title: Real-Time Estimation of the Risk of Death from Novel Coronavirus (COVID-19) Infection: Inference Using Exported Cases

text: The exported cases of 2019 novel coronavirus (COVID-19) infection that were confirmed outside China provide an opportunity to estimate the cumulative incidence and confirmed case fatality risk (cCFR) in mainland China. Knowledge of the cCFR is critical to characterize the severity and understand the pandemic potential of COVID-19 in the early stage of the epidemic. Using the exponential growth rate of the incidence, the present study statistically estimated the cCFR and the basic reproduction number—the average number of secondary cases generated by a single primary case in a naïve population. We modeled epidemic growth either from a single index case with illness onset on 8 December 2019 (Scenario 1), or using the growth rate fitted along with the other parameters (Scenario 2) based on data from 20 exported cases reported by 24 January 2020. The cumulative incidence in China by 24 January was estimated at 6924 cases (95% confidence interval [CI]: 4885, 9211) and 19,289 cases (95% CI: 10,901, 30,158), respectively. The latest estimated values of the cCFR were 5.3% (95% CI: 3.5%, 7.5%) for Scenario 1 and 8.4% (95% CI: 5.3%, 12.3%) for Scenario 2. The basic reproduction number was estimated to be 2.1 (95% CI: 2.0, 2.2) and 3.2 (95% CI: 2.7, 3.7) for Scenarios 1 and 2, respectively. Based on these results, we argued that the current COVID-19 epidemic has a substantial potential for causing a pandemic. The proposed approach provides insights in early risk assessment using publicly available data.


title: Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province

text: BACKGROUND: A novel coronavirus (2019-nCoV) causing an outbreak of pneumonia in Wuhan, Hubei province of China was isolated in January 2020. This study aims to investigate its epidemiologic history, and analyze the clinical characteristics, treatment regimens, and prognosis of patients infected with 2019-nCoV during this outbreak. METHODS: Clinical data from 137 2019-nCoV-infected patients admitted to the respiratory departments of the respiratory departments of nine tertiary hospitals in Hubei province from December 30, 2019 to January 24, 2020 were retrospectively collected, including general status, clinical manifestations, laboratory test results, imaging characteristics, and treatment regimens. RESULTS: None of the 137 patients (61 males, 76 females, aged 20–83 years, median age 57 years) had a definite history of exposure to Huanan Seafood Wholesale Market. Major initial symptoms included fever (112/137, 81.8%), coughing (66/137, 48.2%), and muscle pain or fatigue (44/137, 32.1%), with other, less typical initial symptoms observed at low frequency, including heart palpitations, diarrhea, and headache. Nearly 80% of the patients had normal or decreased white blood cell counts, and 72.3% (99/137) had lymphocytopenia. Lung involvement was present in all cases, with most chest computed tomography scans showing lesions in multiple lung lobes, some of which were dense; ground-glass opacity co-existed with consolidation shadows or cord-like shadows. Given the lack of effective drugs, treatment focused on symptomatic and respiratory support. Immunoglobulin G was delivered to some critically ill patients according to their conditions. Systemic corticosteroid treatment did not show significant benefits. Notably, early respiratory support facilitated disease recovery and improved prognosis. The risk of death was primarily associated with age, underlying chronic diseases, and median interval from the appearance of initial symptoms to dyspnea. CONCLUSIONS: The majority of patients with 2019-nCoV pneumonia present with fever as the first symptom, and most of them still showed typical manifestations of viral pneumonia on chest imaging. Middle-aged and elderly patients with underlying comorbidities are susceptible to respiratory failure and may have a poorer prognosis.


title: Five Challenges When Managing Mass Casualty or Disaster Situations: A Review Study

text: Background: Managing mass casualty or disaster incidents is challenging to any person or organisation. Therefore, this paper identifies and describes common challenges to managing such situations, using case and lessons learned reports. It focuses on sudden onset, man-made or technologically caused mass casualty or disaster situations. Methods: A management review was conducted based on a structured search in the PubMed and Web of Science databases. Results: The review included 20 case—and lessons learned reports covering natural disasters, man-made events, and accidents across Europe, the United States of Amerika (USA), Asia and the Middle East. Five common challenges were identified: (1) to identify the situation and deal with uncertainty, (2) to balance the mismatch between the contingency plan and the reality, (3) to establish a functional crisis organization, (4) to adapt the medical response to the actual and overall situation and (5) to ensure a resilient response. Conclusions: The challenges when managing mass casualty or disaster events involved were mainly related to the ability to manage uncertainty and surprising situations, using structured processes to respond. The ability to change mind set, organization and procedures, both from an organizational- and individual perspective, was essential. Non-medical factors and internal factors influenced the medical management. In order to respond in an effective, timely and resilient way, all these factors should be taken into consideration.


title: Corona Virus (COVID-19) “Infodemic” and Emerging Issues through a Data Lens: The Case of China

text: Coronavirus (COVID-19) is a humanitarian emergency, which started in Wuhan in China in early December 2019, brought into the notice of the authorities in late December, early January 2020, and, after investigation, was declared as an emergency in the third week of January 2020. The WHO declared this as Public Health Emergency of International Concern (PHEIC) on 31th of January 2020, and finally a pandemic on 11th March 2020. As of March 24th, 2020, the virus has caused a casualty of over 16,600 people worldwide with more than 380,000 people confirmed as infected by it, of which more than 10,000 cases are serious. Mainly based on Chinese newspapers, social media and other digital platform data, this paper analyzes the timeline of the key actions taken by the government and people over three months in five different phases. It found that although there was an initial delay in responding, a unique combination of strong governance, strict regulation, strong community vigilance and citizen participation, and wise use of big data and digital technologies, were some of the key factors in China’s efforts to combat this virus. Being inviable and non-measurable (unlike radioactive exposure), appropriate and timely information is very important to form the basic foundation of mitigation and curative measures. Infodemic, as it is termed by WHO, is a key word, where different stakeholder’s participation, along with stricter regulation, is required to reduce the impact of fake news in this information age and social media. Although different countries will need different approaches, focusing on its humanitarian nature and addressing infodemic issues are the two critical factors for future global mitigation efforts.


title: Temporal Relationship of Viral Load, Ribavirin, Interleukin (IL)—6, IL-8, and Clinical Progression in Patients with Severe Acute Respiratory Syndrome

text: Although viral replication and overwhelming immune responses are believed to contribute to the progression of severe acute respiratory syndrome (SARS), little is known about the temporal relationship between viral load, ribavirin, proinflammatory cytokines, and clinical progression. We report that ribavirin was not effective in reducing the SARS coronavirus load in 3 of 8 probable cases studied and that elevated levels of interleukin (IL)—6 and IL-8 subsequent to the peak viral load were found in 8 and 6 cases, respectively. The nadir lymphocyte count during lymphopenia, the peak level of lactate dehydrogenase, and the peak density of pulmonary infiltrates lag further behind the peak viral load by a median of 4, 5, and 3.5 days, respectively. These findings provide important information for therapeutic strategies to treat SARS.


docid: crmlsbpo

title: Biological cryo‐electron microscopy in China

text: Cryo‐electron microscopy (cryo‐EM) plays an increasingly more important role in structural biology. With the construction of an arm of the Chinese National Protein Science Facility at Tsinghua University, biological cryo‐EM has entered a phase of rapid development in China. This article briefly reviews the history of biological cryo‐EM in China, describes its current status, comments on its impact on the various biological research fields, and presents future outlook.


title: Liquorice Health Check, Oro-Dental Implications, and a Case Report

text: Liquorice has an active substance, Glycyrrhizin which inhibits the conversion of precursor cortisol to cortisone by inhibiting the enzyme 11-betahydroxysteroid dehydrogenase. When imbibed, liquorice acts like hyperaldosteronism which presents with typical symptoms including high blood pressure, low blood potassium, and muscle pain and weakness. This article appraises physiological and pharmacological effects on health of liquorice, critiques products containing liquorice, describes a typical case report of liquorice-induced hypertension, and appraises oral effects from consumption of liquorice products.


title: SARS-CoV-2 in the environment: Modes of transmission, early detection and potential role of pollutions

text: Abstract The coronavirus disease 2019 (COVID-19) is spreading globally having a profound effect on lives of millions of people, causing worldwide economic disruption. Curbing the spread of COVID-19 and future pandemics may be accomplished through understanding the environmental context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and adoption of effective detection tools and mitigation policies. This article aims to examine the latest investigations on SARS-CoV-2 plausible environmental transmission modes, employment of wastewater surveillance for early detection of COVID-19, and elucidating the role of solid waste, water, and atmospheric quality on viral infectivity. Transmission of SARS-CoV-2 via faecal-oral or bio-aerosols lacks robust evidence and remains debatable. However, improper disinfection and defected plumbing systems in indoor environments such as hospitals and high-rise towers may facilitate the transport of virus-laden droplets of wastewater causing infection. Clinical and epidemiological studies are needed to present robust evidence that SARS-CoV-2 is transmissible via aerosols, though quantification of virus-laden aerosols at low concentrations presents a challenge. Wastewater surveillance of SARS-CoV-2 can be an effective tool in early detection of outbreak and determination of COVID-19 prevalence within a population, complementing clinical testing and providing decision makers guidance on restricting or relaxing movement. While poor air quality increases susceptibility to diseases, evidence for air pollution impact on COVID-19 infectivity is not available as infections are dynamically changing worldwide. Solid waste generated by households with infected individuals during the lockdown period may facilitate the spread of COVID-19 via fomite transmission route but has received little attention from the scientific community. Water bodies receiving raw sewage may pose risk of infection but this has not been investigated to date. Overall, our understanding of the environmental perspective of SARS-CoV-2 is imperative to detecting outbreak and predicting pandemic severity, allowing us to be equipped with the right tools to curb any future pandemic.


title: Wet Markets and Food Safety: TripAdvisor for Improved Global Digital Surveillance

text: BACKGROUND: Wet markets are markets selling fresh meat and produce. Wet markets are critical for food security and sustainable development in their respective regions. Due to their cultural significance, they attract numerous visitors and consequently generate tourist-geared information on the Web (ie, on social networks such as TripAdvisor). These data can be used to create a novel, international wet market inventory to support epidemiological surveillance and control in such settings, which are often associated with negative health outcomes. OBJECTIVE: Using social network data, we aimed to assess the level of wet markets’ touristic importance on the Web, produce the first distribution map of wet markets of touristic interest, and identify common diseases facing visitors in these settings. METHODS: A Google search was performed on 31 food market–related keywords, with the first 150 results for each keyword evaluated based on their relevance to tourism. Of all these queries, wet market had the highest number of tourism-related Google Search results; among these, TripAdvisor was the most frequently-occurring travel information aggregator, prompting its selection as the data source for this study. A Web scraping tool (ParseHub) was used to extract wet market names, locations, and reviews from TripAdvisor. The latter were searched for disease-related content, which enabled assignment of GeoSentinel diagnosis codes to each. This syndromic categorization was overlaid onto a mapping of wet market locations. Regional prevalence of the most commonly occurring symptom group - food poisoning - was then determined (ie, by dividing the number of wet markets per continent with more than or equal to 1 review containing this syndrome by the total number of wet markets on that continent with syndromic information). RESULTS: Of the 1090 hits on TripAdvisor for wet market, 36.06% (393/1090) conformed to the query’s definition; wet markets were heterogeneously distributed: Asia concentrated 62.6% (246/393) of them, Europe 19.3% (76/393), North America 7.9% (31/393), Oceania 5.1% (20/393), Africa 3.1% (12/393), and South America 2.0% (8/393). Syndromic information was available for 14.5% (57/393) of wet markets. The most frequently occurring syndrome among visitors to these wet markets was food poisoning, accounting for 54% (51/95) of diagnoses. Cases of this syndrome were identified in 56% (22/39) of wet markets with syndromic information in Asia, 71% (5/7) in Europe, and 71% (5/7) in North America. All wet markets in South America and Oceania reported food poisoning cases, but the number of reviews with syndromic information was very limited in these regions (n=2). CONCLUSIONS: The map produced illustrates the potential role of touristically relevant social network data to support global epidemiological surveillance. This includes the possibility to approximate the global distribution of wet markets and to identify diseases (ie, food poisoning) that are most prevalent in such settings.


title: Infección en el trasplante de pulmón

text: Actualmente, el trasplante de pulmón se considera un tratamiento válido para un buen número de pacientes con insuficiencia respiratoria grave. De todas formas, las complicaciones son muy frecuentes y pueden llevar a fracaso del injerto a medio y largo plazo y menor supervivencia. De acuerdo con el registro de la International Society for Heart and Lung Transplantation, las tasas de supervivencia al primer, segundo y quinto año fueron, en 2006, del 74, 65 y 47%, respectivamente. El principal obstáculo para el éxito a largo plazo del trasplante de pulmón es el rechazo crónico, caracterizado histológicamente como bronquiolitis obliterante, que acontece en cerca de dos terceras partes de los pacientes. Uno de los factores más importantes para el desarrollo de bronquiolitis obliterante, además del número de rechazos agudos, es la infección y la enfermedad por citomegalovirus (CMV). Recientemente, se ha destacado el papel de la infección por diferentes virus respiratorios como factores de riesgo para el desarrollo de rechazo crónico en receptores de un trasplante de pulmón. Las complicaciones infecciosas son una causa frecuente de morbimortalidad en este tipo de pacientes, y la causa de muerte de cerca de la mitad de ellos. La infección bacteriana es la complicación más frecuente de un receptor de un trasplante de pulmón. Del total, el 35-66% son bacterianas y el 50-85% de los pacientes presentan como mínimo un episodio de infección bacteriana. La segunda causa más frecuente de infección, después de la bacteriana, es la infección por CMV. A pesar de utilizar diferentes estrategias de prevención, la incidencia sigue siendo elevada, y se sitúa alrededor del 7% el primer año postrasplante. Es el único tipo de trasplante de órgano sólido en el cual la etiología más frecuente de la infección fúngica es Aspergillus spp., a diferencia del resto, en que típicamente se deben a Candida spp. La incidencia de aspergilosis invasora se cifra en alrededor del 4%. Lung transplantation is now considered an established therapeutic option for patients with severe respiratory failure. Nevertheless, complications are frequent and can lead to intermediate- or long-term graft dysfunction and decreased survival. According to the registry of the International Society for Heart and Lung Transplantation, survival rates in these patients at one, two, and five years are 74%, 65%, and 47%, respectively. The main obstacle to long-term success of lung transplantation, however, is chronic rejection, which is characterized histologically as bronchiolitis obliterans and occurs in up to two-thirds of patients. One of the most important risk factors for the development of bronchiolitis obliterans, in addition to the number of previous acute rejection episodes and the incidence of persistent rejection, is cytomegalovirus infection and disease. Moreover, recent evidence has indicated a role for respiratory viruses as risk factors for the development of chronic rejection in lung transplant recipients. Infectious complications are a frequent cause of morbidity and mortality in these patients and are the cause of death in nearly half of them. Bacterial infection is the most frequent infectious complication in lung transplant patients. Among the total of infections, 35%-66% are bacterial and 50%-85% of patients present at least one episode. CMV is the second most frequent cause of infectious complications following lung transplantation. Despite the use of various preventive strategies, the risk of developing CMV disease in lung transplant recipients is over 5% during the first year. This is the only type of solid organ transplant in which the etiology of fungal infection is characteristically Aspergillus spp., in contrast to others in which infection by Candida spp. is most common. The incidence of invasive aspergillosis is about 4%.


title: Factors Influencing Emergency Nurses' Burnout During an Outbreak of Middle East Respiratory Syndrome Coronavirus in Korea

text: Summary Purpose Emergency department (ED) nurses suffer from persistent stress after experiencing the traumatic event of exposure to Middle East respiratory syndrome coronavirus (MERS-CoV), which can subsequently lead to burnout. This study aimed to assess ED nurses' burnout level during an outbreak of MERS-CoV and to identify influencing factors in order to provide basic information for lowering and preventing the level of burnout. Methods Study participants were ED nurses working in eight hospitals designated for treating MERS-CoV-infected patients in Korea. We performed multiple regression analysis to explore the factors influencing burnout. Results The ED nurses' burnout was affected by job stress (β=0.59, p <.001), poor hospital resources for the treatment of MERS-CoV (β = −0.19, p <.001) and poor support from family and friends (β = −0.14, p <.05). These three variables explained 47.3% of the variance in burnout. Conclusions ED nurses taking care of MERS-CoV-infected patients should be aware that burnout is higher for nurses in their divisions than nurses in other hospital departments and that job stress is the biggest influential factor of burnout. To be ready for the outbreak of emerging contagious diseases such as MERS-CoV, efforts and preparations should be made to reduce burnout. Job stress should be managed and resolved. Working conditions for mitigating job stress and systematic stress management programs should be provided, and hospital resources for the treatment of MERS-CoV need to be reinforced. Moreover, promoting support from family and friends is required.


Weaponized Interdependence: China's Economic Statecraft and Social Penetration against Taiwan


title: Chapter 7 Long-Term Virus Evolution in Nature

text: Abstract Viruses spread to give rise to epidemics and pandemics, and some key parameters that include virus and host population numbers determine virus persistence or extinction in nature. Viruses evolve at different rates of evolution depending on the polymerase copying fidelity during genome replication. Calculated rates of evolution in nature vary depending on the time interval between virus isolations. In particular, intra-host evolution is generally more rapid that inter-host evolution and several possible mechanisms for this difference are considered. The mechanisms by which the error-prone viruses evolve render very unlikely the operation of a molecular clock (constant rate of incorporation of mutations in the evolving genomes). Several computational methods are reviewed that permit the alignment of viral sequences and the establishment of phylogenetic relationships among viruses. The evolution of virus in the form of dynamic mutant clouds in each infected individual, together with multiple environmental influences, render the emergence and reemergence of viral pathogens an unpredictable event, another example of biological complexity.


Shifting sands—Molecular coronavirus testing during a time of inconsistent resources


title: HIV-1 and Human PEG10 Frameshift Elements Are Functionally Distinct and Distinguished by Novel Small Molecule Modulators

text: Frameshifting during translation of viral or in rare cases cellular mRNA results in the synthesis of proteins from two overlapping reading frames within the same mRNA. In HIV-1 the protease, reverse transcriptase, and integrase enzymes are in a second reading frame relative to the structural group-specific antigen (gag), and their synthesis is dependent upon frameshifting. This ensures that a strictly regulated ratio of structural proteins and enzymes, which is critical for HIV-1 replication and viral infectivity, is maintained during protein synthesis. The frameshift element in HIV-1 RNA is an attractive target for the development of a new class of anti HIV-1 drugs. However, a number of examples are now emerging of human genes using −1 frameshifting, such as PEG10 and CCR5. In this study we have compared the HIV-1 and PEG10 frameshift elements and shown they have distinct functional characteristics. Frameshifting occurs at several points within each element. Moreover, frameshift modulators that were isolated by high-throughput screening of a library of 114,000 lead-like compounds behaved differently with the PEG10 frameshift element. The most effective compounds affecting the HIV-1 element enhanced frameshifting by 2.5-fold at 10 μM in two different frameshift reporter assay systems. HIV-1 protease:gag protein ratio was affected by a similar amount in a specific assay of virally-infected cultured cell, but the modulation of frameshifting of the first-iteration compounds was not sufficient to show significant effects on viral infectivity. Importantly, two compounds did not affect frameshifting with the human PEG10 element, while one modestly inhibited rather than enhanced frameshifting at the human element. These studies indicate that frameshift elements have unique characteristics that may allow targeting of HIV-1 and of other viruses specifically for development of antiviral therapeutic molecules without effect on human genes like PEG10 that use the same generic mechanism.


docid: ychvxsxn

title: Synthetic biology: From the first synthetic cell to see its current situation and future development

text: Synthetic biology is an emerging field, which, since its birth, has shown great value and potential in many fields including medicine, energy, environment and agriculture. It is also important for the study of the origin and evolution of life. Since the publication of the first synthetic cell in May, 2010, synthetic biology again attracts high attention and leads to extensive discussions all over the world. There have been a number of researches and achievements on synthetic biology in the United States and European countries. While in China, so far there is no systematic research on synthetic biology. In order to promote the development of this new discipline in China, we organized this review to systematically introduce the concept and research content of synthetic biology, summarize the achievements, and investigate the current situation in both China and abroad. We also analyzed the opportunities and challenges in synthetic biology, and looked forward to the future development of synthetic biology, especially its future development in China.


title: Diagnostic electron microscopy is still a timely and rewarding method

text: Abstract Background: Parallel to its technical development starting in the 1930s, electron microscopy (EM) became an important tool in basic and clinical virology. First utilized in the rapid diagnosis of smallpox, it developed to a diagnostic routine in the early 1960s using the negative staining technique. EM was applied to infected cell-cultures and also to ‘dirty’ specimens including urine, feces, vesicle fluid, liquor. With the implementation of molecular biological and genetic techniques, the use of diagnostic EM decreased. Objectives: (1) To give a perspective on future indications and possible uses by discussing the past and the present of diagnostic EM, (2) To describe the system of External Quality Assessment on EM virus diagnosis (EQA-EMV) established in 1994 by our laboratory and its achievements. Study design: EQA-EMV is run to evaluate, to confirm and to improve the quality of diagnostic EM. Two different types of specimen are sent out: (1) prepared grids to assess and train the diagnostic skills of the participants, (2) stabilized virus particle suspensions to assess preparation efficiency. Results: Diagnostic EM differs from other diagnostic tests in its rapidity and its undirected ‘open view’. To emphasize these advantages, the indications for diagnostic EM are discussed, fundamental for a continuing future adaptation. Besides appropriate techniques, quality control measures are required to achieve and keep high diagnostic standards. The results from 6 years of EQA-EMV are presented. Conclusions: In the history of diagnostic EM in virology, a change in use has been seen. Starting in the 1990s and coincident with the broad introduction of ‘modern’ diagnostic techniques, the number of EM diagnostic labs has decreased considerably—in spite of the obvious advantages of this technique. To guarantee the continuing performance of diagnostic EM in the future, EQA runs have to be performed as with other techniques in the diagnostic armament. The growing number of participants and participating countries indicates an interest in as well as a need for this program.


title: Adaptive Evolution of MERS-CoV to Species Variation in DPP4

text: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) likely originated in bats and passed to humans through dromedary camels; however, the genetic mechanisms underlying cross-species adaptation remain poorly understood. Variation in the host receptor, dipeptidyl peptidase 4 (DPP4), can block the interaction with the MERS-CoV spike protein and form a species barrier to infection. To better understand the species adaptability of MERS-CoV, we identified a suboptimal species-derived variant of DPP4 to study viral adaption. Passaging virus on cells expressing this DPP4 variant led to accumulation of mutations in the viral spike which increased replication. Parallel passages revealed distinct paths of viral adaptation to the same DPP4 variant. Structural analysis and functional assays showed that these mutations enhanced viral entry with suboptimal DPP4 by altering the surface charge of spike. These findings demonstrate that MERS-CoV spike can utilize multiple paths to rapidly adapt to novel species variation in DPP4.


docid: xwqhaaij

title: The role and response of palliative care and hospice services in epidemics and pandemics: a rapid review to inform practice during the COVID-19 pandemic

text: Abstract Cases of COVID-19 are escalating rapidly across the globe, with the mortality risk being especially high among those with existing illness and multimorbidity. This study aimed to synthesise evidence for the role and response of palliative care and hospice teams to viral epi/pandemics, to inform the COVID-19 pandemic response. We conducted a rapid systematic review according to PRISMA guidelines in five databases. Of 3094 papers identified, ten were included in this narrative synthesis. Included studies were from West Africa, Taiwan, Hong Kong, Singapore, the United States and Italy. All had an observational design. Findings were synthesised using a previously proposed framework according to ‘systems’ (policies, training and protocols, communication and coordination, data), ‘staff’ (deployment, skill mix, resilience), ‘space’ (community provision, use of technology) and ‘stuff’ (medicines and equipment, personal protective equipment). We conclude that hospice and palliative services have an essential role in the response to COVID-19 by: 1) responding rapidly and flexibly; 2) ensuring protocols for symptom management are available, and training non-specialists in their use; 3) being involved in triage; 4) considering shifting resources into the community; 5) considering redeploying volunteers to provide psychosocial and bereavement care; 6) facilitating camaraderie among staff and adopt measures to deal with stress; 7) using technology to communicate with patients and carers; 8) adopting standardised data collection systems to inform operational changes and improve care.


title: Coronavirus disease 2019 in elderly patients: Characteristics and prognostic factors based on 4-week follow-up

text: Summary Objective To investigate the characteristics and prognostic factors in the elderly patients with COVID-19. Methods Consecutive cases over 60 years old with COVID-19 in Renmin Hospital of Wuhan University from Jan 1 to Feb 6, 2020 were included. The primary outcomes were death and survival till March 5. Data of demographics, clinical features, comorbidities, laboratory tests and complications were collected and compared for different outcomes. Cox regression was performed for prognostic factors. Results 339 patients with COVID-19 (aged 71±8 years,173 females (51%)) were enrolled, including 80 (23.6%) critical, 159 severe (46.9%) and 100 moderate (29.5%) cases. Common comorbidities were hypertension (40.8%), diabetes (16.0%) and cardiovascular disease (15.7%). Common symptoms included fever (92.0%), cough (53.0%), dyspnea (40.8%) and fatigue (39.9%). Lymphocytopenia was a common laboratory finding (63.2%). Common complications included bacterial infection (42.8%), liver enzyme abnormalities (28.7%) and acute respiratory distress syndrome (21.0%). Till Mar 5, 2020, 91 cases were discharged (26.8%), 183 cases stayed in hospital (54.0%) and 65 cases (19.2%) were dead. Shorter length of stay was found for the dead compared with the survivors (5 (3–8) vs. 28 (26–29), P < 0.001). Symptoms of dyspnea (HR 2.35, P = 0.001), comorbidities including cardiovascular disease (HR 1.86, P = 0.031) and chronic obstructive pulmonary disease (HR 2.24, P = 0.023), and acute respiratory distress syndrome (HR 29.33, P < 0.001) were strong predictors of death. And a high level of lymphocytes was predictive of better outcome (HR 0.10, P < 0.001). Conclusions High proportion of severe to critical cases and high fatality rate were observed in the elderly COVID-19 patients. Rapid disease progress was noted in the dead with a median survival time of 5 days after admission. Dyspnea, lymphocytopenia, comorbidities including cardiovascular disease and chronic obstructive pulmonary disease, and acute respiratory distress syndrome were predictive of poor outcome. Close monitoring and timely treatment should be performed for the elderly patients at high risk.


title: A Game Change in Global Health: The Best Is Yet to Come

text: Health will continue to gather strength as a global public domain if it links itself strategically with other transnational agendas and strengthens its political ability to produce global public goods for health. Three new political spaces offer opportunities to take the global health agenda a significant step forward: the emerging new development paradigm, the post-2015 debates at the United Nations and the dynamics created through the increasing trans-border health challenges the World Health Organization (WHO) must deal with under conditions of globalization. Presently there are concerns whether the major initiatives that have boosted global health in the last 20 years will continue to grow and attract sufficient funding. But the more pertinent question is whether they are still suited to address the major concerns global health faces between now and 2030. In addition many of the global health challenges can only be addressed through actions in sectors other than health and by facing the inherently political nature of health as well as strong opposition from parts of the private sector. A well-financed and rules based governance system — adapted to complex multilateralism — is needed to manage, complement and integrate the many issue-based initiatives. The next era of global health will be judged by its political capacity to ensure global health security, build universal health coverage, address the commercial determinants of non-communicable diseases and reduce global health inequalities. This will require a focus on producing global public goods for health (GPGH) through strong international organizations, in particular the WHO, supported by governments who have the political will and the institutional capacity to practice smart sovereignty, reach beyond the heath sector and engage with non-state actors.


Préconisations cardiologiques lors de l’utilisation d’un traitement pouvant entraîner des troubles conductifs ou un allongement de l’intervalle QT dans le COVID-19


docid: luhtkxln

title: International Social Work Student Exchanges

text: Abstract This article identifies the goals, orientation, planning, and outcomes of international social work student exchanges. It argues that cross-cultural communication is a key skill developed by an exchange. The value base proposed includes belief in global interdependence, a willingness to scrutinize the history of student national and cultural identity, and commitment to evaluation. The knowledge base includes human rights, the history of social and economic development, and models of assessment and social justice.


Please cite this paper as: Esposito et al. (2012) Impact of viral infections in children with community‐acquired pneumonia: results of a study of 17 respiratory viruses. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2012.00340.x. Background Little is known about the prevalence of viral infections in children with community‐acquired pneumonia (CAP). Objectives To describe the clinical and virological data collected from children with radiographically confirmed CAP in whom 17 respiratory viruses were sought in respiratory secretion samples during the acute phase of the disease. Patients and methods The study involved 592 children with radiographically confirmed CAP whose respiratory secretion samples were tested using the Luminex xTAG Respiratory Virus Panel Fast assay, which simultaneously detects influenza A virus, influenza B virus, respiratory syncytial virus (RSV)‐A and ‐B, parainfluenzavirus‐1, ‐2, ‐3, and ‐4, adenovirus, human metapneumovirus, coronaviruses 229E, NL63, OC43, and HKU1, enterovirus/rhinovirus, and bocavirus. A real‐time PCR assay was used to identify the rhinovirus in the enterovirus/rhinovirus‐positive samples. Results A total of 435 children (73·5%) were positive for at least one virus: the most frequently detected was RSV, which was found in 188 (31·7%), followed by rhinovirus (n = 144, 24·3%), bocavirus (n = 60, 10·1%), influenza viruses (n = 57, 9·6), and hMPV (n = 49, 8·2%). Viral co‐infections were found in 117 children (19·7% of the enrolled children; 26·9% of those with viral infections). Marginal differences were found between the infections owing to a single virus. Co‐infections showed radiographic evidence of alveolar pneumonia significantly more frequently than single infections (OR 1·72, 95% CI 1·05–2·81). Conclusions The findings of this study highlight the importance of respiratory viruses (mainly RSV and rhinovirus) in children with CAP and show the characteristics of both the single infections and co‐infections associated with the disease.


title: Corticosteroids, but not TNF Antagonists, are Associated with Adverse COVID-19 Outcomes in Patients With Inflammatory Bowel Diseases: Results from an International Registry

text: Background and Aims The impact of Coronavirus disease 2019 (COVID-19) on patients with inflammatory bowel disease (IBD) is unknown. We sought to characterize the clinical course of COVID-19 among IBD patients and evaluate the association between demographics, clinical characteristics, and immunosuppressant treatments on COVID-19 outcomes. Methods Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is a large, international registry created to monitor outcomes of IBD patients with confirmed COVID-19. We calculated age-standardized mortality ratios (SMRs) and utilized multivariable logistic regression to identify factors associated with severe COVID-19, defined as intensive care unit admission, ventilator use, and/or death. Results 525 cases from 33 countries were reported (Median age 43 years, 53% men). Thirty-seven patients (7%) had severe COVID-19, 161 (31%) were hospitalized, and 16 patients died (3% case fatality rate). SMRs for IBD patients were 1.8 (95% confidence interval [CI] 0.9-2.6), 1.5 (95% CI 0.7-2.2), and 1.7 (95% CI 0.9-2.5) relative to data from China, Italy, and the US, respectively. Risk factors for severe COVID-19 among IBD patients included increasing age (adjusted odds ratio [aOR] 1.04, 95% CI 1.01-1.02), ≥2 comorbidities (aOR 2.9, 95% CI 1.1-7.8), systemic corticosteroids (aOR 6.9, 95% CI 2.3-20.5), and sulfasalazine or 5-aminosalicylate use (aOR 3.1, 95% CI 1.3-7.7). TNF antagonist treatment was not associated with severe COVID-19 (aOR 0.9, 95% CI 0.4-2.2). Conclusions Increasing age, comorbidities, and corticosteroids are associated with severe COVID-19 among IBD patients, although a causal relationship cannot be definitively established. Notably, TNF antagonists do not appear to be associated with severe COVID-19.


docid: anaqgzvi

title: Characterization of SARS-CoV-specific memory T cells from recovered individuals 4 years after infection

text: SARS-CoV infection of human results in antigen-specific cellular and humoral immune responses. However, it is critical to determine whether SARS-CoV-specific memory T cells can persist for long periods of time. In this study, we analyzed the cellular immune response from 21 SARS-recovered individuals who had been diagnosed with SARS in 2003 by using ELISA, CBA, ELISpot and multiparameter flow cytometry assays. Our results demonstrated that low levels of specific memory T cell responses to SARS-CoV S, M, E and N peptides were detected in a proportion of SARS-recovered patients, and IFN-γ was the predominant cytokine produced by T cells after stimulation with peptides. Cytometry analysis indicated that the majority of memory CD8(+) T cells produced IFN-γ, whereas memory CD4(+) T cells produced IFN-γ, IL-2 or TNF-α. These results might provide valuable information on the cellular immune response in recovered SARS-CoV patients for the rational design of vaccines against SARS-CoV infection.


title: Pulmonary High-Resolution Computed Tomography (HRCT) Findings of Patients with Early-Stage Coronavirus Disease 2019 (COVID-19) in Hangzhou, China

text: BACKGROUND: The aim of this study was to investigate the imaging manifestations of early-stage coronavirus disease 2019 (COVID-19) and to provide imaging basis for early detection of suspected cases and stratified intervention. MATERIAL/METHODS: From 20 January 2020 to 2 February 2020, 6 patients diagnosed with COVID-19, including 1 male and 5 females, were retrospectively reviewed in Zhejiang Hospital. These cases were clinically assessed and classified as common COVID-19. All patients underwent thoracic high-resolution computed tomography (HRCT) within 2 days after the onset of symptoms, and their images were viewed by 2 radiologists who were blind to their clinical records. RESULTS: CT images of 6 confirmed patients were collected. Two of the 6 patients (33.3%) had bilateral lung involvements and 4 (66.7%) had single-lung involvement. Two cases (33.3%) had a single lesion, 2 cases (33.3%) had 2 lesions, and 2 cases (33.3%) had multiple lesions. There were 2 cases (33.3%) with focal subpleural distribution and 1 case (16.7%) along the bronchial vascular bundle. Five cases (83.3%) had ground-glass opacities, 4 cases (66.7%) had ground-glass nodules, 1 case (16.7%) had thickened lobular septum, 2 cases (33.3%) had thickened bronchial wall, 2 cases (33.3%) had halo sign, 1 case (16.7%) had crazy-paving sign, and 1 case (16.7%) had tree-in-bud sign. CONCLUSIONS: The imaging manifestations of early-stage COVID-19 are relatively mild, and the imaging findings of some patients are not typical, which can easily lead to missed diagnoses. Thus, suspected cases need to be closely monitored, and epidemiological history and clinical laboratory examination should also be considered during diagnosis.


title: In Silico Modeling in Infectious Disease

text: Infectious disease has witnessed the emergence of mathematical modeling a tool of synthesizing data of growing complexity now available to clinicians and basic scientists alike. The purpose of this review is to introduce mathematical tools commonly used to model infectious disease. We will illustrate the use of equation-based, agent-based or statistical modeling approaches to a variety of examples pertaining to acute inflammation, bacterial dynamics, viral dynamics, and signaling pathways, focusing of host-pathogen interactions rather than population models. We will discuss the strengths and weaknesses of these approaches and offer future perspectives for this rapidly evolving field. Section editor: Trevor Trust – AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA


title: Clustering model for transmission of the SARS virus: application to epidemic control and risk assessment

text: Abstract We propose a new four state model for disease transmission and illustrate the model with data from the 2003 SARS epidemic in Hong Kong. The critical feature of this model is that the community is modelled as a small-world network of interconnected nodes. Each node is linked to a fixed number of immediate neighbors and a random number of geographically remote nodes. Transmission can only propagate between linked nodes. This model exhibits two features typical of SARS transmission: geographically localized outbreaks and “super-spreaders”. Neither of these features are evident in standard susceptible-infected-removed models of disease transmission. Our analysis indicates that “super-spreaders” may occur even if the infectiousness of all infected individuals is constant. Moreover, we find that nosocomial transmission in Hong Kong directly contributed to the severity of the outbreak and that by limiting individual exposure time to 3–5 days the extent of the SARS epidemic would have been minimal.


title: Convalescent plasma to treat coronavirus disease 2019 (COVID‐19): considerations for clinical trial design

text: Case series studying convalescent plasma use in the treatment of COVID‐19 have been promising, but additional, high‐quality studies are needed to determine the efficacy of the treatment when applied for prophylaxis, for early phases of illness, and for severe illness. Previous studies of convalescent plasma in treating other viral diseases have identified factors to consider when designing treatment protocols, including timing of administration relative to onset of illness, timing of donation relative to resolution of symptoms, severity of illness of the donor, pretransfusion serology of the recipient, and antibody titers of the donor. There are many clinical trials studying treatment of, and prophylaxis against, COVID‐19 using convalescent plasma. In addition to clinical trials, the FDA also allows treatment through two other pathways: the “Expanded Access to Convalescent Plasma for the Treatment of Patients with COVID‐19” protocol, and emergency investigational new drug applications. The FDA also provides criteria for donation of convalescent plasma.


title: Air and environmental sampling for SARS-CoV-2 around hospitalized patients with coronavirus disease 2019 (COVID-19)

text: BACKGROUND: The role of severe respiratory coronavirus virus 2 (SARS-CoV-2)–laden aerosols in the transmission of coronavirus disease 2019 (COVID-19) remains uncertain. Discordant findings of SARS-CoV-2 RNA in air samples were noted in early reports. METHODS: Sampling of air close to 6 asymptomatic and symptomatic COVID-19 patients with and without surgical masks was performed with sampling devices using sterile gelatin filters. Frequently touched environmental surfaces near 21 patients were swabbed before daily environmental disinfection. The correlation between the viral loads of patients’ clinical samples and environmental samples was analyzed. RESULTS: All air samples were negative for SARS-CoV-2 RNA in the 6 patients singly isolated inside airborne infection isolation rooms (AIIRs) with 12 air changes per hour. Of 377 environmental samples near 21 patients, 19 (5.0%) were positive by reverse-transcription polymerase chain reaction (RT-PCR) assay, with a median viral load of 9.2 × 10(2) copies/mL (range, 1.1 × 10(2) to 9.4 × 10(4) copies/mL). The contamination rate was highest on patients’ mobile phones (6 of 77, 7.8%), followed by bed rails (4 of 74, 5.4%) and toilet door handles (4 of 76, 5.3%). We detected a significant correlation between viral load ranges in clinical samples and positivity rate of environmental samples (P < .001). CONCLUSION: SARS-CoV-2 RNA was not detectable by air samplers, which suggests that the airborne route is not the predominant mode of transmission of SARS-CoV-2. Wearing a surgical mask, appropriate hand hygiene, and thorough environmental disinfection are sufficient infection control measures for COVID-19 patients isolated singly in AIIRs. However, this conclusion may not apply during aerosol-generating procedures or in cohort wards with large numbers of COVID-19 patients.


title: Induction of type I interferons by a novel porcine reproductive and respiratory syndrome virus isolate

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is known to interfere with the signaling of type I interferons (IFNs). Here we found PRRSV A2MC2 induced type I IFNs in cultured cells. A2MC2 replication in MARC-145 cells resulted in the synthesis of IFN-α2 protein, transcript elevation of the IFN-stimulated genes ISG15 and ISG56, and the proteins of the signal transducer and activator of transcription 2 (STAT2) and ISG56. A2MC2 infection of primary porcine pulmonary alveolar macrophages (PAMs) also led to the elevation of the two proteins, but had little cytopathic effect. Furthermore, A2MC2 infection of MARC-145 or PAM cells had no detectable inhibitory effect on the ability of IFN-α to induce an antiviral response. Sequencing analysis indicated that A2MC2 was closely related to VR-2332 and Ingelvac PRRS MLV with an identity of 99.8% at the nucleotide level. The identification of this IFN-inducing PRRSV isolate may be beneficial for vaccine development against PRRS.


title: The influence of preventive strategies on COVID-2019 epidemic in Shenzhen, China

text: Early identification of imported cases, prevention of family clustering transmission, preventive measures in the public area and strict infection control procedure in hospitals were crucial for successful prevention of COVID-19 in Shenzhen, China.


title: Transmission of pathogen-laden expiratory droplets in a coach bus

text: Abstract Droplet dispersion carrying viruses/bacteria in enclosed/crowded buses may induce transmissions of respiratory infectious diseases, but the influencing mechanisms have been rarely investigated. By conducting high-resolution CFD simulations, this paper investigates the evaporation and transport of solid-liquid mixed droplets (initial diameter 10 μm and 50 μm, solid to liquid ratio is 1:9) exhaled in a coach bus with 14 thermal manikins. Five air-conditioning supply directions and ambient relative humidity (RH = 35% and 95%) are considered. Results show that ventilation effectiveness, RH and initial droplet size significantly influence droplet transmissions in coach bus. 50 μm droplets tend to evaporate completely within 1.8 s and 7 s as RH = 35% and 95% respectively, while 0.2 s or less for 10 μm droplets. Thus 10 μm droplets diffuse farther with wider range than 50 μm droplets which tend to deposit more on surfaces. Droplet dispersion pattern differs due to various interactions of gravity, ventilation flows and the upward thermal body plume. The fractions of droplets suspended in air, deposited on wall surfaces are quantified. This study implies high RH, backward supply direction and passengers sitting at nonadjacent seats can effectively reduce infection risk of droplet transmission in buses. Besides taking masks, regular cleaning is also recommended since 85%-100% of droplets deposit on object surfaces.


title: Full Sequencing of Viral Genomes: Practical Strategies Used for the Amplification and Characterization of Foot-and-Mouth Disease Virus

text: Nucleic acid sequencing is now commonplace in most research and diagnostic virology laboratories. The data generated can be used to compare novel strains with other viruses and allow the genetic basis of important phenotypic characteristics, such as antigenic determinants, to be elucidated. Furthermore, virus sequence data can also be used to address more fundamental questions relating to the evolution of viruses. Recent advances in laboratory methodologies allow rapid sequencing of virus genomes. For the first time, this opens up the potential for using genome sequencing to reconstruct virus transmission trees with extremely high resolution and to quickly reveal and identify the origin of unresolved transmission events within discrete infection clusters. Using foot-and-mouth disease virus as an example, this chapter describes strategies that can be successfully used to amplify and sequence the full genomes of RNA viruses. Practical considerations for protocol design and optimization are discussed, with particular emphasis on the software programs used to assemble large contigs and analyze the sequence data for high-resolution epidemiology.


title: Coronaviruses in guano from Pteropus medius bats in Peradeniya, Sri Lanka

text: Bats are a unique group of mammals well suited to be hosts for emerging viruses. With current rates of deforestation and urbanization, redistribution of bat habitats to urban and suburban areas may bring bats into closer contact with livestock and humans. Common flying fox, Pteropus medius (previously known as Pteropus giganteus), forms large communal roosts on treetops, often in close proximity to human habitation in Sri Lanka. This report describes the detection of coronavirus RNA in P. medius bat guano collected in Peradeniya, Sri Lanka. These viruses had >97% nucleotide identity with coronaviruses detected in Cynopterus sphinx, Scotophilus heathii and S. kuhlii bats in Thailand. Pteropus medius is widespread in Asia and appears to excrete group D coronaviruses, which are hitherto confined to bats; however, these findings may have public health implications in the future.


title: The avian influenza virus PA segment mediates strain-specific antagonism of BST-2/tetherin

text: Abstract BST-2 is an antiviral protein described as a powerful cross-species transmission barrier for simian immunodeficiency viruses. Influenza viruses appear to interact with BST-2, raising the possibility that BST-2 may be a barrier for cross-species transmission. An MDCK-based cell line expressing human BST-2 was generated to study human-derived A/Puerto Rico/8/36 (H1N1; PR8) as well as two low pathogenic avian influenza viruses (subtypes H4N6 and H6N1). The H4N6 and H6N1 viruses were less affected by BST-2 expression than PR8, due to their ability to decrease BST-2 levels, a function localized to the PA segment of both avian viruses. Experiments with PA-mutant and -chimeric viruses confirmed that the avian PA segment conferred BST-2 downregulation and antagonism. These results indicate a species-specific ability of PA from low pathogenic avian viruses to mitigate human BST-2 antiviral activity, suggesting that BST-2 is unlikely to be a general cross-species barrier to transmission of such viruses to humans.


title: Ambidextrous Relationships and Social Capability as Employee Well-Being: The Secret Sauce for Research and Development and Sustainable Innovation Performance

text: This study examines the effects that ambidextrous relationships, i.e., oriented relationships within a firm towards the development of exploitation activities and oriented relationships towards the development of exploration activities, have on employee performance in terms of creativity, research and development (R&D), and sustainable innovation performance. We contend that informal relationships affect employee creativity and R&D. However, formal relationships affect employee creativity and sustainable innovation performance. The purpose of this study is to inject new positive relationships into firms by examining ambidextrous relationships and the moderating role of social capability in the relationships–innovation effect. We empirically tested our hypotheses by using multisource data collected from 245 Spanish firms across 14 industries. Our structural equation models suggest that these two types of relationship predict employee creativity, which in turn increases sustainable innovation performance and R&D. The results reveal that the effects between informal relationships and creativity are stronger, as are the effects between formal relationships and sustainable innovation performance. A multigroup structural analysis also reveals that effects between informal and formal relationships, employee creativity, R&D, and sustainable innovation performance are stronger within firms that have employees with high social capability. The efforts and investments made in employee social capital support the development of new ideas, R&D, and innovation success. Support is provided for an ambidextrous Human Resource Management (HRM) approach which is relevant for innovation, and several practical recommendations and implementation guidelines for Small and Medium Enterprises (SMEs) are provided. This study provides a plausible explanation of two important management mechanisms for enhancing creativity—R&D and sustainable innovation performance. Relationships are malleable, and this study suggests that fostering formal and informal relationships might hold the key to sustainable innovation performance and unlocking desirable employee behavior.


title: Survey of AAHKS International Members on the Impact of COVID-19 on Hip and Knee Arthroplasty Practices

text: Abstract Coronavirus disease 2019 (COVID-19) pandemic poses an important risk to global health. This study surveyed 370 international orthopaedic surgeons affiliated with the American Association of Hip and Knee Surgeons to help identify the global impact of the COVID-19 pandemic on patient care. A total of 99 surgeons (27% of those surveyed) completed the questionnaire representing 32 different countries. Except for surgeons in Japan, all respondents noted that their practice had been affected to some degree and 70% of the surgeons have cancelled elective procedures. More than a third of the surgeons have had to close their practices altogether and the remaining open practices were estimated to be sustainable for 7 weeks on average given their current situation. The COVID-19 pandemic has resulted in marked changes to the majority of international arthroplasty practices.


title: Chest CT features of coronavirus disease 2019 (COVID-19) pneumonia: key points for radiologists

text: COVID-19 is an emerging infection caused by a novel coronavirus that is moving so rapidly that on 30 January 2020 the World Health Organization declared the outbreak a Public Health Emergency of International Concern and on 11 March 2020 as a pandemic. An early diagnosis of COVID-19 is crucial for disease treatment and control of the disease spread. Real-time reverse-transcription polymerase chain reaction (RT-PCR) demonstrated a low sensibility; therefore chest computed tomography (CT) plays a pivotal role not only in the early detection and diagnosis, especially for false negative RT-PCR tests, but also in monitoring the clinical course and in evaluating the disease severity. This paper reports the CT findings with some hints on the temporal changes over the course of the disease: the CT hallmarks of COVID-19 are bilateral distribution of ground glass opacities with or without consolidation in the posterior and peripheral lung, but the predominant findings in later phases include consolidations, linear opacities, “crazy-paving” pattern, “reversed halo” sign and vascular enlargement. The CT findings of COVID-19 overlap with the CT findings of other diseases, in particular the viral pneumonia including influenza viruses, parainfluenza virus, adenovirus, respiratory syncytial virus, rhinovirus, human metapneumovirus, etc. There are differences as well as similarities in the CT features of COVID-19 compared with those of the severe acute respiratory syndrome. The aim of this article is to review the typical and atypical CT findings in COVID-19 patients in order to help radiologists and clinicians to become more familiar with the disease.


title: Myocardial injury and COVID-19: Possible mechanisms

text: Abstract Coronavirus Disease 2019 (COVID-19) has quickly progressed to a global health emergency. Respiratory illness is the major cause of morbidity and mortality in these patients with the disease spectrum ranging from asymptomatic subclinical infection, to severe pneumonia progressing to acute respiratory distress syndrome. There is growing evidence describing pathophysiological resemblance of SARS-CoV-2 infection with other coronavirus infections such as Severe Acute Respiratory Syndrome coronavirus and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Angiotensin Converting Enzyme-2 receptors play a pivotal role in the pathogenesis of the virus. Disruption of this receptor leads to cardiomyopathy, cardiac dysfunction, and heart failure. Patients with cardiovascular disease are more likely to be infected with SARS-CoV-2 and they are more likely to develop severe symptoms. Hypertension, arrhythmia, cardiomyopathy and coronary heart disease are amongst major cardiovascular disease comorbidities seen in severe cases of COVID-19. There is growing literature exploring cardiac involvement in SARS-CoV-2. Myocardial injury is one of the important pathogenic features of COVID-19. As a surrogate for myocardial injury, multiple studies have shown increased cardiac biomarkers mainly cardiac troponins I and T in the infected patients especially those with severe disease. Myocarditis is depicted as another cause of morbidity amongst COVID-19 patients. The exact mechanisms of how SARS-CoV-2 can cause myocardial injury are not clearly understood. The proposed mechanisms of myocardial injury are direct damage to the cardiomyocytes, systemic inflammation, myocardial interstitial fibrosis, interferon mediated immune response, exaggerated cytokine response by Type 1 and 2 helper T cells, in addition to coronary plaque destabilization, and hypoxia.


title: Patient-Based Transcriptome-Wide Analysis Identify Interferon and Ubiquination Pathways as Potential Predictors of Influenza A Disease Severity

text: BACKGROUND: The influenza A virus is an RNA virus that is responsible for seasonal epidemics worldwide with up to five million cases of severe illness and 500,000 deaths annually according to the World Health Organization estimates. The factors associated with severe diseases are not well defined, but more severe disease is more often seen among persons aged >65 years, infants, pregnant women, and individuals of any age with underlying health conditions. METHODOLOGY/PRINCIPAL FINDINGS: Using gene expression microarrays, the transcriptomic profiles of influenza-infected patients with severe (N = 11), moderate (N = 40) and mild (N = 83) symptoms were compared with the febrile patients of unknown etiology (N = 73). We found that influenza-infected patients, regardless of their clinical outcomes, had a stronger induction of antiviral and cytokine responses and a stronger attenuation of NK and T cell responses in comparison with those with unknown etiology. More importantly, we found that both interferon and ubiquitination signaling were strongly attenuated in patients with the most severe outcomes in comparison with those with moderate and mild outcomes, suggesting the protective roles of these pathways in disease pathogenesis. CONCLUSION/SIGNIFICANCES: The attenuation of interferon and ubiquitination pathways may associate with the clinical outcomes of influenza patients.


title: The Future of Telehealth in Allergy and Immunology Training

text: Abstract With emerging interest in the use of telemedicine, Allergy-Immunology should be at the forefront of adoption and implementation of these services. Patients report a greater desire for telemedicine services as well as satisfaction with video-based visits with their providers. Interim virtual visits can accommodate overscheduled clinics, reduce burdens of travel to distant sites, improve access to sub-specialty care, and increase adherence during monitoring of chronic allergic conditions. The outpatient nature of Allergy-Immunology coupled with the ease of conducting many aspects of a routine visit via telemedicine makes incorporation of telehealth training into fellowship programs highly desirable. The short-term closure of hospital-affiliated clinics, in particular for vulnerable or immunodeficient patients, in the setting of a global pandemic demonstrates the timeliness of this topic. A framework for implementing telemedicine into the Allergy-Immunology curriculum, training faculty on appropriate supervision, providing elective clinical experience in the form of continuity clinics, and simulating telemedicine delivery is discussed. Proposed telemedicine competencies desired for independent practice of telemedicine are suggested.


title: Single-cell Transcriptome Analysis Indicates New Potential Regulation Mechanism of ACE2 and NPs signaling among heart failure patients infected with SARS-CoV-2

text: BACKGROUND: COVID-19 patients with comorbidities such as hypertension or heart failure (HF) are associated with poor clinical outcomes. Angiotensin-converting enzyme 2 (ACE2), the critical enzyme for SARS-CoV-2 infection, is broadly expressed in many organs including heart. However, the cellular distribution of ACE2 in the human heart, particularly the failing heart is unknown. METHODS: We analyzed single-cell RNA sequencing (scRNA-seq) data in both normal and failing hearts, and characterized the ACE2 gene expression profile in various cell subsets, especially in cardiomyocyte subsets, as well as its interaction with gene networks relating to various defense and immune responses at the single cell level. RESULTS: The results demonstrated that ACE2 is present in cardiomyocytes (CMs), endothelial cells, fibroblasts and smooth muscle cells in the heart, while the number of ACE2-postive (ACE2+) CMs and ACE2 gene expression in these CMs are significantly increased in the failing hearts. Interestingly, both brain natriuretic peptides (BNP) and atrial natriuretic peptide (ANP) are significantly up-regulated in the ACE2+ CMs. Further analysis shows that ANP, BNP and ACE2 may form a negative feedback loop with a group of genes associated with the development of heart failure. To our surprise, we found that genes related to virus entry, virus replication and suppression of interferon-gamma（IFN-γ）signaling are all up-regulated in CMs in failing hearts, and the increases were significantly higher in ACE2+ CMs as compared with ACE2 negative (ACE2−) CMs, suggesting that these ACE2+ CMs may be more vulnerable to virus infection. Since ACE2 expression is correlated with BNP expression, we further performed retrospective analysis of the plasma BNP levels and clinic outcome of 91 COVID-19 patients from a single-center. Patients with higher plasma BNP were associated with significantly higher mortality rate and expression levels of inflammatory and infective markers such as procalcitonin and C-reactive protein. CONCLUSION: In the failing heart, the upregulation of ACE2 and virus infection associated genes, as well as the increased expression of ANP and BNP could facilitate SARS-CoV-2 virus entry and replication in these vulnerable cardiomyocyte subsets. These findings may advance our understanding of the underlying molecular mechanisms of myocarditis associated with COVID-19.


title: A Network Integration Approach to Predict Conserved Regulators Related to Pathogenicity of Influenza and SARS-CoV Respiratory Viruses

text: Respiratory infections stemming from influenza viruses and the Severe Acute Respiratory Syndrome corona virus (SARS-CoV) represent a serious public health threat as emerging pandemics. Despite efforts to identify the critical interactions of these viruses with host machinery, the key regulatory events that lead to disease pathology remain poorly targeted with therapeutics. Here we implement an integrated network interrogation approach, in which proteome and transcriptome datasets from infection of both viruses in human lung epithelial cells are utilized to predict regulatory genes involved in the host response. We take advantage of a novel “crowd-based” approach to identify and combine ranking metrics that isolate genes/proteins likely related to the pathogenicity of SARS-CoV and influenza virus. Subsequently, a multivariate regression model is used to compare predicted lung epithelial regulatory influences with data derived from other respiratory virus infection models. We predicted a small set of regulatory factors with conserved behavior for consideration as important components of viral pathogenesis that might also serve as therapeutic targets for intervention. Our results demonstrate the utility of integrating diverse ‘omic datasets to predict and prioritize regulatory features conserved across multiple pathogen infection models.


Commentary: Pandemic Deployment and Surgical Soldiership


title: Rapid clinical diagnosis of Legionnaires' disease during the “herald wave” of the swine influenza (H1N1) pandemic: The Legionnaires' disease triad

text: Background In adults hospitalized with atypical community-acquired pneumonia (CAP), Legionnaires' disease is not uncommon. Legionnaire's disease can be differentiated from typical CAPs and from other atypical CAPs based on its characteristic pattern of extrapulmonary organ involvement. The first clinically useful diagnostic weighted point score system for the clinical diagnosis of Legionnaires' disease was developed by the Infectious Disease Division at Winthrop-University Hospital in the 1980s. It has proven to be diagnostically accurate and useful for more than two decades, but was time-consuming. Because Legionella spp. diagnostic tests are time-dependent and problematic, a need was perceived for a rapid, simple way to render a clinical, syndromic diagnosis of Legionnaires' disease pending Legionella test results. During the “herald wave” of the swine influenza (H1N1) pandemic in the New York area, our hospital, like others, was inundated with patients who presented to the Emergency Department with influenza-like illnesses (ILIs) for H1N1 testing/evaluation. Most patients with ILIs did not have swine influenza. Hospitalized patients with ILIs who tested positive with rapid influenza diagnostic tests (RIDTs) were placed on influenza precautions and treated with oseltamivir. Unfortunately, approximately 30% of adult patients admitted with an ILI had negative RIDTs. Because the definitive laboratory diagnosis of H1N1 pneumonia by reverse transcription-polymerase chain reaction(RT-PCR), testing was restricted by health departments, resulted in clinical and infection control dilemmas in determining which RIDT-negative patients did, in fact, have H1N1 pneumonia. Objective Accordingly, a diagnostic weighted point score system was developed for H1N1 pneumonia patients, based on RT-PCR positivity by the Infectious Disease Division at Winthrop-University Hospital. This diagnostic point score system for hospitalized adults with negative RIDTs was time-consuming. As the pandemic progressed, a simplified diagnostic swine influenza (H1N1) triad was developed for the rapid clinical diagnosis of probable H1N1 pneumonia, which also differentiated it from its mimics as well as from bacterial pneumonia, eg, Legionnaires' disease. During the “herald wave” of the H1N1 pandemic, we noticed an unexplained increase in Legionnaires' disease CAPs. Because clinical resources were stressed to the maximum during the pandemic, it was critically important to rapidly identify patients rapidly with Legionnaire's disease who did not require influenza precautions or oseltamivir, but who did require anti-Legionella antimicrobial therapy. Methods Based on the Winthrop-University Hospital Infectious Disease Division's diagnostic weighted point score system for Legionnaires' disease (modified), key indicators were identified and became the basis for the diagnostic Legionnaires' disease triad. The diagnostic Legionnaires' disease triad was used to make a clinical diagnosis of Legionnaires' disease until the results of Legionella diagnostic tests were reported. The diagnostic Legionnaires' disease triad diagnosed Legionnaires' disease in hospitalized adults with CAPs with extrapulmonary findings (atypical CAP) and relative bradycardia, accompanied by any three (ie, a triad) of the following: otherwise unexplained relative lymphopenia, early/mildly elevated serum transaminases (SGOT/SGPT), highly increased ferritin levels (≥2 × n), or hypophosphatemia. The diagnostic Legionnaires' disease triad provides clinicians with a rapid way to clinically diagnose Legionnaires' disease, pending Legionella test results. Results The accuracy of the diagnostic Legionnaires' disease triad was confirmed in our 9 cases of Legionnaires' disease by subsequent Legionella diagnostic testing. Conclusions The diagnostic Legionnaires' disease triad is particularly useful in situations where a rapid clinical syndromic diagnosis is needed, ie, during an H1N1 pandemic.


title: Le virus respiratoire syncytial: importance en pathologie, méthodes diagnostiques, traitement et prévention

text: Les bronchiolites à VRS sont fréquentes, épidémiques et nécessitent parfois l'hospitalisation des nourrissons, voire une réanimation. Le déterminisme des lésions pulmonaires est complexe, lié au virus et à la réaction immunitaire. Le traitement est symptomatique, et l'utilisation de la ribavirine est limitée aux formes sévères. Le diagnostic virologique doit être rapide, et la recherche immunologique directe des protéines virales est la technique la plus utilisée


title: Critical Dynamics in Host–Pathogen Systems

text: Host–pathogen interactions provide a fascinating example of two or more active genomes directly exerting mutual influence upon each other. These encounters can lead to multiple outcomes from symbiotic homeostasis to mutual annihilation, undergo multiple cycles of latency and lysogeny, and lead to coevolution of the interacting genomes. Such systems pose numerous challenges but also some advantages to modeling, especially in terms of functional, mathematical genome representations. The main challenges for the modeling process start with the conceptual definition of a genome for instance in the case of host-integrated viral genomes. Furthermore, hardly understood influences of the activity of either genome on the other(s) via direct and indirect mechanisms amplify the needs for a coherent description of genome activity. Finally, genetic and local environmental heterogeneities in both the host’s cellular and the pathogen populations need to be considered in multiscale modeling efforts. We will review here two prominent examples of host–pathogen interactions at the genome level, discuss the current modeling efforts and their shortcomings, and explore novel ideas of representing active genomes which promise being particularly adapted to dealing with the modeling challenges posed by host–pathogen interactions.


title: Investigation of interfacial behavior of glycyrrhizin with a lipid raft model via a Langmuir monolayer study

text: An interaction of glycyrrhizin (GC) with a lipid raft biomembrane model that consisted of N-palmitoyl-d-erythro-sphingosylphosphorylcholine (PSM), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and cholesterol (CHOL) was systematically studied using the Langmuir monolayer technique. To construct the lipid raft model, the surface pressure (π)–molecular area (A) and surface potential (ΔV)–A isotherms for three-component (PSM/DOPC/CHOL) systems on 0.02 M Tris buffer with 0.13 M NaCl (pH 7.4) were primarily measured by changing their compositions. Thermodynamic and interaction parameters for binary PSM/DOPC and PSM/CHOL systems revealed that PSM interacts more strongly with CHOL than with DOPC. In addition, a morphological analysis performed with Brewster angle microscopy (BAM) and fluorescence microscopy (FM) revealed an optimal ratio of PSM/DOPC/CHOL (1/1/1, by mole) as a model of lipid rafts. Second, the interaction of GC with the ternary PSM/DOPC/CHOL monolayers was investigated on Tris buffer solutions containing different GC concentrations (1, 5, 10, 25, and 50 μM). In BAM and FM images, microdomains were found to become smaller by increasing the GC concentration in the subphase, suggesting that GC regulates the size of raft domains, which provide dynamic scaffolding for numerous cellular processes. More interestingly, the distinctive GC striped regions were formed at the interface at 50 μM, which shows that GC divides the ternary monolayer into pieces. This phenomenon was observed only in the presence of CHOL in the monolayer. These results suggest that CHOL plays an essential role in the interaction with GC, which results in one of the major activities associated with saponins' membrane disruption.


title: Ultradeep Sequencing Analysis of Population Dynamics of Virus Escape Mutants in RNAi-Mediated Resistant Plants

text: Plant artificial micro-RNAs (amiRs) have been engineered to target viral genomes and induce their degradation. However, the exceptional evolutionary plasticity of RNA viruses threatens the durability of the resistance conferred by these amiRs. It has recently been shown that viral populations not experiencing strong selective pressure from an antiviral amiR may already contain enough genetic variability in the target sequence to escape plant resistance in an almost deterministic manner. Furthermore, it has also been shown that viral populations exposed to subinhibitory concentrations of the antiviral amiR speed up this process. In this article, we have characterized the molecular evolutionary dynamics of an amiR target sequence in a viral genome under both conditions. The use of Illumina ultradeep sequencing has allowed us to identify virus sequence variants at frequencies as low as 2 × 10(−6) and to track their variation in time before and after the viral population was able of successfully infecting plants fully resistant to the ancestral virus. We found that every site in the amiR-target sequence of the viral genome presented variation and that the variant that eventually broke resistance was sampled among the many coexisting ones. In this system, viral evolution in fully susceptible plants results from an equilibrium between mutation and genetic drift, whereas evolution in partially resistant plants originates from more complex dynamics involving mutation, selection, and drift.


title: Development and clinical evaluation of a rapid diagnostic kit for feline leukemia virus infection

text: Feline leukemia virus (FeLV) causes a range of neoplastic and degenerative diseases in cats. To obtain a more sensitive and convenient diagnosis of the disease, we prepared monoclonal antibodies specific for the FeLV p27 to develop a rapid diagnostic test with enhanced sensitivity and specificity. Among these antibodies, we identified two clones (hybridomas 8F8B5 and 8G7D1) that specifically bound to FeLV and were very suitable for a diagnostic kit. The affinity constants for 8F8B5 and 8G7D1 were 0.35 × 10(9) and 0.86 × 10(9), respectively. To investigate the diagnostic abilities of the rapid kit using these antibodies, we performed several clinical studies. Assessment of analytical sensitivity revealed that the detection threshold of the rapid diagnostic test was 2 ng/mL for recombinant p27 and 12.5 × 10(4) IU/mL for FeLV. When evaluating 252 cat sera samples, the kit was found to have a kappa value of 0.88 compared to polymerase chain reaction (PCR), indicating a significant correlation between data from the rapid diagnostic test and PCR. Sensitivity and specificity of the kit were 95.2% (20/21) and 98.5% (257/261), respectively. Our results demonstrated that the rapid diagnostic test would be a suitable diagnostic tool for the rapid detection of FeLV infection in cats.


title: Put a cork in it: Plugging the M2 viral ion channel to sink influenza

text: Abstract The ongoing threat of seasonal and pandemic influenza to human health requires antivirals that can effectively supplement existing vaccination strategies. The M2 protein of influenza A virus (IAV) is a proton-gated, proton-selective ion channel that is required for virus replication and is an established antiviral target. While licensed adamantane-based M2 antivirals have been historically used, M2 mutations that confer major adamantane resistance are now so prevalent in circulating virus strains that these drugs are no longer recommended. Here we review the current understanding of IAV M2 structure and function, mechanisms of inhibition, the rise of drug resistance mutations, and ongoing efforts to develop new antivirals that target resistant forms of M2.


title: Oligonucleotide array for simultaneous detection of respiratory viruses using a reverse‐line blot hybridization assay

text: The interest in developing new diagnostic methods based on arrays of multiple probes to detect and type simultaneously a wide range of different infectious agents is increasing. This becomes a necessity in the case of infectious agents such as respiratory viruses that cause diseases with very similar signs and symptoms. Such tools will permit rapid and accurate diagnosis of different agents causing respiratory infection leading to the most adequate prevention and/or treatment measures. In this article a reverse‐line blot hybridization (RLB) assay for the detection of a wide range of respiratory viruses is presented and evaluated for its usefulness in routine diagnosis. This assay employs an array of 18 oligonucleotide probes immobilized on a nylon membrane. Biotin‐labeled PCR products obtained with two multiplex reverse transcription (RT)‐polymerase chain reaction (PCR) assays described previously, which allow for the detection of fourteen different groups of respiratory viruses, were hybridized to the oligonucleotide array. Detection was performed using a chemiluminescent method. The standardization of the method showed that the RLB assay could be an alternative to the nested PCR assay for enhancing the sensitivity in the detection of the amplified products, avoiding the problem of cross‐over contamination, increasing the specificity, and therefore simplifying the method. This is of main interest in laboratories with few facilities. The feasibility and accuracy of the RT‐PCR‐RLB assay for detecting respiratory viruses proves that such approach could be a first stage to develop a microarray assay for routine diagnosis of infectious diseases. J. Med. Virol. 76:256–264, 2005. © 2005 Wiley‐Liss, Inc.


title: Lethal murine infection model for human respiratory disease-associated Pteropine orthoreovirus

text: Abstract Pteropine orthoreovirus (PRV) is an emerging bat-borne human pathogen causing severe respiratory illness. To date, however, the evaluation of PRV virulence has largely depended on the limited numbers of clinical cases owing to the lack of animal models. To develop an in vivo model of PRV infection, an inbred C3H mouse strain was infected intranasally with pathogenic PRV strain Miyazaki-Bali/2007. C3H mice suffered severe lung infection with significant body weight reduction and died within 7 days after intranasal infection. Infectious viruses were isolated mainly from the lungs and trachea. Histopathological examination revealed interstitial pneumonia with monocytes infiltration. Following repeated intranasal infection, mice developed antibodies to particular structural and non-structural proteins of PRV. The results of these immunological assays will help to develop laboratory protocols for sero-epidemiological studies. Our small rodent model of lethal respiratory infection will further allow investigation of the molecular mechanisms underlying the high pathogenicity of PRV.


title: Immune response characterization of mice immunized with Lactobacillus plantarum expressing spike antigen of transmissible gastroenteritis virus

text: The highly infectious porcine transmissible gastroenteritis virus (TGEV), which belongs to the coronaviruses (CoVs), causes diarrhea and high mortality rates in piglets, resulting in severe economic losses in the pork industry worldwide. In this study, we used Lactobacillus plantarum (L. plantarum) to anchor the expression of TGEV antigen (S) to dendritic cells (DCs) via dendritic cell-targeting peptides (DCpep). The results show that S antigen could be detected on the surface of L. plantarum by different detection methods. Furthermore, flow cytometry and ELISA techniques were used to measure the cellular, mucosal, and humoral immune responses of the different orally gavaged mouse groups. The obtained results demonstrated the significant effect of the constructed L. plantarum expressing S-DCpep fusion proteins in inducing high expression levels of B7 molecules on DCs, as well as high levels of IgG, secretory IgA, and IFN-γ and IL-4 cytokines compared with the other groups. Accordingly, surface expression of DC-targeted antigens successfully induced cellular, mucosal, and humoral immunity in mice and could be used as a vaccine.


title: Overexpression of HAb18G/CD147 promotes invasion and metastasis via α3β1 integrin mediated FAK-paxillin and FAK-PI3K-Ca(2+) pathways

text: Mechanism of HAb18G/CD147 underlying the metastasis process of human hepatoma cells has not been determined. In the present study, we found that integrin α3β1 colocalizes with HAb18G/CD147 in human 7721 hepatoma cells. The enhancing effect of HAb18G/CD147 on adhesion, invasion capacities and matrix metalloproteinases (MMPs) secretion was decreased by integrin α3β1 antibodies (p<0.01). The expressions of integrin downstream molecules including focal adhesion kinase (FAK), phospho-FAK (p-FAK), paxillin, and phospho-paxillin (p-paxillin) were increased in human hepatoma cells overexpressing HAb18G/CD147. Deletion of HAb18G/CD147 reduces the quantity of focal adhesions and rearranges cytoskeleton. Wortmannin and LY294002, specific phosphatidylinositol kinase (PI3K) inhibitors, reversed the effect of HAb18G/CD147 on the regulation of intracellular Ca(2+) mobilization, significantly reducing cell adhesion, invasion and MMPs secretion potential (p<0.01). Together, these results suggest that HAb18G/CD147 enhances the invasion and metastatic potentials of human hepatoma cells via integrin α3β1-mediated FAK-paxillin and FAKPI3K-Ca(2+) signal pathways.


Letter to the editor: Awake Craniotomy for Intracranial Gliomas during COVID-19 Pandemic


title: Microbial Translocation Contribute to Febrile Episodes in Adults with Chemotherapy-Induced Neutropenia

text: In this study we sought to determine the contribution of microbial translocation to febrile episodes with no attributable microbiological cause (Fever of Unknown Origin, FUO) in an adult febrile neutropaenic cohort. Endotoxin concentrations were measured with the chromogenic Limulus Amoebocyte Assay and used as a direct measure of bacterial products whilst soluble CD14 (sCD14), measured with ELISA was selected as an indicator of the early host response to endotoxins. Endotoxin concentrations in this cohort were generally elevated but did not differ with the presentation of fever. Further stratification of the febrile episodes based on the microbiological findings revealed significantly (p = 0.0077) elevated endotoxin concentrations in FUO episodes compared with episodes with documented bacterial and viral findings. sCD14 concentrations were however, elevated in febrile episodes (p = 0.0066) and no association was observed between sCD14 concentration and microbiological findings. However, FUO episodes and episodes with Gram-negative bacteraemia were associated with higher median sCD14 concentrations than episodes with Gram-positive bacteraemia (p = 0.030). In conclusion, our findings suggest that in the absence of microbiological findings, microbial translocation could contribute to febrile episodes in an adult neutropaenic cohort. We further observed an association between prophylactic antibiotic use and increased plasma endotoxin concentrations (p = 0.0212).


title: Structure-based virtual screening against SARS-3CLpro to identify novel non-peptidic hits

text: Abstract Severe acute respiratory syndrome is a highly infectious upper respiratory tract disease caused by SARS-CoV, a previously unidentified human coronavirus. SARS-3CLpro is a viral cysteine protease critical to the pathogen’s life cycle and hence a therapeutic target of importance. The recently elucidated crystal structures of this enzyme provide an opportunity for the discovery of inhibitors through rational drug design. In the current study, Gold docking program was utilized to conduct extensive docking studies against the target crystal structure to develop a robust and predictive docking protocol. The validated docking protocol was used to conduct a structure-based virtual screening of the Asinex Platinum collection. Biological evaluation of a screened selection of compounds was carried out to identify novel inhibitors of the viral protease.


title: Vitamin D Receptor stimulation to reduce Acute Respiratory Distress Syndrome (ARDS) in patients with Coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166

text: Coronavirus infection is a serious health problem awaiting an effective vaccine and/or antiviral treatment. The major complication of coronavirus disease 2019 (COVID-19), the Acute Respiratory Distress syndrome (ARDS), is due to a variety of mechanisms including cytokine storm, dysregulation of the renin-angiotensin system, neutrophil activation and increased (micro)coagulation. Based on many preclinical studies and observational data in humans, ARDS may be aggravated by vitamin D deficiency and tapered down by activation of the vitamin D receptor. Several randomized clinical trials using either oral vitamin D or oral Calcifediol (25OHD) are ongoing. Based on a pilot study, oral calcifediol may be the most promising approach. These studies are expected to provide guidelines within a few months.


title: COVID-19 Pandemic: Staged Management of Surgical Services for Gynecology and Obstetrics

text: Abstract The COVID-19 pandemic has required an unprecedented global healthcare response requiring maintenance of existing hospital-based services while simultaneously preparing for high-acuity care for infected and sick individuals. Hospitals must protect patients and the diverse healthcare workforce by conserving personal protective equipment and redeployment of facility resources. While each hospital or health system must evaluate their own capabilities and surge capacity, we present principles of management of surgical services during a health emergency and provide specific guidance to help with decision-making. We review the limited evidence from past hospital and community responses to various health emergencies and focus on systematic methods for adjusting surgical services to create capacity, addressing the specific risks of COVID-19. Successful strategies for tiered reduction of surgical cases involve multi-disciplinary engagement of the entire healthcare system and use of a structured risk-assessment categorization scheme which can be applied across the institution. Our institution developed and operationalized this approach over three working days, indicating that immediate implementation is feasible in response to an unforeseen healthcare emergency.


title: The Disulfide Bonds in Glycoprotein E2 of Hepatitis C Virus Reveal the Tertiary Organization of the Molecule

text: Hepatitis C virus (HCV), a major cause of chronic liver disease in humans, is the focus of intense research efforts worldwide. Yet structural data on the viral envelope glycoproteins E1 and E2 are scarce, in spite of their essential role in the viral life cycle. To obtain more information, we developed an efficient production system of recombinant E2 ectodomain (E2e), truncated immediately upstream its trans-membrane (TM) region, using Drosophila melanogaster cells. This system yields a majority of monomeric protein, which can be readily separated chromatographically from contaminating disulfide-linked aggregates. The isolated monomeric E2e reacts with a number of conformation-sensitive monoclonal antibodies, binds the soluble CD81 large external loop and efficiently inhibits infection of Huh7.5 cells by infectious HCV particles (HCVcc) in a dose-dependent manner, suggesting that it adopts a native conformation. These properties of E2e led us to experimentally determine the connectivity of its 9 disulfide bonds, which are strictly conserved across HCV genotypes. Furthermore, circular dichroism combined with infrared spectroscopy analyses revealed the secondary structure contents of E2e, indicating in particular about 28% β-sheet, in agreement with the consensus secondary structure predictions. The disulfide connectivity pattern, together with data on the CD81 binding site and reported E2 deletion mutants, enabled the threading of the E2e polypeptide chain onto the structural template of class II fusion proteins of related flavi- and alphaviruses. The resulting model of the tertiary organization of E2 gives key information on the antigenicity determinants of the virus, maps the receptor binding site to the interface of domains I and III, and provides insight into the nature of a putative fusogenic conformational change.


title: lncRNAs regulate the innate immune response to viral infection

text: Long noncoding RNAs (lncRNAs) are extensively expressed in mammalian cells and play a crucial role as RNA regulators in various cellular processes. Increasing data reveal that they function in innate antiviral immunity through complex mechanisms. Thousands of lncRNAs are regulated by RNA virus or DNA virus infection. The significant differential expression of lncRNAs is induced by virus or host antiviral signaling mediated by interferons (IFNs) and tumor necrosis factor‐α. In turn, these lncRNAs modulate the host immune response including the pathogen recognition receptor (PRR)‐related signaling, the translocation and activation of transcription factors, the production of IFNs and cytokines, the IFN‐activated JAK‐STAT signaling and the transcription of antiviral IFN‐stimulated genes (ISGs). Using gain‐ or loss‐of‐function analysis, the effect of lncRNAs on viral replication has been investigated to elucidate the essential role of lncRNA in the host–virus interaction. lncRNAs have shown specifically elevated or decreased levels in patients with viral diseases, suggesting the possibility of clinical application as biomarkers. Here we review the current advances of viral infection‐associated host lncRNAs, their functional significance in different aspects of antiviral immune response, the specific mechanisms and unsolved issues. We also summarize the regulation of lncRNAs by viruses, PRR agonists and cytokines. In addition, virus‐encoded lncRNAs and their functional involvement in host–virus interaction are addressed. WIREs RNA 2016, 7:129–143. doi: 10.1002/wrna.1321 1.. RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications; 2.. RNA in Disease and Development > RNA in Disease.


title: Epidemiologic Clues to SARS Origin in China

text: An epidemic of severe acute respiratory syndrome (SARS) began in Foshan municipality, Guangdong Province, China, in November 2002. We studied SARS case reports through April 30, 2003, including data from case investigations and a case series analysis of index cases. A total of 1,454 clinically confirmed cases (and 55 deaths) occurred; the epidemic peak was in the first week of February 2003. Healthcare workers accounted for 24% of cases. Clinical signs and symptoms differed between children (<18 years) and older persons (>65 years). Several observations support the hypothesis of a wild animal origin for SARS. Cases apparently occurred independently in at least five different municipalities; early case-patients were more likely than later patients to report living near a produce market (odds ratio undefined; lower 95% confidence interval 2.39) but not near a farm; and 9 (39%) of 23 early patients, including 6 who lived or worked in Foshan, were food handlers with probable animal contact.


title: Vascular endothelial growth factor (VEGF), produced by feline infectious peritonitis (FIP) virus-infected monocytes and macrophages, induces vascular permeability and effusion in cats with FIP

text: Abstract Feline infectious peritonitis virus (FIPV) causes a fatal disease called FIP in Felidae. The effusion in body cavity is commonly associated with FIP. However, the exact mechanism of accumulation of effusion remains unclear. We investigated vascular endothelial growth factor (VEGF) to examine the relationship between VEGF levels and the amounts of effusion in cats with FIP. Furthermore, we examined VEGF production in FIPV-infected monocytes/macrophages, and we used feline vascular endothelial cells to examine vascular permeability induced by the culture supernatant of FIPV-infected macrophages. In cats with FIP, the production of effusion was related with increasing plasma VEGF levels. In FIPV-infected monocytes/macrophages, the production of VEGF was associated with proliferation of virus. Furthermore, the culture supernatant of FIPV-infected macrophages induced hyperpermeability of feline vascular endothelial cells. It was suggested that vascular permeability factors, including VEGF, produced by FIPV-infected monocytes/macrophages might increase the vascular permeability and the amounts of effusion in cats with FIP.


Triagestrategie für COVID-19-Verdachtsfälle bei steigender Patientenzahl


title: Traditional Chinese medicine in the treatment of acute respiratory tract infections

text: Summary Aims To review the evidence from Cochrane systematic reviews for the effectiveness of traditional Chinese medicinal (TCM) herbs for treating acute respiratory tract infections (ARTIs) and to discuss the limitations of current clinical trials of TCM. Findings Evidence from six Cochrane systematic reviews was weak owing to the lack of high-quality TCM trials. Limitations were usually due to biases that influenced the validity of results. Conclusions TCM is widely used for treating ARTIs. However, none of the identified studies has been well designed or conducted. In this overview, we suggest that clinical trials of TCM for ARTIs need to be re-run in accordance with internationally recognized standards.


title: An efficient ribosomal frame-shifting signal in the polymerase-encoding region of the coronavirus IBV.

text: The polymerase-encoding region of the genomic RNA of the coronavirus infectious bronchitis virus (IBV) contains two very large, briefly overlapping open reading frames (ORF), F1 and F2, and it has been suggested on the basis of sequence analysis that expression of the downstream ORF, F2, might be mediated through ribosomal frame-shifting. To examine this possibility a cDNA fragment containing the F1/F2 overlap region was cloned within a marker gene and placed under the control of the bacteriophage SP6 promoter in a recombinant plasmid. Messenger RNA transcribed from this plasmid, when translated in cell-free systems, specified the synthesis of polypeptides whose size was entirely consistent with the products predicted by an efficient ribosomal frame-shifting event within the overlap region. The nature of the products was confirmed by their reactivity with antisera raised against defined portions of the flanking marker gene. This is the first non-retroviral example of ribosomal frame-shifting in higher eukaryotes.