title: Selection of viral variants during persistent infection of insectivorous bat cells with Middle East respiratory syndrome coronavirus

text: Coronaviruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are speculated to have originated in bats. The mechanisms by which these viruses are maintained in individuals or populations of reservoir bats remain an enigma. Mathematical models have predicted long-term persistent infection with low levels of periodic shedding as a likely route for virus maintenance and spillover from bats. In this study, we tested the hypothesis that bat cells and MERS coronavirus (CoV) can co-exist in vitro. To test our hypothesis, we established a long-term coronavirus infection model of bat cells that are persistently infected with MERS-CoV. We infected cells from Eptesicus fuscus with MERS-CoV and maintained them in culture for at least 126 days. We characterized the persistently infected cells by detecting virus particles, protein and transcripts. Basal levels of type I interferon in the long-term infected bat cells were higher, relative to uninfected cells, and disrupting the interferon response in persistently infected bat cells increased virus replication. By sequencing the whole genome of MERS-CoV from persistently infected bat cells, we identified that bat cells repeatedly selected for viral variants that contained mutations in the viral open reading frame 5 (ORF5) protein. Furthermore, bat cells that were persistently infected with ΔORF5 MERS-CoV were resistant to superinfection by wildtype virus, likely due to reduced levels of the virus receptor, dipeptidyl peptidase 4 (DPP4) and higher basal levels of interferon in these cells. In summary, our study provides evidence for a model of coronavirus persistence in bats, along with the establishment of a unique persistently infected cell culture model to study MERS-CoV-bat interactions.


title: Assessment of Patient Experiences in Otolaryngology Virtual Visits During the COVID-19 Pandemic

text: This study evaluates the patient experience during virtual otolaryngology clinic visits implemented during the coronavirus disease 2019 (COVID-19) pandemic. Patient satisfaction surveys were queried from January 1, 2020, to May 1, 2020, for both telehealth and in-person visits. A descriptive analysis of the question responses was performed. There were 195 virtual and 4013 in-person visits with surveys completed in this time period. Ratings related to provider-patient communication were poor for virtual visits. Telehealth has become the new norm for most health care providers in the United States. This study demonstrates some of the initial shortcomings of telehealth in an otolaryngology practice and identifies challenges with interpersonal communication that may need to be addressed as telehealth becomes increasingly prevalent.


COVID-19 outbreak: single center experience in neurosurgical and neuroradiological emergency network tailoring


title: A systematic risk-based strategy to select personal protective equipment for infectious diseases

text: BACKGROUND: Personal protective equipment (PPE) is a primary strategy to protect health care personnel (HCP) from infectious diseases. When transmission-based PPE ensembles are not appropriate, HCP must recognize the transmission pathway of the disease and anticipate the exposures to select PPE. Because guidance for this process is extremely limited, we proposed a systematic, risk-based approach to the selection and evaluation of PPE ensembles to protect HCP against infectious diseases. METHODS: The approach used in this study included the following 4 steps: (1) job hazard analysis, (2) infectious disease hazard analysis, (3) selection of PPE, and (4) evaluation of selected PPE. Selected PPE should protect HCP from exposure, be usable by HCP, and fit for purpose. RESULTS: The approach was demonstrated for the activity of intubation of a patient with methicillin-resistant Staphylococcus aureus or Severe Acute Respiratory Syndrome coronavirus. As expected, the approach led to the selection of different ensembles of PPE for these 2 pathogens. DISCUSSION: A systematic risk-based approach to the selection of PPE will help health care facilities and HCP select PPE when transmission-based precautions are not appropriate. Owing to the complexity of PPE ensemble selection and evaluation, a team with expertise in infectious diseases, occupational health, the health care activity, and related disciplines, such as human factors, should be engaged. CONCLUSIONS: Participation, documentation, and transparency are necessary to ensure the decisions can be communicated, critiqued, and understood by HCP.


title: Persistence of SARS-CoV-2 in the environment and COVID-19 transmission risk from environmental matrices and surfaces()

text: The Coronavirus disease 2019 (COVID-19) is spreading around the world, representing a global pandemic, counting, as of June 5th, 2020, over 6,600,000 confirmed cases and more than 390,000 deaths, with exponentially increasing numbers. In the first half of 2020, because of the widespread of the COVID-19, researches were focused on the monitoring of SARS-CoV-2 in water, wastewater, sludge, air, and on surfaces, in order to assess the risk of contracting the viral infection from contaminated environments. So far, the survival of the novel Coronavirus out of the human body has been reported for short time periods (from hours to few days, in optimized in vitro conditions), mainly because of the need of an host organism which could consent the viral attack, and due to the weak external membrane of the virus. SARS-CoV-2 viral shedding strategies in the environment, either through animate and unanimate matrices, or exploiting the organic matter in water, wastewater, and waste in general, have been discussed in the present article. We concluded that, besides the high infectuousness of the novel Coronavirus, the transmission of the pathogen may be efficiently contained applying the adequate preventive measures (e.g., personal protection equipments, and disinfecting agents), indicated by national and international health authories.


Reply to Notes and Comments on “Proposed Approach 1 for Re-using Surgical Masks in COVID-19 Pandemic”


Prolonged social isolation of the elderly during COVID-19: between benefit and damage


title: Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography

text: We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4%) had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197). Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose.


title: Health screening strategies for international air travelers during an epidemic or pandemic

text: Abstract Air travelers can carry an infectious disease's pathogenic microorganism in their bodies and spread the disease from one country to another in a few days. To delay the spread, health screening stations may be set up at airport terminals to screen travelers. This research tested three different health screening strategies, each with a different combination of screening stations at trip origins, destinations and connecting airports. Discrete event simulations were performed, based on the 2014 to 2016 Ebola virus epidemic, with special focus on travelers from the West African countries traveling to the United States, including travelers who transferred flights at airports in European Union member states. The effectiveness of the screening strategies was analyzed in terms of correct detection, missed detection and false alarm rate. The results showed that exit screening at trip origins brought big improvements in the performance measurements compared to no screening. However, additional screening at the destinations and connecting airports contributed marginal benefits.


title: Homogeneous and heterogeneous AOPs for rapid degradation of Triton X-100 in aqueous media via UV light, nano titania hydrogen peroxide and potassium persulfate

text: Abstract Feasibility of degradation of Triton X-100 as a widely used and resistive surfactant in aqueous media was studied via some homogeneous and heterogeneous AOPs of UV/TiO2, UV/H2O2 and UV/S2O8 2−. For treatment of solutions containing 20mg/L of Triton, the optimum obtained conditions are: 5.0mg/L of nano TiO2, 270.3mg/L of KPS, and 34.0mg/L of H2O2 (1mM of the oxidants), initial natural pH of 5.4 and temperature of 45°C. Under these conditions, the degradation efficiency for the UV/TiO2, UV/H2O2 and UV/S2O8 2− processes exceeds 71.9% (in 60min), 80.9% (in 60min) and 98.5% (in only 30min) respectively. It was found that simultaneous application of these heterogeneous and homogeneous AOPs (UV/TiO2/H2O2 or S2O8 2−) is not desirable due to some physico-chemical retarding effects. The influence of temperature on the reactions was examined in the range of 15–45°C and a kinetic power law model jointed with the Arrhenius equation was introduced. A pseudo first order reaction rate is appropriate for UV/S2O8 2− and UV/TiO2 processes under optimum conditions, while this order for UV/H2O2 process is 2.27. Meanwhile, the initial rates of degradation in UV/TiO2 process can be described well by the Langmuir–Hinshelwood kinetic model. Analysis of energy consumptions (thermal and electrical) revealed that increasing in temperature is an effective factor for lowering the energy cost of the preferred process of UV/S2O8 2−.


Respiratory health in Saudi Arabia


title: Obstacles and advances in SARS vaccine development

text: The emergence of the severe acute respiratory syndrome (SARS) that resulted in a pandemic in 2003 spurred a flurry of interest in the development of vaccines to prevent and treat the potentially deadly viral infection. Researchers around the world pooled their scientific resources and shared early data in an unprecedented manner in light of the impending public health crisis. There are still large gaps in knowledge about the pathogenesis of this virus. While significant advances have been made in the development of animal models, the practicality of their use may be hampered by a lack of pathological similarity with human disease. Described here are issues related to progress in vaccine development and the obstacles that lie ahead for both researchers and regulatory agencies.


title: Hidden threat lurking behind the alcohol sanitizers in COVID‐19 outbreak

text: The ongoing COVID‐19 pandemic has made various challenges for communications all over the world. Nowadays hand hygiene practices with alcohol sanitizers are an unavoidable reality for many people, which cause skin dryness and flaking. The current short communication has been explained about monitoring the quality control of alcohol concentrations and hand rub formulation, which needs more attention and should consider meticulous in this crisis.


title: Clinical Features and Short-term Outcomes of Elderly Patients With COVID-19

text: Abstract Background The outbreak of Coronavirus Disease 2019 (COVID-19) has become a global public health emergency. Methods 204 elderly patients (≥60 years old) diagnosed with COVID-19 in Renmin Hospital of Wuhan University from January 31st to February 20th, 2020 were included in this study. Clinical endpoint was in-hospital death. Results Of the 204 patients, hypertension, diabetes, cardiovascular disease, and chronic obstructive pulmonary disease (COPD) were the most common coexisting conditions. 76 patients died in the hospital. Multivariate analysis showed that dyspnea (hazards ratio (HR) 2.2, 95% confidence interval (CI) 1.414 to 3.517;p < 0.001), older age (HR 1.1, 95% CI 1.070 to 1.123; p < 0.001), neutrophilia (HR 4.4, 95% CI 1.310 to 15.061; p = 0.017) and elevated ultrasensitive cardiac troponin I (HR 3.9, 95% CI 1.471 to 10.433; p = 0.006) were independently associated with death. Conclusion Although so far the overall mortality of COVID-19 is relatively low, the mortality of elderly patients is much higher. Early diagnosis and supportive care are of great importance for the elderly patients of COVID-19.


title: The impact of government measures and human mobility trend on COVID-19 related deaths in the UK

text: Abstract The COVID-19 global pandemic has rapidly expanded, with the UK being one of the countries with the highest number of cases and deaths in proportion to its population. Major clinical and human behavioural measures have been taken by the UK government to control the spread of the epidemic and to support the health system. It remains unclear how exactly human mobility restrictions have affected the virus spread in the UK. This research uses driving, walking and transit real-time data to investigate the impact of government control measures on human mobility reduction, as well as the connection between trends in human-mobility and severe COVID-19 outcomes. Human mobility was observed to gradually decrease as the government was announcing more measures and it stabilized at a scale of around 80% after a lockdown was imposed. The study shows that human-mobility reduction had a significant impact on reducing COVID-19-related deaths, thus providing crucial evidence in support of such government measures.


docid: ocbygkyb

title: Antibody-Dependent Cell-Mediated Cytotoxicity Epitopes on the Hemagglutinin Head Region of Pandemic H1N1 Influenza Virus Play Detrimental Roles in H1N1-Infected Mice

text: Engaging the antibody-dependent cell-mediated cytotoxicity (ADCC) for killing of virus-infected cells and secretion of antiviral cytokines and chemokines was incorporated as one of the important features in the design of universal influenza vaccines. However, investigation of the ADCC epitopes on the highly immunogenic influenza hemagglutinin (HA) head region has been rarely reported. In this study, we determined the ADCC and antiviral activities of two putative ADCC epitopes, designated E1 and E2, on the HA head of a pandemic H1N1 influenza virus in vitro and in a lethal mouse model. Our data demonstrated that sera from the E1-vaccinated mice could induce high ADCC activities. Importantly, the induction of ADCC response modestly decreased viral load in the lungs of H1N1-infected mice. However, the elevated ADCC significantly increased mouse alveolar damage and mortality than that of the PBS-vaccinated group (P < 0.0001). The phenotype was potentially due to an exaggerated inflammatory cell infiltration triggered by ADCC, as an upregulated release of cytotoxic granules (perforin) was observed in the lung tissue of E1-vaccinated mice after H1N1 influenza virus challenge. Overall, our data suggested that ADCC elicited by certain domains of HA head region might have a detrimental rather than protective effect during influenza virus infection. Thus, future design of universal influenza vaccine shall strike a balance between the induction of protective immunity and potential side effects of ADCC.


title: Few organizations immune to perils of securing PPE for staff, patients

text: Finding themselves outside the traditional supply chain for personal protective equipment (PPE) for health care staff, leaders of behavioral health provider organizations have had to devise creative strategies — from the local to the global — in order to secure equipment to protect employees and patients during the COVID‐19 crisis.


title: Temporal Percolation of the Susceptible Network in an Epidemic Spreading

text: In this work, we study the evolution of the susceptible individuals during the spread of an epidemic modeled by the susceptible-infected-recovered (SIR) process spreading on the top of complex networks. Using an edge-based compartmental approach and percolation tools, we find that a time-dependent quantity [Image: see text], namely, the probability that a given neighbor of a node is susceptible at time [Image: see text], is the control parameter of a node void percolation process involving those nodes on the network not-reached by the disease. We show that there exists a critical time [Image: see text] above which the giant susceptible component is destroyed. As a consequence, in order to preserve a macroscopic connected fraction of the network composed by healthy individuals which guarantee its functionality, any mitigation strategy should be implemented before this critical time [Image: see text]. Our theoretical results are confirmed by extensive simulations of the SIR process.


title: Characteristics of oligodeoxyribonucleotides that induce interferon (IFN)-α in the pig and the phenotype of the IFN-α producing cells

text: Abstract The immunostimulatory effects of oligodeoxyribonucleotides (ODN) containing unmethylated CpG dinucleotides (CpG-ODN) in certain base contexts have been extensively studied in man and mice. One major action is their ability to trigger production of massive amounts of interferon-α (IFN-α) by plasmacytoid dendritic cells (PDC), also referred to as natural IFN-α/β producing cells (NIPC). The present study using porcine PBMC activated by CpG-ODN or plasmid DNA revealed a considerable variation in the IFN-α production in response to various CpG-ODN constructs. Several phosphodiester ODNs, such as 5′ TTTTCAATTCGAAGATGAAT 3′ (ODN H), and the plasmid pcDNA3 all required pre-incubation with lipofectin in order to induce IFN-α. Intact unmethylated CpGs were also important, because methylation or substitution of the cytosines and CpG-inversion strongly reduced the IFN-α induction by single- or double-stranded forms of ODN H. Certain CpG-ODNs that contained flanking phosphorothioate or phosphodiester poly-G sequences were potent inducers of IFN-α without pre-incubation with lipofectin, for instance the ODN 2216 (5′ GGGGGACGATCGTCGGGGGG 3′). While poly-G sequences have been suggested to increase uptake of ODNs by cells, they did not obviate the need for lipofectin when added to the ODN H. However, they resulted in up to five-fold increases of the IFN-α levels caused by ODN H upon lipofection, indicating other enhancing effects of poly-G sequences on the induction of IFN-α. The identity of the IFN-α producing cells (IPC) stimulated by CpG-ODN or plasmid DNA was studied by means of flow cytometry using combined staining for intracellular IFN-α and surface markers. Approximately 1–3 IPC/103 PBMC were detected, compared to only 3 IPC/104 PBMC stimulated by Aujeszky’s disease virus. The IPC frequencies were confirmed by detection of IFN-α mRNA positive cells by in situ hybridisation. The IPC induced by CpG-ODN or plasmid DNA had a similar phenotype, expressing CD2 and CD4 and intermediate levels of MHC class II and the myeloid marker SWC3, but not the markers of T and B cells or monocytes (CD3, CD21 and CD14). Consequently, porcine IPC that respond to CpG-DNA seem to correspond to the PDC/NIPC.


3 CLUSTER OF DIFFERENTIATION (CD) ANTIGENS


title: Binding interaction of SARS coronavirus 3CL(pro) protease with vacuolar-H(+) ATPase G1 subunit

text: The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is an important issue for treatment and prevention of SARS. Recently, SARS-CoV 3CL(pro) protease has been implied to be possible relevance to SARS-CoV pathogenesis. In this study, we intended to identify potential 3CL(pro)-interacting cellular protein(s) using the phage-displayed human lung cDNA library. The vacuolar-H(+) ATPase (V-ATPase) G1 subunit that contained a 3CL(pro) cleavage site-like motif was identified as a 3CL(pro)-interacting protein, as confirmed using the co-immunoprecipitation assay and the relative affinity assay. In addition, our result also demonstrated the cleavage of the V-ATPase G1 fusion protein and the immunoprecipitation of cellular V-ATPase G1 by the 3CL(pro). Moreover, loading cells with SNARF-1 pH-sensitive dye showed that the intracellular pH in 3CL(pro)-expressing cells was significantly lower as compared to mock cells.


America's emergency care system and severe acute respiratory syndrome(): Are we ready?


title: Viability of SARS‐CoV‐2 in faecal bio‐aerosols

text: I read with interest the rapid review by Gupta and colleagues [1] concerning the incidence and timing of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) positive faecal samples in patients with coronavirus disease 2019 (COVID‐19). The authors acknowledge insufficient evidence in support of transmission via faeco‐oral route and identify the need for further research regarding the viability of SARS‐CoV‐2 in the context of human faeces. However, it is equally pertinent to consider the viability of the virus in faecal bio‐aerosols generated by toilet plumes [2].


title: Genome Sequence of SARS-CoV-2 Isolate Cali-01, from Colombia, Obtained Using Oxford Nanopore MinION Sequencing

text: We report the genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolate obtained from a patient with symptoms of coronavirus disease 2019 (COVID-19) who was infected in Cali, Colombia. The patient had no recent travel record and did not require hospitalization. The virus genome was obtained using Oxford Nanopore MinION sequencing.


title: Coronavirus‐like particles in adults in melbourne, Australia

text: Coronavirus‐like particle(s) (CVLP) are faecal‐derived pleomorphic membrane bound virus‐like particles characterised by a fringe of clubshaped spikes that measure about 27 nm in length. The association of CVLP with a variety of social, clinical, and epidemiological factors was examined after a 69 month survey of faeces received for routine testing at an infectious diseases hospital. CVLP was found most commonly in three groups: first, intellectually retarded individuals who were usually inmates of institutions; second, recent overseas travellers who were either Indochinese refugees/immigrants or were overseas travellers who had usually visited developing communities for lengthy periods; and, third, male homosexuals who had a history of multiple sexual contacts and/or venereal disease. It was concluded that the excretion of CVLP had a strong association with unhygienic living or working conditions irrespective of any clinical symptoms the individual might show.


title: COVID-19 associated pulmonary aspergillosis (CAPA): An Australian case report

text: As the COVID-19 pandemic has developed, concern for invasive fungal infections in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) has emerged. We describe a clinical case of coronavirus disease (COVID-19) associated pulmonary aspergillus (CAPA) infection and acute respiratory distress syndrome (ARDS) with a good clinical outcome, in a previously well, non-immunocompromised Australian woman.


title: Influence of fireworks emission on aerosol aging process at lower troposphere and associated health risks in an urban region of eastern central India

text: Abstract To study the influence of fireworks in atmospheric aerosols and their effect on health during the extreme firework days, fireworks tracer metals and carbonaceous species in size-distributed aerosols in the lower troposphere at Raipur in eastern central India were investigated during the 2018 Deepawali festival. Aerosol samples were collected, before Deepawali period (BDP, n = 5), during Deepawali period (DDP, n = 5) and after Deepawali period (ADP, n = 5). Bimodal size-distribution with intense fine mode peak was found for Na during DDP. Bimodal distribution with fine mode intense peak was found for K during DDP. The bimodal size distribution of K was found common for other events because of biomass burning emissions, whereas high intense peak during DDP indicated mixed sources from biomass burning and fireworks. During DDP, K and Ca were well correlated (r2 = 0.93) together. Strong metal-metal correlations were found between the following pairs, Zn–Fe, Cu–Fe and Cu–Ca, which indicated the similar firecrackers burning source. The atmospheric aging of aerosols was also found significantly high during fireworks days. Aging of aerosols were higher because of heterogeneous reactions of SO2 and NOx on aerosols directly emitted from fireworks. The observed high values of inhalation dose of elemental carbon during DDP period imposed higher risk of respiratory diseases. This study has provided carbonaceous fractions composition data as a tool to detect the aging processes of fireworks in ultra-fine, fine and coarse mode particles during the extreme firework days. Inhalation doses were calculated to establish potential influence on human health.


title: Information technologies of 21st century and their impact on the society

text: Twenty first century has witnessed emergence of some ground breaking information technologies that have revolutionised our way of life. The revolution began late in 20th century with the arrival of internet in 1995, which has given rise to methods, tools and gadgets having astonishing applications in all academic disciplines and business sectors. In this article we shall provide a design of a ‘spider robot’ which may be used for efficient cleaning of deadly viruses. In addition, we shall examine some of the emerging technologies which are causing remarkable breakthroughs and improvements which were inconceivable earlier. In particular we shall look at the technologies and tools associated with the Internet of Things (IoT), Blockchain, Artificial Intelligence, Sensor Networks and Social Media. We shall analyse capabilities and business value of these technologies and tools. As we recognise, most technologies, after completing their commercial journey, are utilised by the business world in physical as well as in the virtual marketing environments. We shall also look at the social impact of some of these technologies and tools.


title: Detection of rhinovirus in induced sputum at exacerbation of chronic obstructive pulmonary disease

text: Common colds are associated with exacerbations of chronic obstructive pulmonary disease (COPD). However, the role of the common cold virus (human rhinovirus) in the production of symptoms and lower airway inflammation at COPD exacerbation is unknown. Thirty three patients with moderate‐to‐severe COPD were seen at baseline, when the number of chest infections in the previous year was noted, and acutely at COPD exacerbation. Within 48 h after the onset of the exacerbation and at baseline, nasal aspirates and induced sputum were taken for rhinovirus reverse transcriptase polymerase chain reaction (RT‐PCR) analysis and determination of cytokine levels. Symptoms, recorded on diary cards, were noted and forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measured. At exacerbation, mean FEV1 and FVC fell significantly from baseline (p<0.001). Ten of 43 exacerbations were associated with rhinovirus infection, detected in induced sputum. In four of these, nasophageal samples contained no detectable rhinovirus. All baseline samples were negative for rhinovirus. The simultaneous presence of increased nasal discharge/nasal congestion (in 26 of the 43 exacerbations) and increased sputum (29 exacerbations) was strongly associated with the presence of rhinovirus (odds ratio 6.15; p=0.036). Total symptom scores were greater for rhinovirus as compared to nonrhinovirus exacerbations (p=0.039). Median baseline sputum interleukin‐6 levels rose from 90.2 to 140.3 pg·mL(‐1) at exacerbation (p=0.005); the change was greater in the presence of rhinovirus infection (p=0.008). Rhinovirus infection can be detected at chronic obstructive pulmonary disease exacerbation. This is associated with elevation of lower airway interleukin‐6 levels, which may mediate lower airway symptom expression during chronic obstructive pulmonary disease exacerbations.


title: The role of initial chest X-ray in triaging patients with suspected COVID-19 during the pandemic

text: PURPOSE: The purpose of our research is to evaluate the usefulness of chest X-ray for triaging patients with suspected COVID-19 infection. METHODS: IRB approval was obtained to allow a retrospective review of adult patients who presented to the Emergency Department with a complaint of fever, cough, dyspnea or hypoxia and had a chest X-ray between 12 March 2020 and 26 March 2020. The initial chest X-ray was graded on a scale of 0–3 with grade 0 representing no alveolar opacities, grade 1: < 1/3 alveolar opacities of the lung, Grade 2: 1/3 to 2/3 lung with alveolar opacities and grade 3: > 2/3 alveolar opacities of the lung. Past medical history of diabetes and hypertension, initial oxygen saturation, COVID-19 testing results, intubation, and outcome were also collected. RESULTS: Four hundred ten patient chest X-rays were reviewed. Oxygen saturation and X-ray grade were both significantly associated with the length of stay in hospital, the hazard ratio (HR) of discharge was 1.05 (95% CI [1.01, 1.09], p = 0.017) and 0.61 (95% CI [0.51, 0.73], p < 0.001), respectively. In addition, oxygen saturation and X-ray grade were significant predictors of intubation (odds ratio (OR) of intubation is 0.88 (95% CI [0.81, 0.96], p = 0.004) and 3.69 (95% CI [2.25, 6.07], p < 0.001). CONCLUSIONS: Initial chest X-ray is a useful tool for triaging those subjects who might have poor outcomes with suspected COVID-19 infection and benefit most from hospitalization.


title: The Ubiquitin Proteasome System Plays a Role in Venezuelan Equine Encephalitis Virus Infection

text: Many viruses have been implicated in utilizing or modulating the Ubiquitin Proteasome System (UPS) to enhance viral multiplication and/or to sustain a persistent infection. The mosquito-borne Venezuelan equine encephalitis virus (VEEV) belongs to the Togaviridae family and is an important biodefense pathogen and select agent. There are currently no approved vaccines or therapies for VEEV infections; therefore, it is imperative to identify novel targets for therapeutic development. We hypothesized that a functional UPS is required for efficient VEEV multiplication. We have shown that at non-toxic concentrations Bortezomib, a FDA-approved inhibitor of the proteasome, proved to be a potent inhibitor of VEEV multiplication in the human astrocytoma cell line U87MG. Bortezomib inhibited the virulent Trinidad donkey (TrD) strain and the attenuated TC-83 strain of VEEV. Additional studies with virulent strains of Eastern equine encephalitis virus (EEEV) and Western equine encephalitis virus (WEEV) demonstrated that Bortezomib is a broad spectrum inhibitor of the New World alphaviruses. Time-of-addition assays showed that Bortezomib was an effective inhibitor of viral multiplication even when the drug was introduced many hours post exposure to the virus. Mass spectrometry analyses indicated that the VEEV capsid protein is ubiquitinated in infected cells, which was validated by confocal microscopy and immunoprecipitation assays. Subsequent studies revealed that capsid is ubiquitinated on K48 during early stages of infection which was affected by Bortezomib treatment. This study will aid future investigations in identifying host proteins as potential broad spectrum therapeutic targets for treating alphavirus infections.


title: COVID‐19—Associated dyslipidemia: Implications for mechanism of impaired resolution and novel therapeutic approaches

text: The current coronavirus disease 2019 (COVID‐19) pandemic presents a global challenge for managing acutely ill patients and complications from viral infection. Systemic inflammation accompanied by a “cytokine storm,” hemostasis alterations and severe vasculitis have all been reported to occur with COVID‐19, and emerging evidence suggests that dysregulation of lipid transport may contribute to some of these complications. Here, we aim to summarize the current understanding of the potential mechanisms related to COVID‐19 dyslipidemia and propose possible adjunctive type therapeutic approaches that modulate lipids and lipoproteins. Specifically, we hypothesize that changes in the quantity and composition of high‐density lipoprotein (HDL) that occurs with COVID‐19 can significantly decrease the anti‐inflammatory and anti‐oxidative functions of HDL and could contribute to pulmonary inflammation. Furthermore, we propose that lipoproteins with oxidized phospholipids and fatty acids could lead to virus‐associated organ damage via overactivation of innate immune scavenger receptors. Restoring lipoprotein function with ApoA‐I raising agents or blocking relevant scavenger receptors with neutralizing antibodies could, therefore, be of value in the treatment of COVID‐19. Finally, we discuss the role of omega‐3 fatty acids transported by lipoproteins in generating specialized proresolving mediators and how together with anti‐inflammatory drugs, they could decrease inflammation and thrombotic complications associated with COVID‐19.


title: Measurement of hydroxychloroquine in blood from SLE patients using LC-HRMS—evaluation of whole blood, plasma, and serum as sample matrices

text: BACKGROUND: Hydroxychloroquine (HCQ) is the standard of care in the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other inflammatory rheumatic diseases and potentially for the treatment in COVID-19 patients. Determination of HCQ for therapeutic drug monitoring (TDM) can be performed in whole blood (WB), serum, and plasma. Direct comparisons of WB, serum, and plasma levels of HCQ in patients with SLE have not previously been reported. We describe a method for the determination of HCQ in human blood using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and compare the suitability of the three sample matrices. METHODS: A method for the determination of HCQ in human blood using LC-HRMS was developed, validated, and applied for the determination of HCQ levels in WB, serum, and plasma from 26 SLE patients. The reproducibility of the method, in the three matrices, was evaluated using quality control samples and repeated preparations and measurements of patient samples. The performance of the developed method for HCQ measurement in serum was further evaluated by comparison with two previously reported extraction methods. RESULTS: The performance of the presented method demonstrated high accuracy and precision. A large range of HCQ concentrations was observed for the SLE patients in all three matrices (WB, serum, and plasma). The mean levels in WB were approximately two-fold the levels in serum and plasma (813 ng/mL compared to 436 ng/mL and 362 ng/mL, respectively). Spiked quality controls showed high reproducibility for all matrices (coefficient of variation, CV, approx. 5%), whereas in patient samples, equally high-precision was only found using WB as the matrix (CV 3%). The CV for serum and plasma was 14% and 39%, respectively. Two alternative methods applied to serum samples did not demonstrate improved precision. CONCLUSIONS: A LC-HRMS method for the measurement of HCQ in human blood was developed and validated. Whole blood was found to be the superior sample matrix in terms of sample reproducibility. Thus, whole blood samples should be used for HCQ analysis when patients are monitored for HCQ treatment effects. The assay is in clinical use to monitor levels of HCQ in patients.


docid: yqimufdh

title: On the possible viral aetiology of multiple sclerosis


docid: kzljmzzw

title: Specific real-time reverse transcription-polymerase chain reaction for detection and quantitation of turkey coronavirus RNA in tissues and feces from turkeys infected with turkey coronavirus

text: Abstract Turkey coronavirus (TCoV) infection causes acute atrophic enteritis in the turkey poults, leading to significant economic loss in the U.S. turkey industry. Rapid detection, differentiation, and quantitation of TCoV are critical to the diagnosis and control of the disease. A specific one-step real-time reverse transcription-polymerase chain reaction (RRT-PCR) assay for detection and quantitation of TCoV in the turkey tissues was developed using a dual-labeled fluorescent probe. The fluorogenic probe labeled with a reporter dye (FAM, 6-carboxytetramethylrhodamin) and a quencher dye (AbsoluteQuencher™) was designed to bind to a 186 base-pair fragment flanked by the two PCR primers targeting the 3′ end of spike gene of TCoV. The assay was performed on different avian viruses and bacteria to determine the specificity as well as serial dilutions of TCoV for the sensitivity. Three animal trials were conducted to further validate the assay. Ten-day-old turkey poults were inoculated orally with 100 EID50 of TCoV. Intestinal tissues (duodenum, jejunum, ileum, cecum), feces from the cloacal swabs, or feces from the floor were collected at 12h, 1, 2, 3, 5, 7, and/or 14 days post-inoculation (DPI). RNA was extracted from each sample and subjected to the RRT-PCR. The designed primers and probe were specific for TCoV. Other non-TCoV avian viruses and bacteria were not amplified by RRT-PCR. The assay was highly sensitive and could quantitate between 102 and 1010 copies/μl of viral genome. The viral RNA in the intestine segments reached the highest level, 6×1015 copies/μl, in the jejunum at 5 DPI. Eighty-four intestine segments assayed by the developed RRT-PCR and immunofluorescence antibody assay (IFA) revealed that there were 6 segments negative for TCoV by both assays, 45 positive for TCoV by IFA, and 77 positive for TCoV by RRT-PCR. Turkey coronavirus was detected in the feces from the cloacal swabs or floor 1–14 DPI; however, the viral RNA load varied among different turkey poults at different intervals from different trials. The highest amount of viral RNA, 2.8×1010 copies/μl, in the feces was the one from the cloacal swab collected at 1 DPI. The average amount of TCoV RNA in the cloacal fecal samples was 10 times higher than that in the fecal droppings on the floor. Taken together, the results indicated that the developed RRT-PCR assay is rapid, sensitive, and specific for detection, differentiation, and quantitation of TCoV in the turkey tissues and should be helpful in monitoring the progression of TCoV induced acute enteritis in the turkey flocks.


title: Policing a Pandemic: Stay-at-Home Orders and What they Mean for the Police

text: The COVID-19 pandemic has dramatically altered life globally during the first 4 months of 2020. Many countries, including the United States, responded to the pandemic by issuing stay-at-home orders/shelter-in-place orders (SaHOs/SiPOs) to their citizens. By April 2020, more than 90% of the U.S. population was subject to an order. SaHOs/SiPOs raise a number of complex issues for the police, ranging from concerns about infringement of constitutional rights to potential sanctions for violations of an order. This article delves into the issues surrounding SaHOs/SiPOs and highlights their complexity for the police. First, we examine the “why the police?” question, and point to key features of their role which make enforcement of SaHOs/SiPOs the proper business of the police. Second, we examine the relevant legal doctrines that can serve as the basis for police actions against violators of orders, most notably the special needs doctrine. Last, we offer police legitimacy as a lens for viewing the appropriateness of police responses to violators of SaHOs/SiPOs.


title: Human Bocavirus infection and respiratory tract disease identified in a UK patient cohort

text: BACKGROUND: Since its first isolation in 2005, Human Bocavirus (HBoV) has been repeatedly associated with acute respiratory tract infections, although its role in pathogenicity remains unclear due to high co-infection rates. OBJECTIVES: To assess HBoV prevalence and associated disease in a cohort of respiratory patients in the East Midlands, UK between 2015 and 2019. STUDY DESIGN: We initially investigated the undiagnosed burden of HBoV in a retrospective paediatric cohort sampled between 2015 and 2017 using an in-house PCR assay. HBoV was subsequently incorporated into the standard respiratory diagnostic pathway and we audited a calendar year of HBoV positive results between 2018 and 2019. RESULTS: Our retrospective PCR screening of previously routine diagnostic-negative samples from juvenile patients identified a 9% (n = 30) prevalence of HBoV type 1. These apparentHBoV1 mono-infections were frequently associated with respiratory tract symptoms, often severe including ventilation, oxygen and steroid intervention with 31% (n = 9) of individuals requiring intensive care. When HBoV screening was subsequently adopted into the routine respiratory diagnostic pathway, year-round infections were observed in both children and adults peaking in February. 185 of 9098 (2.03%) individuals were found to be HBoV positive with children aged 12-24 months the principally infected group. However, HBoV infection was also observed in patients aged over 60, predominantly as a mono-infection. 23% of the 185 unique patients were HBoV monoinfectedand persistent low-level DNA positivity was observed in 15 individuals up to 6-months after initial presentation. CONCLUSION: HBoV1 is a prevalent respiratory infection in the UK capable of causing serious monoinfections.


title: Predictive value of the user seal check in determining half-face respirator fit

text: Summary Guidelines issued by the Centers for Disease Control and Prevention and the World Health Organization state that healthcare workers should wear N95 masks or higher-level protection during all contact with suspected cases of severe acute respiratory syndrome. Before use, the manufacturer recommends performing a user seal check to ensure that the mask is fitted correctly. This study aimed to test the ability of the user seal check to detect poorly fitting masks. This study is a retrospective review of a mask-fitting programme carried out in the intensive care unit of the Prince of Wales Hospital in Hong Kong. In this programme, all staff were tested with two types of N95 mask and one type of N100 mask. The results of the documented user seal check were then compared with the formal fit-test results from a PortaCount. Using a PortaCount reading of 100 as the criterion for a correctly fitted mask, the user seal check wrongly indicated that the mask fitted on 18–31% of occasions, and wrongly indicated that it did not fit on 21–40% of occasions. These data indicate that the user seal check should not be used as a surrogate fit test. Its usefulness as a pre-use test must also be questioned.


title: Preventing respiratory syncytial virus infections in hospitalized children and adults: should we do better?

text: Summary Objective To compare the burden of nosocomial and community-acquired respiratory syncytial virus (RSV)-associated acute lower respiratory tract infections (ALRIs) in adult and pediatric patients concomitantly admitted to a French tertiary hospital, and to evaluate the effectiveness of existing infection control measures. Patients and methods We prospectively included all adult and pediatric patients admitted to Necker hospital (Paris) between October 2018 and February 2019 with a diagnosis of RSV-associated ALRI. We compared characteristics of ALRIs between patients with community-acquired versus nosocomial infections and, in each group, between children and adults. Results Community-acquired and nosocomial RSV-associated ALRIs were diagnosed in 229 and 11 inpatients, respectively. The burden of community-acquired infections was higher in children than in adults: 2.1% versus 0.2% of the total number of pediatric and adult inpatients, respectively (p < 0.0001); 4.2% versus 0.2% of the total number of hospitalization days in pediatric and adult units, respectively (p < 0.0001). Compared to inpatients with community-acquired ALRIs, those with nosocomial infections were more frequently adults (45.5% versus 2.6%, p = 0.0005) and subjects with at least one chronic complex condition (100.0% versus 41.0%, p < 0.0001). The total number of hospitalization days due to nosocomial ALRIs was higher in adults than in children (0.32% versus 0.11%, p < 0.0001). Conclusions Nosocomial RSV-associated ALRIs rarely occurred, suggesting a good effectiveness of our infection control strategy. However, the burden of nosocomial infection was higher in adults than in children, suggesting that education and training of healthcare personnel, patients and visitors about the risk of nosocomial RSV infections should be reinforced in adult wards.


title: The landscape of host genetic factors involved in infection to common viruses and SARS-CoV-2

text: INTRODUCTION: Humans and viruses have co-evolved for millennia resulting in a complex host genetic architecture. Understanding the genetic mechanisms of immune response to viral infection provides insight into disease etiology and informs public health interventions. METHODS: We conducted a comprehensive study linking germline genetic variation and gene expression with antibody response to 28 antigens for 16 viruses using serological data from 7924 participants in the UK Biobank cohort. Using test results from 2010 UK Biobank subjects, we also investigated genetic determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESULTS: Signals in human leukocyte antigen (HLA) class II region dominated the landscape of viral antibody response, with 40 independent loci and 14 independent classical alleles, 7 of which exhibited pleiotropic effects across viral families. Genome-wide association analyses discovered 7 novel genetic loci associated with viral antibody response (P<5.0×10(−8)), including FUT2 (19q13.33) for human polyomavirus BK (BKV), STING1 (5q31.2) for Merkel cell polyomavirus (MCV), as well as CXCR5 (11q23.3) and TBKBP1 (17q21.32) for human herpesvirus 7. Transcriptome-wide association analyses identified 114 genes associated with response to viral infection, 12 outside of the HLA region, including ECSCR: P=5.0×10(−15) (MCV), NTN5: P=1.1×10(−9) (BKV), and P2RY13: P=1.1×10(−8) (Epstein-Barr virus nuclear antigen). We also demonstrated pleiotropy between viral response genes and complex diseases, such as C4A expression in varicella zoster virus and schizophrenia. Finally, our analyses of SARS-CoV-2 revealed the first genome-wide significant infection susceptibility signal in EHF, an epithelial-specific transcriptional repressor implicated in airway disease. Targeted analyses of expression quantitative trait loci suggest a possible role for tissue-specific ACE2 expression in modifying SARS-CoV-2 susceptibility. CONCLUSIONS: Our study confirms the importance of the HLA region in host response to viral infection and elucidates novel genetic determinants of host-virus interaction. Our results may have implications for complex disease etiology and COVID-19.


title: Infrared thermal imaging in connective tissue diseases

text: Infrared thermal imaging (IRT) is a non-invasive, non-contact technique which allows one to measure and visualize infrared radiation. In medicine, thermal imaging has been used for more than 50 years in various clinical settings, including Raynaud’s phenomenon and systemic sclerosis. Imaging and quantification of surface body temperature provides an indirect measure of the microcirculation’s overall performance. As such, IRT is capable of confirming the diagnosis of Raynaud’s phenomenon, and, with additional cold or heat challenge, of differentiating between the primary and secondary condition. In systemic sclerosis IRT has a potential role in assessing disease activity and monitoring treatment response. Despite certain limitations, thermal imaging can find a place in clinical practice, and with the introduction of small, low-cost infrared cameras, possibly become a part of routine rheumatological evaluation.


title: Extracellular Vesicles and Their Convergence with Viral Pathways

text: Extracellular vesicles (microvesicles), such as exosomes and shed microvesicles, contain a variety of molecules including proteins, lipids, and nucleic acids. Microvesicles appear mostly to originate from multivesicular bodies or to bud from the plasma membrane. Here, we review the convergence of microvesicle biogenesis and aspects of viral assembly and release pathways. Herpesviruses and retroviruses, amongst others, recruit several elements from the microvesicle biogenesis pathways for functional virus release. In addition, noninfectious pleiotropic virus-like vesicles can be released, containing viral and cellular components. We highlight the heterogeneity of microvesicle function during viral infection, addressing microvesicles that can either block or enhance infection, or cause immune dysregulation through bystander action in the immune system. Finally, endogenous retrovirus and retrotransposon elements deposited in our genomes millions of years ago can be released from cells within microvesicles, suggestive of a viral origin of the microvesicle system or perhaps of an evolutionary conserved system of virus-vesicle codependence. More research is needed to further elucidate the complex function of the various microvesicles produced during viral infection, possibly revealing new therapeutic intervention strategies.


title: Phylogenetic distribution and predominant genotype of the avian infectious bronchitis virus in China during 2008-2009

text: BACKGROUND: The nephropathogenic avian infectious bronchitis (IB) caused unprecedented economic losses to the commercial chicken industry of China in 2008-2009. To investigate the prevalence of nephropathogenic IB in China, eighty IBV isolates from different provinces during 2008-2009 were identified by dwarf embryo test and RT-PCR. RESULTS: The strains were mostly isolated in winter and spring with a wide age range of IB outbreaks, from 4 to 69 days. By the virus recovery trials, 70/80 of the strains resulted in the deaths or distresses of birds from nephritis. To learn more about the molecular evolutionary characteristics of the circulating field strains, the coding region of major spike 1 (S1) protein gene of these strains was RT-PCR amplified and sequenced. Compared to the published representative strains, nucleotides and amino acids sequence analysis indicated that the S1 genes of these strains and the reference strains displayed homologies ranging from 75.1% to 99.8% and from 73.1% to 99.8% respectively. S1 protein of the major pandemic strains contained 540 or 542 amino acids with the cleavage site of HRRRR or RRFRR. Phylogenetic analysis revealed that recent field isolates of IBV in China were mostly belonged to A2-branch (QXIBV-branch) and HN08-branch, only one isolate was belonged to Gray-branch and M41-branch respectively. Most of the 80 strains showed evolutionarily distant from vaccine strains. CONCLUSIONS: The results of this study suggested that nephropathogenic IBVs were mainly A2-like strains in China during 2008-2009.


title: Super Resolution Microscopy Reveals that Caveolin-1 Is Required for Spatial Organization of CRFB1 and Subsequent Antiviral Signaling in Zebrafish

text: Understanding spatial distribution and dynamics of receptors within unperturbed membranes is essential for elucidating their role in antiviral signaling, but conventional studies of detergent-resistant membrane fractions cannot provide this information. Caveolae are integral to numerous signaling pathways and these membrane domains have been previously implicated in viral entry but not antiviral defense. This study shows, for the first time, the importance of spatio-temporal regulation of signaling receptors and the importance of the regulation of clustering for downstream signaling. A novel mechanism for virus evasion of host cell defenses is demonstrated through disruption of clusters of signaling molecules organized within caveolin-rich domains. Viral infection leads to a downregulation in Caveolin-1b (Cav-1b), disrupting clusters of CRFB1, a zebrafish type I interferon receptor (–R) subunit. Super-resolution microscopy has enabled the first single-molecule imaging of CRFB1 association with cav-1b-containing membrane domains. Strikingly, downregulation of Cav-1b, the major protein component of caveolae, caused CRFB1 clusters to disperse. Dispersal of CRFB1 clusters led to a suppressed antiviral immune response both in vitro and in vivo, through abrogation of downstream signaling. This response strongly suggests that CRFB1 organization within cav-1b-containing membrane domains is critical for IFN-mediated antiviral defense and presents a previously undescribed antiviral evasion strategy to alter IFN signaling and the antiviral immune response.


title: Characteristic of COVID-19 infection in pediatric patients: early findings from two Italian Pediatric Research Networks

text: Detailed data on clinical presentations and outcomes of children with COVID-19 in Europe are still lacking. In this descriptive study, we report on 130 children with confirmed COVID-19 diagnosed by 28 centers (mostly hospitals), in 10 regions in Italy, during the first months of the pandemic. Among these, 67 (51.5%) had a relative with COVID-19 while 34 (26.2%) had comorbidities, with the most frequent being respiratory, cardiac, or neuromuscular chronic diseases. Overall, 98 (75.4%) had an asymptomatic or mild disease, 11 (8.5%) had moderate disease, 11 (8.5%) had a severe disease, and 9 (6.9%) had a critical presentation with infants below 6 months having significantly increased risk of critical disease severity (OR 5.6, 95% CI 1.3 to 29.1). Seventy-five (57.7%) children were hospitalized, 15 (11.5%) needed some respiratory support, and nine (6.9%) were treated in an intensive care unit. All recovered. Conclusion:This descriptive case series of children with COVID-19, mostly encompassing of cases enrolled at hospital level, suggest that COVID-19 may have a non-negligible rate of severe presentations in selected pediatric populations with a relatively high rates of comorbidities. More studies are needed to further understand the presentation and outcomes of children with COVID-19 in children with special needs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00431-020-03683-8) contains supplementary material, which is available to authorized users.


title: Recent progress and challenges in drug development against COVID-19 coronavirus (SARS-CoV-2) - an update on the status

text: Abstract Coronaviruses are a large group of viruses known to cause illnesses that vary between the common cold and more severe diseases to include severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). A novel coronavirus was identified in December 2019 in Wuhan city, Hubei province, China. This virus represents a new strain that has not been previously identified in humans. The virus is now known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting disease is called coronavirus disease 2019 (COVID-19). The World Health Organization (WHO) declared the novel coronavirus outbreak a global pandemic in March 2020. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with more than 1,948,617 laboratory-confirmed cases and over 121,846 deaths worldwide. Currently, no specific medication is recommended to treat COVID-19 patients. However, governments and pharmaceutical companies are struggling to quickly find an effective drug to defeat the coronavirus. In the current review, we summarize the existing state of knowledge about COVID-19, available medications, and treatment options. Favilavir is an antiviral drug that is approved in Japan for common influenza treatment and is now approved to treat symptoms of COVID-19 in China. Moreover, Chloroquine and hydroxychloroquine, drugs used to treat malaria and arthritis, respectively, were recommended by the National Health Commission of the People's Republic of China for treatment of COVID-19. Presently, chloroquine and hydroxychloroquine are under investigation by the US Food and Drug Administration (FDA) as a treatment for COVID-19. The first COVID-19 vaccine is not expected to be ready for clinical trials before the end of the year.


title: Mental practice as a novel learning strategy for donning and doffing personal protective equipment during the COVID-19 pandemic

text: The coronavirus disease 2019 (COVID-19) pandemic presents challenges to the effective use of personal protective equipment, including equipment shortages, staff unfamiliarity, and physical distancing. Mental practice has been used as an alternative learning strategy in medicine for the development of technical skills. We developed educational materials with the aim of using mental practice to overcome these challenges and increase provider skill and confidence with the use of personal protective equipment. A mental practice script integrating cognitive, kinesthetic, and visual cues with a list of procedural steps was created and iteratively refined. To allow the use of this tool by providers unfamiliar with the principles of mental practice, accompanying explanatory materials were created and disseminated widely through the Free Open Access Medical education (FOAMed) community. By creating easily accessible resources to facilitate effective mental practice, providers may be able to increase their skill and comfort with the procedure while conserving personal protective equipment and respecting physical distancing guidelines.


title: Acute respiratory infections among returning Hajj pilgrims—Jordan, 2014

text: Abstract Background The emergence of Middle East Respiratory Syndrome coronavirus (MERS-CoV) has prompted enhanced surveillance for respiratory infections among pilgrims returning from the Hajj, one of the largest annual mass gatherings in the world. Objectives To describe the epidemiology and etiologies of respiratory illnesses among pilgrims returning to Jordan after the 2014 Hajj. Study design Surveillance for respiratory illness among pilgrims returning to Jordan after the 2014 Hajj was conducted at sentinel health care facilities using epidemiologic surveys and molecular diagnostic testing of upper respiratory specimens for multiple respiratory pathogens, including MERS-CoV. Results Among the 125 subjects, 58% tested positive for at least one virus; 47% tested positive for rhino/enterovirus. No cases of MERS-CoV were detected. Conclusions The majority of pilgrims returning to Jordan from the 2014 Hajj with respiratory illness were determined to have a viral etiology, but none were due to MERS-CoV. A greater understanding of the epidemiology of acute respiratory infections among returning travelers to other countries after Hajj should help optimize surveillance systems and inform public health response practices.


title: Airway Interleukin-33 and type 2 cytokines in adult patients with acute asthma

text: Abstract Background Several animal studies, and one inoculation study in adult asthmatics have shown that interleukin-33 (IL-33) is a major contributor to type-2 inflammation in acute asthma. However, the link between IL-33 and type-2 inflammation has not been shown in naturally occurring asthma exacerbations. Objectives To determine if airway IL-33 is associated with type-2 inflammation measured by type-2 cytokines, FeNO and sputum eosinophils in patients presenting to the Emergency Department with an asthma exacerbations. Methods Adult patients hospitalized due to acute asthma were enrolled. Upper airways were sampled with nasal swabs and lower airways with induced sputum. Cytokines were measured at protein level using a Luminex® assay and mRNA expression level using droplet-digital-PCR. Airway sampling was repeated four weeks after exacerbation. Results At the time of exacerbation, upper airway IL-33 correlated with upper airway IL-5 and IL-13 (R = 0.84, p < 0.01 and R = 0.76, p < 0.01, respectively) and with lower airway IL-13 (R = 0.49, p = 0.03). Similar associations were observed for mRNA expression. Lower airway IL-33 positively correlated with lower airway IL-13 (R = 0.84, p < 0.01). IL-13 and IL-33 were positively correlated with FeNO, and IL-5 with eosinophils. The association between IL-33 and type-2 cytokines were still present four weeks after exacerbation. Conclusion This is the first study to demonstrate that airway IL-33 is associated with type-2 cytokines in naturally occurring asthma exacerbations in adults, providing in vivo evidence supporting that IL-33 may be driving type-2 inflammation in acute asthma. Thus supporting IL-33 as a potential future drug target due to its role, upstream in the immunological cascade.


Bat Coronavirus in Brazil Related to Appalachian Ridge and Porcine Epidemic Diarrhea Viruses


title: Preliminary CT findings of coronavirus disease 2019 (COVID-19)

text: OBJECTIVES: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This paper aims to examine the CT imaging characteristics of COVID-19. METHODS: We evaluated CT images obtained between 10 January 2019 and 16 February 2020 at Taihe Hospital. Scans were conducted 2–6 times per patient and the re-testing interval was 2–7 days. Ninety-five patients with positive SARS-CoV-2 nucleic acid test results were included in this study and we retrospectively analysed their CT imaging characteristics. RESULTS: Ninety-five patients underwent 2–3 SARS-CoV-2 nucleic acid tests and received a definitive diagnosis of COVID-19. Fifty-three were male and 42 were female, and their mean age was 42 ± 12 years (range: 10 months to 81 years). Sixty-nine patients (72.6%) experienced fever, fatigue, and dry cough, while 15 (15.8%) had poor appetite and fatigue, and 11 (11.6%) had a dry cough and no fever. On CT imaging, early stage patients (n = 53, 55.8%) showed peripheral subpleural ground-glass opacities; these were mainly local patches (22/53, 41.5%), while some lesions were accompanied by interlobular septal thickening. Thirty-four (35.8%) patients were classified in the ‘progression stage’ based on CT imaging; these patients typically showed lesions in multiple lung segments and lobes (21/34，61.8%), and an uneven increase in ground-glass opacity density accompanied by consolidation and grid-like or cord-like shadows(30.5%). Two patients (2.1%) showed a severe presentation on CT. These showed diffuse bilateral lung lesions, mixed ground-glass opacities and consolidation with cord-like interstitial thickening and air bronchograms, entire lung involvement with a “white lung” presentation, and mild pleural effusion. Six patients in remission (6.3%), visible lesion absorption, fibrotic lesions. Based on clinical signs, 71 (74.7%), 22 (23.2%), and 2 (2.1%) patients had mild or moderate, severe, and critical disease, respectively. Within the follow-up period, 93 patients recovered and were discharged, including the 53 early stage patients and 34 progression stage patients. The length of hospitalisation was 7–28 days (mean: 10 ± 3.5 days). On discharge, lesions were significantly reduced in area and had in many cases completely disappeared, while slight pulmonary fibrosis was present in some patients. One severe stage patient was still hospitalised at the end of the follow-up period and the other severe stage patient died. The overall mortality rate was 1.05%. CONCLUSIONS: Understanding the CT imaging characteristics of COVID-19 is important for early lesion detection, determining the nature of lesions, and assessing disease severity.


title: Risk of Ischemic Stroke in Patients with Covid-19 versus Patients with Influenza

text: IMPORTANCE: Case series without control groups suggest that Covid-19 may cause ischemic stroke, but whether Covid-19 is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection is uncertain. OBJECTIVE: To compare the rate of ischemic stroke between patients with Covid-19 and patients with influenza, a respiratory viral illness previously linked to stroke. DESIGN: A retrospective cohort study. SETTING: Two academic hospitals in New York City. PARTICIPANTS: We included adult patients with emergency department visits or hospitalizations with Covid-19 from March 4, 2020 through May 2, 2020. Our comparison cohort included adult patients with emergency department visits or hospitalizations with influenza A or B from January 1, 2016 through May 31, 2018 (calendar years spanning moderate and severe influenza seasons). EXPOSURES: Covid-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the nasopharynx by polymerase chain reaction, and laboratory-confirmed influenza A or B. MAIN OUTCOMES AND MEASURES: A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, etiological mechanisms, and outcomes. We used logistic regression to compare the proportion of Covid-19 patients with ischemic stroke versus the proportion among patients with influenza. RESULTS: Among 2,132 patients with emergency department visits or hospitalizations with Covid-19, 31 patients (1.5%; 95% confidence interval [CI], 1.0%-2.1%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78) and 58% were men. Stroke was the reason for hospital presentation in 8 (26%) cases. For our comparison cohort, we identified 1,516 patients with influenza, of whom 0.2% (95% CI, 0.0-0.6%) had an acute ischemic stroke. After adjustment for age, sex, and race, the likelihood of stroke was significantly higher with Covid-19 than with influenza infection (odds ratio, 7.5; 95% CI, 2.3-24.9). CONCLUSIONS AND RELEVANCE: Approximately 1.5% of patients with emergency department visits or hospitalizations with Covid-19 experienced ischemic stroke, a rate 7.5-fold higher than in patients with influenza. Future studies should investigate the thrombotic mechanisms in Covid-19 in order to determine optimal strategies to prevent disabling complications like ischemic stroke.


title: Emerging zoonoses: The challenge for public health and biodefense

text: Abstract The concept of new and emerging diseases has captured the public interest and has revitalized the public health infectious disease research community. This interest has also resulted in competition for funding and turf wars between animal health and public health scientists and public officials and, in some cases, has delayed and hindered progress toward effective prevention, control and biodefense. There is a dynamic list of outbreaks causing substantial morbidity and mortality in humans and often in the reservoir animal species. Some agents have the potential to grow into major epidemics. There are many determinants that influence the emergence of diseases of concern that require the use of current understanding of the nature of agent persistence and spread. Additional factors that are global must be added to plans for prevention and control. To this complex mix has been added the potential for accidental or malicious release of agents. The nature of emerging infectious agents and their impact is largely unpredictable. Models that strive to predict the dynamics of agents may be useful but can also blind us to increasing disease risks if it does not match a specific model. Field investigations of early events will be critical and should drive prevention and control actions. Many disease agents have developed strategies to overcome extremes of reservoir qualities like population size and density. Every infectious agent spreads easier when its hosts are closer together. Zoonoses must be dealt with at the interface of human and animal health by all available information. Lessons learned from the emergence of and response to agents like West Nile virus, H5N1 avian influenza, SARS and bovine spongiform encephalopathy, the cause of new-variant Creutzfeldt–Jakob disease in humans, must be used to create better plans for response and meet the challenge for public health and biodefense.


title: The association between symptom onset and length of hospital stay in 2019 Novel Coronavirus Pneumonia Cases Without Epidemiological Trace

text: Abstract Objective Compared to COVID-19 cases with established epidemiological trace, little is known about the patients without one. This study reports an association between time of symptom onset (TOS) and length of hospital stay (LOS) in COVID-19 infection without epidemiological link. Methods Generalized linear regression models were used to examine the association between symptom onset and primary outcome LOS. A group of patients with established epidemiological link in same medical facility during that period of time were used as controls. Results A total of 38 COVID-19 patients were admitted, 26 of which were found without travel history to infected area or direct contact with a case-patient. TOS was negatively associated with LOS in patients without epidemiological trace (IRR = 0.980; 95% CI = 0.967 to 0.993; P = 0.003). Conclusions In COVID-19 cases without typical epidemiological links, patients with later symptom onset had relatively shorter LOS.


title: An Acute Immune Response to Middle East Respiratory Syndrome Coronavirus Replication Contributes to Viral Pathogenicity

text: Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in a human with severe pneumonia in 2012. Since then, infections have been detected in >1500 individuals, with disease severity ranging from asymptomatic to severe, fatal pneumonia. To elucidate the pathogenesis of this virus and investigate mechanisms underlying disease severity variation in the absence of autopsy data, a rhesus macaque and common marmoset model of MERS-CoV disease were analyzed. Rhesus macaques developed mild disease, and common marmosets exhibited moderate to severe, potentially lethal, disease. Both nonhuman primate species exhibited respiratory clinical signs after inoculation, which were more severe and of longer duration in the marmosets, and developed bronchointerstitial pneumonia. In marmosets, the pneumonia was more extensive, with development of severe airway lesions. Quantitative analysis showed significantly higher levels of pulmonary neutrophil infiltration and higher amounts of pulmonary viral antigen in marmosets. Pulmonary expression of the MERS-CoV receptor, dipeptidyl peptidase 4, was similar in marmosets and macaques. These results suggest that increased virus replication and the local immune response to MERS-CoV infection likely play a role in pulmonary pathology severity. Together, the rhesus macaque and common marmoset models of MERS-CoV span the wide range of disease severity reported in MERS-CoV–infected humans, which will aid in investigating MERS-CoV disease pathogenesis.


title: Proteomics for biodefense applications: progress and opportunities

text: The increasing threat of bioterrorism and continued emergence of new infectious diseases has driven a major resurgence in biomedical research efforts to develop improved treatments, diagnostics and vaccines, as well as increase the fundamental understanding of the host immune response to infectious agents. The availability of multiple mass spectrometry platforms combined with multidimensional separation technologies and microbial genomic databases provides an unprecedented opportunity to develop these much needed resources. An overview of current proteomic strategies applied to microbes and viruses considered potential bioterrorism agents is presented. The emerging area of immunoproteomics as applied to the development of new vaccine targets is also summarized. These powerful research approaches can generate a multitude of potential new protein targets; however, translating these proteomic discoveries to useful counter-bioterrorism products will require large collaborative research efforts across multiple basic science and clinical disciplines. A translational proteomic research paradigm illustrating this approach using influenza virus as an example is discussed.


title: Contagious Disease and Self-Defence

text: This paper gives a self-defence account of the scope and limits of the justified use of compulsion to control contagious disease. It applies an individualistic model of self-defence for state action and uses it to illuminate the constraints on public health compulsion of proportionality and using the least restrictive alternative. It next shows how a self-defence account should not be rejected on the basis of past abuses. The paper then considers two possible limits to a self-defence justification: compulsion of the non-culpable and over-inclusive compulsion. The paper claims that objections to compelling the non-culpable do not greatly restrict the scope of the self-defence justification. The over-included are, however, innocent bystanders, and methods such as compulsory quarantine, vaccination, and screening are not justified in self-defence.


title: Hemagglutination mediated by the spike protein of cell-adapted bovine torovirus

text: Bovine torovirus (BToV)-Aichi, recently isolated in cultured cells, showed hemagglutination (HA) activity, although the virus has a truncated hemagglutinin-esterase (HE) protein, judging from its gene structure, indicating the existence of another viral protein with HA activity. We examined whether the spike (S) protein possesses HA activity. A BToV antiserum used in this study, reactive to S but not to HE, inhibited HA activity. Furthermore, cells infected with BToV and those expressing S showed hemadsorption (HAD) activity, which was inhibited by the anti-BToV serum; however, HAD activity by expressed HE was not blocked. These data indicate that the S protein of BToV-Aichi is responsible for its HA activity.


title: Passive inhalation of dry powder influenza vaccine formulations completely protects chickens against H5N1 lethal viral challenge

text: Abstract Bird to human transmission of high pathogenicity avian influenza virus (HPAIV) poses a significant risk of triggering a flu pandemic in the human population. Therefore, vaccination of susceptible poultry during an HPAIV outbreak might be the best remedy to prevent such transmissions. To this end, suitable formulations and an effective mass vaccination method that can be translated to field settings needs to be developed. Our previous study in chickens has shown that inhalation of a non-adjuvanted dry powder influenza vaccine formulation during normal breathing results in partial protection against lethal influenza challenge. The aim of the present study was to improve the effectiveness of pulmonary vaccination by increasing the vaccine dose deposited in the lungs and by the use of suitable adjuvants. Two adjuvants, namely, Bacterium-like Particles (BLP) and Advax, were spray freeze dried with influenza vaccine into dry powder formulations. Delivery of dry formulations directly at the syrinx revealed that BLP and Advax had the potential to boost either systemic or mucosal immune responses or both. Upon passive inhalation of dry influenza vaccine formulations in an optimized set-up, BLP and Advax/BLP adjuvanted formulations induced significantly higher systemic immune responses than the non-adjuvanted formulation. Remarkably, all vaccinated animals not only survived a lethal influenza challenge, but also did not show any shedding of challenge virus except for two out of six animals in the Advax group. Overall, our results indicate that passive inhalation is feasible, effective and suitable for mass vaccination of chickens if it can be adapted to field settings.


title: Ebola outbreak preparedness planning: a qualitative study of clinicians' experiences

text: Abstract Objectives The 2014–15 Ebola outbreak in West Africa highlighted the challenges many hospitals face when preparing for the potential emergence of highly contagious diseases. This study examined the experiences of frontline health care professionals in an Australian hospital during the outbreak, with a focus on participant views on information, training and preparedness, to inform future outbreak preparedness planning. Study design Semi-structured interviews were conducted with 21 healthcare professionals involved in Ebola preparedness planning, at a hospital in Australia. Methods The data were systematically coded to discover key themes in participants' accounts of Ebola preparedness. Results Three key themes identified were: 1) the impact of high volumes of—often inconsistent—information, which shaped participants' trust in authority; 2) barriers to engagement in training, including the perceived relative risk Ebola presented; and finally, 3) practical and environmental impediments to preparedness. Conclusions These clinicians' accounts of Ebola preparedness reveal a range of important factors which may influence the relative success of outbreak preparedness and provide guidance for future responses. In particular, they illustrate the critical importance of clear communication and guidelines for staff engagement with, and implementation of training. An important outcome of this study was how individual assessments of risk and trust are produced via, and overlap with, the dynamics of communication, training and environmental logistics. Consideration of the dynamic ways in which these issues intersect is crucial for fostering an environment that is suitable for managing an infectious threat such as Ebola.


title: Antiviral Drug Discovery: Norovirus Proteases and Development of Inhibitors

text: Proteases are a major enzyme group playing important roles in a wide variety of biological processes in life forms ranging from viruses to mammalians. The aberrant activity of proteases can lead to various diseases; consequently, host proteases have been the focus of intense investigation as potential therapeutic targets. A wide range of viruses encode proteases which play an essential role in viral replication and, therefore, constitute attractive targets for the development of antiviral therapeutics. There are numerous examples of successful drug development targeting cellular and viral proteases, including antivirals against human immunodeficiency virus and hepatitis C virus. Most FDA-approved antiviral agents are peptidomimetics and macrocyclic compounds that interact with the active site of a targeted protease. Norovirus proteases are cysteine proteases that contain a chymotrypsin-like fold in their 3D structures. This review focuses on our group’s efforts related to the development of norovirus protease inhibitors as potential anti-norovirus therapeutics. These protease inhibitors are rationally designed transition-state inhibitors encompassing dipeptidyl, tripeptidyl and macrocyclic compounds. Highly effective inhibitors validated in X-ray co-crystallization, enzyme and cell-based assays, as well as an animal model, were generated by launching an optimization campaign utilizing the initial hit compounds. A prodrug approach was also explored to improve the pharmacokinetics (PK) of the identified inhibitors.


title: The influence of human walking on the flow and airborne transmission in a six-bed isolation room: Tracer gas simulation

text: Abstract By performing unsteady CFD simulations using RNG k–ɛ model and dynamic mesh technique, this paper investigates how the walking motion of health care worker (HCW) influences gaseous dispersion in a six-bed isolation room with nine downward supplies and six ceiling-level or floor-level exhausts. The flow near and behind HCW is easily affected by HCW motion. The flow disturbance induced by HCW walking with swinging arms and legs is a mixing process. The walking HCW displaces air in front of it and carries air in the wake forwardly, meanwhile pressure difference drives air from two lateral sides into the wake. HCW motion (0–5.4 s) indeed induces a little gaseous dispersion, but the residual flow disturbance after HCW stops (5.4 s–25.4 s) induces more gaseous agent spread and it requires more than 30–60 s to approximately recover to the initial state after HCW stops. Although HCW motion indeed affects airborne transmission, but its effect is less important than ventilation design. No matter with or without HCW motion, the ceiling-level exhausts perform much better in controlling airborne transmission than the floor-level exhausts with the same air change rate (12.9 ACH). Smaller air change rate of 6 ACH experiences higher concentration and more gaseous spread than 12.9 ACH. In contrast to the realistic human walking, the simplified motion of a rectangular block produces stronger flow disturbance. Finally surface heating of HCW produces a stronger thermal body plume and enhances turbulence near HCW, thus slightly strengthens airborne transmission.


Developing approaches to control SARS-CoV-2 in a public hospital


title: Modulation of NF-κB signalling by microbial pathogens

text: The nuclear factor-κB (NF-κB) family of transcription factors plays a central part in the host response to infection by microbial pathogens, by orchestrating the innate and acquired host immune responses. The NF-κB proteins are activated by diverse signalling pathways that originate from many different cellular receptors and sensors. Many successful pathogens have acquired sophisticated mechanisms to regulate the NF-κB signalling pathways by deploying subversive proteins or hijacking the host signalling molecules. Here, we describe the mechanisms by which viruses and bacteria micromanage the host NF-κB signalling circuitry to favour the continued survival of the pathogen.


title: Clinical presentation and initial management critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brescia, Italy

text: Abstract Purpose An ongoing pandemic of COVID-19 that started in Hubei, China has resulted in massive strain on the healthcare infrastructure in Lombardy, Italy. The management of these patients is still evolving. Materials and methods This is a single-center observational cohort study of critically ill patients infected with COVID-19. Bedside clinicians abstracted daily patient data on history, treatment, and short-term course. We describe management and a proposed severity scale for treatment used in this hospital. Results 44 patients were enrolled; with incomplete information on 11. Of the 33 studied patients, 91% were male, median age 64; 88% were overweight or obese. 45% were hypertensive, 12% had been taking an ACE-inhibitor. Noninvasive ventilation was performed on 39% of patients for part or all or their ICU stay with no provider infection. Most patients received antibiotics for pneumonia. Patients also received lopinivir/ritonavir (82%), hydroxychloroquine (79%), and tocilizumab (12%) according to this treatment algorithm. Nine of 10 patients survived their ICU course and were transferred to the floor, with one dying in the ICU. Conclusions ICU patients with COVID-19 frequently have hypertension. Many could be managed with noninvasive ventilation, despite the risk of aerosolization. The use of a severity scale augmented clinician management.


Recognizing and Mitigating the Threat Posed by COVID‐19 to Otolaryngologists: A UK Perspective


title: Porcine sapoviruses: Pathogenesis, epidemiology, genetic diversity, and diagnosis

text: The first porcine Sapovirus (SaV) Cowden strain was discovered in 1980. To date, eight genogroups (GIII, V-IX) and three genogroups (GIII, GV, and GVI) of porcine SaVs have been detected from domestic pigs worldwide and wild boars in Japan, respectively based on the capsid sequences. Although GIII Cowden strain replicated in the villous epithelial cells and caused intestinal lesions in the proximal small intestines (mainly in duodenal and less in jejunum), leading to mild to severe diarrhea, in the orally inoculated neonatal gnotobiotic pigs, the significance of porcine SaVs in different ages of pigs with diarrhea in the field is still undetermined. This is due to two reasons: 1) similar prevalence of porcine SaVs was detected in diarrheic and non-diarrheic pigs; and 2) co-infection of porcine SaVs with other enteric pathogens is common in pigs. Diagnosis of porcine SaV infection is mainly based on the detection of viral nucleic acids using reverse transcription (RT)-PCR and sequencing. Much is unknown about these genetically diverse viruses to understand their role in pig health and to evaluate whether vaccines are needed to prevent SaV infection.


title: Avascular necrosis of bone in severe acute respiratory syndrome

text: Abstract AIM: To report the incidence of avascular osteonecrosis (AVN) in severe acute respiratory syndrome (SARS) patients. MATERIALS AND METHODS: Sixty-seven SARS patients who had large joint pain between March 2003 and May 2003 underwent both plain radiographs and magnetic resonance imaging (MRI) examination on the same day. All patients received steroids and ribavirin treatment. All plain radiographs and MR images were analysed by two experienced musculoskeletal radiologists. Any abnormalities, location, extent, morphology, the number, size and signal intensity of lesions were evaluated. RESULTS: Twenty-eight patients were identified with AVN, The mean time to diagnosis of AVN was 119 days after the onset of SARS, or 116 days after steroid use. Three patients had early bilateral AVN of the femoral head, four patients of one femoral head, five patients of the bilateral hips and knees, four patients of the ipsilateral hip and knees, 10 patients of the knee(s), one patient of the right proximal fibula, and one patient of the knees and talus. Results of hip, knee and ankle plain radiographs were negative. CONCLUSION: AVN can occur in the patients with SARS. AVN had a strong association with steroid use. More studies are required to confirm whether the virus itself can also lead to AVN.


title: Self-disseminating vaccines for emerging infectious diseases

text: Modern human activity fueled by economic development is profoundly altering our relationship with microorganisms. This altered interaction with microbes is believed to be the major driving force behind the increased rate of emerging infectious diseases from animals. The spate of recent infectious disease outbreaks, including Ebola virus disease and Middle East respiratory syndrome, emphasize the need for development of new innovative tools to manage these emerging diseases. Disseminating vaccines are one such novel approach to potentially interrupt animal to human (zoonotic) transmission of these pathogens.


title: Whole genome sequencing in the prevention and control of Staphylococcus aureus infection

text: Summary Background Staphylococcus aureus remains a leading cause of hospital-acquired infection but weaknesses inherent in currently available typing methods impede effective infection prevention and control. The high resolution offered by whole genome sequencing has the potential to revolutionise our understanding and management of S. aureus infection. Aim To outline the practicalities of whole genome sequencing and discuss how it might shape future infection control practice. Methods We review conventional typing methods and compare these with the potential offered by whole genome sequencing. Findings In contrast with conventional methods, whole genome sequencing discriminates down to single nucleotide differences and allows accurate characterisation of transmission events and outbreaks and additionally provides information about the genetic basis of phenotypic characteristics, including antibiotic susceptibility and virulence. However, translating its potential into routine practice will depend on affordability, acceptable turnaround times and on creating a reliable standardised bioinformatic infrastructure. Conclusion Whole genome sequencing has the potential to provide a universal test that facilitates outbreak investigation, enables the detection of emerging strains and predicts their clinical importance.


title: Evolutionary Medicine of Retroviruses in the Human Genome

text: ABSTRACT Humans are infected with many viruses, and the immune system mostly removes viruses and the infected cells. However, certain viruses have entered the human genome. Of the human genome, ∼45% is composed of transposable elements (long interspersed nuclear elements [LINEs], short interspersed nuclear elements [SINEs] and transposons) and 5-8% is derived from viral sequences with similarity to infectious retroviruses. If integration of retrovirus occurs in a germline, the integrated viral sequences are heritable. Accumulation of viral sequences has created the current human genome. This article summarizes recent studies of retroviruses in humans and bridges clinical fields and evolutionary genetics. First, we report the repertories of human-infective retroviruses. Second, we review endogenous retroviruses in the human genome and diseases associated with endogenous retroviruses. Third, we discuss the biological functions of endogenous retroviruses and propose the concept of accelerated human evolution via viruses. Finally, we present perspectives of virology in the field of evolutionary medicine.


title: Reply to: “Current smoking is not associated with COVID-19”

text: Smoking and COPD are risk factors for severe COVID-19 https://bit.ly/2KJxAbp


docid: zojhdnlu

title: Detection of SARS-associated Coronavirus in Throat Wash and Saliva in Early Diagnosis

text: The severe acute respiratory syndrome–associated coronavirus (SARS-CoV) is thought to be transmitted primarily through dispersal of droplets, but little is known about the load of SARS-CoV in oral droplets. We examined oral specimens, including throat wash and saliva, and found large amounts of SARS-CoV RNA in both throat wash (9.58 x 10(2) to 5.93 x 10(6) copies/mL) and saliva (7.08 x 10(3) to 6.38 x 10(8) copies/mL) from all specimens of 17 consecutive probable SARS case-patients, supporting the possibility of transmission through oral droplets. Immunofluorescence study showed replication of SARS-CoV in the cells derived from throat wash, demonstrating the possibility of developing a convenient antigen detection assay. This finding, with the high detection rate a median of 4 days after disease onset and before the development of lung lesions in four patients, suggests that throat wash and saliva should be included in sample collection guidelines for SARS diagnosis.


title: Real‐world assessment of the clinical impact of symptomatic infection with severe acute respiratory syndrome coronavirus (COVID‐19 disease) in patients with Multiple Myeloma receiving systemic anti‐cancer therapy.

text: Infection with the novel coronavirus SARS‐CoV‐2 virus resulting in an acute respiratory disease (COVID‐19 disease) is the cause of the current pneumonia pandemic, with a rapid rise in cases being reported in the European Union and UK (1, 2). The UK index case was identified on the 31(st) of January, 2020 and given the rapid spread and high mortality rate of COVID‐19, it is imperative to define the impact on patients with co‐existing medical conditions(3).


title: Cross-sectional survey of selected enteric viruses in Polish turkey flocks between 2008 and 2011

text: BACKGROUND: Enteric diseases are an important health problem for the intensive poultry industry, resulting in considerable economic losses. Apart from such microbiological agents associated with enteritis as bacteria and parasites, a lot of research has been recently conducted on viral origin of enteric diseases. However, enteric viruses have been identified in intestinal tract of not only diseased but also healthy poultry, so their role in enteritis is still unclear. The present study aimed at determination of the prevalence of four enteric viruses, namely astrovirus, coronavirus, parvovirus and rotavirus in meat-type turkey flocks in Poland as well as at statistical evaluation of the occurrence of the studied viruses and their relationships with the health status and the age of birds. Two hundred and seven flocks of birds aged 1-20 weeks originating from different regions of the country were investigated between 2008 and 2011. Clinical samples (10 individual faecal swabs/flock) were duly processed and examined using molecular methods targeting the conservative regions of viral genomes: RNA-dependent RNA polymerase gene of astrovirus, non-structural 1 gene of parvovirus, non-structural protein 4 gene of rotavirus, and 5′ untranslated region fragment of turkey coronavirus. Different statistical methods (i.e. the independence chi-square test, the correspondence analysis and the logistic regression model) were used to establish any relationships between the analyzed data. RESULTS: Overall, 137 (66.2%, 95% CI: 59.3-72.6) of the 207 turkey flocks sampled were infected with one or more enteric viruses. Among the 137 flocks, 74 (54%, 95% CI: 45.3-62.6) were positive for one virus, whereas 54 (39.4%, 9 5% CI: 31.2-48.1) and 9 (6.6%, 95% CI: 3.1-12.1) were co-infected with two or three different enteric viruses, respectively. No flock was simultaneously infected with all four viruses studied. The prevalence of astrovirus infection was 44.9% (95% CI: 38.0-52.0), parvovirus 27.5% (95% CI: 21.6-34.2), rotavirus 18.8% (95% CI: 13.8-24.8), and coronavirus 9.7% (95% CI: 6.0-14.5). Young turkeys aged 1-4 weeks old had the highest (82.1%, 95% CI:71.7-89.8) prevalence of viral infection. Applied statistical methods have indicated the dependence of rotavirus infection as well as the co-infection with multiple viruses and the health status of turkeys. Furthermore, our results statistically confirm that especially young birds are susceptible to infection with rotavirus and astrovirus. CONCLUSIONS: The study demonstrated the presence of astrovirus, coronavirus, parvovirus and rotavirus infections in Polish turkey farms. These viruses were detected in both healthy and diseased birds. However, the presented results provide valuable feedback which could help to evaluate the role of some enteric viruses in the etiology of enteritis in turkey.


title: Heterologous Boosting of Recombinant Adenoviral Prime Immunization With a Novel Vesicular Stomatitis Virus–vectored Tuberculosis Vaccine

text: Pulmonary tuberculosis (TB) remains a serious health problem worldwide. Effective vaccination strategies are needed. We report the development of a novel TB vaccine using vesicular stomatitis virus (VSV) as a viral vector system to express Ag85A. VSVAg85A was shown to be immunogenic when given to mice by either an intranasal or an intramuscular (IM) route. Although distinct T-cell profiles resulted from both routes of immunization, only intranasal delivery generated a mucosal T-cell response that was protective upon pulmonary Mycobacterium tuberculosis (M.tb) challenge. While this protection manifested at an early time-point after immunization, it was not sustained. The potential of VSVAg85A to be used as a mucosal booster for parenteral priming by an adenoviral TB vaccine expressing Ag85A (AdAg85A) was investigated. VSVAg85A immunization markedly boosted antigen-specific T-cell responses in the airway lumen while also augmenting immune activation in the systemic compartment, after AdAg85A priming. This translated into significantly better protective efficacy against pulmonary challenge with M.tb than either vaccine used alone. Our study therefore suggests that VSV as a vector system is a promising candidate to be used in a heterologous viral prime-boost immunization regimen against intracellular bacterial infection.


title: Human Adenovirus Type 55 Distribution, Regional Persistence, and Genetic Variability

text: Human adenovirus type 55 (HAdV-55) causes acute respiratory disease of variable severity and has become an emergent threat in both civilian and military populations. HAdV-55 infection is endemic to China and South Korea, but data from other regions and time periods are needed for comprehensive assessment of HAdV-55 prevalence from a global perspective. In this study, we subjected HAdV-55 isolates from various countries collected during 1969–2018 to whole-genome sequencing, genomic and proteomic comparison, and phylogenetic analyses. The results show worldwide distribution of HAdV-55; recent strains share a high degree of genomic homogeneity. Distinct strains circulated regionally for several years, suggesting persistent local transmission. Several cases of sporadic introduction of certain strains to other countries were documented. Among the identified amino acid mutations distinguishing HAdV-55 strains, some have potential impact on essential viral functions and may affect infectivity and transmission.


title: Straight talk with...Tom Inglesby

text: When letters containing anthrax spores were mailed to several US senators and media offices in September 2001, just one week after the 9/11 attacks, bioterrorism catapulted to the national stage. Political leaders and public health officials, desperate for guidance on this once-theoretical scenario, turned to experts including Tom Inglesby, then deputy director of the Johns Hopkins Center for Civilian Biodefense Strategies, a bioterrorism research and analysis think tank in Baltimore. In the years that followed, Inglesby and his colleagues ran exercises to simulate bioterror incidents, established a peer-reviewed journal on biodefense and advised government agencies on how to reduce the public health impact of biological threats. Today, he continues his work with the think tank, which moved to the University of Pittsburgh Medical Center (UPMC) in 2003 (although it stayed headquartered in Baltimore) and which was recently renamed the UPMC Center for Health Security. As director and chief executive officer for the past four years, Inglesby has expanded the center's focus toward preventing public health crises arising from infectious diseases, pandemics and major natural disasters, in addition to biological, chemical and nuclear accidents or threats. Inglesby spoke with Kevin Jiang about how responses to bioterrorism, pandemics and natural disasters aren't all that different.