title: Understanding the September asthma epidemic

text: The highly predictable increase in emergency department visits, hospital admissions, and unscheduled physician consultations for childhood asthma in North America every September is uniquely related to school return. Rhinovirus infection is likely the major trigger, initially affecting asthma in school-age children, followed by similar but lesser increases in asthma morbidity in younger children and in adults. Low use of asthma medications during summer may fuel the epidemic, which may be attenuated by the short-term addition of an effective controller therapy.


COVID‐19 convalescent plasma donor recruitment: beware the Faustian bargains


docid: mfnwuwfd

title: Short-Term Effects of Ambient Ozone, PM(2.5,) and Meteorological Factors on COVID-19 Confirmed Cases and Deaths in Queens, New York

text: The outbreak of coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, has been rapidly increasing in the United States. Boroughs of New York City, including Queens county, turn out to be the epicenters of this infection. According to the data provided by the New York State Department of Health, most of the cases of new COVID-19 infections in New York City have been found in the Queens county where 42,023 people have tested positive, and 3221 people have died as of 20 April 2020. Person-to-person transmission and travels were implicated in the initial spread of the outbreaks, but factors related to the late phase of rapidly spreading outbreaks in March and April are still uncertain. A few previous studies have explored the links between air pollution and COVID-19 infections, but more data is needed to understand the effects of short-term exposures of air pollutants and meteorological factors on the spread of COVID-19 infections, particularly in the U.S. disease epicenters. In this study, we have focused on ozone and PM(2.5), two major air pollutants in New York City, which were previously found to be associated with respiratory viral infections. The aim of our regression modeling was to explore the associations among ozone, PM(2.5), daily meteorological variables (wind speed, temperature, relative humidity, absolute humidity, cloud percentages, and precipitation levels), and COVID-19 confirmed new cases and new deaths in Queens county, New York during March and April 2020. The results from these analyses showed that daily average temperature, daily maximum eight-hour ozone concentration, average relative humidity, and cloud percentages were significantly and positively associated with new confirmed cases related to COVID-19; none of these variables showed significant associations with new deaths related to COVID-19. The findings indicate that short-term exposures to ozone and other meteorological factors can influence COVID-19 transmission and initiation of the disease, but disease aggravation and mortality depend on other factors.


title: Multiplex SYBR Green Real-Time PCR Assay for Detection of Respiratory Viruses

text: BACKGROUND: It is often difficult for a physician to distinguish between viral and bacterial causes of respiratory infections and this may result in overuse of antibiotics. In many cases of community-acquired respiratory infections, clinicians treat patients empirically. The development of molecular methods for direct detection of viruses has been progressed recently. OBJECTIVES: The objective of this study was recognizing the panel of respiratory RNA viruses by multiplex SYBR Green real-time polymerase chain reaction (PCR). MATERIALS AND METHODS: Randomized 172 influenza-negative respiratory specimens of all age groups of hospitalized patients were collected. After RNA extraction, cDNA was synthesized. Three SYBR Green multiplex real-time PCR assays were developed for simultaneous detection of 12 respiratory RNA viruses. Each set of multiplex methods detected four viruses, the first set: respiratory syncytial virus, human metapneumovirus, rhinovirus, enterovirus; the second set: parainfluenza viruses 1 - 4 (PIV1-4); the third set: coronaviruses NL63, 229E, severe acute respiratory syndrome (SARS), and OC43. RESULTS: Application of the multiplex SYBR Green real-time PCR in clinical samples from 172 patients in a one-year study resulted in detection of 19 (11.04%) PIV3, 9 (5.23%) PIV4, and 1 (0.58%) coronavirus NL63. All the positive samples were detected during December to March (2011 - 2012). CONCLUSIONS: Multiplex SYBR Green real-time PCR is a rapid and relatively inexpensive method for detection of respiratory viruses.


title: MERS-CoV virus-like particles produced in insect cells induce specific humoural and cellular imminity in rhesus macaques

text: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease in humans with a case fatality rate of over 39%, and poses a considerable threat to public health. A lack of approved vaccine or drugs currently constitutes a roadblock in controlling disease outbreak and spread. In this study, we generated MERS-CoV VLPs using the baculovirus expression system. Electron microscopy and immunoelectron microscopy results demonstrate that MERS-CoV VLPs are structurally similar to the native virus. Rhesus macaques inoculated with MERS-CoV VLPs and Alum adjuvant induced virus-neutralizing antibodies titers up to 1:40 and induced specific IgG antibodies against the receptor binding domain (RBD), with endpoint titers reaching 1:1,280. MERS-CoV VLPs also elicited T-helper 1 cell (Th1)-mediated immunity, as measured by ELISpot. These data demonstrate that MERS-CoV VLPs have excellent immunogenicity in rhesus macaques, and represent a promising vaccine candidate.


title: Novel strategies and approaches to develop the next generation of vaccines against porcine reproductive and respiratory syndrome virus (PRRSV)

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important swine pathogen. Since its discovery in the early 1990s, tremendous progresses have been made in understanding the molecular biology and pathogenesis of PRRSV. Although modified live-attenuated vaccines (MLVs) and inactivated vaccines against PRRSV have been available for more than a decade, the disease remains difficult to control. The efficacies of these vaccines especially against heterologous strains remain questionable: the MLVs were generally effective against homologous strains but variable in success against heterologous strains, and the outcomes of inactivated vaccines in the field are not very promising. With the development of PRRSV reverse genetics systems and the acquisition of new understanding on anti-PRRSV immunity, rational design of the next generation of PRRSV vaccines can now be explored. In this review, we discussed the recent advances in anti-PRRSV immunity and vaccinology, the recent progresses in PRRSV vaccine development particularly the reverse genetics system-based vaccine development, and provided a perspective on potential novel strategies and approaches that may be applicable to the development of the next generation of PRRSV vaccines.


title: Coronavirus confinement: A chance to learn on oral cancer—The Spanish experience

text: Since January 11th , when the first 40 cases of infection by SARS-Cov-2 (COVID-19 disease) were communicated from Wuhan, in the Chinese province of Hubei, about 4.5 million confirmed cases have been reported worldwide. During this three-month period, 80,000 new cases and 11,000 deaths were registered daily. Spain holds the sad privilege of leading the European raking of confirmed cases (>228,000) and deaths (>27,000) with no consensus on the actual figures.


title: Cystatins in Health and Diseases

text: The Cystatins constitute a large group of evolutionary related proteins with diverse biological activities. They have been recently realized as instrumental in myriad of pathophysiological conditions. They have been implicated in various pathological conditions. The degree of malignancy of various types of cancer cells has been found to be inversely associated with the expression of cystatins. Cystatins have been found to have various antimicrobial, antiviral and immunomodulatory properties. Keeping in view as their being prospective drug targets and anti-disease options this review explores the role of cytoplasmic and cell secreted cystatins in various human diseases.


Drug repurposing in the era of COVID‐19: a call for leadership and government investment


title: Rhinovirus is an important pathogen in upper and lower respiratory tract infections in Mexican children

text: BACKGROUND: Most of the studies characterizing the incidence of rhinovirus (RV) have been carried out in hospitalized children and in developed countries. In those studies, RV-C has been associated with more severe respiratory tract infections than RV species A and B. In this study we determined the frequency and diversity of RV strains associated with upper and lower respiratory tract infections (URTI, LRTI) in Mexico, and describe the clinical characteristics of the illness associated with different RV species. METHODS: A prospective surveillance of 526 and 250 children with URTI and LRTI was carried out. Respiratory samples were analyzed by RT-PCR for viruses. The 5′ untranslated region of the RV genome was amplified and sequenced. RESULTS: In the case of URTI, 17.5% were positive for RV, while this virus was found in 24.8% of LRTI. The RV species was determined in 73 children with URTI: 61.6% were RV-A, 37% RV-C and, 1.4% RV-B; and in 43 children with LRTI: 51.2% were RV-A, 41.8% RV-C, and 7% RV-B. No significant differences in clinical characteristics were found in patients with RV-A or RV-C infections. A high genetic diversity of RV strains was found in both URTI and LRTI. CONCLUSIONS: Both RV-A and RV-C species were frequently found in hospitalized as well as in outpatient children. This study underlines the high prevalence and genetic diversity of RV strains in Mexico and the potential severity of disease associated with RV-A and RV-C infections.


title: Clinical Effectiveness of Influenza Vaccination After Allogeneic Hematopoietic Stem Cell Transplantation: A Cross-sectional, Prospective, Observational Study

text: BACKGROUND: Vaccination is the primary method for preventing influenza respiratory virus infection (RVI). Although the influenza vaccine is able to achieve serological responses in some allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, its clinical benefits are still uncertain. METHODS: In this prospective, cross-sectional study, we retrospectively analyzed the effect of inactivated trivalent influenza vaccination on the prevalence of influenza RVI in a consecutive cohort of 136 allo-HSCT adult recipients who developed 161 RVI over 5 flu seasons (from 2013 to 2018). Respiratory viruses in upper– and/or lower–respiratory tract specimens were tested using multiplex polymerase chain reaction panel assays. RESULTS: Overall, we diagnosed 74 episodes (46%) of influenza RVI in 70 allo-HSCT recipients. Influenza RVI occurred in 51% of the non-vaccinated compared to 36% of the vaccinated recipients (P = .036). A multivariate analysis showed that influenza vaccination was associated with a lower prevalence of influenza RVI (odds ratio [OR] 0.39, P = .01). A multivariate risk factor analysis of lower–respiratory tract disease (LRTD) identified 2 conditions associated with the probability of influenza RVI progression: influenza vaccination (OR 0.12, 95% confidence interval [CI] 0.014–1, P = .05) and a high-risk immunodeficiency score (OR 36, 95% CI 2.26–575, P = .011). Influenza vaccination was also associated with a lower likelihood of an influenza-related hospital admission (14% vs 2%, P = .04). CONCLUSIONS: This study shows that influenza vaccination may have a clinical benefit in allo-HSCT recipients with virologically-confirmed RVI, in terms of a lower influenza RVI prevalence, slower LRTD progression, and lower likelihood of hospital admission.


title: Electrospun nanomaterials for ultrasensitive sensors

text: Increasing demands for ever more sensitive sensors for global environmental monitoring, food inspection and medical diagnostics have led to an upsurge of interests in nanostructured materials such as nanofibers and nanowebs. Electrospinning exhibits the unique ability to produce diverse forms of fibrous assemblies. The remarkable specific surface area and high porosity bring electrospun nanomaterials highly attractive to ultrasensitive sensors and increasing importance in other nanotechnological applications. In this review, we summarize recent progress in developments of the electrospun nanomaterials with applications in some predominant sensing approaches such as acoustic wave, resistive, photoelectric, optical, amperometric, and so on, illustrate with examples how they work, and discuss their intrinsic fundamentals and optimization designs. We are expecting the review to pave the way for developing more sensitive and selective nanosensors.


title: Critical role of cellular cholesterol in bovine rotavirus infection

text: BACKGROUND: Bovine rotavirus (BRV) is a non-enveloped dsRNA virus that cause neonatal calf diarrhea. Lipid rafts are cholesterol-enrich membrane mircodomains that play a vital role in many cellular processes. In this study, the effect of cellular cholesterol depletion on infection of MA-104 cells with bovine rotavirus was investigated. RESULTS: We demonstrated that cholesterol depletion of the plasma membrane by MβCD had no effect on BRV binding to cells but significantly impaired BRV entry in a dose-dependent manner and the effect was partially reversed by addition of exogenous cholesterol, suggesting the reduction of BRV infection by MβCD was specifically due to cholesterol depletion. Cholesterol depletion after virus entry did not reduce BRV replication, whereas affected virus assembly. CONCLUSIONS: Taken together, our results demonstrate that cell membrane cholesterol is essential to BRV infectivity.


title: Emerging trends of Nipah virus: A review

text: Since emergence of the Nipah virus (NiV) in 1998 from Malaysia, the NiV virus has reappeared on different occasions causing severe infections in human population associated with high rate of mortality. NiV has been placed along with Hendra virus in genus Henipavirus of family Paramyxoviridae. Fruit bats (Genus Pteropus) are known to be natural host and reservoir of NiV. During the outbreaks from Malaysia and Singapore, the roles of pigs as intermediate host were confirmed. The infection transmitted from bats to pigs and subsequently from pigs to humans. Severe encephalitis was reported in NiV infection often associated with neurological disorders. First NiV outbreak in India occurred in Siliguri district of West Bengal in 2001, where direct transmission of the NiV virus from bats‐to‐human and human‐to‐human was reported in contrast to the role of pigs in the Malaysian NiV outbreak. Regular NiV outbreaks have been reported from Bangladesh since 2001 to 2015. The latest outbreak of NiV has been recorded in May, 2018 from Kerala, India which resulted in the death of 17 individuals. Due to lack of vaccines and effective antivirals, Nipah encephalitis poses a great threat to public health. Routine surveillance studies in the infected areas can be useful in detecting early signs of infection and help in containment of these outbreaks.


title: 19 Genomics of Infectious Diseases and Private Industry

text: The last 15 years have seen the emergence of new technologies with very high value for laboratories involved in genomics research or in clinical diagnostics of infectious diseases. In the 1990s, microarray technologies revolutionized bacterial or viral genomes comparisons for the detection of polymorphisms and gene expression profiling. Next-Generation Sequencing (NGS) platforms are a major breakthrough for genomic research. Because they allow terabase outputs, they have dramatically reduced the times and budgets required to sequence complete genomes compared to classical sequencing. They are invaluable tools for metagenomics and the study of microbes’ flora. They provide extremely powerful alternatives to microarrays for resequencing, gene expression profiling, and epigenomics. The different microarray and NGS platforms have advantages and drawbacks and all require further improvements in terms of data accuracy. They require powerful software solutions to analyze the tremendous amounts of data they generate. Many companies specialized in technologies for genomics analysis have been created since the beginning of the 1990s, many of them as small biotech companies exploiting patents from renowned Universities. Most of them have now been acquired by major in vitro diagnostic companies. Currently, their sales are mostly to research institutes. Translating research to molecular diagnostics for clinical applications in the field of infectious diseases will require further validation of the use of complex sequence data, clinician education, and further efforts from the companies to provide simpler, more robust equipment and reduce the cost of reagents.


title: Fibrillarin Ribonuclease Activity is Dependent on the GAR Domain and Modulated by Phospholipids

text: Fibrillarin is a highly conserved nucleolar methyltransferase responsible for ribosomal RNA methylation across evolution from Archaea to humans. It has been reported that fibrillarin is involved in the methylation of histone H2A in nucleoli and other processes, including viral progression, cellular stress, nuclear shape, and cell cycle progression. We show that fibrillarin has an additional activity as a ribonuclease. The activity is affected by phosphoinositides and phosphatidic acid and insensitive to ribonuclease inhibitors. Furthermore, the presence of phosphatidic acid releases the fibrillarin-U3 snoRNA complex. We show that the ribonuclease activity localizes to the GAR (glycine/arginine-rich) domain conserved in a small group of RNA interacting proteins. The introduction of the GAR domain occurred in evolution in the transition from archaea to eukaryotic cells. The interaction of this domain with phospholipids may allow a phase separation of this protein in nucleoli.


title: Early warning of some notifiable infectious diseases in China by the artificial neural network

text: In order to accurately grasp the timing for the prevention and control of diseases, we established an artificial neural network model to issue early warning signals. The real-time recurrent learning (RTRL) and extended Kalman filter (EKF) methods were performed to analyse four types of respiratory infectious diseases and four types of digestive tract infectious diseases in China to comprehensively determine the epidemic intensities and whether to issue early warning signals. The numbers of new confirmed cases per month between January 2004 and December 2017 were used as the training set; the data from 2018 were used as the test set. The results of RTRL showed that the number of new confirmed cases of respiratory infectious diseases in September 2018 increased abnormally. The results of the EKF showed that the number of new confirmed cases of respiratory infectious diseases increased abnormally in January and February of 2018. The results of these two algorithms showed that the number of new confirmed cases of digestive tract infectious diseases in the test set did not have any abnormal increases. The neural network and machine learning can further enrich and develop the early warning theory.


title: The Collision of COVID-19 and the U.S. Health System

text: In this article, leaders from the American College of Physicians (ACP) discuss key recommendations from ACP's vision for U.S. health care that can advise how we can act now during the COVID-19 pandemic and in the future in service to patients, our peers, and the profession.


title: Tilorone: A Broad-Spectrum Antiviral For Emerging Viruses

text: Tilorone is a 50-year-old synthetic small-molecule compound with antiviral activity that is proposed to induce interferon after oral administration. This drug is used as a broad-spectrum antiviral in several countries of the Russian Federation. We have recently described activity in vitro and in vivo against the Ebola Virus. After a broad screening of additional viruses, we now describe in vitro activity against Chikungunya virus (CHIK) and Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV).


title: A water-focused one-health approach for early detection and prevention of viral outbreaks

text: Despite consistent efforts to protect public health there is still a heavy burden of viral disease, both in the United States and abroad. In addition to conventional medical treatment, there is a need for a holistic approach for early detection and prevention of viral outbreaks at a population level. One-Health is a relatively new integrative approach to the solving of global health challenges. A key component to the One-Health approach is the notion that human health, animal health, and environmental health are all innately interrelated. One-Health interventions, initiated by veterinary doctors, have proven to be effective in controlling outbreaks, but thus far the applications focus on zoonotic viruses transmitted from animals to humans. Environmental engineers and environmental scientists hold a critical role in the further development of One-Health approaches that include water-related transport and transmission of human, animal, and zoonotic viruses. In addition to waterborne viruses, the proposed approach is applicable to a wide range of viruses that are found in human excrement since contaminated water-based surveillance systems may be used for early detection of viral disease. This paper proposes a greater One-Health based framework that involves water-related pathways. The first step in the proposed framework is the identification of critical exposure pathways of viruses in the water environment. Identification of critical pathways informs the second and third steps, which include water-based surveillance systems for early detection at a population level and implementation of intervention approaches to block the critical pathways of exposure.


Hypertension, renin–angiotensin–aldosterone system inhibition, and COVID-19


title: Effect of temperature and relative humidity on ultraviolet (UV254) inactivation of airborne porcine respiratory and reproductive syndrome virus

text: Abstract The objective of this research was to estimate the effects of temperature and relative humidity on the inactivation of airborne porcine reproductive and respiratory syndrome (PRRS) virus by ultraviolet light (UV254). Aerosols of PRRS virus were exposed to one of four doses of UV254 under nine combinations of temperature (n =3) and relative humidity (n =3). Inactivation constants (k), defined as the absolute value of the slope of the linear relationship between the survival fraction of the microbial population and the UV254 exposure dose, were estimated using the random coefficient model. The associated UV254 half-life dose for each combination of environmental factors was determined as (log10 2/k) and expressed as UV254 mJ per unit volume. The effects of UV254 dose, temperature, and relative humidity were all statistically significant, as were the interactions between UV254 dose×temperature and UV254 dose×relative humidity. PRRS virus was more susceptible to ultraviolet as temperature decreased; most susceptible to ultraviolet inactivation at relative humidity between 25% and 79%, less susceptible at relative humidity ≤24%, and least susceptible at ≥80% relative humidity. The current study allows for calculating the dose of UV254 required to inactivate airborne PRRS virus under various laboratory and field conditions using the inactivation constants and UV254 half-life doses reported therein.


title: Les aspects radiologiques du SRAS ne sont pas spécifiques ; quatre tableaux radiologiques évolutifs ont été individualisés K.T. Wong

text: Unknown


title: A H1 hemagglutinin of a human influenza A virus with a carbohydrate-modulated receptor binding site and an unusual cleavage site

text: Abstract Two receptor binding variants of the influenza virus A/Tübingen/12/85 (H1N1) were separated by their different plaque formation in MDCK cells. Hemagglutination of variant I was restricted to red blood cells of guinea pigs, whereas variant II also hemagglutinated chicken cells. The variants differed also in their ability to bind to α2,6-linked sialic acid. Evidence is presented that this difference is determined by a complex carbohydrate side chain at asparagine131 near the receptor binding site which is absent in variant II. With both variants, the arginine found at the cleavage site of all other human isolates analyzed so far was replaced by lysine.


title: Redefining syndromic surveillance

text: Abstract With growing concerns about international spread of disease and expanding use of early disease detection surveillance methods, the field of syndromic surveillance has received increased attention over the last decade. The purpose of this article is to clarify the various meanings that have been assigned to the term syndromic surveillance and to propose a refined categorization of the characteristics of these systems. Existing literature and conference proceedings were examined on syndromic surveillance from 1998 to 2010, focusing on low- and middle-income settings. Based on the 36 unique definitions of syndromic surveillance found in the literature, five commonly accepted principles of syndromic surveillance systems were identified, as well as two fundamental categories: specific and non-specific disease detection. Ultimately, the proposed categorization of syndromic surveillance distinguishes between systems that focus on detecting defined syndromes or outcomes of interest and those that aim to uncover non-specific trends that suggest an outbreak may be occurring. By providing an accurate and comprehensive picture of this field’s capabilities, and differentiating among system types, a unified understanding of the syndromic surveillance field can be developed, encouraging the adoption, investment in, and implementation of these systems in settings that need bolstered surveillance capacity, particularly low- and middle-income countries.


title: Quantitative real-time single particle analysis of virions

text: Abstract Providing information about single virus particles has for a long time been mainly the domain of electron microscopy. More recently, technologies have been developed—or adapted from other fields, such as nanotechnology—to allow for the real-time quantification of physical virion particles, while supplying additional information such as particle diameter concomitantly. These technologies have progressed to the stage of commercialization increasing the speed of viral titer measurements from hours to minutes, thus providing a significant advantage for many aspects of virology research and biotechnology applications. Additional advantages lie in the broad spectrum of virus species that may be measured and the possibility to determine the ratio of infectious to total particles. A series of disadvantages remain associated with these technologies, such as a low specificity for viral particles. In this review we will discuss these technologies by comparing four systems for real-time single virus particle analysis and quantification.


docid: zwslhjju

title: Access to a polymerase chain reaction assay method targeting 13 respiratory viruses can reduce antibiotics: a randomised, controlled trial

text: BACKGROUND: Viral respiratory infections are common worldwide and range from completely benign disease to life-threatening illness. Symptoms can be unspecific, and an etiologic diagnosis is rarely established because of a lack of suitable diagnostic tools. Improper use of antibiotics is common in this setting, which is detrimental in light of the development of bacterial resistance. It has been suggested that the use of diagnostic tests could reduce antibiotic prescription rates. The objective of this study was to evaluate whether access to a multiplex polymerase chain reaction (PCR) assay panel for etiologic diagnosis of acute respiratory tract infections (ARTIs) would have an impact on antibiotic prescription rate in primary care clinical settings. METHODS: Adult patients with symptoms of ARTI were prospectively included. Nasopharyngeal and throat swabs were analysed by using a multiplex real-time PCR method targeting thirteen viruses and two bacteria. Patients were recruited at 12 outpatient units from October 2006 through April 2009, and samples were collected on the day of inclusion (initial visit) and after 10 days (follow-up visit). Patients were randomised in an open-label treatment protocol to receive a rapid or delayed result (on the following day or after eight to twelve days). The primary outcome measure was the antibiotic prescription rate at the initial visit, and the secondary outcome was the total antibiotic prescription rate during the study period. RESULTS: A total sample of 447 patients was randomised. Forty-one were excluded, leaving 406 patients for analysis. In the group of patients randomised for a rapid result, 4.5% (9 of 202) of patients received antibiotics at the initial visit, compared to 12.3% (25 of 204) (P = 0.005) of patients in the delayed result group. At follow-up, there was no significant difference between the groups: 13.9% (28 of 202) in the rapid result group and 17.2% (35 of 204) in the delayed result group (P = 0.359), respectively. CONCLUSIONS: Access to a rapid method for etiologic diagnosis of ARTIs may reduce antibiotic prescription rates at the initial visit in an outpatient setting. To sustain this effect, however, it seems necessary to better define how to follow and manage the patient according to the result of the test, which warrants further investigation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01133782.


docid: mbngwwhy

title: Moving Beyond a Peak Mentality: Plateaus, Shoulders, Oscillations and Other ‘Anomalous’ Behavior-Driven Shapes in COVID-19 Outbreaks

text: The COVID-19 pandemic has caused more than 300,000 reported deaths globally, of which more than 83,000 have been reported in the United States as of May 16, 2020. Public health interventions have had significant impacts in reducing transmission and in averting even more deaths. Nonetheless, in many jurisdictions (both at national and local levels) the decline of cases and fatalities after apparent epidemic peaks has not been rapid. Instead, the asymmetric decline in cases appears, in some cases, to be consistent with plateau- or shoulder-like phenomena. Here we explore a model of fatality-driven awareness in which individual protective measures increase with death rates. In this model, epidemic dynamics can be characterized by plateaus, shoulders, and lag-driven oscillations after exponential rises at the outset of disease dynamics. We also show that incorporating long-term awareness can avoid peak resurgence and accelerate epidemic decline. We suggest that awareness of epidemic severity is likely to play a critical role in disease dynamics, beyond that imposed by intervention-driven policies.


title: Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China

text: BACKGROUND: Cancer patients are regarded as a highly vulnerable group in the current Coronavirus Disease 2019 (COVID-19) pandemic. To date, the clinical characteristics of COVID-19-infected cancer patients remain largely unknown. PATIENTS AND METHODS: In this retrospective cohort study, we included cancer patients with laboratory-confirmed COVID-19 from three designated hospitals in Wuhan, China. Clinical data were collected from medical records from 13 January 2020 to 26 February 2020. Univariate and multivariate analyses were carried out to assess the risk factors associated with severe events defined as a condition requiring admission to an intensive care unit, the use of mechanical ventilation, or death. RESULTS: A total of 28 COVID-19-infected cancer patients were included; 17 (60.7%) patients were male. Median (interquartile range) age was 65.0 (56.0–70.0) years. Lung cancer was the most frequent cancer type (n = 7; 25.0%). Eight (28.6%) patients were suspected to have hospital-associated transmission. The following clinical features were shown in our cohort: fever (n = 23, 82.1%), dry cough (n = 22, 81%), and dyspnoea (n = 14, 50.0%), along with lymphopaenia (n = 23, 82.1%), high level of high-sensitivity C-reactive protein (n = 23, 82.1%), anaemia (n = 21, 75.0%), and hypoproteinaemia (n = 25, 89.3%). The common chest computed tomography (CT) findings were ground-glass opacity (n = 21, 75.0%) and patchy consolidation (n = 13, 46.3%). A total of 15 (53.6%) patients had severe events and the mortality rate was 28.6%. If the last antitumour treatment was within 14 days, it significantly increased the risk of developing severe events [hazard ratio (HR) = 4.079, 95% confidence interval (CI) 1.086–15.322, P = 0.037]. Furthermore, patchy consolidation on CT on admission was associated with a higher risk of developing severe events (HR = 5.438, 95% CI 1.498–19.748, P = 0.010). CONCLUSIONS: Cancer patients show deteriorating conditions and poor outcomes from the COVID-19 infection. It is recommended that cancer patients receiving antitumour treatments should have vigorous screening for COVID-19 infection and should avoid treatments causing immunosuppression or have their dosages decreased in case of COVID-19 coinfection.


title: Microarray-in-a-Tube for Detection of Multiple Viruses

text: Background: The detection of multiple viruses is important for pathogenic diagnosis and disease control. Microarray detection is a good method, but requires complex procedures for multiple virus detection. Methods: We developed a novel PCR assay, the microarray-in-a-tube system, which integrates multiple PCR processes and DNA microarrays for multiple virus detection. A 5 × 5 oligonucleotide microarray for detecting 4 respiratory tract viruses (severe acute respiratory syndrome–associated coronavirus, influenza A virus, influenza B virus, and enterovirus) with inner controls was arranged on the inner surface of a specially designed Eppendorf cap with a flat, optically transparent window. Results: We were able to perform all detection processes in the encapsulated system without opening the cap. The 4 viruses were successfully amplified by one-step reverse transcription–PCR in the encapsulated tube. After the PCR process, the microarray-in-a-tube was inverted, and the fluorescence-labeled PCR products were directly hybridized on the microarray. Hybridization signals were obtained with an ordinary fluorescent microscope. The sensitivity of the system for virus detection reached 10(2) copies/μL. With the help of inner controls, the system provided reliable results without false negatives and false positives. Conclusions: The microarray-in-a-tube system is a rapid, labor-saving tool for multiple virus detection with several advantages, such as convenience, prevention of cross-contamination of the PCR products, and potential for multiple-gene detection.


title: Recombinant Lactococcus Lactis Expressing M1-HA2 Fusion Protein Provides Protective Mucosal Immunity Against H9N2 Avian Influenza Virus in Chickens

text: H9N2 subtype low pathogenicity avian influenza virus (LPAIV) is distributed worldwide and causes enormous economic losses in the poultry industry. Despite immunization of almost all chickens with inactivated vaccines, the disease still remains widespread. We speculated that improving mucosal or cellular immune responses could contribute to improved control of H9N2 viruses. In this study, we constructed a novel Lactococcus lactis (L. lactis) strain expressing a recombinant fusion protein consisting of the M1 and HA2 proteins derived from an antigenically conserved endemic H9N2 virus strain. The M1-HA2 fusion protein was cloned downstream of a gene encoding a secretory peptide, and we subsequently confirmed that the fusion protein was secreted from L. lactis by Western blotting. We assessed the immunogenicity and protective effects of this recombinant L. lactis strain. Eighty 1-day-old chickens were divided into four groups, and the experimental groups were orally vaccinated twice with the recombinant L. lactis strain. Fecal and intestinal samples, sera, and bronchoalveolar lavage fluid were collected at 7, 14, and 21 days post-vaccination (dpv). Chickens vaccinated with the recombinant L. lactis strain showed significantly increased levels of serum antibodies, T cell-mediated immune responses, and mucosal secretory IgA (SIgA). Following challenge with H9N2 virus at 21 dpv, chickens vaccinated with the recombinant L. lactis strain showed decreased weight loss, lower viral titers in the lung, and reduced lung pathological damage. In summary, our results demonstrated that a recombinant L. lactis strain expressing an H9N2 M1-HA2 fusion protein could induce protective mucosal and systemic immunity. This oral vaccine is H9N2 virus-specific and represents a significant design improvement compared with previous studies. Our study provides a theoretical basis for improving mucosal immune responses to prevent and control H9N2 virus infection.


title: Interferon-γ in the serum and effusions of cats with feline coronavirus infection

text: Abstract The aim of this study was to quantify and compare interferon-γ (IFN-γ) concentrations in the serum of clinically normal cats infected with feline coronavirus (FCoV) with its concentration in the sera and effusions of cats with feline infectious peritonitis (FIP), a disease associated with infection with a mutated form of FCoV. Clinically normal FCoV-infected cats living in catteries with a high prevalence of FIP had the highest serum IFN-γ concentrations. The serum concentration of IFN-γ was not significantly different in cats with FIP compared with clinically normal FCoV-infected animals living in catteries with a low prevalence of the disease. Moreover, the concentration of IFN-γ was significantly higher in the effusions than in the serum of cats with FIP, probably due to IFN-γ production within lesions. These findings support the hypothesis that there is a strong, ‘systemic’ cell mediated immune response in clinically normal, FCoV-infected cats and that a similar process, albeit at a tissue level, is involved in the pathogenesis of FIP.


title: Molecular modelling of S1 and S2 subunits of SARS coronavirus spike glycoprotein

text: Abstract The S1 and S2 subunits of the spike glycoprotein of the coronavirus which is responsible for the severe acute respiratory syndrome (SARS) have been modelled, even though the corresponding amino acid sequences were not suitable for tertiary structure predictions with conventional homology and/or threading procedures. An indirect search for a protein structure to be used as a template for 3D modelling has been performed on the basis of the genomic organisation similarity generally exhibited by coronaviruses. The crystal structure of Clostridium botulinum neurotoxin B appeared to be structurally adaptable to human and canine coronavirus spike protein sequences and it was successfully used to model the two subunits of SARS coronavirus spike glycoprotein. The overall shape and the surface hydrophobicity of the two subunits in the obtained models suggest the localisation of the most relevant regions for their activity.


title: Personal Protective Equipment: Current Best Practices for Orthopaedic Teams

text: Abstract The COVID-19 pandemic caused by the SARS-CoV-2 virus is challenging healthcare providers across the world. Current best practices for personal protective equipment (PPE) during this time are rapidly evolving and fluid due to the novel and acute nature of the pandemic and the dearth of high-level evidence. Routine infection control practices augmented by airborne precautions are paramount when treating the COVID-19 positive patient. Best practices for PPE use in patients who have unknown COVID-19 status are a highly charged and emotional issue. The variables to be considered include protection of patients and healthcare providers, accuracy and availability of testing, and responsible use of PPE resources. This article also explores the concerns of surgeons regarding possible transmission to their own family members as a result of caring for COVID-19 patients.


title: Design and synthesis of novel Imidazo[2,1-b]thiazole derivatives as potent antiviral and antimycobacterial agents

text: Abstract A series of novel acyl-hydrazone (4a-d) and spirothiazolidinone (5a-d, 6a-d) derivatives of imidazo[2,1-b]thiazole were synthesized and evaluated for their antiviral and antimycobacterial activity. The antituberculosis activity was evaluated by using the Microplate Alamar Blue Assay and the antiviral activity was evaluated against diverse viruses in mammalian cell cultures. According to the biological activity studies of the compounds, 5a-c displayed hope promising antitubercular activity, 6d was found as potent for Coxsackie B4 virus, 5d was found as effective against Feline corona and Feline herpes viruses. Consequently, the obtained results displayed that, 5a-d and 6d present a leading structure for future drug development due to its straightforward synthesis and relevant bioactivity.


title: Participant and Caregiver Perspectives on Clinical Research During Covid‐19 Pandemic

text: BACKGROUND/OBJECTIVES: The COVID‐19 pandemic has massively disrupted essential clinical research. Many regulatory organizations have rightfully advocated to temporarily halt enrollment and curtail all face‐to‐face interactions. Views and opinions of patients and their caregivers are seldom considered while making such decisions. The objective was to study older participantsʼ and their caregiversʼ perspectives to participate in ongoing clinical research during the COVID‐19 pandemic. DESIGN: Cross‐sectional. SETTING: VISN‐16/Geriatric Research, Education and Clinical Center (GRECC), Department of Veterans Affairs. PARTICIPANTS: Older participants and their caregivers (N = 51) enrolled in ongoing clinical research studies. MEASUREMENTS: Questions about perceptions of safety to attend research visit, the level of panic among the general public, and medical centerʼs preparedness in handling the pandemic. Other questions identified the source of pandemic information and the preference of a phone or in‐person visit. RESULTS: Mean age was 69.3 (±9.4) years, 53% were male, 39% were caregivers, and 65% were Caucasian. Majority (78%) of the participants felt safe/very safe attending the scheduled research appointment; 63% felt that the extra screening made them feel safe/very safe; 82% felt that the medical center was prepared/very prepared for the pandemic. Participants split evenly on their preference for phone versus in‐person visits. Family members and television news media were the commonly used sources of pandemic information irrespective of their education. Perceptions were influenced by gender and source of information, not by age or education. Females perceived higher level of panic compared to males (P = .02). Those relying on news media felt safer compared to those that relied on family members (P = .008). CONCLUSION: Even though informants felt that the medical center was prepared to handle the pandemic, only half the participants preferred the in‐person visit. Pandemic information was obtained from family members or the television news media. Knowing patientsʼ perspectives may help researchers be better prepared for future pandemics.


title: Wastewater-based epidemiology pilot study to examine drug use in the Western United States

text: Abstract The extent of prescription and illicit drug abuse in geographically isolated rural and micropolitan communities in the intermountain western United States (US) has not been well tracked. The goal of this pilot study was to accurately measure drug dose consumption rates (DCR) between two select populations, normalize the data and compare the DCRs to similar communities. To learn about patterns of drug abuse between the two disparate communities, we used the emergent field of wastewater-based epidemiology (WBE). A rapid, quantitative and systematic process for the determination of multiple classes of prescribed and illicit drugs was applied to influent wastewater samples. Influent samples were collected over the course of three months (April to June 2019) at two wastewater treatment plants representing a small urban and a rural community. Collection of sewage influent included 24-h composite samples and the use of polar organic chemical integrative samplers (POCIS), time-weighted samplers. Using the results from the composite sampling data, DCRs per 1000 population could be calculated from the concentration data and the use of excretion correction factors. The following 18 compounds: amphetamine, methamphetamine, MDA, MDMA, morphine, 6-acetylmorphine, methadone, EDDP, codeine, benzoylecgonine, hydrocodone, hydromorphone, oxycodone, noroxycodone, ketamine, fluoxetine, tramadol, and ritalinic acid; represent a subset of the targeted analytes that were consistently measured at detectable concentration levels, and present at both sites. Following normalization of the drug measurements to influent flow rates and per capita, the small urban community demonstrated greater collective excretion rates (CER) than the rural community, with the exceptions of amphetamine and methamphetamine.


title: Effective immunotherapy against canine visceral leishmaniasis with the FML-vaccine

text: The potential effect of the fucose mannose ligand (FML)-vaccine on immunotherapy of canine visceral leishmaniasis was assayed on five mongrel dogs experimentally infected with Leishmania donovani and on 21 Leishmania chagasi naturally infected dogs when seropositive to FML but completely asymptomatic. The clinical signs of the experimentally infected, symptomatic dogs only disappeared after the complete vaccination. Protection was obtained in 3/5 animals that remained asymptomatic, IDR positive and parasite free, 1 year after infection. Furthermore, the asymptomatic, FML-vaccine treated dogs showed stable anti-FML IgG1 levels, increasing IgG2 levels and 79–95% of positive DTH response, during the whole experiment. Twenty-two months after complete vaccination, no obits due to visceral leishmaniasis were recorded and 90% of these dogs were still asymptomatic, healthy and parasite free. On the other hand, 37% (17/46 dogs) kala-azar obits were recorded in a control group that received no treatment during the same period, and that was FML-seropositive and asymtpomatic at the beginning of the assay. Our results indicate that the FML-vaccine was effective in the immunotherapy against visceral leishmaniasis of asymptomatic infected dogs. Normal proportions of CD4 and CD21 lymphocytes were detected in PBMC by FACS analysis, in dogs submitted to immunotherapy, suggesting their non-infectious condition. All animals showed as well significantly increased percents of CD8 lymphocytes as expected for Quillaja saponin (QuilA) vaccine treatments.


title: Biochemical Characterization of Middle East Respiratory Syndrome Coronavirus Helicase

text: Middle East respiratory syndrome coronavirus (MERS-CoV) helicase is a superfamily 1 helicase containing seven conserved motifs. We have cloned, expressed, and purified a Strep-fused recombinant MERS-CoV nonstructural protein 13 (M-nsp13) helicase. Characterization of its biochemical properties showed that it unwound DNA and RNA similarly to severe acute respiratory syndrome CoV nsp13 (S-nsp13) helicase. We showed that M-nsp13 unwound in a 5′-to-3′ direction and efficiently unwound the partially duplex RNA substrates with a long loading strand relative to those of the RNA substrates with a short or no loading strand. Moreover, the K(m) of ATP for M-nsp13 is inversely proportional to the length of the 5′ loading strand of the partially duplex RNA substrates. Finally, we also showed that the rate of unwinding (ku) of M-nsp13 is directly proportional to the length of the 5′ loading strand of the partially duplex RNA substrate. These results provide insights that enhance our understanding of the biochemical properties of M-nsp13. IMPORTANCE Coronaviruses are known to cause a wide range of diseases in humans and animals. Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans in the Middle East, Europe, North Africa, and the United States of America. Helicases are motor proteins that catalyze the processive separation of double-stranded nucleic acids into two single-stranded nucleic acids by utilizing the energy derived from ATP hydrolysis. MERS-CoV helicase is one of the most important viral replication enzymes of this coronavirus. Herein, we report the first bacterial expression, enzyme purification, and biochemical characterization of MERS-CoV helicase. The knowledge obtained from this study might be used to identify an inhibitor of MERS-CoV replication, and the helicase might be used as a therapeutic target.


Impact of COVID‐19 outbreak on dermatology services: Dermatology in isolation


Too much but less effective: Managing the cognitive load while designing the distance learning instructional formats


title: Single Stranded DNA Viruses Associated with Capybara Faeces Sampled in Brazil

text: Capybaras (Hydrochoerus hydrochaeris), the world’s largest rodents, are distributed throughout South America. These wild herbivores are commonly found near water bodies and are well adapted to rural and urban areas. There is limited information on the viruses circulating through capybaras. This study aimed to expand the knowledge on the viral diversity associated with capybaras by sampling their faeces. Using a viral metagenomics approach, we identified diverse single-stranded DNA viruses in the capybara faeces sampled in the Distrito Federal, Brazil. A total of 148 complete genomes of viruses in the Microviridae family were identified. In addition, 14 genomoviruses (family Genomoviridae), a novel cyclovirus (family Circoviridae), and a smacovirus (family Smacoviridae) were identified. Also, 37 diverse viruses that cannot be assigned to known families and more broadly referred to as unclassified circular replication associated protein encoding single-stranded (CRESS) DNA viruses were identified. This study provides a snapshot of the viral diversity associated with capybaras that may be infectious to these animals or associated with their microbiota or diet.


title: Are stock and real estate markets integrated? An empirical study of six Asian economies

text: Abstract Rising asset prices spurred by Asia's emerging economy have drawn much attention recently. This study examines one source of growth patterns in asset prices by analyzing the integration relationship between stock markets and real estate markets in Asia. Six economies are selected for empirical analysis: China, Hong Kong, Japan, Singapore, South Korea, and Taiwan. Results show that stock markets are integrated with real estate markets in Japan, and partially integrated with real estate markets in China, Hong Kong, and Taiwan. This implies that these two investment vehicles are substitutable in China, Hong Kong, Japan, and Taiwan, and provide diversification potential for investment portfolios in South Korea and Singapore. Examining the timing of market changes, we found the real estate market leading the stock market in some countries, and the stock market leading the real estate market in others. We conclude that stock and real estate markets show a variety of inter-relationships depending on economic and political policy environments.


title: Sentinel surveillance of selected veterinary and public health pathogens in camel population originating from Southern Punjab province, Pakistan

text: Abstract An extended range of host susceptibility including camel has been evidenced for some of the important veterinary and public health pathogens, such as brucellosis, peste des petits ruminants (PPR) and bluetongue (BT). However, in disease endemic settings across many parts of the globe, most of the disease control interventions accounts for small and large ruminants, whereas unusual hosts and/or natural reservoirs, such as camels, remain neglected for disease control measures including routine vaccination. Such a policy drawback not only plays an important role in disease epizootiology particularly in settings where disease is endemic, but also serves an obstacle in disease control and subsequent eradication in future. With this background, using pre-validated ELISA and molecular assays [multiplex PCR, reverse transcriptase (RT)-PCR and real-time (rt)-PCR], we conducted a large-scale pathogen- and antibody-based surveillance for brucellosis, peste des petits ruminants and bluetongue in camel population (n = 992) originating from a wide geographical region in southern part of the Punjab province, Pakistan. Varying in each of the selected districts, the seroprevalence was found to be maximum for bluetongue [n = 697 (70.26%, 95% CI: 67.29–73.07)], followed by PPR [n = 193 (19.46%, 95% CI: 17.07–22.09)] and brucellosis [n = 66 (6.65%, 95% CI: 5.22–8.43)]. Odds of seroprevalence were more significantly associated with pregnancy status (non-pregnant, OR = 2.23, 95% CI: 1.86–5.63, p<0.01), farming system (mixed-animal, OR = 2.59, 95% CI: 1.56–4.29, p<0.01), breed (Desi, OR = 1.97, 95% CI: 1.28–4.03, p<0.01) and farmer education (illiterate, OR = 3.17, 95% CI: 1.45–6.93, p<0.01) for BTV, body condition (normal, OR = 3.54, 95% CI: 1.92–6.54, p<0.01) and breed (Desi, OR = 2.19, 95% CI: 1.09–4.40, p<0.01) for brucellosis, and feeding system for PPR (grazing, OR = 2.75, 95% CI: 1.79–4.22, p<0.01). Among the total herds included (n = 74), genome corresponding to BT virus (BTV) and brucellosis was detected in 14 (18.92%, 95 CI: 11.09–30.04) and 19 herds (25.68%, 95% CI: 16.54–37.38), respectively. None of the herds was detected with genome of PPR virus (PPRV). Among the positive herds, serotype 1, 8 and 11 were detected for BTV while all the herds were exclusively positive to B. abortus. Taken together, the study highlights the role of potential disease reservoirs in the persistence and transmission of selected diseases in their susceptible hosts and, therefore, urges necessary interventions (e.g., inclusion of camels for vaccine etc.) for the control of diseases from their endemic setting worldwide.


title: Nipah virus fusion protein: Importance of the cytoplasmic tail for endosomal trafficking and bioactivity

text: Abstract Nipah virus (NiV) is a highly pathogenic paramyxovirus which encodes two surface glycoproteins: the receptor-binding protein G and the fusion protein F. As for all paramyxoviruses, proteolytic activation of the NiV-F protein is an indispensable prerequisite for viral infectivity. Interestingly, proteolytic activation of NiV-F differs principally from other paramyxoviruses with respect to protease usage (cathepsins instead of trypsin- or furin-like proteases), and the subcellular localization where cleavage takes place (endosomes instead of Golgi or plasma membrane). To allow efficient F protein activation needed for productive virus replication and cell-to-cell fusion, the NiV-F cytoplasmic tail contains a classical tyrosine-based endocytosis signal (Y525RSL) that we have shown earlier to be needed for F uptake and proteolytic activation. In this report, we furthermore revealed that an intact endocytosis signal alone is not sufficient for full bioactivity. The very C-terminus of the cytoplasmic tail is needed in addition. Deletions of more than four residues did not affect F uptake or endosomal cleavage but downregulated the surface expression, likely by delaying the intracellular trafficking through endosomal-recycling compartments. Given that the NiV-F cytoplasmic tail is needed for timely and correct intracellular trafficking, endosomal cleavage and fusion activity, the influence of tail truncations on NiV-mediated cell-to-cell fusion and on pseudotyping lentiviral vectors is discussed.


docid: dgjypnga

title: Community pharmacists: On the frontline of health service against COVID-19

text: Abstract The COVID-19 outbreak is a global public health crisis which has affected healthcare practice across professions. In the context of this pandemic, there is a need to highlight the roles and responsibilities of pharmacists. Community pharmacists are the most accessible healthcare professionals to the general public and have a lot to offer amid the COVID-19 response. This have led to significant changes in the health systems of many countries. This article seeks to highlight additional roles and activities relating to the public health response that can be undertaken by community pharmacists that could help to reduce pressure on general practice and other areas of the health service.


title: Evaluation of a polymerase chain reaction–electrospray ionization time-of-flight mass spectrometry for the detection and subtyping of influenza viruses in respiratory specimens

text: Abstract Background PCR coupled to electrospray ionization mass spectrometry technology (PCR/ESI-TOF-MS) (PLEX-ID system, Abbott Ibis Biosciences) was developed to characterize microbial pathogens. Objectives To evaluate the performance of the PLEX-ID flu detection™ kit for detecting Influenza viruses by comparison with the multiplex RespiFinder® Kit (PathoFinder). Study design Acute-phase respiratory samples (n =293) were analysed for this purpose. A subpopulation of influenza type A positive samples, identified with the RespiFinder® kit (n =64), were subtyped with the RealTime ready Inf A/H1N1 Detection Set® (Roche Molecular Diagnostics) and results were compared to the PLEX-ID Flu Detection™ kit. Results 274 samples gave concordant results (93.5%, p <0.0001): 65 influenza A-positive, 18 influenza B-positive and 191 negative samples. Of these, 7 samples were PLEX-ID positive/RespiFinder® negative (5 influenza A and 2 influenza B) and 12 were PLEX-ID positive/RespiFinder® negative (10 influenza A and 2 influenza B). PLEX-ID showed one sample as an influenza A and B co-infection while the RespiFinder® assay showed it to be influenza A-positive. The sensitivity, specificity, positive and negative predictive values of the PLEX-ID™ system were 87.4%, 96.5%, 92.2% and 94.1% respectively. Thirteen of 19 discordant samples available for retesting were investigated further with the Anyplex™II RV16 Detection kit (Seegene): seven were RespiFinder® concordant, while six were PLEX-ID™ concordant. Subtyping of 61/64 influenza A samples was concordant (95.3%): 55 were H1N1pdm09 and six were non-H1N1pdm09. Three samples gave negative PLEX-ID™ results (one H1N1pdm09 and two non-H1N1pdm09). Conclusions PCR/ESI-TOF-MS technology showed good diagnostic performances to detect and subtype influenza viruses.


title: Structural and Functional Bases for Broad-Spectrum Neutralization of Avian and Human Influenza A Viruses

text: Influenza virus remains a constant public health threat, owing to its ability to evade immune surveillance through rapid genetic drift and reassortment. Monoclonal antibody (mAb)-based immunotherapy is a promising strategy for disease control. Here we use a human Ab phage display library and H5 hemagglutinin (HA) ectodomain to select ten neutralizing mAbs (nAbs) with a remarkably broad range among Group 1 influenza viruses, including the H5N1 “bird flu” and the H1N1 “Spanish flu” strains. Notably, nine of the Abs utilize the same germline gene, VH1-69. The crystal structure of one mAb bound to H5N1 HA reveals that only the heavy chain inserts into a highly conserved pocket in the HA stem, inhibiting the conformational changes required for membrane fusion. Our studies indicate that nAbs targeting this pocket could provide broad protection against both seasonal and pandemic influenza A infections.


title: Characterization, Pathogenicity and Protective efficacy of a Cell Culture-Derived Porcine Deltacoronavirus

text: Abstract Porcine deltacoronavirus (PDCoV) is a novel swine enteropathogenic coronavirus that causes acute diarrhea, vomiting, dehydration and mortality in neonatal piglets, resulting in significant economic losses to the pig industry. However, there is currently little information on vaccine studies and commercially available vaccines for PDCoV. Hence, herein, a PDCoV strain, CH/XJYN/2016, was successfully isolated and serially propagated in vitro, and its biological characteristics were determined. Compared to that of previously reported and recently isolated PDCoV strains from China and the United States, the S gene of the CH/XJYN/2016 strain contains novel mutations. Infection studies revealed that CH/XJYN/2016 is pathogenic to suckling piglets and conventional weaned pigs. In addition, the median pig diarrhea dose (PDD50) of PDCoV in conventional weaned pigs was determined (2.0 log10PDD50/3 mL). Furthermore, an inactivated cell-adapted CH/XJYN/2016-based vaccine candidate was developed with different adjuvants. Compared with nonvaccinated pigs, conventional weaned pigs given the inactivated vaccine developed a potent humoral immune response and showed no clinical signs or viral shedding after challenge, indicating a potent protective effect of the vaccine against PDCoV infection. Therefore, the PDCoV vaccine developed in this study is a promising vaccine candidate that can be used for the control of PDCoV infection in pigs.


title: Wheezing due to rhinovirus infection in infancy: Bronchial hyperresponsiveness at school age

text: Background: Characteristics related to decreased lung function and increased bronchial responsiveness after early childhood wheezing requiring hospitalization are not fully established. Methods: Seventy‐nine children with wheezing requiring hospitalization at age <2 years were prospectively followed up and re‐investigated at age 5.6–8.8 years when the measurements of baseline lung function and bronchial responsiveness to exercise were performed. Results: At early school age, 23% of children had decreased lung function, and 13% had increased bronchial responsiveness to exercise. Predictors of decreased lung function were maternal history of smoking during pregnancy (odds ratio [OR], 12.8; 95% confidence interval [CI]: 1.2–139.6), parental history of asthma (OR, 4.3; 95%CI: 1.1–17.1), and female gender (OR, 4.0; 95%CI: 1.2–13.7). Increased bronchial responsiveness was associated with rhinovirus infection‐induced wheezing in infancy (OR, 6.5; 95%CI: 1.2–36.3), and early cat or dog exposure leading to sensitization (OR, 26.6; 95%CI: 1.3–525.2). Inhaled anti‐inflammatory therapy was common in children with rhinovirus infection‐induced wheezing in infancy (n = 13/19; P = 0.001 vs children with other/no confirmed virus infection etiology for wheezing in infancy, n = 16/60), which may have improved lung function and attenuated bronchial responsiveness in them. Conclusions: After early childhood wheezing requiring hospitalization, one‐fourth of children will have decreased lung function and one‐eighth of children will show increased bronchial responsiveness at school age. Gender, heredity of asthma, and antenatal exposure to tobacco smoke are predictors of decreased lung function, whereas rhinovirus infection etiology of wheeze and early animal exposure leading to sensitization are associated with increased bronchial responsiveness later in childhood.


title: A one-year prospective study of infectious etiology in patients hospitalized with acute exacerbations of COPD and concomitant pneumonia

text: Summary Aim This study assessed the infectious etiology of patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with concomitant pneumonia. Methods Patients admitted to medical wards in an acute hospital were recruited prospectively from May 1, 2004 to April 30, 2005. Sputum culture, blood culture, paired serology, and nasopharyngeal aspirates (NPA) viral culture and polymerase chain reaction (PCR) studies were performed. Spirometry was assessed in stable phase at 2–3 months post-hospital discharge. Results Seventy eight subjects were admitted for AECOPD with concomitant pneumonia. The mean (SD) age was 77.1 (7.5) years, with FEV1 of 41.5 (20.8)% predicted normal. Overall, an infectious etiology could be established in 48.7% of the subjects. Among the 71 subjects with sputum collected, 40.8% had positive bacterial culture. The commonest bacteria identified were Streptococcus pneumoniae (8[11.3%]), Pseudomonas aeruginosa (7[9.9%]) and Haemophilus influenzae (7[9.9%]). Among the 66 subjects with NPA collected, 9.0 and 12.2% had positive viral culture and PCR results, respectively. The commonest viruses identified by NPA PCR were influenza A (4[6.1%] subjects) and rhinovirus (2[3.0%]). Paired serology was positive in 4.4%. Patients on high dose inhaled corticosteroid (ICS) (>1000mcg beclomethasone-equivalent/day) had a higher rate of positive sputum bacterial culture than those on low-medium dose of ICS (50.0% vs 18.2%, p =0.02). Conclusion An infectious etiology could be established in about half of patients hospitalized with AECOPD and concomitant pneumonia. The majority of identifiable causes were bacterial. Patients on high dose ICS might have impaired airway defense as reflected by the higher rate of positive sputum culture.


title: Emerging infectious diseases

text: Abstract The spectrum of human pathogens and the infectious diseases they cause is continuously changing through evolution, selection and changes in the way human populations interact with their environment and each other. New human pathogens often emerge or re-emerge from an animal reservoir, emphasizing the central role that non-human reservoirs play in human infectious diseases. Pathogens can also re-emerge with new characteristics, such as multidrug resistance, or in different places, such as Ebola virus in West Africa in 2013 and Zika virus in Brazil in 2015, to cause new epidemics. Most human pathogens have a history of evolution in which they first emerge and cause epidemics, become unstably adapted, re-emerge periodically and then – without intervention – eventually become endemic, with the potential for future outbreaks.


title: Derivation of attenuated porcine epidemic diarrhea virus (PEDV) as vaccine candidate

text: Abstract The field isolate of porcine epidemic diarrhea virus (PEDV) was serially passaged in Vero cells. The cell passaged PEDV, designated KPEDV-9, was tested for its pathogenicity in the neonatal pigs, immunogenicity and safety in the pregnant sows. The result indicated that KPEDV-9 at the 93rd passage revealed reduced pathogenicity in the neonatal pigs. Pregnant sows inoculated with the attenuated virus showed increased immune responses by ELISA. In addition, delivered piglets were protected from challenge of wild type PEDV. The safety test in pregnant sows indicated that all inoculated animals farrowed the average numbers of litters of piglets. The results of this study supported that the attenuated virus derived from serial passage could be applied as vaccine for protecting suckling piglets against PEDV infection.


title: Contributions of the US Centers for Disease Control and Prevention in Implementing the Global Health Security Agenda in 17 Partner Countries

text: The Global Health Security Agenda (GHSA), a partnership of nations, international organizations, and civil society, was launched in 2014 with a mission to build countries’ capacities to respond to infectious disease threats and to foster global compliance with the International Health Regulations (IHR 2005). The US Centers for Disease Control and Prevention (CDC) assists partner nations to improve IHR 2005 capacities and achieve GHSA targets. To assess progress through these CDC-supported efforts, we analyzed country activity reports dating from April 2015 through March 2017. Our analysis shows that CDC helped 17 Phase I countries achieve 675 major GHSA accomplishments, particularly in the cross-cutting areas of public health surveillance, laboratory systems, workforce development, and emergency response management. CDC’s engagement has been critical to these accomplishments, but sustained support is needed until countries attain IHR 2005 capacities, thereby fostering national and regional health protection and ensuring a world safer and more secure from global health threats.


title: Evidence for Limited Early Spread of COVID-19 Within the United States, January–February 2020

text: From January 21 through February 23, 2020, public health agencies detected 14 U.S. cases of coronavirus disease 2019 (COVID-19), all related to travel from China (1,2). The first nontravel-related U.S. case was confirmed on February 26 in a California resident who had become ill on February 13 (3). Two days later, on February 28, a second nontravel-related case was confirmed in the state of Washington (4,5). Examination of four lines of evidence provides insight into the timing of introduction and early transmission of SARS-CoV-2, the virus that causes COVID-19, into the United States before the detection of these two cases. First, syndromic surveillance based on emergency department records from counties affected early by the pandemic did not show an increase in visits for COVID-19-like illness before February 28. Second, retrospective SARS-CoV-2 testing of approximately 11,000 respiratory specimens from several U.S. locations beginning January 1 identified no positive results before February 20. Third, analysis of viral RNA sequences from early cases suggested that a single lineage of virus imported directly or indirectly from China began circulating in the United States between January 18 and February 9, followed by several SARS-CoV-2 importations from Europe. Finally, the occurrence of three cases, one in a California resident who died on February 6, a second in another resident of the same county who died February 17, and a third in an unidentified passenger or crew member aboard a Pacific cruise ship that left San Francisco on February 11, confirms cryptic circulation of the virus by early February. These data indicate that sustained, community transmission had begun before detection of the first two nontravel-related U.S. cases, likely resulting from the importation of a single lineage of virus from China in late January or early February, followed by several importations from Europe. The widespread emergence of COVID-19 throughout the United States after February highlights the importance of robust public health systems to respond rapidly to emerging infectious threats.


title: Potential detrimental effects of rodent viral infections on long-term experiments

text: Healthy animals are of paramount importance in obtaining meaningful, reliable scientific results. Viral infections of rodents often have a significant impact on various types of biomedical research. Laboratory animal specialists and researchers must be aware of the possible consequences associated with the use of infected animals. The objective of the paper is a discussion of the frequently encountered viral infections that can complicate or invalidate the interpretation of results by altering the host's response.


docid: faymgnts

title: Diagnostics of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) nucleocapsid antigen using chicken immunoglobulin Y

text: Abstract The goal of this study was to develop a quantitative detection system for severe acute respiratory syndrome-associated coronavirus (SARS-CoV), targeting the nucleocapsid protein (NP), to determine the presence and degree of infection in suspected individuals. Because the NP is the viral protein shed during infection and its template mRNA is the most abundant subgenomic RNA, it is a suitable candidate for developing antibodies for diagnostic applications. In this study, we have prepared full-length SARS-CoV NP expressed in Escherichia coli and purified. Full-length NP was used for the preparation of mouse monoclonal antibody and chicken polyclonal IgY antibodies for the development of heterosandwich ELISA for early diagnostics of SARS-suspected individuals. The sensitivity of the developed heterosandwich ELISA can detect the viral antigen at 18.5 pg/mL of recombinant NP. This study describes ultrasensitive ELISA using 19B6 monoclonal antibody as the capture antibody and IgY as the detecting antibody against the most abundant SARS-CoV NP antigens. One of the most important findings was the use of inexpensive polyclonal IgY antibody to increase the sensitivity of the detection system for SARS-CoV at the picogram level. Furthermore, the immunoassay of SARS-CoV NP antigen developed could be an effective and sensitive method of diagnosing SARS-suspected individuals during a future SARS-CoV outbreak.


Proposed imaging guidelines for pregnant women suspected of having COVID-19


title: Electrophilic and nucleophilic pathways in ligand oxide mediated reactions of phenylsulfinylacetic acids with oxo(salen)chromium(V) complexes

text: Abstract The mechanism of oxidative decarboxylation of phenylsulfinylacetic acids (PSAA) by oxo(salen)Cr(V)+ ion in the presence of ligand oxides has been studied spectrophotometrically in acetonitrile medium. Addition of ligand oxides (LO) causes a red shift in the λ max values of oxo(salen) complexes and an increase in absorbance with the concentration of LO along with a clear isobestic point. The reaction shows first-order dependence on oxo(salen)-chromium(V)+ ion and fractional-order dependence on PSAA and ligand oxide. Michaelis–Menten kinetics without kinetic saturation was observed for the reaction. The order of reactivity among the ligand oxides is picoline N-oxide>pyridine N-oxide>triphenylphosphine oxide. The low catalytic activity of TPPO was rationalized. Both electron-withdrawing and electron-donating substituents in the phenyl ring of PSAA facilitate the reaction rate. The Hammett plots are non-linear upward type with negative ρ value for electron-donating substituents, (ρ − =−0.740 to −4.10) and positive ρ value for electron-withdrawing substituents (ρ + =+0.057 to +0.886). Non-linear Hammett plot is explained by two possible mechanistic scenarios, electrophilic and nucleophilic attack of oxo(salen)chromium(V)+-LO adduct on PSAA as the substituent in PSAA is changed from electron-donating to electron-withdrawing. The linearity in the log k vs. E ox plot confirms single-electron transfer (SET) mechanism for PSAAs with electron-donating substituents.


title: Early events during human coronavirus OC43 entry to the cell

text: The Coronaviridae family clusters a number of large RNA viruses, which share several structural and functional features. However, members of this family recognize different cellular receptors and exploit different entry routes, what affects their species specificity and virulence. The aim of this study was to determine how human coronavirus OC43 enters the susceptible cell. Using confocal microscopy and molecular biology tools we visualized early events during infection. We found that the virus employs caveolin-1 dependent endocytosis for the entry and the scission of virus-containing vesicles from the cell surface is dynamin-dependent. Furthermore, the vesicle internalization process requires actin cytoskeleton rearrangements. With our research we strove to broaden the understanding of the infection process, which in future may be beneficial for the development of a potential therapeutics.


title: Managing the sales force through the unexpected exogenous COVID-19 crisis

text: Abstract The COVID-19 pandemic is bringing about immediate, wide-ranging, and severe challenges for many B2B sales forces. Such challenges call attention to the importance of frameworks that can be applied to aid sales managers in understanding the impact of and responses to COVID-19. Leavitt's model of organizational change, and socio-technical systems theory, point to the importance of considering four inter-related social (i.e., human and structure) and technical (i.e., task and technology) variables when examining organizational change, and recognizing that change to one variable can be predicated upon and/or bring about change to other variables. We tailor Leavitt's model to the B2B sales context and recognize the potential for exogenous shocks such as COVID-19 to impact each variable. In doing so, we conduct a review of practitioner-oriented articles, interviews with key informants working for B2B organizations, and a webinar with sales professionals. These efforts lead to a rich discussion and set of considerations that can help B2B sales forces better understand and respond to the COVID-19 pandemic and other crises.


title: Arch-shaped multiple-target sensing for rapid diagnosis and identification of emerging infectious pathogens

text: Abstract Rapid identification of emerging infectious pathogens is crucial for preventing public health threats. Various pathogen detection techniques have been introduced; however, most techniques are time-consuming and lack multiple-target detection specificity. Although multiple-target detection techniques can distinguish emerging infectious pathogens from related pathogens, direct amplification methods have not been widely examined. Here, we present a novel arch-shaped multiple-target sensor capable of rapid pathogen identification using direct amplification in clinical samples. In this study, an arch-shaped amplification containing primer sequences was designed to rapidly amplify multiple targets. Further, the sensing platform allowed for sensitive and specific detection of human coronavirus, Middle East respiratory syndrome, Zika virus, and Ebola virus down to several copies. This platform also simultaneously distinguished between Middle East respiratory syndrome and human coronavirus in clinical specimens within 20 min. This arch-shaped multiple-target sensing assay can provide rapid, sensitive, and accurate diagnoses of emerging infectious diseases in clinical applications.


title: Infectious Disease Threats in the Twenty-First Century: Strengthening the Global Response

text: The world has developed an elaborate global health system as a bulwark against known and unknown infectious disease threats. The system consists of various formal and informal networks of organizations that serve different stakeholders; have varying goals, modalities, resources, and accountability; operate at different regional levels (i.e., local, national, regional, or global); and cut across the public, private-for-profit, and private-not-for-profit sectors. The evolving global health system has done much to protect and promote human health. However, the world continues to be confronted by longstanding, emerging, and reemerging infectious disease threats. These threats differ widely in terms of severity and probability. They also have varying consequences for morbidity and mortality, as well as for a complex set of social and economic outcomes. To various degrees, they are also amenable to alternative responses, ranging from clean water provision to regulation to biomedical countermeasures. Whether the global health system as currently constituted can provide effective protection against a dynamic array of infectious disease threats has been called into question by recent outbreaks of Ebola, Zika, dengue, Middle East respiratory syndrome, severe acute respiratory syndrome, and influenza and by the looming threat of rising antimicrobial resistance. The concern is magnified by rapid population growth in areas with weak health systems, urbanization, globalization, climate change, civil conflict, and the changing nature of pathogen transmission between human and animal populations. There is also potential for human-originated outbreaks emanating from laboratory accidents or intentional biological attacks. This paper discusses these issues, along with the need for a (possibly self-standing) multi-disciplinary Global Technical Council on Infectious Disease Threats to address emerging global challenges with regard to infectious disease and associated social and economic risks. This Council would strengthen the global health system by improving collaboration and coordination across organizations (e.g., the WHO, Gavi, CEPI, national centers for disease control, pharmaceutical manufacturers, etc.); filling in knowledge gaps with respect to (for example) infectious disease surveillance, research and development needs, financing models, supply chain logistics, and the social and economic impacts of potential threats; and making high-level, evidence-based recommendations for managing global risks associated with infectious disease.


title: Trends in the Development and Approval of Monoclonal Antibodies for Viral Infections

text: Monoclonal antibodies (mAbs) developed for either the prevention or treatment of viral diseases represent a small, but valuable, class of products. Since 1985, commercial firms have initiated clinical studies involving a total of 28 mAbs. To date, one product (palivizumab) has been approved and eight candidates are currently in clinical study. Most commercial mAbs studied as antiviral agents in the clinic have either directly or indirectly targeted human immunodeficiency virus, respiratory syncytial virus, or hepatitis C virus infections. However, the ability of mAbs to bind to specific targets and utilize various anti-infective modes of action would seem to make them well suited for the prevention and/or treatment of a wider variety of viral diseases. A number of factors, including the continuing need for innovative medicines for viral infections, the global spread of viral infections, and increased government funding for the study of pathogen countermeasures, have prompted companies to reconsider mAbs as antiviral agents. Public sector research into the use of mAbs against emerging pathogens, such as severe acute respiratory syndrome coronavirus, may have already provided candidates for further development.


title: A SURGEON’S role in fighting a medical pandemic: Experiences from the unit at the epicentre of COVID-19 in Singapore – A cohort perspective

text: IMPORTANCE: Although Singapore was one of the first countries outside of China to be affected by COVID-19, for the first 2.5 months since its first reported case on January 23, 2020, it remained one of the few nations with successful containment of spread of the pandemic with little mortality and zero intra-hospital transmissions, without instituting a major lockdown of the country. In times of an infectious epidemic where medical subspecialties lead the frontline, a surgeon’s role becomes rather vague. However, the only obstacle that stands in between the surgeon and fighting in the frontline of an infectious disease outbreak, is the traditional perception of what a surgeon can do. By presenting the strategies employed by our institution and its surgical unit, which remains the epicenter of the COVID-19 fight in Singapore, together with our medical counterparts, we hope to be able to improve our practices to respond and prevent the pandemic from escalating further as a collective community of surgeons across the globe. OBSERVATIONS: Contingencies should be in place for prioritization of existing patients, triaging and treatment of suspected patients, infection control, manpower management and novel strategies for inter-disciplinary communications and education in a hospital’s surgical unit during a pandemic. Working in a high risk environment with manpower and resource limitations for prolonged periods of time has effect on morale and affects surgeon burn-out. Transparent communication, avenues to address psychological needs of surgeons and leadership by example are key strategies in ensuring a sustainable fight against the pandemic. CONCLUSIONS: and Relevance: With the varies strategies implemented, every surgical discipline and every surgeon to work together and place their desire to operate aside. There should not be any differentiation between surgeon and physician, but instead, everyone has to work together as one united health care front battling the common enemy – COVID-19.


title: Inflammation and infections in asthma

text: INTRODUCTION: Asthma is driven by an inflammatory response against normally harmless environmental inorganic and organic compounds in the respiratory tract. Immune responses to airborne pathogens such as viruses and bacteria may reduce the allergic responses but are also known to trigger asthma attacks and eventually lead to severe disease condition. OBJECTIVE: To investigate the role of respiratory pathogens concerning the induction or protection against acute or chronic asthma manifestations. METHODS: We included 131 articles for the final review according to their relevance with the subject. RESULTS: There is apparently contradictory interaction of respiratory germs in the airways of asthmatics which may be protective on one angle but deleterious on the other. CONCLUSION: The relationship between inflammation and remodeling and the pathogenic role of viral and bacterial infection in the airways of asthmatic patients is still highly debatable and incompletely understood.


title: On the benefits of flattening the curve: A perspective()

text: The many variations on a graphic illustrating the impact of non-pharmaceutical measures to mitigate pandemic influenza that have appeared in recent news reports about COVID-19 suggest a need to better explain the mechanism by which social distancing reduces the spread of infectious diseases. And some reports understate one benefit of reducing the frequency or proximity of interpersonal encounters, a reduction in the total number of infections. In hopes that understanding will increase compliance, we describe how social distancing a) reduces the peak incidence of infections, b) delays the occurrence of this peak, and c) reduces the total number of infections during epidemics. In view of the extraordinary efforts underway to identify existing medications that are active against SARS-CoV-2 and to develop new antiviral drugs, vaccines and antibody therapies, any of which may have community-level effects, we also describe how pharmaceutical interventions affect transmission.


title: Differential effects of a common splice site polymorphism on the generation of OAS1 variants in human bronchial epithelial cells

text: The 2′,5′-oligoadenylate synthetase 1 (OAS1) is one of the major interferon-inducible proteins and a critical component of the host defense system against viral infection. A single nucleotide polymorphism (SNP), rs10774671, presumably responsible for alternate splicing of this gene, has frequently been associated with a variety of viral diseases, including emerging respiratory infections. We investigated the SNP-dependent expression of OAS1 variants in primary cultured human bronchial epithelial cells. Total RNA was subjected to real-time RT-PCR with specific primer sets designed to amplify each transcript variant. We found that the p46 transcript was mainly expressed in cells with the GG genotype, whereas the p42 transcript was highly expressed, and the p44a (alternate exon in intron 5), p48, and p52 transcripts were expressed to a lesser extent, in cells with the AA genotype. Immunoblot analysis revealed that the p46 isoform and a smaller amount of the p42 isoform were present in cells with the GG genotype, whereas only the p42 isoform was clearly observed in cells with the AA genotype. Cellular DNA fragmentation induced by neutrophil elastase was more preferentially found in cells with the AA genotype. Thus, our findings provide insights into the potential role of OAS1 polymorphisms in respiratory infection.


title: Hemophagocytic lymphohistiocytosis: a review inspired by the COVID-19 pandemic

text: Hemophagocytic syndrome (HPS) or hemophagocytic lymphohistiocytosis (HLH) is an acute and rapidly progressive systemic inflammatory disorder characterized by cytopenia, excessive cytokine production, and hyperferritinemia. Common clinical manifestations of HLH are acute unremitting fever, lymphadenopathy, hepatosplenomegaly, and multiorgan failure. Due to a massive cytokine release, this clinical condition is considered as a cytokine storm syndrome. HPS has primary and acquired (secondary, reactive) forms. Its primary form is mostly seen in childhood and caused by various mutations with genetic inheritance and, therefore, is called familial HLH. Secondary HLH may be caused in the presence of an underlying disorder, that is, secondary to a malignant, infectious, or autoimmune/autoinflammatory stimulus. This paper aims to review the pathogenesis and the clinical picture of HLH, and its severe complication, the cytokine storm, with a special emphasis on the developed classification criteria sets for rheumatologists, since COVID-19 infection has clinical symptoms resembling those of the common rheumatologic conditions and possibly triggers HLH. MED-LINE/Pubmed was searched from inception to April 2020, and the following terms were used for data searching: “hemophagocytic syndrome” OR “macrophage activation syndrome” OR “hemophagocytic lymphohistiocytosis”, OR “cytokine storm”. Finally, AND “COVID-19” was included in this algorithm. The selection is restricted to the past 5 years and limited numbers of earlier key references were manually selected. Only full-text manuscripts, published in an English language peer-reviewed journal were included. Manuscript selection procedure and numbers are given in Fig. 2. Briefly, the database search with the following terms of “Hemophagocytic syndrome” OR “Macrophage activation syndrome” OR “Hemophagocytic lymphohistiocytosis” OR “Cytokine storm” yielded 6744 results from inception to April 2020. The selection is restricted to the past 5 years and only limited numbers of earlier key references were selected, and this algorithm resulted in 3080 manuscripts. The addition of (AND “COVID-19”) resulted in 115 publications of which 47 studies, together with four sections of an online book were used in the final review. No statistical method was used. HLH is triggered by genetic conditions, infections, malignancies, autoimmune-autoinflammatory diseases, and some drugs. In COVID-19 patients, secondary HLH and cytokine storm may be responsible for unexplained progressive fever, cytopenia, ARDS, neurological and renal impairment. Differentiation between the primary and secondary forms of HLH is utterly important, since primary form of HLH requires complicated treatments such as hematopoietic stem cell transplantation. Further studies addressing the performance of HScore and other recommendations in the classification of these patients is necessary.


title: Estimates of the ongoing need for social distancing and control measures post-“lockdown” from trajectories of COVID-19 cases and mortality

text: By 21st May 2020, SARS-CoV-2 had caused more than 5 million cases of COVID-19 across more than 200 countries. Most countries with significant outbreaks have introduced social distancing or “lockdown” measures to reduce viral transmission. So the key question now is when, how, and to what extent, these measures can be lifted. Publically available data, on daily numbers of newly-confirmed cases and mortality, were used to fit regression models estimating trajectories, doubling times and the reproduction number (R(0)) of the disease, before and under the control measures. These data ran up to 21st May 2020, and were sufficient for analysis in 89 countries. The estimates of R(0), before lockdown, based on these data were broadly consistent with those previously published: between 2.0 and 3.7 in the countries with the largest number of cases available for analysis (USA, Italy, Spain, France and UK). There was little evidence to suggest that the restrictions had reduced R far below 1 in many places, with France having the most rapid reductions – R(0) 0.76 (95%CI 0.72–0.82), based on cases and 0.77 (95%CI 0.73–0.80) based on mortality. Intermittent lockdown has been proposed as a means of controlling the outbreak while allowing periods of increase freedom and economic activity. These data suggest that few countries could have even 1 week per month unrestricted without seeing resurgence of the epidemic. Similarly, restoring 20% of the activity that has been prevented by the lockdowns looks difficult to reconcile with preventing the resurgence of the disease in most countries.


docid: ghjseynl

title: A Highly Unusual Palindromic Transmembrane Helical Hairpin Formed by SARS Coronavirus E Protein

text: Abstract The agent responsible for the recent severe acute respiratory syndrome (SARS) outbreak is a previously unidentified coronavirus. While there is a wealth of epidemiological studies, little if any molecular characterization of SARS coronavirus (SCoV) proteins has been carried out. Here we describe the molecular characterization of SCoV E protein, a critical component of the virus responsible for virion envelope morphogenesis. We conclusively show that SCoV E protein contains an unusually short, palindromic transmembrane helical hairpin around a previously unidentified pseudo-center of symmetry, a structural feature which seems to be unique to SCoV. The hairpin deforms lipid bilayers by way of increasing their curvature, providing for the first time a molecular explanation of E protein's pivotal role in viral budding. The molecular understanding of this critical component of SCoV may represent the beginning of a concerted effort aimed at inhibiting its function, and consequently, viral infectivity.


title: Quantitative and Chemical Fingerprint Analysis for the Quality Evaluation of Isatis indigotica based on Ultra-Performance Liquid Chromatography with Photodiode Array Detector Combined with Chemometric Methods

text: A simple and reliable method of ultra-performance liquid chromatography with photodiode array detector (UPLC-PDA) was developed to control the quality of Radix Isatidis (dried root of Isatis indigotica) for chemical fingerprint analysis and quantitative analysis of eight bioactive constituents, including R,S-goitrin, progoitrin, epiprogoitrin, gluconapin, adenosine, uridine, guanosine, and hypoxanthine. In quantitative analysis, the eight components showed good regression (R > 0.9997) within test ranges, and the recovery method ranged from 99.5% to 103.0%. The UPLC fingerprints of the Radix Isatidis samples were compared by performing chemometric procedures, including similarity analysis, hierarchical clustering analysis, and principal component analysis. The chemometric procedures classified Radix Isatidis and its finished products such that all samples could be successfully grouped according to crude herbs, prepared slices, and adulterant Baphicacanthis cusiae Rhizoma et Radix. The combination of quantitative and chromatographic fingerprint analysis can be used for the quality assessment of Radix Isatidis and its finished products.


docid: ojpcvlpe

title: Mass Screening of Suspected Febrile Patients with Remote-sensing Infrared Thermography: Alarm Temperature and Optimal Distance

text: Background/Purpose Detection of fever has become an essential step in identifying patients who may have severe acute respiratory syndrome (SARS) or avian influenza. This study evaluated infrared thermography (IRT) and compared the influence of different imagers, ambient temperature discrepancy, and the distance between the subject and imager. Methods IRT-digital infrared thermal imaging (IRT-DITI), thermoguard, and ear drum IRT were used for visitors to Municipal Wang Fang Hospital, Taipei, Taiwan. The McNemar and c2 test, standard Pearson correlation, ANOVA, intraclass correlation coefficient (ICC), and receiver operating characteristic curve (ROC) analysis were used to calculate the alarm temperature for each imager. Results A total of 1032 subjects were recruited. Different distances and ambient temperature discrepancy had a significant influence on thermoguard, and lateral and frontal view DITI. By ICC analysis, a significant difference was found at 10 m distance between ear drum IRT and thermoguard (r = 0.45), lateral view DITI (r = 0.37), and frontal view DITI (r = 0.44). With ROC analysis, the optimal preset cut-off temperatures for the different imagers were: 36.05°C for thermoguard (area under the curve [AUC], 0.716), 36.25°C for lateral view DITI (AUC, 0.801), and 36.25°C for frontal view DITI (AUC, 0.812). Conclusion The temperature readings obtained by IRT may be used as a proxy for core temperature. An effective IRT system with a strict operating protocol can be rapidly implemented at the entrance of a hospital during SARS or avian influenza epidemics.


title: Combined IL‐6 and JAK‐STAT inhibition therapy in COVID‐19 related sHLH, potential game changer

text: Coronavirus disease 2019 (COVID‐19), caused by novel SARS‐CoV‐2, leads to significant mortality and morbidity with increasing evidence for inflammatory pathways being implicated in the lung damage it causes. (1,2) Severe COVID‐19 patients present with increased inflammatory markers, akin to secondary haemophagocytic lymphohistiocytosis (sHLH), that have been shown to predict mortality. (3,4) There is emerging evidence for the use of an interleukin 6 (IL‐6) inhibitor, tocilizumab (TCZ), for suppression of the inflammatory cytokine storm in this context. (5–7) Ruxolitinib (RXB), a JAK‐STAT inhibitor, has also been shown to have proven efficacy in the treatment of sHLH. (8) Both agents appear to be promising in the fight against SARS‐CoV‐2 infection, (9,10) leading to an increasing number of trials being registered with their use. (11,12) Until this point, no single agent has shown a survival benefit against SARS‐CoV‐2 and it is possible that monotherapy may not suppress inflammation enough to overcome the COVID‐19 related cytokine storm and hyper‐inflammation.