title: SARS

text: Severe acute respiratory syndrome (SARS) emerged in southern China in late 2002. It first spread within Guangdong Province and then to other parts of China. Via air travelers, it quickly reached various countries around the globe, causing several major hospital outbreaks. Within weeks, the causative agent, a previously unknown coronavirus (SARS-CoV), was identified, thanks to an unprecedented international effort led by the World Health Organization (WHO). Its origin was quickly traced to wild animals traded locally for culinary purposes. Masked palm civet and some other species seem to have acted as intermediate hosts. Since then, SARS-like coronaviruses were found in different bat species in China and elsewhere, and bats are now regarded as the wildlife reservoir for SARS-CoV. Fortunately, the SARS outbreak could be contained within months. Until July 2003, it had caused 8096 cases, with 774 deaths. Once adequate measures such as isolating patients and quarantining their contacts were strictly adhered to, further transmission between human beings could be interrupted. SARS is an example of how rapidly an infectious agent can spread in the modern world. At the same time, it should serve as a showcase of how international cooperation and modern science can help to combat the spread of infectious diseases.


title: Virological and serological findings in dogs with naturally occurring distemper

text: Abstract Canine distemper virus (CDV) is the cause of a severe and highly contagious disease in dogs. The unpredictable and variable course of CDV-related disease may hamper correct diagnosis of infection and makes it crucial the collection of samples suitable for laboratory confirmation. In the present study we were able to follow the disease in two dogs infected naturally, collecting different biological matrices during the entire period of infection. By real time RT-PCR, viral RNA was detected and quantified, suggesting that urine and rectal swabs would be useful for ante-mortem diagnosis of distemper in dogs, regardless of the clinical stage and form of the illness.


Commentary: When a cardiac surgeon takes care of patients with Coronavirus Disease 2019: It’s gonna be ok!


Frontiers in the Convergence of Bioscience and Information Technology


title: Respiratory infections in immunocompromised patients: Lung findings using chest computed tomography

text: Abstract Respiratory infections and subsequent complications are one of the leading causes of high mortality in immunocompromised patients. Although chest radiograph and computed tomography are the commonly used diagnostic tools for the early diagnosis of lung manifestations of infections, they lack the specificity for the wide range of chest infections which can occur in immunocompromised patients. Systematic analysis of the imaging findings in correlation with the clinical settings along with comparison with the old images can expedite early and accurate diagnosis for subsequent appropriate management. Computer tomography findings in immunocompromised patients with respiratory infections, with regards to various clinical settings, will be discussed here.


title: Epidemic Trend of COVID-19 Transmission in India During Lockdown-1 Phase

text: To assess the current epidemic trend of COVID-19/SARS-CoV-2 in India, the epidemic dynamics of COVID-19 cases in India in terms of Case Fatality Rate (CFR), Case Recovery Rate (CRR) and Mortality rate (MR) COVID-19 have been evaluated during Lockdown-1. The analysis includes (i) epidemic curve of Covid-19 cases (ii) demographic analysis (iii) calculation of the CFR and CRR by different methods (iv) calculation of MR (v) Geo-temporal analysis (vi) epidemiological transmission factor (vii) evaluation of the effects and impact of infection, prevention and control in India. A total of 10,815 COVID-19 confirmed cases have been reported in 31 states/union territories as of April 14, 2020 with 9272 active cases (85.73%), 1190 cured/discharged (11%), and 353 deaths (3.23%). Among confirmed cases, most cases (59%) are aged 20–49 which is working age in India and 76% cases are reported for men. The median age of Indian COVID-19 patients found to be 39. As of April 14, the CFR per total cases in India is 3.32% and per closed cases is 23.27%. The CRR per total cases in India is 11.00% and per closed cases is 76.72%, which indicates that the recovery rate of COVID-19 is more than the fatality rate in India. The prevention and control measures taken by the state and central governments at all levels and measure of maintenance of social distancing by people have resulted in effective curbing in the COVID-19 transmission in India.


title: Common principles and intermediates of viral protein-mediated fusion: the HIV-1 paradigm

text: Enveloped viruses encode specialized fusion proteins which promote the merger of viral and cell membranes, permitting the cytosolic release of the viral cores. Understanding the molecular details of this process is essential for antiviral strategies. Recent structural studies revealed a stunning diversity of viral fusion proteins in their native state. In spite of this diversity, the post-fusion structures of these proteins share a common trimeric hairpin motif in which the amino- and carboxy-terminal hydrophobic domains are positioned at the same end of a rod-shaped molecule. The converging hairpin motif, along with biochemical and functional data, implies that disparate viral proteins promote membrane merger via a universal "cast-and-fold" mechanism. According to this model, fusion proteins first anchor themselves to the target membrane through their hydrophobic segments and then fold back, bringing the viral and cellular membranes together and forcing their merger. However, the pathways of protein refolding and the mechanism by which this refolding is coupled to membrane rearrangements are still not understood. The availability of specific inhibitors targeting distinct steps of HIV-1 entry permitted the identification of key conformational states of its envelope glycoprotein en route to fusion. These studies provided functional evidence for the direct engagement of the target membrane by HIV-1 envelope glycoprotein prior to fusion and revealed the role of partially folded pre-hairpin conformations in promoting the pore formation.


title: The 2(nd) sialic acid-binding site of influenza A virus neuraminidase is an important determinant of the hemagglutinin-neuraminidase-receptor balance

text: Influenza A virus (IAV) neuraminidase (NA) receptor-destroying activity and hemagglutinin (HA) receptor-binding affinity need to be balanced with the host receptor repertoire for optimal viral fitness. NAs of avian, but not human viruses, contain a functional 2(nd) sialic acid (SIA)-binding site (2SBS) adjacent to the catalytic site, which contributes to sialidase activity against multivalent substrates. The receptor-binding specificity and potentially crucial contribution of the 2SBS to the HA-NA balance of virus particles is, however, poorly characterized. Here, we elucidated the receptor-binding specificity of the 2SBS of N2 NA and established an important role for this site in the virion HA-NA-receptor balance. NAs of H2N2/1957 pandemic virus with or without a functional 2SBS and viruses containing this NA were analysed. Avian-like N2, with a restored 2SBS due to an amino acid substitution at position 367, was more active than human N2 on multivalent substrates containing α2,3-linked SIAs, corresponding with the pronounced binding-specificity of avian-like N2 for these receptors. When introduced into human viruses, avian-like N2 gave rise to altered plaque morphology and decreased replication compared to human N2. An opposite replication phenotype was observed when N2 was combined with avian-like HA. Specific bio-layer interferometry assays revealed a clear effect of the 2SBS on the dynamic interaction of virus particles with receptors. The absence or presence of a functional 2SBS affected virion-receptor binding and receptor cleavage required for particle movement on a receptor-coated surface and subsequent NA-dependent self-elution. The contribution of the 2SBS to virus-receptor interactions depended on the receptor-binding properties of HA and the identity of the receptors used. We conclude that the 2SBS is an important and underappreciated determinant of the HA-NA-receptor balance. The rapid loss of a functional 2SBS in pandemic viruses may have served to balance the novel host receptor-repertoire and altered receptor-binding properties of the corresponding HA protein.


Recommendations on key practical measures in laparoscopic surgery during the COVID‐19 pandemic


title: Impacts of biodiversity on the emergence and transmission of infectious diseases

text: Current unprecedented declines in biodiversity reduce the ability of ecological communities to provide many fundamental ecosystem services. Here we evaluate evidence that reduced biodiversity affects the transmission of infectious diseases of humans, other animals and plants. In principle, loss of biodiversity could either increase or decrease disease transmission. However, mounting evidence indicates that biodiversity loss frequently increases disease transmission. In contrast, areas of naturally high biodiversity may serve as a source pool for new pathogens. Overall, despite many remaining questions, current evidence indicates that preserving intact ecosystems and their endemic biodiversity should generally reduce the prevalence of infectious diseases. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature09575) contains supplementary material, which is available to authorized users.


title: INFECCIÓN GRAVE POR CORONAVIRUS SARS-CoV-2: Experiencia en un hospital de tercer nivel con pacientes afectados por COVID-19 durante la pandemia 2020

text: Abstract Objective: To describe the clinical and respiratory characteristics of a cohort of 43 patients with COVID-19 after an evolutive period of 28 days. Design: A prospective, single-center observational study was carried out. Setting: Intensive care. Patients: Patients admitted due to COVID-19 and respiratory failure. Interventions: None. Variables: Automatic recording was made of demographic variables, severity parameters, laboratory data, assisted ventilation (HFO: high-flow oxygen therapy and IMV: invasive mechanical ventilation), oxygenation (PaO2, PaO2/FiO2) and complications. The patients were divided into three groups: survivors (G1), deceased (G2) and patients remaining under admission (G3). The chi-squared test or Fisher exact test (categorical variables) was used, along with the Mann-Whitney U-test or Wilcoxon test for analyzing the differences between medians. Statistical significance was considered for p<0.05. Results: A total of 43 patients were included (G1=28 [65.1%], G2=10 [23.3%] and G3=5[11.6%]), with a mean age of 65 years (range 52-72), 62% males, APACHE II 18 (15-24), SOFA 6 (4-7). Arterial hypertension (30.2%) and obesity (25.6%) were the most frequent comorbidities. High-flow oxygen therapy was used in 62.7% of the patients, with failure in 85%. In turn, 95% of the patients required IMV and 85% received ventilation in prone decubitus. In the general population, initial PaO2/FiO2 improved after 7 days (165 [125-210] vs.194 [153-285]; p=0.02), in the same way as in G1 (164 [125-197] vs. 207 [160-294]; p=0.07), but not in G2 (163 [95-197] vs. 135 [85-177]). No bacterial coinfection was observed. The incidence of IMV-associated pneumonia was high (13 episodes/1000 days of IMV). Conclusions: Patients with COVID-19 require early IMV, a high frequency of ventilation in prone decubitus, and have a high incidence of failed HFO. The lack of improvement of PaO2/FiO2 at 7 days could be a prognostic marker. Resumen Objetivo: Describir las características clínicas y respiratorias de una cohorte de 43 pacientes con COVID-19 tras 28 días de evolución. Diseño: Prospectivo observacional en un solo centro Ámbito: Medicina intensiva Pacientes: Pacientes ingresados por COVID-19 e insuficiencia respiratoria Intervenciones: Ninguna Variables: Se obtuvieron de forma automática variables demográficas, de gravedad, de laboratorio, de asistencia ventilatoria recibida (OAF: oxigenoterapia alto flujo y VMI: ventilación mecánica invasiva), de oxigenación (PaO2, PaO2/FiO2) y de complicaciones. Los pacientes se dividieron en 3 grupos: supervivientes(G1), fallecidos(G2) y aquellos que continuaban ingresados(G3). Se utilizó “chi” cuadrado o Fisher (variables categóricas) y “U” Mann-Whitney o Wilcoxon para analizar la diferencia entre medianas. Se consideró significativo un valor de p<0.05. Resultados: Se incluyeron 43 pacientes (G1=28[65,1%],G2=10[23,3%] y G3=5[11,6%]), edad 65(52-72) años, 62% hombres, APACHE II 18(15-24), SOFA 6(4-7), Hipertensión arterial(30,2%) y obesidad(25,6%) fueron las comorbilidades más frecuentes. La OAF fue usada en el 62,7% de pacientes, 85% fracasó. El 95% de los pacientes necesitó VMI y el 85% ventilación en prono. En la población general, la PaO2/FiO2 inicial mejoró a los 7 días (165[125-210] vs. 194[153-285], p=0.02), al igual que en G1(164[125-197] vs. 207[160-294], p=0.07) pero no en G2 (163[95-197] vs. 135[85-177]). No se observó co-infección bacteriana. El desarrollo de neumonía asociada a la VMI fue elevado (13 episodios/1000 días de VMI) Conclusiones: Los pacientes con Covid-19 requieren VMI precoz, elevada frecuencia de ventilación en prono y presentan alta prevalencia de fracaso a OAF. La falta de mejoría de la PaO2/FiO2 a los 7 días podría ser un marcador de pronóstico.


title: Comparative genome analysis and molecular epidemiology of the reemerging porcine epidemic diarrhea virus strains isolated in Korea

text: Abstract Porcine epidemic diarrhea virus (PEDV), a member of the Coronaviridae family, is an enveloped, positive-sense, single-stranded RNA virus, which causes severe diarrhea and dehydration in suckling pigs. We detected three PEDV strains from ten small intestine samples from piglets with acute diarrhea and we determined the complete genome sequences of the reemerging Korean PEDV field isolates, except for the noncoding regions from both ends. The complete genome sequences of the strains were identical or almost identical (one synonymous single-nucleotide polymorphism (SNP) in the ORF1a/1b genomic sequence). Interestingly, comparative genome analysis of recent Korean PEDV isolates and other strains revealed that the complete genome sequences of recent Korean strains were almost identical (99.9%) to those of the US PEDV strains isolated in 2013. These results suggest that the three reemerging Korean strains are distinct from previous endemic Korean PEDV strains and has been recently introduced into Korea from oversea with high likelihood.


title: The Impacts of Young Consumers’ Health Values on Functional Beverages Purchase Intentions

text: Internationally, there is increasing recognition of the importance of proper diet values and habits, a balanced intake of healthy food products, and rates of obesity control encompassing information on fat content and calories. In this context, some beverage manufacturers have shifted to marketing their products as having fewer calories and more functional benefits. This study aims to develop an extended value–attitude–behavior (VAB) research model that includes three constructs, namely, cue to action, self-efficacy, and health orientation, to explore the impacts of university students’ health values on their purchase intentions concerning functional beverages. The results indicated that university students’ interest in functional beverages was significantly affected by their health values. Besides, both interests in functional beverages and health orientation were significant predictors of purchase intention, while cue to action and self-efficacy were not. Based on these results, enhancing consumers’ education about food security is suggested. Furthermore, the findings provide crucial insights for marketing channels, suggesting the beverage industry can target consumers’ health values concerning health beverages as the key to purchase intention and attract business by developing practical marketing strategies.


title: An Investigation of the Outcomes of PGY Students’ Cognition of and Persistent Behavior in Learning through the Intervention of the Flipped Classroom in Taiwan

text: The Postgraduate Year (PGY) Program allows doctors-in-training to learn about the diagnosis, treatment and nursing of various common, general diseases. These items form the core curriculum and are mostly learned through caring for patients and clinical teaching. Doctors-in-training are evaluated for their knowledge through written tests or assignments, based on which the effectiveness of their training is also assessed; however, this generally produces a negative learning attitude among them. So we introduced the flipped classroom into PGY training program to change PGY students’ learning behavior. Although the flipped classroom is highly valued and has been practiced by teachers in schools of various levels, very few attempts have been made until now to report the learning outcomes achieved through the flipped classroom by means of rigorous research methods. Therefore we tried to employed Ajzen and Fishbein’s (1980) theory of reasoned action and Bandura’s self-efficacy to predict and explain the participants’ behavioral intention when participating in the core curriculum learning of the flipped classroom and to assess the change in students’ learning behavior and learning effectiveness. From August 2013 to July 2014, 39 PGY students from the General Surgery of the Tri-Service General Hospital were selected as the participants of this study. The control group included 43 students of the previous year, that is, the year before the intervention of the flipped classroom. A comparative analysis was performed. The questionnaire’s related matrices indicated highest correlation between self-efficacy and behavioral intention (r = 0.491, P < 0.01), followed by attitude (r = 0.365, P < 0.01) and subjective norms (r = 0.360, P < 0.01.) All three showed positive correlations with behavioral intention; among attitude, subjective norms, and self-efficacy, the pairwise correlations also reached significance level. The flipped classroom can indeed change PGY students’ the learning behavior from “passive learning” to “active learning.”


Deep inside the pandemic, from inactivity to action: let´s be ready


title: A lung rescue team improves survival in obesity with acute respiratory distress syndrome

text: BACKGROUND: Limited data exist regarding ventilation in patients with class III obesity [body mass index (BMI) > 40 kg/m(2)] and acute respiratory distress syndrome (ARDS). The aim of the present study was to determine whether an individualized titration of mechanical ventilation according to cardiopulmonary physiology reduces the mortality in patients with class III obesity and ARDS. METHODS: In this retrospective study, we enrolled adults admitted to the ICU from 2012 to 2017 who had class III obesity and ARDS and received mechanical ventilation for > 48 h. Enrolled patients were divided in two cohorts: one cohort (2012–2014) had ventilator settings determined by the ARDSnet table for lower positive end-expiratory pressure/higher inspiratory fraction of oxygen (standard protocol-based cohort); the other cohort (2015–2017) had ventilator settings determined by an individualized protocol established by a lung rescue team (lung rescue team cohort). The lung rescue team used lung recruitment maneuvers, esophageal manometry, and hemodynamic monitoring. RESULTS: The standard protocol-based cohort included 70 patients (BMI = 49 ± 9 kg/m(2)), and the lung rescue team cohort included 50 patients (BMI = 54 ± 13 kg/m(2)). Patients in the standard protocol-based cohort compared to lung rescue team cohort had almost double the risk of dying at 28 days [31% versus 16%, P = 0.012; hazard ratio (HR) 0.32; 95% confidence interval (CI95%) 0.13–0.78] and 3 months (41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16–0.74), and this effect persisted at 6 months and 1 year (incidence of death unchanged 41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16–0.74). CONCLUSION: Individualized titration of mechanical ventilation by a lung rescue team was associated with decreased mortality compared to use of an ARDSnet table. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13054-019-2709-x) contains supplementary material, which is available to authorized users.


title: Culturing of respiratory viruses in well-differentiated pseudostratified human airway epithelium as a tool to detect unknown viruses

text: BACKGROUND: Currently, virus discovery is mainly based on molecular techniques. Here, we propose a method that relies on virus culturing combined with state-of-the-art sequencing techniques. The most natural ex vivo culture system was used to enable replication of respiratory viruses. METHOD: Three respiratory clinical samples were tested on well-differentiated pseudostratified tracheobronchial human airway epithelial (HAE) cultures grown at an air–liquid interface, which resemble the airway epithelium. Cells were stained with convalescent serum of the patients to identify infected cells and apical washes were analyzed by VIDISCA-454, a next-generation sequencing virus discovery technique. RESULTS: Infected cells were observed for all three samples. Sequencing subsequently indicated that the cells were infected by either human coronavirus OC43, influenzavirus B, or influenzavirus A. The sequence reads covered a large part of the genome (52%, 82%, and 57%, respectively). CONCLUSION: We present here a new method for virus discovery that requires a virus culture on primary cells and an antibody detection. The virus in the harvest can be used to characterize the viral genome sequence and cell tropism, but also provides progeny virus to initiate experiments to fulfill the Koch's postulates.


“NUEVAS EVIDENCIAS QUE DESCARTAN LA POSIBLE TRANSMISIÓN VERTICAL DEL SARS-CoV-2 DURANTE LA GESTACIÓN”


title: Pitfalls of possible reporting of same patients with COVID‐19 in dermatology journals

text: The Editor in chief and Deputy Editors of the JAMA recently shared their concern regarding possible reporting of patients in more than one manuscript, while this has not been clearly indicated in the submission [1]. Although the unprecedented context of the COVID‐19 outbreak justifies efforts for rapid dissemination of knowledge, such practice may be responsible for inaccurate interpretation and overestimation of published data [1]. Similar concern applies to dermatology. In Spain, the national COVID Piel study have reported 372 patients with skin manifestations related with COVID‐19, including 71 patients with pseudo‐chilblains, from April 3(rd) to April 16(th) [2].


title: Myricetin: A Dietary Molecule with Diverse Biological Activities

text: Myricetin is a common plant-derived flavonoid and is well recognised for its nutraceuticals value. It is one of the key ingredients of various foods and beverages. The compound exhibits a wide range of activities that include strong anti-oxidant, anticancer, antidiabetic and anti-inflammatory activities. It displays several activities that are related to the central nervous system and numerous studies have suggested that the compound may be beneficial to protect against diseases such as Parkinson’s and Alzheimer’s. The use of myricetin as a preserving agent to extend the shelf life of foods containing oils and fats is attributed to the compound’s ability to protect lipids against oxidation. A detailed search of existing literature revealed that there is currently no comprehensive review available on this important molecule. Hence, the present work includes the history, synthesis, pharmaceutical applications and toxicity studies of myricetin. This report also highlights structure-activity relationships and mechanisms of action for various biological activities.


title: Baculovirus expression of cloned porcine arterivirus generates infectious particles in both insect and mammalian cells

text: Abstract Studies on several viral pathogens have been hampered by the lack of appropriate in vitro systems for their propagation and amplification. Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus containing a single-stranded positive-sense RNA genome (∼15kb), was served as a model virus and its genomic cDNA was recombinated into baculovirus. We investigated whether infectious virus particles could be generated by expression of the full-length cloned genome from the modified baculovirus vector. The recombinant baculovirus, AcAPRRS, was used to infect sf9 cells. Immunofluorescence assay demonstrated the presence of PRRSV nonstructural protein (nsp) 2 and nucleocapsid (N) protein and electron microscopy revealed PRRSV particles in the culture supernatant. Infectious PRRSV particles were also produced in susceptible MARC-145 cells inoculated with AcAPRRS, and the growth characteristics of the PRRSV generated were similar to those of the parental PRRSV strain. Infectious PRRSV particles were also generated following AcAPRRS transduction of BHK-21 cells and Vero cells that are not sensitive to PRRSV. Titers of PRRSV obtained from BHK-21 and Vero cells were up to 104.05 TCID50/ml. These findings open a new route to the propagation of the virus in vitro and will be of utility in vaccine development.


COVID‐19 pandemic and physicians in training


title: Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV

text: Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002–2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients’ sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.


title: Reconstituted fresh whole blood improves clinical outcomes compared with stored component blood therapy for neonates undergoing cardiopulmonary bypass for cardiac surgery: A randomized controlled trial

text: Objective This study compared the effects of reconstituted fresh whole blood against standard blood component therapy in neonates undergoing cardiac surgery. Methods Patients less than 1 month of age were randomized to receive either reconstituted fresh whole blood (n = 31) or standard blood component therapy (n = 33) to prime the bypass circuit and for transfusion during the 24 hours after cardiopulmonary bypass. Primary outcome was chest tube drainage; secondary outcomes included transfusion needs, inotrope score, ventilation time, and hospital length of stay. Results Patients who received reconstituted fresh whole blood had significantly less postoperative chest tube volume loss per kilogram of body weight (7.7 mL/kg vs 11.8 mL/kg; P = .03). Standard blood component therapy was associated with higher inotropic score (6.6 vs 3.3; P = .002), longer ventilation times (164 hours vs 119 hours; P = .04), as well as longer hospital stays (18 days vs 12 days; P = .006) than patients receiving reconstituted fresh whole blood. Of the different factors associated with the use of reconstituted fresh whole blood, lower platelet counts at 10 minutes and at the end of cardiopulmonary bypass, older age of cells used in the prime and throughout bypass, and exposures to higher number of allogeneic donors were found to be independent predictors of poor clinical outcomes. Conclusions Reconstituted fresh whole blood used for the prime, throughout cardiopulmonary bypass, and for all transfusion requirements within the first 24 hours postoperatively results in reduced chest tube volume loss and improved clinical outcomes in neonatal patients undergoing cardiac surgery.


title: Hepatitis B surface antigen assembles in a post-ER, pre-Golgi compartment

text: Expression of hepatitis B surface antigen (HBsAg), the major envelope protein of the virus, in the absence of other viral proteins leads to its secretion as oligomers in the form of disk-like or tubular lipoprotein particles. The observation that these lipoprotein particles are heavily disulphide crosslinked is paradoxical since HBsAg assembly is classically believed to occur in the ER, and hence in the presence of high levels of protein disulphide isomerase (PDI) which should resolve these higher intermolecular crosslinks. Indeed, incubation of mature, highly disulphide crosslinked HBsAg with recombinant PDI causes the disassembly of HBsAg to dimers. We have used antibodies against resident ER proteins in double immunofluorescence studies to study the stages of the conversion of the HBsAg from individual protein subunits to the secreted, crosslinked, oligomer. We show that HBsAg is rapidly sorted to a post-ER, pre-Golgi compartment which excludes PDI and other major soluble resident ER proteins although it overlaps with the distribution of rab2, an established marker of an intermediate compartment. Kinetic studies showed that disulphide-linked HBsAg dimers began to form during a short (2 min) pulse, increased in concentration to peak at 60 min, and then decreased as the dimers were crosslinked to form higher oligomers. These higher oligomers are the latest identifiable intracellular form of HBsAg before its secretion (t 1/2 = 2 h). Brefeldin A treatment does not alter the localization of HBsAg in this PDI excluding compartment, however, it blocks the formation of new oligomers causing the accumulation of dimeric HBsAg. Hence this oligomerization must occur in a pre-Golgi compartment. These data support a model in which rapid dimer formation, catalyzed by PDI, occurs in the ER, and is followed by transport of dimers to a pre-Golgi compartment where the absence of PDI and a different lumenal environment allow the assembly process to be completed.


title: A consensus guideline of herbal medicine for coronavirus disease 2019

text: BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), which originated in Wuhan, Hubei Province, China in late December 2019, is the cause of ongoing pandemic. We analyzed the symptoms of SARS-CoV-2, a classification of the Chinese medicine dialectic and treatment regimen, and promptly enacted the recommendation of Korean medicine preparations in herbal medicine covered under domestic medical insurance benefits depending on the circumstances in our country. METHOD: The clinical practice guideline (CPG) for the treatment of SARS-CoV-2 was developed based on consensus from a group of experts. RESULTS: Two kinds of herbal medicines (HM) were recommended for the prevention of SARS-CoV-2; Youngyopaedoc-san plus Bojungikgitang, and Youngyopaedoc-san plus Saengmaek-san. Two herbal preparations were recommended for people with a history of exposure to SARS-CoV-2; Youngyopaedoc-san plus Bulhwangeumjeonggi-san, and Youngyopaedoc-san plus Bojungikgi-tang. Three herbal preparations were recommended for mildly symptomatic COVID-19 patients; Youngyopaedoc-san plus Galgunhaegui-tang was recommended for those without pneumonia with wind-warmth disease invading the lungs; Sosiho-tang plus Bulhwangeumjeonggi-san was recommended for those with dampness-heat disease in the lungs. For the recovery stage, Samchulkunbi-tang plus Saengmaek-san, or Samchulkunbi-tang plus Chungseuiki-tang was recommended. CONCLUSION: The CPG was developed to guide the use of Korean herbal medicine in the treatment of SARS-CoV-2, and it is expected that this will be the basis for providing proper treatment of similar infectious diseases in the future.


title: Inhibition of SARS-CoV 3CL protease by flavonoids

text: There were severe panics caused by Severe Acute Respiratory Syndrome (SARS) and Middle-East Respiratory Syndrome-Coronavirus. Therefore, researches targeting these viruses have been required. Coronaviruses (CoVs) have been rising targets of some flavonoids. The antiviral activity of some flavonoids against CoVs is presumed directly caused by inhibiting 3C-like protease (3CLpro). Here, we applied a flavonoid library to systematically probe inhibitory compounds against SARS-CoV 3CLpro. Herbacetin, rhoifolin and pectolinarin were found to efficiently block the enzymatic activity of SARS-CoV 3CLpro. The interaction of the three flavonoids was confirmed using a tryptophan-based fluorescence method, too. An induced-fit docking analysis indicated that S1, S2 and S3′ sites are involved in binding with flavonoids. The comparison with previous studies showed that Triton X-100 played a critical role in objecting false positive or overestimated inhibitory activity of flavonoids. With the systematic analysis, the three flavonoids are suggested to be templates to design functionally improved inhibitors.


title: National post-market surveillance assessment of veterinary medicines in Korea during the past decade

text: BACKGROUND: Veterinary medicines have been widely used for the prevention and treatment of diseases, growth promotion, and to promote feeding efficacy in livestock. As the veterinary medicine industry has steadily grown, it is crucial to set up a baseline for the quality of medicine as well as the insufficiency or excessiveness of the active ingredients in drug products to ensure the compliance, safety and efficacy of these medicines. Thus, the 10 years data of post-marketing quality control study was summarized to determine the rate and extent of non-compliance of these medicines and to establish baseline data for future quality control measures of veterinary medicine. RESULTS: In this study, 1650 drugs for veterinary use were collected per year from each city and province in Korea and analysed for the quantity of active ingredients according to the “national post-market surveillance (NPMS) system” over the past decade. The NPMS assessment was performed using liquid and gas chromatography, titration, UV/Vis spectrophotometry, and bioassays. A total of 358 cases were deemed noncompliant, with the average noncompliance rate for all medicine types being 2.0%. The average noncompliance rates for antibiotics, biologics and other chemical drugs except antibiotics (OCD) were 1.1%, 1.2%, and 3.0%, respectively. The first leading cause for noncompliant products was insufficient quantity of major ingredients (283 cases), and the second leading cause was the existence of excess amount of active ingredients (60 cases). Tylosin, spiramycin, ampicillin, tetracyclines and penicillins were most frequently found to be noncompliant among antibiotics. Among the OCD, the noncompliance was found commonly in vitamin A. CONCLUSION: The overall trend presented gradually decreasing violation rates, suggesting that the quality of veterinary medicines has improved. Consistent application of the NPMS assessment and the establishment of the Korea Veterinary Good Manufacturing Practice (KVGMP) will help to maintain the good quality of medicine.


title: Clinical and Epidemiological Characteristics of 1,420 European Patients with mild‐to‐moderate Coronavirus Disease 2019

text: BACKGROUND: The clinical presentation of European patients with mild‐to‐moderate Covid‐19 infection is still unknown. OBJECTIVE: To study the clinical presentation of Covid‐19 in Europe. METHODS: Patients with positive diagnosis of Covid‐19 were recruited from 18 European hospitals. Epidemiological and clinical data were obtained through a standardized questionnaire. Bayesian analysis was used for analyzing the relationship between outcomes. RESULTS: 1,420 patients completed the study (962 females, 30.7% of health care workers). The mean age of patients was 39.17±12.09 years. The most common symptoms were headache (70.3%), loss of smell (70.2%), nasal obstruction (67.8%), cough (63.2%), asthenia (63.3%), myalgia (62.5%), rhinorrhea (60.1%), gustatory dysfunction (54.2%) and sore throat (52.9%). Fever was reported by on 45.4%. The mean duration of Covid‐19 symptoms of mild‐to‐moderate cured patients was 11.5±5.7 days. The prevalence of symptoms significantly varied according to age and sex. Young patients more frequently had ear, nose, and throat complaints, whereas elderly individuals often presented fever, fatigue and loss of appetite. Loss of smell, headache, nasal obstruction and fatigue were more prevalent in female patients. The loss of smell was a key symptom of mild‐to‐moderate Covid19 patients and was not associated with nasal obstruction and rhinorrhea. Loss of smell persisted at least 7 days after the disease in 37.5% of cured patients. CONCLUSION: The clinical presentation of mild‐to‐moderate Covid‐19 substantially varies according to the age and the sex characteristics of patients. Olfactory dysfunction seems to be an important underestimated symptom of mild‐to‐moderate Covid‐19 that needs to be recognized as such by the WHO.


title: Immunogenicity of adenovirus-vector vaccine targeting hepatitis B virus: non-clinical safety assessment in non-human primates

text: BACKGROUND: A new promising therapeutic approach has emerged for patients chronically infected by the hepatitis B virus (HBV) with the development of a non-replicative adenovirus vector vaccine candidate (Ad-HBV). The vaccine encodes a fusion protein composed of a truncated HBV core protein, mutated polymerase protein, and two envelope domains. In this study, we assessed the immunogenicity of Ad-HBV administered to cynomolgus monkeys during a non-clinical safety assessment. METHODS: The virus was subcutaneously administered at 1.0 × 10(9) viral particles (VP)/animal (low-dose group), 1.0 × 10(10) VP/animal (mid-dose group), and 1.0 × 10(11) VP/animal (high-dose group); the control groups were administered an Ad5-null virus (1.0 × 10(11) VP/animal) and saline only. RESULTS: Except for inflammatory cell infiltration under the skin at the injection sites and transient elevation of body temperature and serum albumin, no Ad-HBV-related toxic effects were noted in any treatment group. Moreover, interferon (IFN)-γ enzyme-linked immunospot assays showed that Ad-HBV induced the targeting of T cells to a broad spectrum of HBV-specific epitopes spanning all three of the selected HBV immunogens (core, polymerase, and envelope domains) in a dose-dependent manner. Although anti-Ad antibody was produced in all groups (except for the saline control), the antibody titers were significantly lower in the high-dose Ad-HBV group than in the group that received the same dose of the Ad-null empty vector. In addition, the IFN-γ and IL-2 expression levels in the liver were significantly improved for the mid-dose, high-dose, and Ad-null control group (p < 0.05), but not for the low-dose group. CONCLUSIONS: Taken together, this safety assessment indicates that the Ad-HBV candidate vaccine is a potent specific immunotherapeutic agent, supporting its further clinical development as an anti-HBV infection vaccine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1026-3) contains supplementary material, which is available to authorized users.


title: Enclosure with augmented airflow to decrease risk of exposure to aerosolized pathogens including coronavirus during endotracheal intubation. Can the reduction in aerosolized particles be quantified?

text: As the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2 or COVID‐19) has impacted hospital routines in recent weeks, recommendations to reduce health care worker infections are being developed. We report preliminary experience with the efficacy of an enclosure with augmented airflow to decrease the risk of exposure to aerosolized pathogens during airway management including endotracheal intubation. A particle generator was used to test the efficacy of the reduction of aerosolized particles by measuring their concentration within the enclosure and in the environment. No reductionin the concentration of aerosolized particles was noted with the enclosure flap open, whether the interior suction was on or off. However, with the enclosure closed and no augmented air flow (suction off), the particle concentration decreased to 1.2% of baseline. The concentration decreased even further, to 0.8% of baseline with the enclosure closed with augmented airflow (suction on). Aerosolized particulate contamination in the operating room can be decreased using a clear plastic enclosure with minimal openings and augmented airflow. This may serve to decrease the exposure of healthcare providers to aerosolized pathogens.


title: Étude comparée de trois souches du coronavirus de la gastroentérite transmissible: Conditions de la réplicationvirale et de la synthèse des antigènes structuraux

text: Summary Purdue-115 and D-52 strains of TGEV were compared with the 188-SG strain, which was obtained by means of a survivor selection process in gastric juice of adult pig. The 188-SG strain was characterized by (a) low infectivity, (b) delayed and restricted growth associated with low and delayed RNA synthesis, and (c) a high content of structural antigens. In contrast, Purdue-115 and D-52 strains were characterized by (a) high infectivity, and (b) a normal pattern of virus replication and RNA and structural antigen synthesis. Tunicamycin induced the inhibition of synthesis of El and E2 glycoproteins (detected by the ELISA test using monoclonal and polyclonal antibodies) as well as a significant reduction in the NP protein. The inhibitory effect of tunicamycin was influenced by the cell type and virus strain.


title: Application prospect of polysaccharides in the development of anti-novel coronavirus drugs and vaccines

text: Since the outbreak of the novel coronavirus disease COVID-19, caused by the SARS-CoV-2 virus, it has spread rapidly worldwide and poses a great threat to public health. This is the third serious coronavirus outbreak in <20 years, following SARS in 2002–2003 and MERS in 2012. So far, there are almost no specific clinically effective drugs and vaccines available for COVID-19. Polysaccharides with good safety, immune regulation and antiviral activity have broad application prospects in anti-virus, especially in anti-coronavirus applications. Here, we reviewed the antiviral mechanisms of some polysaccharides, such as glycosaminoglycans, marine polysaccharides, traditional Chinese medicine polysaccharides, and their application progress in anti-coronavirus. In particular, the application prospects of polysaccharide-based vaccine adjuvants, nanomaterials and drug delivery systems in the fight against novel coronavirus were also analyzed and summarized. Additionally, we speculate the possible mechanisms of polysaccharides anti-SARS-CoV-2, and propose the strategy of loading S or N protein from coronavirus onto polysaccharide capped gold nanoparticles vaccine for COVID-19 treatment. This review may provide a new approach for the development of COVID-19 therapeutic agents and vaccines.


First COVID-19 case in the Rohingya camp in Bangladesh: Needs proper attention


It’s in our hands: a rapid, international initiative to translate a hand hygiene song during the COVID-19 pandemic


title: Early Cardiac Allograft Vasculopathy: Are the Viruses to Blame?

text: This paper describes a case of early (7 months after transplant) cardiac allograft vasculopathy. This-43-year-old (CMV positive, EBV negative) female patient underwent an orthotopic heart transplant with a (CMV negative, EBV positive) donor heart. She had a history of herpes zoster infection and postherpetic neuralgia in the past. The patient's panel reactive antibodies had been almost undetectable on routine surveillance testing, and her surveillance endomyocardial biopsies apart from a few episodes of mild-to-moderate acute cellular rejection (treated adequately with steroids) never showed any evidence of humoral rejection. The postoperative course was complicated by multiple admissions for upper respiratory symptoms, and the patient tested positive for entero, rhino, and coronaviruses serologies. During her last admission (seven months postoperatively) the patient developed mild left ventricular dysfunction with an ejection fraction of 40%. The patient's endomyocardial biopsy done at that time revealed concentric intimal proliferation and inflammation resulting in near-total luminal occlusion in the epicardial and the intramyocardial coronary vessels, suggestive of graft vasculopathy with no evidence of rejection, and the patient had a fatal ventricular arrhythmia.


title: Novel Antiviral Agents for Respiratory Viral Infection in Immunocompromised Adults

text: Respiratory viruses cause significant morbidity and mortality in immunocompromised populations such as stem cell transplant and solid organ transplant patients. Few viruses causing respiratory tract infection have an approved therapy, and many of the viruses have no therapeutic options at all. In this article, we describe novel agents under development for treatment options against several respiratory viruses.


title: Obesity risk during collective quarantine for the COVID-19 epidemic

text: In March 2020, when COVID-19 epidemics involved several countries, the WHO defined the infection as a pandemic. Government adopted measures to prevent the diffusion of infection; i.e. quarantine and isolation. One of the consequences of quarantine-induced stress is a change in lifestyle and eating habits leading to obesity. The present commentary briefly analyzes the effects of quarantine on obesity.


title: Molecular approaches to the diagnosis and monitoring of production diseases in pigs

text: Abstract Production disease in pigs is caused by a variety of different pathogens, mainly enteric and respiratory and can result in significant economic loss. Other factors such as stress, poor husbandry and nutrition can also contribute to an animal's susceptibility to disease. Molecular biomarkers of production disease could be of immense value by improving diagnosis and risk analysis to determine best practice with an impact on increased economic output and animal welfare. In addition to the use of multiplex PCR or microarrays to detect individual or mixed pathogens during infection, these technologies can also be used to monitor the host response to infection via gene expression. The patterns of gene expression associated with cellular damage or initiation of the early immune response may indicate the type of pathology and, by extension the types of pathogen involved. Molecular methods can therefore be used to monitor both the presence of a pathogen and the host response to it during production disease. The field of biomarker discovery and implementation is expanding as technologies such as microarrays and next generation sequencing become more common. Whilst a large number of studies have been carried out in human medicine, further work is needed to identify molecular biomarkers in veterinary medicine and in particular those associated with production disease in the pig industry. The pig transcriptome is highly complex and still not fully understood. Further gene expression studies are needed to identify molecular biomarkers which may have predictive value in identifying the environmental, nutritional and other risk factors which are associated with production diseases in pigs.


title: Clinical presentation, immunologic features, and hematopoietic stem cell transplant outcomes for IKBKB immune deficiency

text: Abstract IKBKB immune deficiency is a rare but life-threatening primary immunodeficiency disorder, involving activation defects in adaptive and innate immunity. We present sixteen cases of a homozygous IKBKB mutation (c.1292dupG) in infants characterized by early-onset bacterial, viral, fungal and Mycobacterial infections. In most cases, T- and B-cells were quantitatively normal, but phenotypically naïve, with severe hypogammaglobulinemia. T-cell receptor excision circles were normal, meaning newborn screening by TREC analysis would miss IKBKB cases. Although IKBKB immune deficiency does not meet traditional laboratory based definitions for SCID, this combined immune deficiency appears to be at least as profound. Urgent HSCT, performed in eight patients, remains the only known curative therapy, although only three patients are survivors. Ongoing infections after transplant remain a concern, and may be due to combinations of poor social determinants of health, secondary graft failure, and failure of HSCT to replace non-hematopoietic cells important in immune function and dependent upon IKK/NF-κB pathways.


title: Communicating the Risk of Death from Novel Coronavirus Disease (COVID-19)

text: To understand the severity of infection for a given disease, it is common epidemiological practice to estimate the case fatality risk, defined as the risk of death among cases. However, there are three technical obstacles that should be addressed to appropriately measure this risk. First, division of the cumulative number of deaths by that of cases tends to underestimate the actual risk because deaths that will occur have not yet observed, and so the delay in time from illness onset to death must be addressed. Second, the observed dataset of reported cases represents only a proportion of all infected individuals and there can be a substantial number of asymptomatic and mildly infected individuals who are never diagnosed. Third, ascertainment bias and risk of death among all those infected would be smaller when estimated using shorter virus detection windows and less sensitive diagnostic laboratory tests. In the ongoing COVID-19 epidemic, health authorities must cope with the uncertainty in the risk of death from COVID-19, and high-risk individuals should be identified using approaches that can address the abovementioned three problems. Although COVID-19 involves mostly mild infections among the majority of the general population, the risk of death among young adults is higher than that of seasonal influenza, and elderly with underlying comorbidities require additional care.


title: Structure of the X (ADRP) domain of nsp3 from feline coronavirus

text: The structure of the X (or ADRP) domain of a pathogenic variant of feline coronavirus (FCoV) has been determined in tetragonal and cubic crystal forms to 3.1 and 2.2 Å resolution, respectively. In the tetragonal crystal form, glycerol‐3‐phosphate was observed in the ADP‐ribose‐binding site. Both crystal forms contained large solvent channels and had a solvent content of higher than 70%. Only very weak binding of this domain to ADP‐ribose was detected in vitro. However, the structure with ADP‐ribose bound was determined in the cubic crystal form at 3.9 Å resolution. The structure of the FCoV X domain had the expected macro‐domain fold and is the first structure of this domain from a coronavirus belonging to subgroup 1a.


title: Safety guidelines for non‐surgical facial procedures during covid‐19 outbreak

text: BACKGROUND: The novel coronavirus (COVID‐19) pandemic is expected to last for an extended time, making strict safety precautions for office procedures unavoidable. The lockdown is going to be lifted in many areas, and strict guidelines detailing the infection control measures for aesthetic clinics are going to be of particular importance. METHODS: A virtual meeting was conducted with the members (n=12) of the European Academy of Facial Plastic Surgery Focus Group to outline the safety protocol for the non‐surgical facial aesthetic procedures for aesthetic practices in order to protect the clinic staff and the patients from SARS‐CoV‐2 infection. The data analysis was undertaken by thematic and iterative approach. RESULTS: Consensus guidelines for non‐surgical facial aesthetic procedures based on current knowledge are provided for three levels: precautions before visiting the clinic, precautions during the clinic visit, and precautions after the clinic visit. CONCLUSIONS: Sound infection control measures are mandatory for non‐surgical aesthetic practices all around the world. These may vary from country to country, but this logical approach can be customized according to the respective country laws and guidelines.


title: Multivalent Sialosides: A Tool to Explore the Role of Sialic Acids in Biological Processes

text: Sialic acids (Sias) are fascinating nine‐carbon monosaccharides that are primarily found on the terminus of the oligosaccharide chains of glycoproteins and glycolipids on cell surfaces. These Sias undergo a variety of structural modifications at their hydroxy and amine positions, thereby resulting in structural diversity and, hence, coordinating a variety of biological processes. However, deciphering the structural functions of such interactions is highly challenging, because the monovalent binding of Sias is extremely weak. Over the last decade, several multivalent Sia ligands have been synthesized to modulate their binding affinity with proteins/lectins. In this Minireview, we highlight recent developments in the synthesis of multivalent Sia probes and their potential applications. We will discuss four key multivalent families, that is, polymers, dendrimers, liposomes, and nanoparticles, and will emphasize the major parameters that are essential for the specific interactions of these molecules with proteins in biological systems.


title: Cloning, Prokaryotic Soluble Expression, and Analysis of Antiviral Activity of Two Novel Feline IFN-ω Proteins

text: Cats are becoming more popular as household companions and pets, forming close relationships with humans. Although feline viral diseases can pose serious health hazards to pet cats, commercialized preventative vaccines are lacking. Interferons (IFNs), especially type I IFNs (IFN-α, IFN-β, and interferon omega (IFN-ω)), have been explored as effective therapeutic drugs against viral diseases in cats. Nevertheless, there is limited knowledge regarding feline IFN-ω (feIFN-ω), compared to IFN-α and IFN-β. In this study, we cloned the genes encoding feIFN-ωa and feIFN-ωb from cat spleen lymphocytes. Homology and phylogenetic tree analysis revealed that these two genes belonged to new subtypes of feIFN-ω. The recombinant feIFN-ωa and feIFN-ωb proteins were expressed in their soluble forms in Escherichia coli, followed by purification. Both proteins exhibited effective anti-vesicular stomatitis virus (VSV) activity in Vero, F81 (feline kidney cell), Madin–Darby bovine kidney (MDBK), Madin–Darby canine kidney (MDCK), and porcine kidney (PK-15) cells, showing broader cross-species antiviral activity than the INTERCAT IFN antiviral drug. Furthermore, the recombinant feIFN-ωa and feIFN-ωb proteins demonstrated antiviral activity against VSV, feline coronavirus (FCoV), canine parvovirus (CPV), bovine viral diarrhea virus (BVDV), and porcine epidemic diarrhea virus (PEDV), indicating better broad-spectrum antiviral activity than the INTERCAT IFN. The two novel feIFN-ω proteins (feIFN-ωa and feIFN-ωb) described in this study show promising potential to serve as effective therapeutic agents for treating viral infections in pet cats.


title: Putative papain-related thiol proteases of positive-strand RNA viruses Identification of rubi- and aphthovirus proteases and delineation of a novel conserved domain associated with proteases of rubi-, α- and coronaviruses

text: Abstract A computer-assisted comparative analysis of the amino acid sequences of (putative) thiol proteases encoded by the genomes of several diverse groups or positive-stranded RNA viruses and distantly related to the family of cellular papain-like proteases is presented. A high level of similarity was detected between the leader protease of foot-and-mouth-disease virus and the protease of murine hepatitis coronavirus which cleaves the N-terminal p28 protein from the polyprotein. Statistically significant alignment of a portion of the rubella virus polyprotein with cellular papain-like proteases was obtained, leading to tentative identification of the papain-like protease as the enzyme mediating processing of the non-structural proteins of this virus. Specific grouping between the sequences of the proteases of α-viruses, and poty- and bymoviruses was revealed. It was noted that papain-like proteases of positive-stranded RNA viruses are much more variable both in their sequences and in genomic locations than chymotrypsin-related proteases found in the same virus class. A novel conserved domain of unknown function has also been identified which flanks the papain-like proteases of α-, rubi- and coronaviruses.


title: It’s not over until it’s over: the chameleonic behavior of COVID-19 over a six-day period

text: The current global outbreak of COVID-19 represents a major challenge in terms of epidemiology, contagiousness, treatment, as well as clinical and radiological behavior of this disease. Radiological imaging plays a key role in the diagnostic process and during the monitoring of the clinical conditions especially of patients with severe symptoms. According to the preliminary data collected in our tertiary center, we have documented a peculiar behavior in patients requiring endotracheal intubation who underwent seriate chest X-rays. In fact, the radiological pattern of COVID-19 patients may worsen despite a prompt amelioration after the onset of mechanical ventilation. Thus, according to our initial evidence, we recommend to perform seriate chest X-rays in the days following the onset of mechanical ventilation even if the immediate monitoring suggests an improvement. Studies on a larger scale are necessary to fully assess the findings at chest radiographs of critical, mechanically ventilated patients and their correlation with the long-term outcome.


title: Emerging 2019 Novel Coronavirus (2019-nCoV) Pneumonia

text: BACKGROUND: The chest CT findings of patients with 2019 Novel Coronavirus (2019-nCoV) pneumonia have not previously been described in detail. PURPOSE: To investigate the clinical, laboratory, and imaging findings of emerging 2019-nCoV pneumonia in humans. MATERIALS AND METHODS: Fifty-one patients (25 men and 26 women; age range 16–76 years) with laboratory-confirmed 2019-nCoV infection by using real-time reverse transcription polymerase chain reaction underwent thin-section CT. The imaging findings, clinical data, and laboratory data were evaluated. RESULTS: Fifty of 51 patients (98%) had a history of contact with individuals from the endemic center in Wuhan, China. Fever (49 of 51, 96%) and cough (24 of 51, 47%) were the most common symptoms. Most patients had a normal white blood cell count (37 of 51, 73%), neutrophil count (44 of 51, 86%), and either normal (17 of 51, 35%) or reduced (33 of 51, 65%) lymphocyte count. CT images showed pure ground-glass opacity (GGO) in 39 of 51 (77%) patients and GGO with reticular and/or interlobular septal thickening in 38 of 51 (75%) patients. GGO with consolidation was present in 30 of 51 (59%) patients, and pure consolidation was present in 28 of 51 (55%) patients. Forty-four of 51 (86%) patients had bilateral lung involvement, while 41 of 51 (80%) involved the posterior part of the lungs and 44 of 51 (86%) were peripheral. There were more consolidated lung lesions in patients 5 days or more from disease onset to CT scan versus 4 days or fewer (431 of 712 lesions vs 129 of 612 lesions; P < .001). Patients older than 50 years had more consolidated lung lesions than did those aged 50 years or younger (212 of 470 vs 198 of 854; P < .001). Follow-up CT in 13 patients showed improvement in seven (54%) patients and progression in four (31%) patients. CONCLUSION: Patients with fever and/or cough and with conspicuous ground-glass opacity lesions in the peripheral and posterior lungs on CT images, combined with normal or decreased white blood cells and a history of epidemic exposure, are highly suspected of having 2019 Novel Coronavirus (2019-nCoV) pneumonia. © RSNA, 2020


title: Cancellation of Elective Surgery and Intensive Care Unit Capacity in New York State: A Retrospective Cohort Analysis

text: BACKGROUND: In response to the coronavirus disease 2019 (COVID-19) pandemic, New York State ordered the suspension of all elective surgeries to increase intensive care unit (ICU) bed capacity. Yet the potential impact of suspending elective surgery on ICU bed capacity is unclear. METHODS: We retrospectively reviewed 5 years of New York State data on ICU usage. Descriptions of ICU utilization and mechanical ventilation were stratified by admission type (elective surgery, emergent/urgent/trauma surgery, and medical admissions) and by geographic location (New York metropolitan region versus the rest of New York State). Data are presented as absolute numbers and percentages and all adult and pediatric ICU patients were included. RESULTS: Overall, ICU admissions in New York State were seen in 10.1% of all hospitalizations (n = 1,232,986/n = 12,251,617) and remained stable over a 5-year period from 2011 to 2015. Among n = 1,232,986 ICU stays, sources of ICU admission included elective surgery (13.4%, n = 165,365), emergent/urgent admissions/trauma surgery (28.0%, n = 345,094), and medical admissions (58.6%, n = 722,527). Ventilator utilization was seen in 26.3% (n = 323,789/n = 1232,986) of all ICU patients of which 6.4% (n = 20,652), 32.8% (n = 106,186), and 60.8% (n = 196,951) was for patients from elective, emergent, and medical admissions, respectively. New York City holds the majority of ICU bed capacity (70.0%; n = 2496/n = 3566) in New York State. CONCLUSIONS: Patients undergoing elective surgery comprised a small fraction of ICU bed and mechanical ventilation use in New York State. Suspension of elective surgeries in response to the COVID-19 pandemic may thus have a minor impact on ICU capacity when compared to other sources of ICU admission such as emergent/urgent admissions/trauma surgery and medical admissions. More study is needed to better understand how best to maximize ICU capacity for pandemics requiring heavy use of critical care resources.


455. Targeting of a Non-Human Coronavirus to Human Tumor Cells by Using a Bispecific Single-Chain Antibody


title: The Role of Chest Imaging in Patient Management during the COVID-19 Pandemic: A Multinational Consensus Statement from the Fleischner Society

text: With more than 900,000 confirmed cases worldwide and nearly 50,000 deaths during the first three months of 2020, the COVID-19 pandemic has emerged as an unprecedented healthcare crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, healthcare delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and healthcare workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. While mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography (CXR) and computed tomography (CT) are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pre-test probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing COVID-19 patients across a spectrum of healthcare environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based upon the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of CXR and CT in the management of COVID-19.


title: Analytical performance of the automated multianalyte point-of-care mariPOC® for the detection of respiratory viruses

text: Abstract The analytical performance of mariPOC® respi test (ArcDia® Laboratories, Turku, Finland) was evaluated using nucleic acid amplification techniques (NAATs) as the gold standard. The mariPOC assay allows automated detection of antigens from 8 respiratory viruses: influenza A and B viruses, respiratory syncytial virus, adenovirus, human metapneumovirus, and parainfluenza viruses 1–3. Positive results from samples with high viral load are available in 20min. Nasopharyngeal aspirates (n=192) from patients with acute respiratory infection and from previously positive samples were analyzed by mariPOC and NAATs (SimplexaTM FluA/FluB & RSV kit [n=118] and Luminex® Respiratory virus panel xTAG® RVP FAST [n=74]). Sensitivity, specificity, positive predictive value, and negative predictive value of mariPOC were 85.4%, 99.2%, 95.9%, and 97%, respectively, and 84.6% of positive results were reported in 20min. The good analytical performance and extended portfolio of mariPOC show this rapid assay as a good alternative for the etiological diagnosis of acute respiratory infection in laboratories that are not equipped with molecular assays.


Comparative seasonalities of influenza A, B and ‘common cold’ coronaviruses – setting the scene for SARSCoV-2 infections and possible unexpected host immune interactions


title: Biliothorax in a Siamese cat

text: A 2-year-old male neutered cat presented for further investigation of biliothorax. The cat was initially treated for pyothorax, including bilateral chest drains for lavage of the pleural space. Five days later, the pleural effusion turned clear-yellow and had a bilirubin concentration of 427μmol/l compared to the serum bilirubin concentration of 15μmol/l. Exploratory surgery revealed a 2mm tear in the diaphragm, with a corresponding 2mm defect in the diaphragmatic surface of the gall bladder, creating a fistula between the gall bladder and the pleural cavity. The defects were repaired routinely and the cat made a full recovery. It was suspected that the tears had been created at the time of the thoracostomy tube placement. Biliothorax has not been described before in a cat, and appears to be a rare complication following thoracostomy tube placement.


title: Estimates of the risk of large or long-lasting outbreaks of Middle East respiratory syndrome after importations outside the Arabian Peninsula

text: Abstract We quantify outbreak risk after importations of Middle East respiratory syndrome outside the Arabian Peninsula. Data from 31 importation events show strong statistical support for lower transmissibility after early transmission generations. Our model projects the risk of ≥10, 100, and 500 transmissions as 11%, 2%, and 0.02%, and ≥1, 2, 3, and 4 generations as 23%, 14%, 0.9%, and 0.05%, respectively. Our results suggest tempered risk of large, long-lasting outbreaks with appropriate control measures.


title: Association of Dynamic Changes in the CD4 T-Cell Transcriptome With Disease Severity During Primary Respiratory Syncytial Virus Infection in Young Infants

text: BACKGROUND: Nearly all children are infected with respiratory syncytial virus (RSV) within the first 2 years of life, with a minority developing severe disease (1%–3% hospitalized). We hypothesized that an assessment of the adaptive immune system, using CD4(+) T-lymphocyte transcriptomics, would identify gene expression correlates of disease severity. METHODS: Infants infected with RSV representing extremes of clinical severity were studied. Mild illness (n = 23) was defined as a respiratory rate (RR) < 55 and room air oxygen saturation (SaO(2)) ≥ 97%, and severe illness (n = 23) was defined as RR ≥ 65 and SaO2 ≤ 92%. RNA from fresh, sort-purified CD4(+) T cells was assessed by RNA sequencing. RESULTS: Gestational age, age at illness onset, exposure to environmental tobacco smoke, bacterial colonization, and breastfeeding were associated (adjusted P < .05) with disease severity. RNA sequencing analysis reliably measured approximately 60% of the genome. Severity of RSV illness had the greatest effect size upon CD4 T-cell gene expression. Pathway analysis identified correlates of severity, including JAK/STAT, prolactin, and interleukin 9 signaling. We also identified genes and pathways associated with timing of symptoms and RSV group (A/B). CONCLUSIONS: These data suggest fundamental changes in adaptive immune cell phenotypes may be associated with RSV clinical severity.


title: Airborne Aerosol Generation During Endonasal Procedures in the Era of COVID-19: Risks and Recommendations

text: OBJECTIVE: In the era of SARS-CoV-2, the risk of infectious airborne aerosol generation during otolaryngologic procedures has been an area of increasing concern. The objective of this investigation was to quantify airborne aerosol production under clinical and surgical conditions and examine efficacy of mask mitigation strategies. STUDY DESIGN: Prospective quantification of airborne aerosol generation during surgical and clinical simulation. SETTING: Cadaver laboratory and clinical examination room. SUBJECTS AND METHODS: Airborne aerosol quantification with an optical particle sizer was performed in real time during cadaveric simulated endoscopic surgical conditions, including hand instrumentation, microdebrider use, high-speed drilling, and cautery. Aerosol sampling was additionally performed in simulated clinical and diagnostic settings. All clinical and surgical procedures were evaluated for propensity for significant airborne aerosol generation. RESULTS: Hand instrumentation and microdebridement did not produce detectable airborne aerosols in the range of 1 to 10 μm. Suction drilling at 12,000 rpm, high-speed drilling (4-mm diamond or cutting burs) at 70,000 rpm, and transnasal cautery generated significant airborne aerosols (P < .001). In clinical simulations, nasal endoscopy (P < .05), speech (P < .01), and sneezing (P < .01) generated 1- to 10-μm airborne aerosols. Significant aerosol escape was seen even with utilization of a standard surgical mask (P < .05). Intact and VENT-modified (valved endoscopy of the nose and throat) N95 respirator use prevented significant airborne aerosol spread. CONCLUSION: Transnasal drill and cautery use is associated with significant airborne particulate matter production in the range of 1 to 10 μm under surgical conditions. During simulated clinical activity, airborne aerosol generation was seen during nasal endoscopy, speech, and sneezing. Intact or VENT-modified N95 respirators mitigated airborne aerosol transmission, while standard surgical masks did not.


title: Progress on the Implementation of Environmental Surveillance in the African Region, 2011-2016

text: OBJECTIVE: This article summarises the progress made since the introduction of environmental surveillance in the African Region. METHOD: Country selection was based on the poor AFP performance indicators i.e. Non polio AFP rate and stool adequacy. It was recommended that any country not meeting the required indicators should consider environmental surveillance activity as an additional tool to support AFP surveillance. The sites selection considered proximity to the target population, the size of the population to be sampled and the sensitivity of the sampling site. RESULTS: One hundred and fifty three sites have been established in Africa since 2011. In 2011, Nigeria was first country to introduce environmental surveillance and currently with of 59 validated sites, followed by Kenya in 2013 validating and sampling 9 sites and Angola 4 active sites in 2014. In 2014, Cameroon introduced ES and 31 sites followed by Niger with 9 sites and Madagascar with 23 sites. Later in the same year, Chad introduced ES activity and 4 active sites were selected. In 2015 Senegal introduced 3 sites, Guinea and Burkina Faso introduced 4 sites each., and. In 2016, a total of 179 Sabins, 36 Sabin 2s, 196 non polio enteroviruses (NPEV) and 1 vaccine-derived polioviruses (VDPV) were reported in Nigeria. Cameroon and Chad isolated 14 and 4 Sabins and 72 and 40 NPEV respectively. In Madagascar a total of 39 Sabins, 11 Sabin 2s and 277 NPEV were isolated. In other countries a majority of NPEV were isolated (data not shown). CONCLUSION: This report describes the progress and expansion of environmental surveillance that contributed to the identification of polioviruses from the environment and the interruption of wild poliovirus transmission in the African Region.


title: External Quality Assessment of MERS-CoV Molecular Diagnostics During the 2015 Korean Outbreak

text: BACKGROUND: The largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection outside Middle East Asia in 2015 has necessitated the rapid expansion of laboratories that conduct MERS-CoV molecular testing in Korea, together with external quality assessment (EQA) to evaluate the assays used. METHODS: The EQA program consisted of two phases; self-validation and blind assessment. For the first EQA phase, in vitro transcribed upstream region of the envelope gene (upE) and the open reading frame (ORF)1a RNAs were used at a concentration of 1,000 copies/µL. The test panel for the second EQA phase consisted of RNA extracts from three samples, which were obtained from two MERS-CoV positive patients and one MERS-CoV negative patient. RESULTS: The first EQA phase results for 46 participants showed a linear relationship between the threshold cycle (C(T)) values of RNA materials and the logarithmic concentrations for both upE and ORF1a gene targets (R(2)=0.73 and 0.75, respectively). The mean C(T) value for each concentration was different depending on which commercial kit was used for the assay. Among the three commonly used kits, PowerChek MERS Real-Time PCR kit (KogeneBiotech, Korea) showed the lowest C(T) values at all concentrations of upE and most concentrations of ORF1a. The second EQA phase results for 47 participants were 100% correct for all tested samples. CONCLUSIONS: This EQA survey demonstrates that the MERS-CoV molecular testing performed in Korea during the 2015 outbreak is of robust capability. However, careful establishment and validation of a cut-off value are recommended to ensure good analytical sensitivity.


title: Attenuation of influenza A virus disease severity by viral co-infection in a mouse model

text: Influenza viruses and rhinoviruses are responsible for a large number of acute respiratory viral infections in human populations and are detected as co-pathogens within hosts. Clinical and epidemiological studies suggest that co-infection by rhinovirus and influenza virus may reduce disease severity and that they may also interfere with each other’s spread within a host population. To determine how co-infection by these two unrelated respiratory viruses affects pathogenesis, we established a mouse model using a minor serogroup rhinovirus (RV1B) and mouse-adapted influenza A virus (PR8). Infection of mice with RV1B two days before PR8 reduced pathogenesis of mild to moderate, but not severe PR8 infections. Disease attenuation was associated with an early inflammatory response in the lungs and enhanced clearance of PR8. However, co-infection by RV1B did not reduce PR8 viral loads early in infection or inhibit replication of PR8 within respiratory epithelia or in vitro. Inflammation in co-infected mice remained focal, in comparison to diffuse inflammation and damage in the lungs of mice infected by PR8. These findings suggest that RV1B stimulates an early immune response that clears PR8 while limiting excessive pulmonary inflammation. The timing of RV1B co-infection was a critical determinant of protection, suggesting that sufficient time is needed to induce this response. Finally, disease attenuation was not unique to RV1B: co-infection by a murine coronavirus two days before PR8 also reduced disease severity. This model will be critical for understanding the mechanisms responsible for attenuation of influenza disease during co-infection by unrelated respiratory viruses.


Molecular Farming: Transgenic Animals as Bioreactors


title: Partial comparison of the NxTAG Respiratory Pathogen Panel Assay with the Luminex xTAG Respiratory Panel Fast Assay V2 and singleplex real-time polymerase chain reaction for detection of respiratory pathogens

text: Abstract In this study, 185 nasopharyngeal swabs were tested to compare the sensitivity and specificity of the Luminex NxTAG (NxTAG) Respiratory Pathogen Panel (RPP) Assay with those of the Luminex Respiratory Virus Panel (RVP) Fast Assay v2 and singleplex real-time polymerase chain reaction (PCR). The NxTAG Assay identified at least one infectious agent in 164 (88.7%) of the swabs. In 91 (6.2%) tests with negative results with the RVP Fast Assay v2, a virus was identified by the NxTAG (P < 0.001). With the NxTAG Assay, the detection rates were significantly higher for respiratory syncytial virus (P = 0.003), human metapneumovirus (P < 0.001), human rhinovirus/human enterovirus (P = 0.009) and human adenovirus (P < 0.001). Finally, the NxTAG Assay identified M. pneumoniae in 32 of 44 (72.7%) PCR-positive samples. However, the concordance with real-time PCR results was low for both assays. In conclusion, the results indicate that the NxTAG Assay overcomes some of the limitations of previous Luminex assays, although further studies are needed for a more complete evaluation of the new assay.


title: O-linked oligosaccharides of mouse egg ZP3 account for its sperm receptor activity

text: Abstract Previously, we reported that ZP3, one of three different glycoproteins present in the mouse egg's zona pellucida, serves as a sperm receptor. Furthermore, small glycopeptides derived from egg ZP3 retain full sperm receptor activity, suggesting a role for carbohydrate, rather than polypeptide chain in receptor function. Here, we report that removal of O-linked oligosaccharides from ZP3 destroys its sperm receptor activity, whereas removal of O-linked oligosaccharides has no effect. A specific size class of O-linked oligosaccharides, recovered following mild alkaline hydrolysis and reduction of ZP3, is shown to possess sperm receptor activity and to bind to sperm. The results presented strongly suggest that mouse sperm bind to eggs via O-linked oligosaccharides present on ZP3.


title: Immunogenicity and Protection from Receptor-Binding Domains of Toxins as Potential Vaccine Candidates for Clostridium difficile

text: The receptor-binding domains (RBDs) located in toxin A and toxin B of Clostridium difficile are known to be nontoxic and immunogenic. We need to develop a new type vaccine based on RBDs. In this study, we expressed and purified recombinant proteins (named RBD-TcdA and RBD-TcdB) as vaccine candidates containing the RBDs of toxin A and toxin B, respectively, from the C. difficile reference strain VPI10463. The immunogenicity and protection of the vaccine candidates RBD-TcdA, RBD-TcdB, and RBD-TcdA/B was evaluated by ELISA and survival assays. The data indicated that mice immunized with all vaccine candidates displayed potent levels of RBD-specific serum IgG. Following intramuscular immunization of mice with RBD-TcdA and/or RBD-TcdB, these vaccine candidates triggered immune responses that protected mice compared to mice immunized with aluminum hydroxide alone. Taken together, the results of this study reveal that recombinant proteins containing RBDs of C. difficile toxins can be used for vaccine development. Additionally, we found that an RBD-TcdA/B vaccine can elicit a stronger humoral immune response and provide better immunoprotection than the univalent vaccines. This RBD vaccine candidate conferred significant protection against disease symptoms and death caused by toxins from a wild-type C. difficile strain.


title: Marburg virus regulates the IRE1/XBP1-dependent unfolded protein response to ensure efficient viral replication

text: Viruses regulate cellular signalling pathways to ensure optimal viral replication. During Marburg virus (MARV) infection, large quantities of the viral glycoprotein GP are produced in the ER; this may result in the activation of the unfolded protein response (UPR). The most conserved pathway to trigger UPR is initiated by IRE1. Activation of IRE1 results in auto-phosphorylation, splicing of the XBP1 mRNA and translation of the XBP1s protein. XBP1s binds cis-acting UPR elements (UPRE) which leads to the enhanced expression of genes which should restore ER homeostasis. XBP1u protein is translated, if IRE1 is not activated. Here we show that ectopic expression of MARV GP activated the IRE1-XBP1 axis of UPR as monitored by UPRE luciferase assays. However, while at 24 h of infection with MARV IRE1 was phosphorylated, expression of XBP1s was only slightly enhanced and UPRE activity was not detected. The IRE1-XBP1 axis was not active at 48 h p.i. Co-expression studies of MARV proteins demonstrated that the MARV protein VP30 suppressed UPRE activation. Co-immunoprecipitation analyses revealed an RNA-dependent interaction of VP30 with XBP1u. Knock-out of IRE1 supported MARV infection at late time points. Taken together, these results suggest that efficient MARV propagation requires specific regulation of IRE1 activity.


title: Structure and Function of the C-terminal Domain of the Polymerase Cofactor of Rabies Virus

text: The phosphoprotein (P) of rabies virus binds the viral polymerase to the nucleoprotein (N)-RNA template for transcription and replication. By limited protease digestion we defined a monomeric C-terminal domain of P that can bind to N-RNA. The atomic structure of this domain was determined and previously described mutations that interfere with binding of P to N-RNA could now be interpreted. There appears to be two features involved in this activity situated at opposite surfaces of the molecule: a positively charged patch and a hydrophobic pocket with an exposed tryptophan side-chain. Other previously published work suggests a conformational change in P when it binds to N-RNA, which may imply the repositioning of two helices that would expose a hydrophobic groove for interaction with N. This domain of rabies virus P is structurally unrelated to the N-RNA binding domains of the phosphoproteins of Sendai and measles virus that are members of the same order of viruses, the non-segmented negative strand RNA viruses. The implications of this finding for the evolution of this virus group are discussed.


title: A VLP vaccine for epidemic Chikungunya virus protects non-human primates against infection

text: Chikungunya virus (CHIKV) has infected millions of people in Africa, Europe, and Asia1,2 since its re-emergence in Kenya in 2004. The severity of disease and spread of this epidemic virus present a serious public health threat in the absence of vaccines or anti-viral therapies. Here, we describe a novel vaccine that protects against emerging CHIKV infection of non-human primates (NHP). We show that selective expression of viral structural proteins gives rise to virus-like particles (VLPs) in vitro that resemble replication-competent alphaviruses. Immunization with these VLPs elicited neutralizing antibodies against envelope proteins from different CHIKV strains. Monkeys immunized with VLPs produced high titer neutralizing antibodies that protected against viremia after high dose challenge. We transferred these antibodies into immunodeficient mice, where they protected against subsequent lethal CHIKV challenge, establishing a humoral mechanism of protection. Immunization with alphavirus VLP vaccines represents a strategy to contain the spread of CHIKV and related pathogenic viruses in humans.


title: Autoclave Sterilization and Ethanol Treatment of Re-used Surgical Masks and N95 Respirators during COVID-19: Impact on their Performance and Integrity

text: BACKGROUND: An exceptionally high demand for surgical masks and N95 filtering facepiece respirators (FFRs) during the COVID-19 pandemic has considerably exceeded their supply. These disposable devices are generally not approved for routine decontamination and re-use as standard of care while this practice has widely occurred in hospitals. The US Centers for Disease Control and Prevention allowed it “as a crisis capacity strategy.” However, limited testing was conducted on the impact of specific decontamination methods on the performance of N95 FFRs and no data was presented for surgical masks. AIM: We evaluated common surgical masks and N95 respirators with respect to the changes in their performance and integrity resulting from autoclave sterilization and a 70% ethanol treatment; these methods are frequently utilized for re-used filtering facepieces in hospitals. METHODS: The filter collection efficiency and pressure drop were determined for unused masks and N95 FFRs, and for those subjected to the treatments in a variety of ways. The collection efficiency was measured for particles of approximately 0.037–3.2 μm to represent aerosolized single viruses, their agglomerates, bacteria and larger particles carriers. FINDINGS: The initial collection efficiency and the filter breathability may be compromised by sterilization in an autoclave and ethanol treatment. The effect depends on a protective device, particle size, breathing flow rate, type of treatment and other factors. Additionally, physical damages were observed in N95 respirators after autoclaving. CONCLUSION: Strategies advocating decontamination and re-use of filtering facepieces in hospitals should be re-assessed considering the data obtained in this study.


title: Use of Functional Genomics to Understand Influenza–Host Interactions

text: Abstract Infection with influenza typically results in mild‐to‐moderate illness in healthy individuals; however, it is responsible for 30,000–40,000 deaths each year in the United States. In extreme cases, such as the influenza pandemic of 1918, tens of millions of people have died from the infection. To prepare for future influenza outbreaks, it is necessary to understand how the virus interacts with the host and to determine what makes certain strains of influenza highly pathogenic. Functional genomics provides a unique approach to this effort by allowing researchers to examine the effect of influenza infection on global host mRNA levels. Researchers are making increasing use of this approach to study virus–host interactions using a variety of model systems. For example, data obtained using microarray technology, in combination with mouse and macaque infection models, is providing exciting new insights into the pathogenicity of the 1918 virus. These studies suggest that the lethality associated with this virus is in part due to an aberrant and unchecked immune response. Progress is also being made toward using functional genomics in the diagnosis and prognosis of acute lung infections and in the development of more effective influenza vaccines and antivirals.


Emerging respiratory tract infections


title: Infection control throughout history Andrew Cliff Matthew Smallman-Raynor

text: Unknown


title: RIG-I-like receptors: their regulation and roles in RNA sensing

text: Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are key sensors of virus infection, mediating the transcriptional induction of type I interferons and other genes that collectively establish an antiviral host response. Recent studies have revealed that both viral and host-derived RNAs can trigger RLR activation; this can lead to an effective antiviral response but also immunopathology if RLR activities are uncontrolled. In this Review, we discuss recent advances in our understanding of the types of RNA sensed by RLRs in the contexts of viral infection, malignancies and autoimmune diseases. We further describe how the activity of RLRs is controlled by host regulatory mechanisms, including RLR-interacting proteins, post-translational modifications and non-coding RNAs. Finally, we discuss key outstanding questions in the RLR field, including how our knowledge of RLR biology could be translated into new therapeutics.


title: Novel Immunoglobulin Domain Proteins Provide Insights into Evolution and Pathogenesis of SARS-CoV-2-Related Viruses

text: A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was recently identified as the causative agent for the coronavirus disease 2019 (COVID-19) outbreak that has generated a global health crisis. We use a combination of genomic analysis and sensitive profile-based sequence and structure analysis to understand the potential pathogenesis determinants of this virus. As a result, we identify several fast-evolving genomic regions that might be at the interface of virus-host interactions, corresponding to the receptor binding domain of the Spike protein, the three tandem Macro fold domains in ORF1a, and the uncharacterized protein ORF8. Further, we show that ORF8 and several other proteins from alpha- and beta-CoVs belong to novel families of immunoglobulin (Ig) proteins. Among them, ORF8 is distinguished by being rapidly evolving, possessing a unique insert, and having a hypervariable position among SARS-CoV-2 genomes in its predicted ligand-binding groove. We also uncover numerous Ig domain proteins from several unrelated metazoan viruses, which are distinct in sequence and structure but share comparable architectures to those of the CoV Ig domain proteins. Hence, we propose that SARS-CoV-2 ORF8 and other previously unidentified CoV Ig domain proteins fall under the umbrella of a widespread strategy of deployment of Ig domain proteins in animal viruses as pathogenicity factors that modulate host immunity. The rapid evolution of the ORF8 Ig domain proteins points to a potential evolutionary arms race between viruses and hosts, likely arising from immune pressure, and suggests a role in transmission between distinct host species.


title: Anti-influenza virus activity and structure–activity relationship of aglycoristocetin derivatives with cyclobutenedione carrying hydrophobic chains

text: Abstract Previous studies have demonstrated that glycopeptide compounds carrying hydrophobic substituents can have favorable pharmacological (i.e. antibacterial and antiviral) properties. We here report on the in vitro anti-influenza virus activity of aglycoristocetin derivatives containing hydrophobic side chain-substituted cyclobutenedione. The lead compound 8e displayed an antivirally effective concentration of 0.4μM, which was consistent amongst influenza A/H1N1, A/H3N2 and B viruses, and a selectivity index ≥50. Structural analogues derived from aglycovancomycin were found to be inactive. The hydrophobic side chain was shown to be an important determinant of activity. The narrow structure–activity relationship and broad activity against several human influenza viruses suggest a highly conserved interaction site, which is presumably related to the influenza virus entry process. Compound 8e proved to be inactive against several unrelated RNA and DNA viruses, except for varicella-zoster virus, against which a favorable activity was noted.


title: Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions

text: COVID-19 has become a global pandemic. Immune dysregulation has been implicated, but immune responses remain poorly understood. We analyzed 71 COVID-19 patients compared to recovered and healthy subjects using high dimensional cytometry. Integrated analysis of ~200 immune and >30 clinical features revealed activation of T cell and B cell subsets, but only in some patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses could reach >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable to uninfected subjects. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. These analyses identified three “immunotypes” associated with poor clinical trajectories versus improving health. These immunotypes may have implications for therapeutics and vaccines.


title: Recomendaciones sobre el tratamiento antitrombótico durante la pandemia COVID-19. Posicionamiento del Grupo de Trabajo de Trombosis Cardiovascular de la Sociedad Española de Cardiología

text: RESUMEN La pandemia producida por la infección del nuevo coronavirus SARS-CoV-2, que da lugar a una enfermedad altamente contagiosa (COVID-19), ha producido un colapso de los sistemas sanitarios de todo el mundo. Se ha descrito que estos pacientes sufren un estado inflamatorio que condiciona un alto riesgo trombótico. Sin embargo, apenas hay información sobre cómo abordar el riesgo trombótico, la coagulopatía y el tratamiento anticoagulante de estos pacientes. Por otra parte, incluso los pacientes no infectados por COVID-19 sufren una tremenda influencia en su abordaje habitual por la situación sanitaria actual. El objetivo del presente documento, elaborado por el Grupo de Trabajo de Trombosis Cardiovascular de la Sociedad Española de Cardiología, es presentar la información disponible y dar unas pautas sencillas de tratamiento con fármacos antitrombóticos. ABSTRACT The new coronavirus SARS-CoV-2, which gives rise to the highly contagious COVID-19 disease, has caused a pandemic that is overwhelming health care systems worldwide. Affected patients have been reported to have a heightened inflammatory state that increases their thrombotic risk. However, there is very scarce information on the management of thrombotic risk, coagulation disorders, and anticoagulant therapy. In addition, the situation has also greatly influenced usual care in patients not infected with COVID-19. This article by the Working Group on Cardiovascular Thrombosis of the Spanish Society of Cardiology aims to summarize the available information and to provide a practical approach to the management of antithrombotic therapy.


title: Lockdown, one, two, none, or smart. Modeling containing covid-19 infection. A conceptual model

text: Abstract A mathematical model has been created with the Systems Dynamics methodology. It is based on a SIR model, with the addition of auxiliary and state variables that represent hospital capacity, contacts, contacts with infected, deaths, giving, as a result, a model of four stock variables. Similarly, using piecewise functions, it was possible to model the “quarantines” or lockdowns, and the effectiveness of reduction in the contacts, Results show the decrease in infected people due to the quarantines. The model was simulated for a population of 100,000. The simulations show trends of infections that could occur in three different scenarios: A) one extended lockdown (60 days), B) two medium lockdowns of 30 days, with a 30-day smart lockdown space, and C) an initial 40-day lockdown and then a 30-day smart lockdown. All the lockdowns start on day 25 after the first reported infection. The model presents a compact structure of broad understanding and successful capture of a COVID-19 outbreak and therefore provides an overview to improve knowledge of outbreak trends and quarantine effectiveness in reducing infection.


title: Handling and Processing of Blood Specimens from Patients with COVID‐19 for Safe Studies on Cell Phenotype and Cytokine Storm

text: The pandemic caused by severe acute respiratory syndrome coronavirus 2 heavily involves all those working in a laboratory. Samples from known infected patients or donors who are considered healthy can arrive, and a colleague might be asymptomatic but able to transmit the virus. Working in a clinical laboratory is posing several safety challenges. Few years ago, International Society for Advancement of Cytometry published guidelines to safely analyze and sort human samples that were revised in these days. We describe the procedures that we have been following since the first patient appeared in Italy, which have only slightly modified our standard one, being all human samples associated with risks. © 2020 International Society for Advancement of Cytometry


title: Evolution of codon usage in Zika virus genomes is host and vector specific

text: The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak. An interplay between codon adaptation and deoptimization may have allowed the virus to adapt to multiple host and vectors and is reported for the first time in ZIKV genomes. Combining our codon analysis with geographical data on Aedes populations in the Americas suggested that ZIKV has evolved host- and vector-specific codon usage patterns to maintain successful replication and transmission chains within multiple hosts and vectors.