical outcomes were collected and compared. The primary endpoint was in-hospital death, the secondary endpoints were composite clinical adverse outcomes including in-hospital death, admission to intensive care unit (ICU) and requiring invasive mechanical ventilation support (IMV). Multivariable Cox regression, Kaplan-Meier plots and log-rank test were used to explore risk factors related to in-hospital death and in-hospital adverse outcomes. Results: Of 703 patients, 55 (8%) developed adverse outcomes (including 33 deceased), 648 (92%) discharged without any adverse outcome. Multivariable regression analysis showed risk factors associated with in-hospital death included ≥ 2 comorbidities (hazard ratio [HR], 6.734; 95% CI; 3.239-14.003, p < 0.001), leukocytosis (HR, 9.639; 95% CI, 4.572-20.321, p < 0.001), lymphopenia (HR, 4.579; 95% CI, 1.334-15.715, p = 0.016) and CT severity score > 14 (HR, 2.915; 95% CI, 1.376-6.177, p = 0.005) on admission, while older age (HR, 2.231; 95% CI, 1.124-4.427, p = 0.022), ≥ 2 comorbidities (HR, 4.778; 95% CI; 2.451-9.315, p < 0.001), leukocytosis (HR, 6.349; 95% CI; 3.330-12.108, p < 0.001), lymphopenia (HR, 3.014; 95% CI; 1.356-6.697, p = 0.007) and CT severity score > 14 (HR, 1.946; 95% CI; 1.095-3.459, p = 0.023) were associated with increased odds of composite adverse outcomes. Conclusion: The risk factors of older age, multiple comorbidities, leukocytosis, lymphopenia and higher CT severity score could help clinicians identify patients with potential adverse events. |
5 | qci7khki | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | The potential of drug repositioning as a short-term strategy for the control and treatment of COVID-19 (SARS-CoV-2): a systematic review The novel human coronavirus (SARS-CoV-2), the causative agent of COVID-19, has quickly become a threat to the public health and economy worldwide. Despite the severity of some cases, there are no current pathogen-specific antivirals available to treat the disease. Therefore, many studies have focused on the evaluation of the anti-SARS-CoV-2 activity of clinically available drugs. Here, we conducted a systematic review to describe the drug repositioning strategy against SARS-CoV-2 and to discuss the clinical impact of this approach in the current pandemic context. The systematic review was performed on March 23, 2020, using PubMed/MEDLINE, Scopus, Cochrane Library, and Biblioteca Virtual de Saúde (BVS). The data were summarized in tables and critically analyzed. After the database search, 12 relevant studies were identified as eligible for the review. Among the drugs reported in these studies, 57 showed some evidence of antiviral activity. Antivirals, especially antiretrovirals, are the main class of therapeutic agents evaluated against COVID-19. Moreover, studies have reported the anti-SARS-CoV-2 activity of antitumor (16%; 9/57), antimalarial (7%, 4/57), and antibacterial (5%; 3/57) agents. Additionally, seven pharmacological agents (chloroquine, tetrandrine, umifenovir (arbidol), carrimycin, damageprevir, lopinavir/ritonavir) are in phase IV of clinical trials. Due to the evidence of the anti-SARS-CoV-2 activity of various clinically available agents, drug repositioning stands out as a promising strategy for a short-term response in the fight against the novel coronavirus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04693-5) contains supplementary material, which is available to authorized users. |
29 | ypcs3rxu | which SARS-CoV-2 proteins-human proteins interactions indicate potential for drug targets. Are there approved drugs that can be repurposed based on this information? | A Mouse Model for MERS Coronavirus Induced Acute Respiratory Distress Syndrome Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that emerged in 2012, causing acute respiratory distress syndrome (ARDS), severe pneumonia-like symptoms, and multi-organ failure, with a case fatality rate of ~36%. Limited clinical studies indicate that humans infected with MERS-CoV exhibited pathology consistent with late stages of ARDS, which is reminiscent of disease observed in patients infected with SARS coronavirus. Models of MERS-CoV-induced severe respiratory disease have been difficult to achieve, and small animal models traditionally used to investigate viral pathogenesis (mouse, hamster, guinea pig, and ferret) are naturally resistant to MERS-CoV. Therefore, we used CRISPR/Cas9 to modify the mouse genome to encode two human amino acids (288 and 330) in the dipeptidyl peptidase 4 receptor, making mice susceptible to MERS-CoV replication. Serial MERS-CoV passage in these engineered mice was then used to generate a mouse-adapted virus that replicated efficiently within the lungs, and evoked symptoms indicative of severe acute respiratory distress syndrome (ARDS), including decreased survival, extreme weight loss, decreased pulmonary function, pulmonary hemorrhage, and pathological signs indicative of end stage lung disease. Importantly, therapeutic countermeasures comprising MERS-CoV neutralizing antibody treatment or a MERS-CoV spike protein vaccine protected engineered mice against MERS-CoV-induced ARDS. |
27 | hkm8yspk | what is known about those infected with Covid-19 but are asymptomatic? | [Screening and management of asymptomatic infection of 2019-novel coronavirus]. At present, the prevention and control of COVID-19 in China has entered a critical period. Recently, various areas outside Hubei Province have gradually begun to resume work and production, but the development of the epidemic situation is still uncertain and complex. A few days ago, researchers gradually began to pay attention to asymptomatic infection of 2019-novel coronavirus and described the disease process of asymptomatic infection and the possibility of being a source of infection. This provided a scientific basis for further optimizing and improving epidemic prevention and control measures. Paying attention to the screening and self-protection of high-risk groups and strengthening the level of detection should be helpful to the detection and management of asymptomatic infection. |
8 | h2h4bnd5 | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Aerodynamic Characteristics and RNA Concentration of SARS-CoV-2 Aerosol in Wuhan Hospitals during COVID-19 Outbreak Background The ongoing outbreak of COVID-19 has spread rapidly and sparked global concern. While the transmission of SARS-CoV-2 through human respiratory droplets and contact with infected persons is clear, the aerosol transmission of SARS-CoV-2 has been little studied. Methods Thirty-five aerosol samples of three different types (total suspended particle, size segregated and deposition aerosol) were collected in Patient Areas (PAA) and Medical Staff Areas (MSA) of Renmin Hospital of Wuhan University (Renmin) and Wuchang Fangcang Field Hospital (Fangcang), and Public Areas (PUA) in Wuhan, China during COVID-19 outbreak. A robust droplet digital polymerase chain reaction (ddPCR) method was employed to quantitate the viral SARS-CoV-2 RNA genome and determine aerosol RNA concentration. Results The ICU, CCU and general patient rooms inside Renmin, patient hall inside Fangcang had undetectable or low airborne SARS-CoV-2 concentration but deposition samples inside ICU and air sample in Fangcang patient toilet tested positive. The airborne SARS-CoV-2 in Fangcang MSA had bimodal distribution with higher concentration than those in Renmin during the outbreak but turned negative after patients number reduced and rigorous sanitization implemented. PUA had undetectable airborne SARS-CoV-2 concentration but obviously increased with accumulating crowd flow. Conclusions Room ventilation, open space, proper use and disinfection of toilet can effectively limit aerosol transmission of SARS-CoV-2. Gathering of crowds with asymptomatic carriers is a potential source of airborne SARS-CoV-2. The virus aerosol deposition on protective apparel or floor surface and their subsequent resuspension is a potential transmission pathway and effective sanitization is critical in minimizing aerosol transmission of SARS-CoV-2. |
43 | do8gd539 | How has the COVID-19 pandemic impacted violence in society, including violent crimes? | COVID-19: Increased Risk to the Mental Health and Safety of Women Living with HIV in South Africa |
15 | egkd5o1u | how long can the coronavirus live outside the body | World Pneumonia Day — November 12, 2014 |
41 | 14ba5sro | What are the impacts of COVID-19 among African-Americans that differ from the rest of the U.S. population? | Predicting COVID-19 Incidence Using Anosmia and Other COVID-19 Symptomatology: Preliminary Analysis Using Google and Twitter OBJECTIVE: To determine the relative correlations of Twitter and Google Search user trends concerning smell loss with daily coronavirus disease 2019 (COVID-19) incidence in the United States, compared to other severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) symptoms. To describe the effect of mass media communications on Twitter and Google Search user trends. STUDY DESIGN: Retrospective observational study. SETTING: United States. SUBJECTS AND METHODS: Google Search and "tweet" frequency concerning COVID-19, smell, and nonsmell symptoms of COVID-19 generated between January 1 and April 8, 2020, were collected using Google Trends and Crimson Hexagon, respectively. Spearman coefficients linking each of these user trends to COVID-19 incidence were compared. Correlations obtained after excluding a short timeframe (March 22 to March 24) corresponding to the publication of a widely read lay media publication reporting anosmia as a symptom of infection was performed for comparative analysis. RESULTS: Google searches and tweets concerning all nonsmell symptoms (0.744 and 0.761, respectively) and COVID-19 (0.899 and 0.848) are more strongly correlated with disease incidence than smell loss (0.564 and 0.539). Twitter users tweeting about smell loss during the study period were more likely to be female (52%) than users tweeting about COVID-19 more generally (47%). Tweet and Google Search frequency pertaining to smell loss increased significantly (>2.5 standard deviations) following a widely read media publication linking smell loss and SARS-CoV-2 infection. CONCLUSIONS: Google Search and tweet frequency regarding fever and shortness of breath are more robust indicators of COVID-19 incidence than anosmia. Mass media communications represent important confounders that should be considered in future analyses. |
22 | 0s0n2kxv | are cardiac complications likely in patients with COVID-19? | [Impact of the COVID-19 pandemic on heart failure hospitalizations]. |
38 | jutof78v | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | A systems approach to inflammation identifies therapeutic targets in SARS-CoV-2 infection Background Infection with SARS-CoV-2 manifests itself as a mild respiratory tract infection in the majority of individuals, which progresses to a severe pneumonia and acute respiratory distress syndrome (ARDS) in 10-15% of patients. Inflammation plays a crucial role in the pathogenesis of ARDS, with immune dysregulation in severe COVID-19 leading to a hyperinflammatory response. A comprehensive understanding of the inflammatory process in COVID-19 is lacking. Methods In this prospective, multicenter observational study, patients with PCR-proven or clinically presumed COVID-19 admitted to the intensive care unit (ICU) or clinical wards were included. Demographic and clinical data were obtained and plasma was serially collected. Concentrations of IL-6, TNF-, complement components C3a, C3c and the terminal complement complex (TCC) were determined in plasma by ELISA. Additionally, 269 circulating biomarkers were assessed using targeted proteomics. Results were compared between ICU and non ICU patients. Findings A total of 119 (38 ICU and 91 non ICU) patients were included. IL-6 plasma concentrations were elevated in COVID-19 (ICU vs. non ICU, median 174.5 pg/ml [IQR 94.5-376.3 vs. 40.0 pg/ml [16.5-81.0]), whereas TNF- concentrations were relatively low and not different between ICU and non ICU patients (median 24.0 pg/ml [IQR 16.5-33.5] and 21.5 pg/ml [IQR 16.0-33.5], respectively). C3a and terminal complement complex (TCC) concentrations were significantly higher in ICU vs. non ICU patients (median 556.0 ng/ml [IQR 333.3-712.5]) vs. 266.5 ng/ml [IQR 191.5-384.0 for C3a and 4506 mAU/ml [IQR 3661-6595 vs. 3582 mAU/ml [IQR 2947-4300] for TCC) on the first day of blood sampling. Targeted proteomics demonstrated that IL-6 (logFC 2.2), several chemokines and hepatocyte growth factor (logFC 1.4) were significantly upregulated in ICU vs. non ICU patients. In contrast, stem cell factor was significantly downregulated (logFC -1.3) in ICU vs. non ICU patients, as were DPP4 (logFC -0.4) and protein C inhibitor (log FC -1.0), the latter two factors also being involved in the regulation of the kinin-kallikrein pathway. Unsupervised clustering pointed towards a homogeneous pathogenetic mechanism in the majority of patients infected with SARS-CoV-2, with patient clustering mainly based on disease severity. Interpretation We identified important pathways involved in dysregulation of inflammation in patients with severe COVID-19, including the IL-6, complement system and kinin-kallikrein pathways. Our findings may aid the development of new approaches to host-directed therapy. |
38 | nc1rn95h | What is the mechanism of inflammatory response and pathogenesis of COVID-19 cases? | The course of Covid 19 in Inflammatory Bowel Disease: protective role of TNF antagonists Response to: Corticosteroids, but not TNF Antagonists, are Associated with Adverse COVID-19 Outcomes in Patients With Inflammatory Bowel Diseases: Results from an International Registry |
11 | 4a51q84d | what are the guidelines for triaging patients infected with coronavirus? | Clinical characteristics of older patients: The experience of a geriatric short-stay unit dedicated to patients with COVID-19 in France |
44 | yx9oa2ra | How much impact do masks have on preventing the spread of the COVID-19? | Face Masks Considerably Reduce Covid-19 Cases in Germany We use the synthetic control method to analyze the effect of face masks on the spread of Covid-19 in Germany. Our identification approach exploits regional variation in the point in time when face masks became compulsory. Depending on the region we analyse, we find that face masks reduced the cumulative number of registered Covid-19 cases between 2.3% and 13% over a period of 10 days after they became compulsory. Assessing the credibility of the various estimates, we conclude that face masks reduce the daily growth rate of reported infections by around 40%. |
19 | 1fdmmdll | what type of hand sanitizer is needed to destroy Covid-19? | Still puzzling questions in immunology (infection and immunity) |
4 | qmelt1m9 | what causes death from Covid-19? | Science Education in the Light of COVID-19: The Contribution of History, Philosophy and Sociology of Science In this position paper, I examine how the history, philosophy and sociology of science (HPS) can contribute to science education in the era of the COVID-19 pandemic. I discuss shortcomings in the ways that history is often used in school science, and examine how knowledge of previous pandemics might help in teaching about COVID-19. I look at the potential of issues to do with measurement in the context of COVID-19 (e.g. measurement of mortality figures) to introduce school students to issues about philosophy of science, and I show how COVID-19 has the affordance to broaden and deepen the moral philosophy that students typically meet in biology lessons. COVID-19 also provides opportunities to introduce students to sociological ways of thinking, examining data and questioning human practices. It can also enable students to see how science, economics and politics inter-relate. In the final part of the paper, I suggest that there are strong arguments in favour of an interdisciplinary approach in tackling zoonoses like COVID-19 and that there is much to be said for such interdisciplinarity in school science lessons when teaching about socio-scientific issues and issues intended to raise scientific literacy. |
17 | 1cx2l2do | are there any clinical trials available for the coronavirus | Intrinsic resistance of feline peritoneal macrophages to coronavirus infection correlates with in vivo virulence. Cats infected with virulent feline coronavirus strains develop feline infectious peritonitis, an invariably fatal, immunologically mediated disease; avirulent strains cause either clinically inapparent infection or mild enteritis. Four virulent coronavirus isolates and five avirulent isolates were assessed by immunofluorescence and virus titration for their ability to infect and replicate in feline peritoneal macrophages in vitro. The avirulent coronaviruses infected fewer macrophages, produced lower virus titers, were less able to sustain viral replication, and spread less efficiently to other susceptible macrophages than the virulent coronaviruses. Thus, the intrinsic resistance of feline macrophages may play a pivotal role in the outcome of coronavirus infection in vivo. |
31 | kh9whqzd | How does the coronavirus differ from seasonal flu? | Scientometric Trends for Coronaviruses and Other Emerging Viral Infections COVID-19 is the most rapidly expanding coronavirus outbreak in the past two decades. To provide a swift response to a novel outbreak, prior knowledge from similar outbreaks is essential. Here, we study the volume of research conducted on previous coronavirus outbreaks, specifically SARS and MERS, relative to other infectious diseases by analyzing over 35 million papers from the last 20 years. Our results demonstrate that previous coronavirus outbreaks have been understudied compared to other viruses. We also show that the research volume of emerging infectious diseases is very high after an outbreak and drops drastically upon the containment of the disease. This can yield inadequate research and limited investment in gaining a full understanding of novel coronavirus management and prevention. Independent of the outcome of the current COVID-19 outbreak, we believe that measures should be taken to encourage sustained research in the field. |
40 | 9xueqdri | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Three adjacent nucleotide changes spanning two residues in SARS-CoV-2 nucleoprotein: possible homologous recombination from the transcription-regulating sequence The COVID-19 pandemic is caused by the single-stranded RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus of zoonotic origin that was first detected in Wuhan, China in December 2019. There is evidence that homologous recombination contributed to this cross-species transmission. Since that time the virus has demonstrated a high propensity for human-to-human transmission. Here we report two newly identified adjacent amino acid polymorphisms in the nucleocapsid at positions 203 and 204 (R203K/G204R) due to three adjacent nucleotide changes across the two codons (i.e. AGG GGA to AAA CGA). This new strain within the LGG clade may have arisen by a form of homologous recombination from the core sequence (CS-B) of the transcription-regulating sequences of SAS-CoV-2 itself and has rapidly increased to approximately one third of reported sequences from Europe during the month of March 2020. We note that these polymorphisms are predicted to reduce the binding of an overlying putative HLA-C*07-restricted epitope and that HLA-C*07 is prevalent in Caucasians being carried by >40% of the population. The findings suggest that homologous recombination may have occurred since its introduction into humans and be a mechanism for increased viral fitness and adaptation of SARS-CoV-2 to human populations. |
16 | v09jj3a2 | how long does coronavirus remain stable on surfaces? | Factors associated with nosocomial SARS-CoV transmission among healthcare workers in Hanoi, Vietnam, 2003 BACKGROUND: In March of 2003, an outbreak of Severe Acute Respiratory Syndrome (SARS) occurred in Northern Vietnam. This outbreak began when a traveler arriving from Hong Kong sought medical care at a small hospital (Hospital A) in Hanoi, initiating a serious and substantial transmission event within the hospital, and subsequent limited spread within the community. METHODS: We surveyed Hospital A personnel for exposure to the index patient and for symptoms of disease during the outbreak. Additionally, serum specimens were collected and assayed for antibody to SARS-associated coronavirus (SARS-CoV) antibody and job-specific attack rates were calculated. A nested case-control analysis was performed to assess risk factors for acquiring SARS-CoV infection. RESULTS: One hundred and fifty-three of 193 (79.3%) clinical and non-clinical staff consented to participate. Excluding job categories with <3 workers, the highest SARS attack rates occurred among nurses who worked in the outpatient and inpatient general wards (57.1, 47.4%, respectively). Nurses assigned to the operating room/intensive care unit, experienced the lowest attack rates (7.1%) among all clinical staff. Serologic evidence of SARS-CoV infection was detected in 4 individuals, including 2 non-clinical workers, who had not previously been identified as SARS cases; none reported having had fever or cough. Entering the index patient's room and having seen (viewed) the patient were the behaviors associated with highest risk for infection by univariate analysis (odds ratios 20.0, 14.0; 95% confidence intervals 4.1–97.1, 3.6–55.3, respectively). CONCLUSION: This study highlights job categories and activities associated with increased risk for SARS-CoV infection and demonstrates that a broad diversity of hospital workers may be vulnerable during an outbreak. These findings may help guide recommendations for the protection of vulnerable occupational groups and may have implications for other respiratory infections such as influenza. |
27 | 7kidc16v | what is known about those infected with Covid-19 but are asymptomatic? | Novel coronavirus infection and pregnancy |
40 | eyi5609q | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Phylogenetic Analysis of the Novel Coronavirus Reveals Important Variants in Indian Strains Recently classified as a pandemic by WHO, novel Corononavirus 2019 has affected almost every corner of the globe causing human deaths in a range of hundred thousands. The virus having its roots in Wuhan (China) has been spread over the world by its own property to change itself accordingly. These changes correspond to its transmission and pathogenicity due to which the concept of social distancing appeared into the picture. In this paper, a few findings from the whole genome sequence analysis of viral genome sequences submitted from India are presented. The data used for analysis comprises 440 collective genome sequences of virus submitted in GenBank, GISAID, and SRA projects, from around the world as well as 28 viral sequences from India. Multiple sequence alignment of all genome sequences was performed and analysed. A novel non-synonymous mutation 4809C>T (S1515F) in NSP3 gene of SARS-CoV2 Indian strains is reported along with other frequent and important changes from around the world: 3037C>T, 14408C>T, and 23403A>G. The novel change was observed in samples collected in the month of March, whereas was found to be absent in samples collected in January with the respective persons' travel history to China. Phylogenetic analysis clustered the sequences with this change as one separate clade. Mutation was predicted as stabilising change by insilco tool DynaMut. A second patient in the world to our knowledge with multiple (Wuhan and USA) strain contraction was observed in this study. The infected person is among the two early infected patients with travel history to China. Strains sequenced in Iran stood out to have different variants, as most of the reported frequent variants were not observed. The objective of this paper is to highlight the similarities and changes observed in the submitted Indian viral strains. This helps to keep track on the activity, that how virus is changing into a new subtype. Major strains observed were European with the novel change in India and other being emergent clade of Iran. Its important to observe the changes in NSP3 gene, as this gene has been reported with extensive positive selection as well as potential drug target. Extensive Positive Selection Drives the Evolution of Nonstructural Proteins. With the limited number of sequences this was the only frequent novel non-synonymous change observed from Indian strains, thereby making this change vulnerable for investigation in future. This paper has a special focus on tracking of Indian viral sequences submitted in public domain. |
30 | n7gfsyxs | is remdesivir an effective treatment for COVID-19 | Enisamium is a small molecule inhibitor of the influenza A virus and SARS-CoV-2 RNA polymerases Influenza A virus and coronavirus strains cause a mild to severe respiratory disease that can result in death. Although vaccines exist against circulating influenza A viruses, such vaccines are ineffective against emerging pandemic influenza A viruses. Currently, no vaccine exists against coronavirus infections, including pandemic SARS-CoV-2, the causative agent of the Coronavirus Disease 2019 (COVID-19). To combat these RNA virus infections, alternative antiviral strategies are needed. A key drug target is the viral RNA polymerase, which is responsible for viral RNA synthesis. In January 2020, the World Health Organisation identified enisamium as a candidate therapeutic against SARS-CoV-2. Enisamium is an isonicotinic acid derivative that is an inhibitor of multiple influenza B and A virus strains in cell culture and clinically approved in 11 countries. Here we show using in vitro assays that enisamium and its putative metabolite, VR17-04, inhibit the activity of the influenza virus and the SARS-CoV-2 RNA polymerase. VR17-04 displays similar efficacy against the SARS-CoV-2 RNA polymerase as the nucleotide analogue remdesivir triphosphate. These results suggest that enisamium is a broad-spectrum small molecule inhibitor of RNA virus RNA synthesis, and implicate it as a possible therapeutic option for treating SARS-CoV-2 infection. Unlike remdesivir, enisamium does not require intravenous administration which may be advantageous for the development of COVID-19 treatments outside a hospital setting. |
44 | f9syysdw | How much impact do masks have on preventing the spread of the COVID-19? | 'Masking the evidence': perspectives of the COVID‐19 pandemic The COVID‐19 pandemic presents a severe and acute public health emergency around the world. The event of the pandemic has seen an upsurge in the general public wearing of disposable surgical masks (DSM) and other types of face masks. The World Health Organisation of mask wearing has been widely debated in the press a(WHO) have changed their advice, to now recommend the routine wearing of fabric masks by the general public as a means of preventing the spread of COVID‐19 (WHO 2020a). |
40 | uhru7rn8 | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Whole-Genome Sequences of the Severe Acute Respiratory Syndrome Coronavirus-2 obtained from Romanian patients between March and June of 2020 Impact of mutations on the evolution of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) are needed for ongoing global efforts to track and trace the current pandemic, in order to enact effective prevention and treatment options. SARS-Co-V-2 viral genomes were detected and sequenced from 18 Romanian patients suffering from coronavirus disease-2019. Viral Spike S glycoprotein sequences were used to generate model structures and assess the role of mutations on protein stability. We integrated the phylogenetic tree within the available European SARS-Co-V-2 genomic sequences. We further provide an epidemiological overview of the pre-existing conditions that are lethal in relevant Romanian patients. Non-synonymous mutations in the viral Spike glycoprotein relating to infectivity are constructed in models of protein structures. Continuing search to limit and treat SARS-CoV-2 benefit from our contribution in delineating the viral Spike glycoprotein mutations, as well as from assessment of their role on protein stability or complex formation with human receptor angiotensin-converting enzyme 2. Our results help implement and extend worldwide genomic surveillance of coronavirus disease-2019. |
35 | 9tybviyk | What new public datasets are available related to COVID-19? | Neuartiges Coronavirus (SARS-CoV-2) |
20 | dqxfcwyu | are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19? | Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2 Coronavirus disease 2019 (COVID-19) is a new emerging human infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, also previously known as 2019-nCoV), originated in Wuhan seafood and animal market, China. Since December 2019, more than 69,000 cases of COVID-19 have been confirmed in China and quickly spreads to other counties. Currently, researchers put their best efforts to identify effective drugs for COVID-19. The neutralizing antibody, which binds to viral capsid in a manner that inhibits cellular entry of virus and uncoating of the genome, is the specific defense against viral invaders. In this study, we investigate to identify neutralizing antibodies that can bind to SARS-CoV-2 Sipke (S) protein and interfere with the interaction between viral S protein and a host receptor by bioinformatic methods. The sequence analysis of S protein showed two major differences in the RBD region of the SARS-CoV-2 S protein compared to SARS-CoV and SARS-CoV related bat viruses (btSARS-CoV). The insertion regions were close to interacting residues with the human ACE2 receptor. Epitope analysis of neutralizing antibodies revealed that SARS-CoV neutralizing antibodies used conformational epitopes, whereas MERS-CoV neutralizing antibodies used a common linear epitope region, which contributes to form the β-sheet structure in MERS-CoV S protein and deleted in SARS-CoV-2 S protein. To identify effective neutralizing antibodies for SARS-CoV-2, the binding affinities of neutralizing antibodies with SARS-CoV-2 S protein were predicted and compared by antibody-antigen docking simulation. The result showed that CR3022 neutralizing antibody from human may have higher binding affinity with SARS-CoV-2 S protein than SARS-CoV S protein. We also found that F26G19 and D12 mouse antibodies could bind to SARS-CoV S protein with high affinity. Our findings provide crucial clues towards the development of antigen diagnosis, therapeutic antibody, and the vaccine against SARS-CoV-2. |
15 | viliwzyq | how long can the coronavirus live outside the body | Continuous on-line glucose measurement by microdialysis in a central vein. A pilot study. INTRODUCTION Tight glucose control in the ICU has been proven difficult with an increased risk for hypoglycaemic episodes. Also the variability of glucose may have an impact on morbidity. An accurate and feasible on-line/continuous measurement is therefore desired. In this study a central vein catheter with a microdialysis membrane in combination with an on-line analyzer for continuous monitoring of circulating glucose and lactate by the central route was tested. METHODS A total of 10 patients scheduled for major upper abdominal surgery were included in this observational prospective study at a university hospital. The patients received an extra central venous catheter with a microdialysis membrane placed in the right jugular vein. Continuous microdialysis measurement proceeded for 20 hours and on-line values were recorded every minute. Reference arterial plasma glucose and blood lactate samples were collected every hour. RESULTS Mean microdialysis-glucose during measurements was 9.8 ± 2.4 mmol/l.No statistical difference in the readings was seen using a single calibration compared to eighth hour calibration (P =0.09; t-test). There was a close agreement between the continuous reading and the reference plasma glucose values with an absolute difference of 0.6+0.8 mmol, or 6.8+9.3% and measurements showed high correlation to plasma readings (r = 0.92). The limit of agreement was 23.0%(1.94 mmol/l) compared to arterial plasma values with a line of equality close to zero.However, in a Clarke-Error Grid 93.3% of the values are in the A-area,and the remaining part in the B-area.Mean microdialysis-lactate was 1.3 ± 1.1 mmol/l. The measurements showed high correlation to the blood readings (r = 0.93). CONCLUSION Continuous on-line microdialysis glucose measurement in a central vein is a potential useful technique for continuous glucose monitoring in critically ill patients, but more improvements and testing are needed. |
15 | ltyqrg81 | how long can the coronavirus live outside the body | Protection from SARS coronavirus conferred by live measles vaccine expressing the spike glycoprotein Abstract The recent identification of a novel human coronavirus responsible of a SARS-like illness in the Middle-East a decade after the SARS pandemic, demonstrates that reemergence of a SARS-like coronavirus from an animal reservoir remains a credible threat. Because SARS is contracted by aerosolized contamination of the respiratory tract, a vaccine inducing mucosal long-term protection would be an asset to control new epidemics. To this aim, we generated live attenuated recombinant measles vaccine (MV) candidates expressing either the membrane-anchored SARS-CoV spike (S) protein or its secreted soluble ectodomain (Ssol). In mice susceptible to measles virus, recombinant MV expressing the anchored full-length S induced the highest titers of neutralizing antibodies and fully protected immunized animals from intranasal infectious challenge with SARS-CoV. As compared to immunization with adjuvanted recombinant Ssol protein, recombinant MV induced stronger and Th1-biased responses, a hallmark of live attenuated viruses and a highly desirable feature for an antiviral vaccine. |
14 | ogrlidrs | what evidence is there related to COVID-19 super spreaders | Superspreading in Early Transmissions of COVID-19 in Indonesia We estimate the basic reproduction number R0 and the overdispersion parameter K at two COVID-19 clusters in Indonesia: Jakarta-Depok and Batam. Based on the first 397 confirmed cases in both clusters, we find a high degree of individual-level variation in the transmission. The basic reproduction number R0 is estimated at 6.79 and 2.47, while the overdispersion parameter K of a negative-binomial distribution is estimated at 0.08 and 0.2 for Jakarta-Depok and Batam, respectively. This suggests that superspreading events played a key role in the early stage of the outbreak, i.e., a small number of infected individuals are responsible for large amounts of COVID-19 transmission. |
9 | 34uorjgw | how has COVID-19 affected Canada | The Association Between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and the Number of Covid-19 Confirmed Cases and Deaths in the United States: Geospatial Study Background: The novel coronavirus SARS-Cov2 uses the angiotensin-converting enzyme 2 (ACE2) receptor as an entry point to the cell. Cardiovascular disease (CVD) is a risk factor for the novel coronavirus disease (Covid-19) with poor outcomes. We hypothesized that the rate of ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) use is associated with the rate of Covid-19 confirmed cases and deaths. Methods: We conducted a geospatial study using publicly available county-level data. The Medicare ACEIs and ARBs prescription rate was exposure. The Covid-19 confirmed case and death rates were outcomes. Spatial autoregression models were adjusted for the percentage of Black residents, children, residents with at least some college degree, median household income, air quality index, CVD hospitalization rate in Medicare beneficiaries, and CVD death rate in a total county population. Results: The ACEI use had no effect on Covid-19 confirmed case rate. An average ACEIs use (compared to no-use) was associated with a higher Covid-19 death rate by 1.1 (95%CI 0.4-1.8)%. If the use of ACEIs increases by 0.5% for all counties, the Covid-19 death rate will drop by 0.4% to 0.7(95%CI 0.3-1.1)%; P<0.0001. An average ARBs use (compared to no-use) was associated with a higher Covid-19 confirmed case rate (by 4.2; 95%CI 4.1-4.3 %) and death rate (by 1.1; 95%CI 0.7-1.5 %). Each percent increase in ARBs use was associated with an increase in confirmed case rate by 0.2(0.03-0.4)% and death rate by 0.14(0.08-0.21)%. Conclusions: ARBs, but not ACEIs use rate, is associated with Covid-19 confirmed case rate. |
35 | ajw4j8b8 | What new public datasets are available related to COVID-19? | Collective response to the media coverage of COVID-19 Pandemic on Reddit and Wikipedia The exposure and consumption of information during epidemic outbreaks may alter risk perception, trigger behavioural changes, and ultimately affect the evolution of the disease. It is thus of the uttermost importance to map information dissemination by mainstream media outlets and public response. However, our understanding of this exposure-response dynamic during COVID-19 pandemic is still limited. In this paper, we provide a characterization of media coverage and online collective attention to COVID-19 pandemic in four countries: Italy, United Kingdom, United States, and Canada. For this purpose, we collect an heterogeneous dataset including 227,768 online news articles and 13,448 Youtube videos published by mainstream media, 107,898 users posts and 3,829,309 comments on the social media platform Reddit, and 278,456,892 views to COVID-19 related Wikipedia pages. Our results show that public attention, quantified as users activity on Reddit and active searches on Wikipedia pages, is mainly driven by media coverage and declines rapidly, while news exposure and COVID-19 incidence remain high. Furthermore, by using an unsupervised, dynamical topic modeling approach, we show that while the attention dedicated to different topics by media and online users are in good accordance, interesting deviations emerge in their temporal patterns. Overall, our findings offer an additional key to interpret public perception/response to the current global health emergency and raise questions about the effects of attention saturation on collective awareness, risk perception and thus on tendencies towards behavioural changes. |
11 | nf2vd6o1 | what are the guidelines for triaging patients infected with coronavirus? | Eosinopenia and elevated C-reactive protein facilitate triage of COVID-19 patients in fever clinic: a retrospective case-control study Abstract Background Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a pandemic affecting over 200 countries. Many cities have established designated fever clinics to triage suspected COVID-19 patients from other patients with similar symptoms. However, given the limited availability of the nucleic acid test as well as long waiting time for both the test and radiographic examination, the quarantine or therapeutic decisions for a large number of mixed patients were often not made in time. We aimed to identify simple and quickly available laboratory biomarkers to facilitate effective triage at the fever clinics for sorting suspected COVID-19 patients from those with COVID-19-like symptoms. Methods We collected clinical, etiological, and laboratory data of 989 patients who visited the Fever Clinic at Wuhan Union Hospital, Wuhan, China, from Jan 31 to Feb 21. Based on polymerase chain reaction (PCR) nucleic acid testing for SARS-CoV-2 infection, they were divided into two groups: SARS-CoV-2-positive patients as cases and SARS-CoV-2-negative patients as controls. We compared the clinical features and laboratory findings of the two groups, and analyzed the diagnostic performance of several laboratory parameters in predicting SARS-CoV-2 infection and made relevant comparisons to the China diagnosis guideline of having a normal or decreased number of leukocytes (≤9•5 109/L) or lymphopenia (<1•1 109/L). Findings Normal or decreased number of leukocytes (≤9•5 109/L), lymphopenia (<1•1 109/L), eosinopenia (<0•02 109/L), and elevated hs-CRP (≥4 mg/L) were presented in 95•0%, 52•2%, 74•7% and 86•7% of COVID-19 patients, much higher than 87•2%, 28•8%, 31•3% and 45•2% of the controls, respectively. The eosinopenia produced a sensitivity of 74•7% and specificity of 68•7% for separating the two groups with the area under the curve (AUC) of 0•717. The combination of eosinopenia and elevated hs-CRP yielded a sensitivity of 67•9% and specificity of 78•2% (AUC=0•730). The addition of eosinopenia alone or the combination of eosinopenia and elevated hs-CRP into the guideline-recommended diagnostic parameters for COVID-19 improved the predictive capacity with higher than zero of both net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Interpretation The combination of eosinopenia and elevated hs-CRP can effectively triage suspected COVID-19 patients from other patients attending the fever clinic with COVID-19-like initial symptoms. This finding would be particularly useful for designing triage strategies in an epidemic region having a large number of patients with COVID-19 and other respiratory diseases while limited medical resources for nucleic acid tests and radiographic examination. Funding This work was supported by the National Natural Science Foundation of China (NSFC) and the Major Scientific and Technological Innovation Projects of Hubei Province (MSTIP). |
33 | ivoukz7h | What vaccine candidates are being tested for Covid-19? | Vaccines for the 21st century In the last century, vaccination has been the most effective medical intervention to reduce death and morbidity caused by infectious diseases. It is believed that vaccines save at least 2–3 million lives per year worldwide. Smallpox has been eradicated and polio has almost disappeared worldwide through global vaccine campaigns. Most of the viral and bacterial infections that traditionally affected children have been drastically reduced thanks to national immunization programs in developed countries. However, many diseases are not yet preventable by vaccination, and vaccines have not been fully exploited for target populations such as elderly and pregnant women. This review focuses on the state of the art of recent clinical trials of vaccines for major unmet medical needs such as HIV, malaria, TB, and cancer. In addition, we describe the innovative technologies currently used in vaccine research and development including adjuvants, vectors, nucleic acid vaccines, and structure‐based antigen design. The hope is that thanks to these technologies, more diseases will be addressed in the 21st century by novel preventative and therapeutic vaccines. |
48 | gn6hg6oc | what are the benefits and risks of re-opening schools in the midst of the COVID-19 pandemic? | Antihyperglycemic properties of hydroxychloroquine in patients with diabetes: risks and benefits at the time of COVID‐19 pandemic The antimalarial drug hydroxychloroquine (HCQ) has long been used as a disease‐modifying antirheumatic drug for the treatment of several inflammatory rheumatic diseases. Over the last three decades, various studies have shown that HCQ plays also a role in the regulation of glucose homeostasis. Although the mechanisms of action underlying the glucose‐lowering properties of HCQ are still not entirely clear, evidence suggests that this drug may exert multifaceted effects on glucose regulation, including improvement of insulin sensitivity, increase of insulin secretion, reduction of hepatic insulin clearance and reduction of systemic inflammation. Preliminary studies have shown the safety and efficacy of HCQ (at a dose ranging from 400 to 600 mg/day) in patients with type 2 diabetes over a short‐term period. In 2014, HCQ has been approved in India as an add‐on hypoglycemic agent for patients with uncontrolled type 2 diabetes. However, large randomized controlled trials are needed to establish the safety and efficacy profile of HCQ in patients with type 2 diabetes over a long‐term period. With regard to the COVID‐19 pandemic, several medications (including HCQ) have been used as off‐label drugs due to the lack of proven effective therapies. However, emerging evidence shows limited benefit from HCQ use in COVID‐19 in general. The aim of this manuscript is to comprehensively summarize the current knowledge on the antihyperglycemic properties of HCQ and to critically evaluate the potential risks and benefits related to HCQ use in patients with diabetes, even in light of the current pandemic scenario. This article is protected by copyright. All rights reserved. |
33 | g9ev443o | What vaccine candidates are being tested for Covid-19? | Neonatal vaccine effectiveness and the role of adjuvants Introduction: Neonates are less responsive to vaccines than adults, making it harder to protect newborns against infection. Neonatal differences in antigen-presenting cell, B and T cell function, all likely contribute. A key question is whether novel adjuvants might be able to make neonatal vaccines more effective. Areas covered: This review addresses the issues of how to improve neonatal vaccines, which we have defined as vaccines given in the first 4 weeks of life in a human infant or the first week of life in a mouse. A search was performed using keywords including 'neonatal immunity', 'neonatal immunisation', 'vaccine' and 'adjuvant' of PubMed articles published between 1960 and 2018. Expert opinion: Sugar-like structures have recently been shown to prime the infant adaptive immune system to respond to vaccines, being potentially more effective than traditional adjuvants. Sugar-based compounds with beneficial adjuvant effects in neonatal vaccine models include delta inulin (Advax), curdlan, and trehalose 6,6ʹ-dibehenate. Such compounds make interesting neonatal adjuvant candidates, either used alone or in combination with traditional innate immune adjuvants. |
11 | j9be6occ | what are the guidelines for triaging patients infected with coronavirus? | Clinical characteristics and risk assessment of newborns born to mothers with COVID-19 Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is causing an outbreak of pneumonia in Wuhan, Hubei Province, China, and other international areas. Objective Here, we report the clinical characteristics of the newborns delivered by SARS-CoV-2 infected pregnant women. Methods We prospectively collected and analyzed the clinical features, laboratory data and outcomes of 7 newborns delivered by SARS-CoV-2 infected pregnant women in Zhongnan Hospital of Wuhan University during January 20 to January 29, 2020. Results 4 of the 7 newborns were late preterm with gestational age between 36 weeks and 37 weeks, and the other 3 were full-term infants. The average birth weight was 2096 ± 660 g. All newborns were born without asphyxia. 2 premature infants performed mild grunting after birth, but relieved rapidly with non-invasive continuous positive airway pressure (nCPAP) ventilation. 3 cases had chest X-ray, 1 was normal and 2 who were supported by nCPAP presented mild neonatal respiratory distress syndrome (NRDS). Samples of pharyngeal swab in 6 cases, amniotic fluid and umbilical cord blood in 4 cases were tested by qRT-PCR, and there was no positive result of SARS-CoV-2 nucleic acid in all cases. Conclusions The current data show that the infection of SARS-CoV-2 in late pregnant women does not cause adverse outcomes in their newborns, however, it is necessary to separate newborns from mothers immediately to avoid the potential threats. |
40 | mu8isrut | What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur? | Rational Design of the Remdesivir Binding Site in the RNA-dependent RNA Polymerase of SARS-CoV-2: Implications for Potential Resistance SARS-CoV-2 is rapidly evolving with the continuous emergence of new mutations. There is no specific antiviral therapy for COVID-19, and the use of Remdesivir for treating COVID-19 will likely continue before clinical trials are completed. Due to the lengthening pandemic and evolving nature of the virus, predicting potential residues prone to mutations is crucial for the management of Remdesivir resistance. We used a rational ligand-based interface design complemented with mutational mapping to generate a total of 100,000 mutations and provide insight into the functional outcome of mutations in the Remdesivir-binding site in nsp12. After designing 56 residues in the Remdesivir binding site of nsp12, the designs retained 96-98% sequence identity, which suggests that SARS-CoV-2 attains resistance and develops further infectivity with very few mutations in the nsp12. We also identified affinity-attenuating Remdesivir binding designs of nsp12. Several mutants acquired decreased binding affinity with Remdesivir, which suggested drug resistance. These hotspot residues had a higher probability of undergoing selective mutations in the future to develop Remdesivir and related drug-based resistance. A comparison of 21 nsp12 Remdesivir-bound designs to the 13 EIDD-2801-bound nsp12 designs suggested that EIDD-2801 would be more effective in preventing the emergence of resistant mutations and against Remdesivir-resistance strains due to the restricted mutational landscape. Combined with the availability of more genomic data, our information on mutation repertoires is critical to guide scientists to rational structure-based drug discovery. Knowledge of the potential residues prone to mutation improves our understanding and management of drug resistance and disease pathogenesis. |
18 | vt8w7z01 | what are the best masks for preventing infection by Covid-19? | All eyes on Coronavirus—What do we need to know as ophthalmologists |
23 | zr19c351 | what kinds of complications related to COVID-19 are associated with hypertension? | Highlights for management of patients with Autoimmune Liver Disease during COVID-19 pandemia |
11 | nvsj435z | what are the guidelines for triaging patients infected with coronavirus? | Diagnostic power of chest CT for COVID-19: to screen or not to screen Background: chest CT is increasingly used for COVID-19 screening in healthcare systems with limited SARS-CoV-2 PCR capacity. Its diagnostic value was supported by studies with methodological concerns and its use is controversial. Here we investigated its potential to diagnose COVID-19 in symptomatic patients and to screen asymptomatic patients in a prospective study with minimal selection bias. Methods: From March 19, 2020 to April 20, 2020 we performed parallel SARS-CoV-2 PCR and CT with categorization of COVID-19 suspicion by CO-RADS, in 859 patients with COVID-19 symptoms and 1138 controls admitted to the hospital for COVID-19 unrelated medical urgencies. CT-CORADS was categorized on a 5-point scale from 1 (very low suspicion) to 5 (very high suspicion). AUC under ROC curve were calculated in symptomatic versus asymptomatic patients to predict positive SARS-CoV-2 positive PCR and likelihood ratios for each CO-RADS score were used for rational selection of diagnostic thresholds. Findings: CT-CORADS had significant (P<0.0001) diagnostic power in both symptomatic (AUC=0.891) and asymptomatic (AUC=0.700) patients hospitalized during SARS-CoV-2 peak prevalence. In symptomatic patients (41.7% PCR+), CO-RADS [≥] 3 detected positive PCR with high sensitivity (89.1%) and 72.5% specificity. In asymptomatic patients (5.3% PCR+), a CO-RADS score [≥] 3 detected SARS-CoV-2 infection with low sensitivity (45.0%) but high specificity (88.8%). Interpretation: CT-CORADS has meaningful diagnostic power in symptomatic patients, supporting its application for time-sensitive triage. Sensitivity in asymptomatic patients is insufficient to justify its use as screening approach. Incidental detection of CO-RADS [≥] 3 in asymptomatic patients should trigger reflex testing for respiratory pathogens. |
33 | 0nplh22v | What vaccine candidates are being tested for Covid-19? | Two decades of vaccine innovations for global public good: Report of the Developing Countries' Vaccine Manufacturers Network 20th meeting, 21–23 october 2019, Rio de Janeiro, Brazil The Developing Countries' Vaccine Manufacturers Network, joined by global health organizations, held its 20th meeting celebrating two decades of vaccine innovations for global public good. Health leaders from industry, academia and global health organizations reviewed efforts to accelerate innovation, improve access to vaccines, overcome inequalities and strengthen technological and public-health management capabilities. Discussion topics included World Health Organization's immunization strategy, Pan American Health Organization's system-strengthening efforts, Gavi's evaluation of vaccine coverage in middle income countries and developments on public-market intelligence. Health market trends, delivery gaps, integration of system-wide needs, costs and benefits, and implications for stakeholder decision-making were areas of focus. Novel thinking was discussed on integration of policy, financing, regulatory pathways and alignment of innovation priorities to improve efficiency in vaccine development pathways. The Vaccine Innovation Prioritization Strategy collaboration presented nine global innovation priorities, and many other partners and members presented updates on their priorities. Novel technologies and platforms, such as RNA-based vaccines, adenoviral vectors, bioconjugation, blow-fill-seal and two-dimensional barcodes, provided opportunities to accelerate vaccine innovations. Challenges in planning and operations at global level included those in health security, polio eradication, re-emergence of diseases, disparities between forecasts and orders and heterogeneous regulatory requirements. Manufacturers were urged to accelerate innovation and prequalification of high-impact vaccines, such as pneumococcal, human papillomavirus and rotavirus vaccines, to strengthen immunization globally. |
13 | 1x66nxgx | what are the transmission routes of coronavirus? | Will COVID-19 pandemic diminish by summer-monsoon in India? Lesson from the first lockdown The novel Coronavirus (2019-nCoV) was identified in Wuhan, Hubei Province, China, in December 2019 and has created a medical emergency worldwide. It has spread rapidly to multiple countries and has been declared a pandemic by the World Health Organization. In India, it is already reported more than 18 thousand cases and more than 600 deaths due to Coronavirus disease 2019 (COVID-19) till April 20, 2020. Previous studies on various viral infections like influenza have supported an epidemiological hypothesis that the cold and dry (low absolute humidity) environments favor the survival and spread of droplet-mediated viral diseases. These viral transmissions found attenuated in warm and humid (high absolute humidity) environments. However, the role of temperature, humidity, and absolute humidity in the transmission of COVID-19 has not yet been well established. Therefore the study to investigate the meteorological condition for incidence and spread of COVID-19 infection, to predict the epidemiology of the infectious disease, and to provide a scientific basis for prevention and control measures against the new disease is required for India. In this work, we analyze the local weather patterns of the Indian region affected by the COVID-19 virus for March and April months, 2020. We have investigated the effect of meteorological parameters like Temperature, relative humidity, and absolute humidity on the rate of spread of COVID-19 using daily confirm cases in India. We have used daily averaged meteorological data for the last three years (2017-2019) for March and April month and the same for the year 2020 for March 1 to April 15. We found a positive association (Pearsons r=0.56) between temperature and daily COVID-19 cases over India. We found a negative association of humidity (RH and AH) with daily COVID-19 Cases (Persons r=-0.62, -0.37). We have also investigated the role of aerosol in spreading the pandemic across India because its possible airborne nature. For this, we have investigated the association of aerosols (AOD) and other pollutions (NO2) with COVID-19 cases during the study period and also during the first lockdown period (25 March-15 April) in India. We found a negative association in March when there were few cases, but in April, it shows positive association when the number of cases is more (for AOD it was r=-0.41 and r=0.28 respectively). During the lockdown period, aerosols (AOD) and other pollutants (NO2; an indicator of PM2.5) reduced sharply with a percentage drop of about 36 and 37, respectively. This reduction may have reduced the risk for COVID-19 through air transmission due to the unavailability of aerosol particles as a base. HYSPLIT forward trajectory model also shows that surface aerosols may travel up to 4 km according to wind and direction within three h of its generation. If coronavirus becomes airborne as suggested by many studies, then it may have a higher risk of transmission by aerosols particles. So relaxing in the lockdown and environmental rules in terms of pollutant emissions from power plants, factories, and other facilities would be a wrong choice and could result in more COVID-19 incidences and deaths in India. Therefore the current study, although limited, suggests that it is doubtful that the spread of COVID-19 would slow down in India due to meteorological factors, like high temperature and high humidity. Because a large number of cases have already been reported in the range of high Tem, high Relative, and high absolute humidity regions of India. Thus our results in no way suggest that COVID-19 would not spread in warm, humid regions or during summer/monsoon. So effective public health interventions should be implemented across India to slow down the transmission of COVID-19. If COVID-19 is indeed sensitive to environmental factors, it could be tested in the coming summer-monsoon for India. So the only summer is not going to help India until monsoon is coming. Only government mitigations strategies would be helpful, whether its lockdown, aggressive and strategic testing, medical facilities, imposing social distancing, encouraging to use face mask or monitoring by a mobile application (Aarogya Setu). |
45 | c7weqc03 | How has the COVID-19 pandemic impacted mental health? | Les professionnels de santé face à la pandémie de la maladie à coronavirus (COVID-19) : quels risques pour leur santé mentale ?/ [Health professionals facing the coronavirus disease 2019 (COVID-19) pandemic: What are the mental health risks?] OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has caused major sanitary crisis worldwide. Half of the world has been placed in quarantine. In France, this large-scale health crisis urgently triggered the restructuring and reorganization of health service delivery to support emergency services, medical intensive care units and continuing care units. Health professionals mobilized all their resources to provide emergency aid in a general climate of uncertainty. Concerns about the mental health, psychological adjustment, and recovery of health care workers treating and caring for patients with COVID-19 are now arising. The goal of the present article is to provide up-to-date information on potential mental health risks associated with exposure of health professionals to the COVID-19 pandemic. METHODS: Authors performed a narrative review identifying relevant results in the scientific and medical literature considering previous epidemics of 2003 (SARS-CoV-1) and 2009 (H1N1) with the more recent data about the COVID-19 pandemic. We highlighted most relevant data concerning the disease characteristics, the organizational factors and personal factors that may contribute to developing psychological distress and other mental health symptoms. RESULTS: The disease characteristics of the current COVID-19 pandemic provoked a generalized climate of wariness and uncertainty, particularly among health professionals, due to a range of causes such as the rapid spread of COVID-19, the severity of symptoms it can cause in a segment of infected individuals, the lack of knowledge of the disease, and deaths among health professionals. Stress may also be caused by organizational factors, such as depletion of personal protection equipment, concerns about not being able to provide competent care if deployed to new area, concerns about rapidly changing information, lack of access to up-to-date information and communication, lack of specific drugs, the shortage of ventilators and intensive care unit beds necessary to care for the surge of critically ill patients, and significant change in their daily social and family life. Further risk factors have been identified, including feelings of being inadequately supported, concerns about health of self, fear of taking home infection to family members or others, and not having rapid access to testing through occupational health if needed, being isolated, feelings of uncertainty and social stigmatization, overwhelming workload, or insecure attachment. Additionally, we discussed positive social and organizational factors that contribute to enhance resilience in the face of the pandemic. There is a consensus in all the relevant literature that health care professionals are at an increased risk of high levels of stress, anxiety, depression, burnout, addiction and post-traumatic stress disorder, which could have long-term psychological implications. CONCLUSIONS: In the long run, this tragic health crisis should significantly enhance our understanding of the mental health risk factors among the health care professionals facing the COVID-19 pandemic. Reporting information such as this is essential to plan future prevention strategies. Protecting health care professionals is indeed an important component of public health measures to address large-scale health crisis. Thus, interventions to promote mental well-being in health care professionals exposed to COVID-19 need to be immediately implemented, and to strengthen prevention and response strategies by training health care professionals on mental help and crisis management. |
10 | 5kv2j7nn | has social distancing had an impact on slowing the spread of COVID-19? | Model of a Testing-and-Quarantine Strategy to Slow-Down the COVID-19 Outbreak in Guadeloupe Using a stochastic epidemic model explicitly considering the entire population of Guadeloupe (1), we explore the domain of solutions presenting an efficient slowing down of the COVID-19 epidemic spread during the post-containment period. The considered model parameters are the basic reproduction number R0 to simulate the effects of social distancing, the time delay {delta}TQ elapsed between the detection of a symptomatic person and her/his placement in quarantine to suppress her/his contagiousness, and the number Na of asymptomatic people tested positively and isolated. We show that acceptable solutions are obtained for a wide range of parameter values. Thanks to a good control of the initial epidemic spread resulting from an early containment and efficient communication by the sanitary and administrative authorities, the present situation corresponds to a pre-epidemic state. The most safe solutions are a combinations of social distancing, numerous testing to perform a systematic isolation of symptomatic patients and guided detection of asymptomatic people in the entourage of localised symptomatic patients. |
34 | cthgz65m | What are the longer-term complications of those who recover from COVID-19? | Nuevo coronavirus (2019-nCov): ¿tiene suficientes unidades de cuidados intensivos? |
37 | tnfgbl05 | What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence? | Identification of super-transmitters of SARS-CoV-2 A newly emerged coronavirus, SARS-CoV-2, caused severe outbreaks of pneumonia in China in December 2019 and has since spread to various countries around the world. To probe the origin and transmission dynamics of this virus, we performed phylodynamic analysis of 247 high quality genomic sequences of viruses available in the GISAID platform as of March 05, 2020. A substantial number of earliest sequences reported in Wuhan in December 2019, including those of viruses recovered from the Huanan Seafood Market (HNSM), the site of the initial outbreak, were genetically diverse, suggesting that viruses of multiple sources were involved in the original outbreak. The viruses were subsequently disseminated to different parts of China and other countries, with diverse mutational profiles being recorded in strains recovered subsequently. Interestingly, four genetic clusters defined as Super-transmitters (STs) were found to become dominant and were responsible for the major outbreaks in various countries. Among the four clusters, ST1 is widely disseminated in Asia and the US and mainly responsible for outbreaks in the states of Washington and California in the US as well as those in South Korea at the end of February and early March, whereas ST4 contributed to the pandemic in Europe. Each ST cluster carried a signature mutation profile which allowed us to trace the origin and transmission patterns of specific viruses in different parts of the world. Using the signature mutations as markers of STs, we further analysed 1539 genome sequences reported after February 29, 2020. We found that around 90% of these genomes belonged to STs with ST4 being the dominant one and their contribution to pandemic in different continents were also depicted. The identification of these super-transmitters provides insight into the control of further transmission of SARS-CoV-2. |
36 | dir0jtyb | What is the protein structure of the SARS-CoV-2 spike? | In silico studies on the comparative characterization of the interactions of SARS-CoV-2 spike glycoprotein with ACE-2 receptor homologs and human TLRs Coronavirus disease-2019 (COVID-19) outbreak due to novel coronavirus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has come out as a major threat for mankind in recent times. It is continually taking an enormous toll on mankind by means of increasing number of deaths, associated comorbidities, and socioeconomic loss around the globe. Unavailability of chemotherapeutics/vaccine has posed tremendous challenges to scientists and doctors for developing an urgent therapeutic strategy. In this connection, the present in silico study aims to understand the sequence divergence of spike protein (the major infective protein of SARS-CoV-2), its mode of interaction with the angiotensin-converting enzyme-2 receptor (ACE2) receptor of human and related animal hosts/reservoir. Moreover, the involvement of the human Toll-like receptors (TLRs) against the spike protein has also been demonstrated. Our data indicated that the spike glycoprotein of SARS-CoV-2 is phylogenetically close to bat coronavirus and strongly binds with ACE2 receptor protein from both human and bat origin. We have also found that cell surface TLRs, especially TLR4 is most likely to be involved in recognizing molecular patterns from SARS-CoV-2 to induce inflammatory responses. The present study supported the zoonotic origin of SARS-CoV-2 from a bat and also revealed that TLR4 may have a crucial role in the virus-induced inflammatory consequences associated with COVID-19. Therefore, selective targeting of TLR4-spike protein interaction by designing competitive TLR4-antagonists could pave a new way to treat COVID-19. Finally, this study is expected to improve our understanding on the immunobiology of SARS-CoV-2 and could be useful in adopting spike protein, ACE2, or TLR-guided intervention strategy against COVID-19 shortly. |
46 | fmt3354i | what evidence is there for dexamethasone as a treatment for COVID-19? | IFN-γ–induced protein 10 is a novel biomarker of rhinovirus-induced asthma exacerbations Background Rhinovirus-induced acute asthma is the most frequent trigger for asthma exacerbations. Objective We assessed which inflammatory mediators were released from bronchial epithelial cells (BECs) after infection with rhinovirus and then determined whether they were also present in subjects with acute virus-induced asthma, with the aim to identify a biomarker or biomarkers for acute virus-induced asthma. Methods BECs were obtained from bronchial brushings of steroid-naive asthmatic subjects and healthy nonatopic control subjects. Cells were infected with rhinovirus 16. Inflammatory mediators were measured by means of flow cytometry with a cytometric bead array. Subjects with acute asthma and virus infection were recruited; they were characterized clinically by using lung function tests and had blood taken to measure the inflammatory mediators identified as important by the BEC experiments. Results IFN-γ–induced protein 10 (IP-10) and RANTES were released in the greatest quantities, followed by IL-6, IL-8, and TNF-α. Dexamethasone treatment of BECs only partially suppressed IP-10 and TNF-α but was more effective at suppressing RANTES, IL-6, and IL-8. In acute clinical asthma serum IP-10 levels were increased to a greater extent in those with acute virus-induced asthma (median of 604 pg/mL compared with 167 pg/mL in those with non–virus-induced acute asthma, P < .01). Increased serum IP-10 levels were predictive of virus-induced asthma (odds ratio, 44.3 [95% CI, 3.9-100.3]). Increased serum IP-10 levels were strongly associated with more severe airflow obstruction (r = −0.8; P < .01). Conclusions IP-10 release is specific to acute virus-induced asthma. Clinical implications Measurement of serum IP-10 could be used to predict a viral trigger to acute asthma. |
4 | 0lvsvuf2 | what causes death from Covid-19? | COVID-19 in children: the link in the transmission chain |
5 | tj4m01s4 | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Perspectives on the development of neutralizing antibodies against SARS-CoV-2 SARS-CoV-2 gains entry to human cells through its spike (S) protein binding to angiotensin-converting enzyme 2 (ACE2). Therefore, the receptor binding domain (RBD) of the S protein is the primary target for neutralizing antibodies. Selection of broad-neutralizing antibodies against SARS-CoV-2 and SARS-CoV is attractive and might be useful for treating not only COVID-19 but also future SARS-related CoV infections. Broad-neutralizing antibodies, such as 47D11, S309, and VHH-72, have been reported to target a conserved region in the RBD of the S1 subunit. The S2 subunit required for viral membrane fusion might be another target. Due to their small size and high stability, single-domain antibodies might have the ability to be administered by an inhaler making them potentially attractive therapeutics for respiratory infections. A cocktail strategy combining two (or more) antibodies that recognize different parts of the viral surface that interact with human cells might be the most effective. |
33 | rzr8qjw8 | What vaccine candidates are being tested for Covid-19? | Tackling Corona Virus Disease 2019 (COVID 19) in Workplaces Coronaviruses are zoonotic viruses and six species of Coronaviruses are known to cause human disease such as cause common cold, severe acute respiratory syndrome and the Middle East Respiratory Syndrome. In January 2020, scientists in Wuhan, China isolated a novel coronavirus (SARS-CoV-2), responsible for an outbreak of unknown pneumonia that had not been previously reported among humans. This virus spreads from person to person, through respiratory droplets, close contact, and by touching surfaces or objects contaminated by the virus. The incubation period varies between 2 days and 14 days. Symptoms usually include fever, cough, difficulty in breathing, pneumonia, severe acute respiratory syndrome. Older age and co-morbid conditions increase the fatality. Any person with a history of travel to and from COVID-19 affected countries in the past 14 days or any person who has had close contact with a laboratory confirmed COVID-19 are suspect cases and needs evaluation. Currently no vaccine is available and treatment is mainly supportive. Measures at workplace should include- avoiding non-essential travel, identifying and isolating sick employees at the earliest, hand hygiene, respiratory hygiene, environmental hygiene and social distancing. |
34 | hnutdxh5 | What are the longer-term complications of those who recover from COVID-19? | COVID-19Base: A knowledgebase to explore biomedical entities related to COVID-19 We are presenting COVID-19Base, a knowledgebase highlighting the biomedical entities related to COVID-19 disease based on literature mining. To develop COVID-19Base, we mine the information from publicly available scientific literature and related public resources. We considered seven topic-specific dictionaries, including human genes, human miRNAs, human lncRNAs, diseases, Protein Databank, drugs, and drug side effects, are integrated to mine all scientific evidence related to COVID-19. We have employed an automated literature mining and labeling system through a novel approach to measure the effectiveness of drugs against diseases based on natural language processing, sentiment analysis, and deep learning. To the best of our knowledge, this is the first knowledgebase dedicated to COVID-19, which integrates such large variety of related biomedical entities through literature mining. Proper investigation of the mined biomedical entities along with the identified interactions among those, reported in COVID-19Base, would help the research community to discover possible ways for the therapeutic treatment of COVID-19. |
3 | f0xsisdg | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Deducing the N- and O- glycosylation profile of the spike protein of novel coronavirus SARS-CoV-2 The current emergence of the novel coronavirus pandemic caused by SARS-CoV-2 demands the development of new therapeutic strategies to prevent rapid progress of mortalities. The coronavirus spike (S) protein, which facilitates viral attachment, entry and membrane fusion is heavily glycosylated and plays a critical role in the elicitation of the host immune response. The spike protein is comprised of two protein subunits (S1 and S2), which together possess 22 potential N-glycosylation sites. Herein, we report the glycosylation mapping on spike protein subunits S1 and S2 expressed on human cells through high resolution mass spectrometry. We have characterized the quantitative N-glycosylation profile on spike protein and interestingly, observed unexpected O-glycosylation modifications on the receptor binding domain (RBD) of spike protein subunit S1. Even though O-glycosylation has been predicted on the spike protein of SARS-CoV-2, this is the first report of experimental data for both the site of O-glycosylation and identity of the O-glycans attached on the subunit S1. Our data on the N- and O-glycosylation is strengthened by extensive manual interpretation of each glycopeptide spectra in addition to using bioinformatics tools to confirm the complexity of glycosylation in the spike protein. The elucidation of the glycan repertoire on the spike protein provides insights into the viral binding studies and more importantly, propels research towards the development of a suitable vaccine candidate. |
9 | dl45plby | how has COVID-19 affected Canada | Special Article: Risk Communication During COVID-19 Abstract: During the unprecedented times caused by the novel coronavirus COVID-19, there is rapidly evolving information and guidance. However, a focus must also be on proper and effective risk communication. This is especially the case during pandemics that have high rates of infection, significant morbidity, lack of therapeutic measures, and rapid increases in cases, all of which apply to the current COVID-19 pandemic. A consequence of poor risk communication and heightened risk perception is hoarding behavior, which can lead to lack of medications and personal protective equipment. One potential way to ensure appropriate risk communication is utilizing social media channels, and ensuring an ongoing consistent media presence. Another important step is to include all stakeholders including members of the allergy community in broader public health messaging. As we continue to face unprecedented times in the allergy community, an understanding and appreciation of risk communication will be essential as we communicate with, and inform, our patients, and our colleagues, moving forward. |
3 | k38u414m | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Mouse Hepatitis Virus This chapter attempts to provide an overview of the important aspects of mouse hepatitis virus (MHV) experimental biology while emphasizing the virus as a naturally occurring mouse pathogen. Even this is complicated, as it is impossible to generalize with this virus, due to marked differences in the biologic behavior of the myriad virus strains, plus the marked effects of a large number of host factors. It is now known that the MHV group is represented by numerous variants that are constantly mutating, and that these viruses can be biologically separated into respiratory (polytropic) MHVs and enterotropic MHVs, with distinctly different patterns of tissue tropism. This dichotomy is emphasized for discussion, but biology is never absolute. Many of the early MHV isolations are made as a result of contamination of biological materials that correlated with their polytropic biologic behavior. Their stated tropisms frequently were the result of the investigators' research interests and many have therefore been subjected to selective passage that favors a particular tissue tropism. All MHV isolates are related genetically and antigenically, but isolates can be differentiated by genetic sequencing, cross-serum neutralization, or with monoclonal antibodies. Genetic and antigenic relationships are not predictive of biologic behavior. |
5 | 1f9x5li8 | what drugs have been active against SARS-CoV or SARS-CoV-2 in animal studies? | Coronavirus Infections in Children Including COVID-19: An Overview of the Epidemiology, Clinical Features, Diagnosis, Treatment and Prevention Options in Children Coronaviruses (CoVs) are a large family of enveloped, single-stranded, zoonotic RNA viruses. Four CoVs commonly circulate among humans: HCoV2-229E, -HKU1, -NL63 and -OC43. However, CoVs can rapidly mutate and recombine leading to novel CoVs that can spread from animals to humans. The novel CoVs severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. The 2019 novel coronavirus (SARS-CoV-2) is currently causing a severe outbreak of disease (termed COVID-19) in China and multiple other countries, threatening to cause a global pandemic. In humans, CoVs mostly cause respiratory and gastrointestinal symptoms. Clinical manifestations range from a common cold to more severe disease such as bronchitis, pneumonia, severe acute respiratory distress syndrome, multi-organ failure and even death. SARS-CoV, MERS-CoV and SARS-CoV-2 seem to less commonly affect children and to cause fewer symptoms and less severe disease in this age group compared with adults, and are associated with much lower case-fatality rates. Preliminary evidence suggests children are just as likely as adults to become infected with SARS-CoV-2 but are less likely to be symptomatic or develop severe symptoms. However, the importance of children in transmitting the virus remains uncertain. Children more often have gastrointestinal symptoms compared with adults. Most children with SARS-CoV present with fever, but this is not the case for the other novel CoVs. Many children affected by MERS-CoV are asymptomatic. The majority of children infected by novel CoVs have a documented household contact, often showing symptoms before them. In contrast, adults more often have a nosocomial exposure. In this review, we summarize epidemiologic, clinical and diagnostic findings, as well as treatment and prevention options for common circulating and novel CoVs infections in humans with a focus on infections in children. |
8 | pnvs65mr | how has lack of testing availability led to underreporting of true incidence of Covid-19? | Early impact of COVID-19 on transplant center practices and policies in the United States COVID-19 is a novel, rapidly changing pandemic: consequently, evidence-based recommendations in solid organ transplantation (SOT) remain challenging and unclear. To understand the impact on transplant activity across the United States, and center-level variation in testing, clinical practice, and policies, we conducted a national survey between March 24, 2020 and March 31, 2020 and linked responses to the COVID-19 incidence map. Response rate was a very high 79.3%, reflecting a strong national priority to better understand COVID-19. Complete suspension of live donor kidney transplantation was reported by 71.8% and live donor liver by 67.7%. While complete suspension of deceased donor transplantation was less frequent, some restrictions to deceased donor kidney transplantation were reported by 84.0% and deceased donor liver by 73.3%; more stringent restrictions were associated with higher regional incidence of COVID-19. Shortage of COVID-19 tests was reported by 42.5%. Respondents reported a total of 148 COVID-19 recipients from <1 to >10 years posttransplant: 69.6% were kidney recipients, and 25.0% were critically ill. Hydroxychloroquine (HCQ) was used by 78.1% of respondents; azithromycin by 46.9%; tocilizumab by 31.3%, and remdesivir by 25.0%. There is wide heterogeneity in center-level response across the United States; ongoing national data collection, expert discussion, and clinical studies are critical to informing evidence-based practices. |
30 | vuqbli6g | is remdesivir an effective treatment for COVID-19 | ISUOG Interim Guidance on 2019 novel coronavirus infection during pregnancy and puerperium: information for healthcare professionals |
49 | 9skvbk8m | do individuals who recover from COVID-19 show sufficient immune response, including antibody levels and T-cell mediated immunity, to prevent re-infection? | Serological differentiation between COVID-19 and SARS infections In response to the coronavirus disease 2019 (COVID-19) outbreak, caused by SARS-CoV-2, multiple diagnostic tests are required for acute disease diagnosis, contact tracing, monitoring asymptomatic infection rates and assessing herd immunity. While PCR remains the frontline test of choice in the acute diagnostic setting, serological tests are urgently needed. Unlike PCR tests which are highly specific, cross-reactivity is a major challenge for COVID-19 antibody tests considering there are six other coronaviruses known to infect humans. SARS-CoV is genetically related to SARS-CoV-2 sharing approximately 80% sequence identity and both belong to the species SARS related coronavirus in the genus Betacoronavirus of family Coronaviridae. We developed and compared the performance of four different serological tests to comprehensively assess the cross-reactivity between COVID-19 and SARS patient sera. There is significant cross-reactivity when N protein of either virus is used. The S1 or RBD regions from the spike (S) protein offers better specificity. Amongst the different platforms, capture ELISA performed best. We found that SARS survivors all have significant levels of antibodies remaining in their blood 17 years after infection. Anti-N antibodies waned more than anti-RBD antibodies, and the latter is known to play a more important role in providing protective immunity. |
36 | spnps6t5 | What is the protein structure of the SARS-CoV-2 spike? | Autocorrelation of the susceptible-infected-susceptible process on networks In this paper, we focus on the autocorrelation of the susceptible-infected-susceptible (SIS) process on networks. The [Formula: see text]-intertwined mean-field approximation (NIMFA) is applied to calculate the autocorrelation properties of the exact SIS process. We derive the autocorrelation of the infection state of each node and the fraction of infected nodes both in the steady and transient states as functions of the infection probabilities of nodes. Moreover, we show that the autocorrelation can be used to estimate the infection and curing rates of the SIS process. The theoretical results are compared with the simulation of the exact SIS process. Our work fully utilizes the potential of the mean-field method and shows that NIMFA can indeed capture the autocorrelation properties of the exact SIS process. |
9 | ass2u6y8 | how has COVID-19 affected Canada | Intervention strategies against COVID-19 and their estimated impact on Swedish healthcare capacity Objectives: During March 2020, the COVID-19 pandemic has rapidly spread globally, and non-pharmaceutical interventions are being used to reduce both the load on the healthcare system as well as overall mortality. Design: Individual-based transmission modelling using Swedish demographic and Geographical Information System data and conservative COVID-19 epidemiological parameters. Setting: Sweden Participants: A model to simulate all 10.09 million Swedish residents. Interventions: 5 different non-pharmaceutical public-health interventions including the mitigation strategy of the Swedish government as of 10 April; isolation of the entire household of confirmed cases; closure of schools and non-essential businesses with or without strict social distancing; and strict social distancing with closure of schools and non-essential businesses. Main outcome measures: Estimated acute care and intensive care hospitalisations, COVID-19 attributable deaths, and infections among healthcare workers from 10 April until 29 June. Findings: Our model for Sweden shows that, under conservative epidemiological parameter estimates, the current Swedish public-health strategy will result in a peak intensive-care load in May that exceeds pre-pandemic capacity by over 40-fold, with a median mortality of 96,000 (95% CI 52,000 to 183,000). The most stringent public-health measures examined are predicted to reduce mortality by approximately three-fold. Intensive-care load at the peak could be reduced by over two-fold with a shorter period at peak pandemic capacity. Conclusions: Our results predict that, under conservative epidemiological parameter estimates, current measures in Sweden will result in at least 40-fold over-subscription of pre-pandemic Swedish intensive care capacity, with 15.8 percent of Swedish healthcare workers unable to work at the pandemic peak. Modifications to ICU admission criteria from international norms would further increase mortality. |
19 | slapc5xt | what type of hand sanitizer is needed to destroy Covid-19? | A Chinese Case of Coronavirus Disease 2019 (COVID-19) Did Not Show Infectivity During the Incubation Period: Based on an Epidemiological Survey Controversy remains over whether the coronavirus disease 2019 (COVID-19) virus may have infectivity during the incubation period before the onset of symptoms. The author had the opportunity to examine the infectivity of COVID-19 during the incubation period by conducting an epidemiological survey on a confirmed patient who had visited Jeju Island during the incubation period. The epidemiological findings support the claim that the COVID-19 virus does not have infectivity during the incubation period. |
4 | txcy91w7 | what causes death from Covid-19? | Active surveillance for suspected COVID-19 cases in inpatients with information technology |
26 | st8wyybq | what are the initial symptoms of Covid-19? | Covid-19 Has Come Home to Roost in Gastroenterology |
3 | lec1kplh | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | SARS-CoV-2-specific T cells exhibit unique features characterized by robust helper function, lack of terminal differentiation, and high proliferative potential Convalescing COVID-19 patients mount robust T cell responses against SARS-CoV-2, suggesting an important role for T cells in viral clearance. To date, the phenotypes of SARS-CoV-2-specific T cells remain poorly defined. Using 38-parameter CyTOF, we phenotyped longitudinal specimens of SARS-CoV-2-specific CD4+ and CD8+ T cells from four individuals who recovered from mild COVID-19. SARS-CoV-2-specific CD4+ T cells were exclusively Th1 cells, and predominantly Tcm with phenotypic features of robust helper function. SARS-CoV-2-specific CD8+ T cells were predominantly atypical Temra cells in a state of less terminal differentiation and therefore capable of expansion. Subsets of SARS-CoV-2-specific T cells exhibit features of being long-lived and capable of homeostatic proliferation consistent with their persistence for over two months. Our results suggest that long-lived and robust T cell immunity is generated following natural SARS-CoV-2 infection, and support an important role for SARS-CoV-2-specific T cells in host control of COVID-19. |
15 | fdkwklzj | how long can the coronavirus live outside the body | Severe acute respiratory syndrome vaccine development: experiences of vaccination against avian infectious bronchitis coronavirus Vaccines against infectious bronchitis of chickens (Gallus gallus domesticus) have arguably been the most successful, and certainly the most widely used, of vaccines for diseases caused by coronaviruses, the others being against bovine, canine, feline and porcine coronaviruses. Infectious bronchitis virus (IBV), together with the genetically related coronaviruses of turkey (Meleagris gallopavo) and ring-necked pheasant (Phasianus colchicus), is a group 3 coronavirus, Severe acute respiratory syndrome (SARS) coronavirus being tentatively in group 4, the other known mammalian coronaviruses being in groups 1 and 2. IBV replicates not only in respiratory tissues (including the nose, trachea, lungs and airsacs, causing respiratory disease), but also in the kidney (associated with minor or major nephritis), oviduct, and in many parts of the alimentary tract—the oesophagus, proventriculus, duodenum, jejunum, bursa of Fabricius, caecal tonsils, rectum and cloaca, usually without clinical effects. The virus can persist, being re-excreted at the onset of egg laying (4 to 5 months of age), believed to be a consequence of the stress of coming into lay. Genetic lines of chickens differ in the extent to which IBV causes mortality in chicks, and in respect of clearance of the virus after the acute phase. Live attenuated (by passage in chicken embryonated eggs) IBV strains were introduced as vaccines in the 1950s, followed a couple of decades later by inactivated vaccines for boosting protection in egg-laying birds. Live vaccines are usually applied to meat-type chickens at 1 day of age. In experimental situations this can result in sterile immunity when challenged by virulent homologous virus. Although 100% of chickens may be protected (against clinical signs and loss of ciliary activity in trachea), sometimes 10% of vaccinated chicks may not respond with a protective immune response. Protection is short lived, the start of the decline being apparent 9 weeks after vaccination with vaccines based on highly attenuated strains. IBV exists as scores of serotypes (defined by the neutralization test), cross-protection often being poor. Consequently, chickens may be re-vaccinated, with the same or another serotype, two or three weeks later. Single applications of inactivated virus has generally led to protection of <50% of chickens. Two applications have led to 90 to 100% protection in some reports, but remaining below 50% in others. In practice in the field, inactivated vaccines are used in laying birds that have previously been primed with two or three live attenuated virus vaccinations. This increases protection of the laying birds against egg production losses and induces a sustained level of serum antibody, which is passed to progeny. The large spike glycoprotein (S) comprises a carboxy-terminal S2 subunit (approximately 625 amino acid residues), which anchors S in the virus envelope, and an amino-terminal S1 subunit (approximately 520 residues), believed to largely form the distal bulbous part of S. The S1 subunit (purified from IBV virus, expressed using baculovirus or expressed in birds from a fowlpoxvirus vector) induced virus neutralizing antibody. Although protective immune responses were induced, multiple inoculations were required and the percentage of protected chickens was too low (<50%) for commercial application. Remarkably, expression of S1 in birds using a non-pathogenic fowl adenovirus vector induced protection in 90% and 100% of chickens in two experiments. Differences of as little as 5% between the S1 sequences can result in poor cross-protection. Differences in S1 of 2 to 3% (10 to 15 amino acids) can change serotype, suggesting that a small number of epitopes are immunodominant with respect to neutralizing antibody. Initial studies of the role of the IBV nucleocapsid protein (N) in immunity suggested that immunization with bacterially expressed N, while not inducing protection directly, improved the induction of protection by a subsequent inoculation with inactivated IBV. In another study, two intramuscular immunizations of a plasmid expressing N induced protective immunity. The basis of immunity to IBV is not well understood. Serum antibody levels do not correlate with protection, although local antibody is believed to play a role. Adoptive transfer of IBV-infection-induced αβ T cells bearing CD8 antigen protected chicks from challenge infection. In conclusion, live attenuated IBV vaccines induce good, although short-lived, protection against homologous challenge, although a minority of individuals may respond poorly. Inactivated IBV vaccines are insufficiently efficacious when applied only once and in the absence of priming by live vaccine. Two applications of inactivated IBV are much more efficacious, although this is not a commercially viable proposition in the poultry industry. However, the cost and logistics of multiple application of a SARS inactivated vaccine would be more acceptable for the protection of human populations, especially if limited to targeted groups (e.g. health care workers and high-risk contacts). Application of a SARS vaccine is perhaps best limited to a minimal number of targeted individuals who can be monitored, as some vaccinated persons might, if infected by SARS coronavirus, become asymptomatic excretors of virus, thereby posing a risk to non-vaccinated people. Looking further into the future, the high efficacy of the fowl adenovirus vector expressing the IBV S1 subunit provides optimism for a live SARS vaccine, if that were deemed to be necessary, with the possibility of including the N protein gene. |
47 | 7pvigsy0 | what are the health outcomes for children who contract COVID-19? | Ethical decision-making for children with neuromuscular disorders in the COVID-19 crisis The sudden appearance and proliferation of COVID-19 has forced societies and governmental authorities across the world to confront the possibility of resource constraints when critical care facilities are overwhelmed by the sheer numbers of grievously ill patients. As governments and health care systems develop and update policies and guidelines regarding the allocation of resources, patients and families affected by chronic disabilities, including many neuromuscular disorders that affect children and young adults, have become alarmed at the possibility that they may be determined to have less favorable prognoses due to their underlying diagnoses and thus be assigned to lower priority groups. It is important for health care workers, policymakers, and government officials to be aware that the long term prognoses for children and young adults with neuromuscular disorders are often more promising than previously believed, due to a better understanding of the natural history of these diseases, benefits of multidisciplinary supportive care, and novel molecular therapies that can dramatically improve the disease course. Although the realities of a global pandemic have the potential to require a shift from our usual, highly individualistic standards of care to crisis standards of care, shifting priorities should nonetheless be informed by good facts. Resource allocation guidelines with the potential to affect children and young adults with neuromuscular disorders should take into account the known trajectory of acute respiratory illness in this population, and rely primarily on contemporary long-term outcome data. |
13 | wowiqi57 | what are the transmission routes of coronavirus? | Use of a modified ventilation mask to avoid aerosolizing spread of droplets for short endoscopic procedures during coronavirus COVID-19 outbreak |
34 | jhv8mtvn | What are the longer-term complications of those who recover from COVID-19? | Potentially irreversible olfactory and gustatory impairments in COVID-19: indolent vs. fulminant SARS-CoV-2 neuroinfection |
3 | qcgc2bo3 | will SARS-CoV2 infected people develop immunity? Is cross protection possible? | Design of a Novel Multi Epitope-Based Vaccine for Pandemic Coronavirus Disease (COVID-19) by Vaccinomics and Probable Prevention Strategy against Avenging Zoonotics The emergence and rapid expansion of the coronavirus disease (COVID-19) require the development of effective countermeasures especially a vaccine to provide active acquired immunity against the virus. This study presented a comprehensive vaccinomics approach applied to the complete protein data published so far in the National Center for Biotechnological Information (NCBI) coronavirus data hub. We identified non-structural protein 8 (Nsp8), 3C-like proteinase, and spike glycoprotein as potential targets for immune responses to COVID-19. Epitopes prediction illustrated both B-cell and T-cell epitopes associated with the mentioned proteins. The shared B and T-cell epitopes: DRDAAMQRK and QARSEDKRA of Nsp8, EDMLNPNYEDL and EFTPFDVVR of 3C-like proteinase, and VNNSYECDIPI of the spike glycoprotein are regions of high potential interest and have a high likelihood of being recognized by the human immune system. The vaccine construct of the epitopes shows stimulation of robust primary immune responses and high level of interferon gamma. Also, the construct has the best conformation with respect to the tested innate immune receptors involving vigorous molecular mechanics and solvation energy. Designing of vaccination strategies that target immune response focusing on these conserved epitopes could generate immunity that not only provide cross protection across Betacoronaviruses but additionally resistant to virus evolution. |
10 | tbpr30ic | has social distancing had an impact on slowing the spread of COVID-19? | Forecasting the effect of social distancing on COVID-19 autumn-winter outbreak in the metropolitan area of Buenos Aires. Forecasting the extent of the domestic health risk of epidemics by mathematical modeling is a useful tool for evaluating the feasibility of policies for controlling outbreaks. The objective of this study was to develop a time-dependent dynamic simulation model to forecast the COVID-19 autumn-winter outbreak in the metropolitan area of Buenos Aires, and to assess the effect of social distancing on epidemic spread. The model used was the "Susceptible-Exposed-Infectious-Recovered" framework which incorporated appropriate compartments relevant to interventions such as quarantine, isolation and treatment. In a low-intervention scenario including only 2-week isolation for international travelers and their contacts, the model estimated a maximum peak of nearly 90 000 symptomatic cases for early May. For an intervention scenario with mandatory quarantine during a 5-month period, the curve of cases flattened and receded as the proportion of quarantined individuals increased. The maximum peak was expected to appear between May 8 and Jul 8 depending on the quarantine strategy, and the average number of infectious symptomatic cases were 46 840, 30 494, 23 164, 16 179, and 13 196 when 10%, 20%, 30%, 40%, and 50% of the population remained in a 5-month-term continuous quarantine, respectively. Only mandatory quarantine was able to delay the maximum peak of infection and significantly reduce the total number of infected individuals and deaths at a 150-day term. The interruption of the quarantine before 120 days of its beginning could generate an even more serious outbreak 30 days later, and surpass the scarce medical resources available for the intensive care of critically-ill patients. |
7 | 9lswjro2 | are there serological tests that detect antibodies to coronavirus? | Development of an enzyme-linked immunosorbent assay for the monitoring and surveillance of antibodies to porcine epidemic diarrhea virus based on a recombinant membrane protein Abstract The recent dramatic increase in reported cases of porcine epidemic diarrhea (PED) in pig farms is a potential threat to the global swine industry. Therefore, the accurate diagnosis, serological monitoring, and surveillance of specific antibodies in pigs resulting from porcine epidemic diarrhea virus (PEDV) infection or vaccination would be essential in helping to control the spread of PED. We developed and validated an indirect enzyme-linked immunosorbent assay (ELISA) based on the recombinant membrane (M) protein of PEDV. To detect PEDV antibodies in eight herds, 382 serum samples were collected from sows that had been immunized with a PED vaccine, and screened using the developed ELISA in parallel with a serum neutralization (SN) assay. Of the tested samples, 276 were positive for the presence of PEDV antibodies according to both assays, while 98 were negative. An excellent agreement between the ELISA and the SN assay was observed (kappa=0.947; 95% confidence interval=0.910–0.984; McNemar's test, P =0.727). No cross-reaction was detected for the developed ELISA with other coronaviruses or other common pig pathogens. The developed ELISA could be used for serological evaluation and indirect diagnosis of PED infection. |
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