title: The challenges and opportunities of a global health crisis: the management and business implications of COVID-19 from an Asian perspective

text: On March 11, 2020, the World Health Organization (WHO) declared the coronavirus (COVID-19) outbreak a pandemic. As the evolution and implications of the COVID-19 crisis are still unfolding, we posit that exploring the experiences and strategic responses of Asian countries may shed light on ways to combat COVID-19 for the rest of the world. In this paper, we first articulate the importance of resilience, strategic agility, and entrepreneurship in the context of the fight against COVID-19. Then, with the focus on China, South Korea, and Singapore, we discuss the impact COVID-19 is having on economies and businesses, governmental support for businesses and societies, and implications for global supply chain disruptions. We hope that the global health system will recover quickly, and that the world economy will be revitalized with the contributions and collaboration of science (including social science), industry, and governments.


“ANESTHESIA STAT” TO INTUBATE A COVID-19 PATIENT: IMPLICATIONS FOR THE ANESTHESIOLOGIST


title: Middle East respiratory syndrome coronavirus (MERS-CoV): what lessons can we learn?

text: Summary The Middle East Respiratory Coronavirus (MERS-CoV) was first isolated from a patient who died with severe pneumonia in June 2012. As of 19 June 2015, a total of 1,338 MERS-CoV infections have been notified to the World Health Organization (WHO). Clinical illness associated with MERS-CoV ranges from mild upper respiratory symptoms to rapidly progressive pneumonia and multi-organ failure. A significant proportion of patients present with non-respiratory symptoms such as headache, myalgia, vomiting and diarrhoea. A few potential therapeutic agents have been identified but none have been conclusively shown to be clinically effective. Human to human transmission is well documented, but the epidemic potential of MERS-CoV remains limited at present. Healthcare-associated clusters of MERS-CoV have been responsible for the majority of reported cases. The largest outbreaks have been driven by delayed diagnosis, overcrowding and poor infection control practices. However, chains of MERS-CoV transmission can be readily interrupted with implementation of appropriate control measures. As with any emerging infectious disease, guidelines for MERS-CoV case identification and surveillance evolved as new data became available. Sound clinical judgment is required to identify unusual presentations and trigger appropriate control precautions. Evidence from multiple sources implicates dromedary camels as natural hosts of MERS-CoV. Camel to human transmission has been demonstrated, but the exact mechanism of infection remains uncertain. The ubiquitously available social media have facilitated communication and networking amongst healthcare professionals and eventually proved to be important channels for presenting the public with factual material, timely updates and relevant advice.


title: EGR1 upregulation following Venezuelan equine encephalitis virus infection is regulated by ERK and PERK pathways contributing to cell death

text: Abstract Venezuelan equine encephalitis virus (VEEV) is a neurotropic virus that causes significant disease in both humans and equines. Here we characterized the impact of VEEV on signaling pathways regulating cell death in human primary astrocytes. VEEV productively infected primary astrocytes and caused an upregulation of early growth response 1 (EGR1) gene expression at 9 and 18 h post infection. EGR1 induction was dependent on extracellular signal-regulated kinase1/2 (ERK1/2) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), but not on p38 mitogen activated protein kinase (MAPK) or phosphoinositide 3-kinase (PI3K) signaling. Knockdown of EGR1 significantly reduced VEEV-induced apoptosis and impacted viral replication. Knockdown of ERK1/2 or PERK significantly reduced EGR1 gene expression, dramatically reduced viral replication, and increased cell survival as well as rescued cells from VEEV-induced apoptosis. These data indicate that EGR1 activation and subsequent cell death are regulated through ERK and PERK pathways in VEEV infected primary astrocytes.


title: PERSONAS MAYORES, DEPENDENCIA Y VULNERABILIDAD EN LA PANDEMIA POR CORONAVIRUS: EMERGENCIA DE UNA INTEGRACIÓN SOCIAL Y SANITARIA

text: Resumen La pandemia actual por SARS-CoV-2 (COVID-19) afecta con mayor incidencia y gravedad a las personas mayores en todo el mundo. En España, el 68% del total de hospitalizaciones por coronavirus, corresponden a mayores de 60 años. Este trabajo tiene como objetivo incrementar la evidencia sobre las medidas a implementar con directrices actuales y futuras en diferentes escenarios. Destaca la necesidad de prepararnos para la acción mediante la implementación de protocolos de carácter internacional. Existe una tendencia hacia la atención biopsicosocial de las personas mayores en todos los entornos donde se encuentran, adecuando la atención y personalizando decisiones de ingresos hospitalarios, cuidados paliativos, atendiendo, entre otros criterios, a los años ajustados a la calidad de vida, así como alternativas para el monitoreo y tratamiento de la patología por COVID-19 y otras ya existentes. Son necesarias medidas de reducción de la transmisión del virus a través de la higiene y el distanciamiento, atendiendo a la salud biopsicosocial de los mayores aislados. Como alternativas innovadoras se propone la comunicación intersectorial, y el uso de herramientas tecnológicas, acompañado de una adecuada alfabetización digital en salud. Las líneas futuras se centran en garantizar los derechos sociales y sanitarios, equiparando al mismo nivel el sistema social y de salud, y consiguiendo una coordinación real. Un nuevo marco de atención centrada en la persona podría ser un gran aliado para conseguir una atención integrada a los mayores, guiada por un aumento de los recursos destinados a la financiación de proyectos de investigación sobre longevidad. Abstract The current SARS-CoV-2 pandemic (COVID-19) is affecting elderly people worldwide with greater incidence and severity. In Spain, 68% of all coronavirus hospitalizations correspond to those over 60 years of age. This work aims to highlight the evidence about the measures to be implemented through current and future guidelines. The need to prepare for action by implementing international protocols stand out. There is a trend towards biopsychosocial care of elderly people in all settings where they are, adapting care and personalizing decisions on hospital admissions, palliative care, among other criteria, to years adjusted to quality of life, as well as alternatives for monitoring and treatment of COVID-19 pathology and others existing in this population group. Measures to reduce the transmission of the virus through hygiene and social distancing are necessary, attending to biopsychosocial health of the elderly isolated. Intersectoral communication is proposed as innovative alternatives, and the use of technological tools, accompanied by adequate digital health literacy. Future lines focus on guaranteeing social and health rights, equating the social and health system at the same level, and achieving real coordination. A new framework of person-centered care could be a great ally to achieve integrated care for the elderly, guided by an increase in resources bound to funding longevity research projects.


title: Computational analysis of protein interaction networks for infectious diseases

text: Infectious diseases caused by pathogens, including viruses, bacteria and parasites, pose a serious threat to human health worldwide. Frequent changes in the pattern of infection mechanisms and the emergence of multidrug-resistant strains among pathogens have weakened the current treatment regimen. This necessitates the development of new therapeutic interventions to prevent and control such diseases. To cater to the need, analysis of protein interaction networks (PINs) has gained importance as one of the promising strategies. The present review aims to discuss various computational approaches to analyse the PINs in context to infectious diseases. Topology and modularity analysis of the network with their biological relevance, and the scenario till date about host–pathogen and intra-pathogenic protein interaction studies were delineated. This would provide useful insights to the research community, thereby enabling them to design novel biomedicine against such infectious diseases.


title: The impact of ethnicity on clinical outcomes in COVID-19: A systematic review

text: BACKGROUND: The relationship between ethnicity and COVID-19 is uncertain. We performed a systematic review to assess whether ethnicity has been reported in patients with COVID-19 and its relation to clinical outcomes. METHODS: We searched EMBASE, MEDLINE, Cochrane Library and PROSPERO for English-language citations on ethnicity and COVID-19 (1(st) December 2019-15(th) May 2020). We also reviewed: COVID-19 articles in NEJM, Lancet, BMJ, JAMA, clinical trial protocols, grey literature, surveillance data and preprint articles on COVID-19 in MedRxiv to evaluate if the association between ethnicity and clinical outcomes were reported and what they showed. PROSPERO:180654. FINDINGS: Of 207 articles in the database search, five reported ethnicity; two reported no association between ethnicity and mortality. Of 690 articles identified from medical journals, 12 reported ethnicity; three reported no association between ethnicity and mortality. Of 209 preprints, 34 reported ethnicity – 13 found Black, Asian and Minority Ethnic (BAME) individuals had an increased risk of infection with SARS-CoV-2 and 12 reported worse clinical outcomes, including ITU admission and mortality, in BAME patients compared to White patients. Of 12 grey literature reports, seven with original data reported poorer clinical outcomes in BAME groups compared to White groups. INTERPRETATION: Data on ethnicity in patients with COVID-19 in the published medical literature remains limited. However, emerging data from the grey literature and preprint articles suggest BAME individuals are at an increased risk of acquiring SARS-CoV-2 infection compared to White individuals and also worse clinical outcomes from COVID-19. Further work on the role of ethnicity in the current pandemic is of urgent public health importance. FUNDING: NIHR


title: Unknown SARS-CoV-2 pneumonia detected by PET/CT in patients with cancer

text: INTRODUCTION: In January 2020, the coronavirus disease 2019 (COVID-19) outbreak in Italy necessitated rigorous application of more restrictive safety procedures in the management and treatment of patients with cancer to ensure patient and staff protection. Identification of respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was a challenge during the pandemic owing to a large number of asymptomatic or mildly symptomatic patients. METHODS: We report 5 patients with unknown SARS-CoV-2 infection undergoing positron emission tomography (PET)/computed tomography (CT) with radiopharmaceuticals targeting different tumor processes: (18)F-FDG, (18)F-choline (FCH), and (68)Ga-PSMA. RESULTS: In all patients, PET/CT showed increased tracer uptake in the lungs corresponding to CT findings of SARS-CoV-2 pneumonia. Quantitative assessment of tracer uptake showed more elevated values for the glucose analogue (18)F-FDG (mean SUVmax 5.4) than for the other tracers (mean SUVmax 3.5). CONCLUSIONS: Our findings suggest that PET/CT is a sensitive modality to hypothesize SARS-CoV-2 pneumonia in patients with cancer, even when asymptomatic. More data are needed to verify the correlation among immune response to SARS-CoV-2 infection, clinical evolution, and PET results. Under the strict safety measures implemented at the PET center, the number of potentially SARS-CoV-2–positive patients undergoing PET/CT was very low (1.6%), and no staff member has been diagnosed with infection as of April 30, 2020.


title: Modulation of Protease Activated Receptor 1 Influences Human Metapneumovirus Disease Severity in a Mouse Model

text: Human metapneumovirus (hMPV) infection causes acute respiratory tract infections (RTI) which can result in hospitalization of both children and adults. To date, no antiviral or vaccine is available for this common viral infection. Immunomodulators could represent an interesting strategy for the treatment of severe viral infection. Recently, the role of protease-activated receptors (PAR) in inflammation, coagulation and infection processes has been of growing interest. Herein, the effects of a PAR1 agonist and a PAR1 antagonist on hMPV infection were investigated in BALB/c mice. Intranasal administration of the PAR1 agonist resulted in increased weight loss and mortality of infected mice. Conversely, the PAR1 antagonist was beneficial to hMPV infection by decreasing weight loss and clinical signs and by significantly reducing pulmonary inflammation, pro-inflammatory cytokine levels (including IL-6, KC and MCP-1) and recruitment of immune cells to the lungs. In addition, a significant reduction in pulmonary viral titers was also observed in the lungs of PAR1 antagonist-treated mice. Despite no apparent direct effect on virus replication during in vitro experiments, an important role for PAR1 in the regulation of furin expression in the lungs was shown for the first time. Further experiments indicated that the hMPV fusion protein can be cleaved by furin thus suggesting that PAR1 could have an effect on viral infectivity in addition to its immunomodulatory properties. Thus, inhibition of PAR1 by selected antagonists could represent an interesting strategy for decreasing the severity of paramyxovirus infections.


title: Characterization of a Bivalent Vaccine Capable of Inducing Protection Against Both Ebola and Cross-clade H5N1 Influenza in Mice

text: Background. Ebola virus (EBOV) is a lethal pathogen that causes up to 90% mortality in humans, whereas H5N1 avian influenza has a 60% fatality rate. Both viruses are considered pandemic threats. The objective was to evaluate the protective efficacy of a bivalent, recombinant vesicular stomatitis virus vaccine expressing both the A/Hanoi/30408/2005 H5N1 hemagglutinin and the EBOV glycoprotein (VSVΔG-HA-ZGP) in a lethal mouse model of infection. Methods. Mice were vaccinated 28 days before or 30 minutes after a lethal challenge with mouse-adapted EBOV or selected H5N1 influenza viruses from clades 0, 1, and 2. Animals were monitored for weight loss and survival, in addition to humoral and cell-mediated responses after immunization. Results. A single VSVΔG-HA-ZGP injection was efficacious when administered 28 days before a homologous H5N1 and/or mouse-adapted EBOV challenge, as well as a heterologous H5N1 challenge. Postexposure protection was only observed in vaccinated animals challenged with homologous H5N1 and/or mouse-adapted EBOV. Analysis of the adaptive immune response postvaccination revealed robust specific T- and B-cell responses, including a potent hemagglutinin inhibition antibody response against all H5N1 strains tested. Conclusions. The results highlight the ability of vesicular stomatitis virus–vectored vaccines to rapidly confer protection against 2 unrelated pathogens and stimulate cross-protection against H5N1 influenza viruses.


title: Inhibition of Hepatitis B virus gene expression by single and dual small interfering RNA treatment

text: Abstract RNA interference (RNAi) has been successfully applied in suppression of Hepatitis B virus (HBV) replication. To circumvent the problem that mutation in HBV genome may result in resistance when siRNA is further developed as an anti-viral drug, in this study, we established a dual small interfering RNA (siRNA) expression system, which could simultaneously express two different siRNA molecules that can specifically target two genes. To test the effectiveness of this system, we applied this new approach to express simultaneously two different 21-bp hairpin siRNA duplexes that specifically attack the HBs and HBx genes of HBV, respectively, in Bel-7402 and HepG2.2.15 cells. Results indicated that dual siRNA could simultaneously inhibit the expression of HBs and HBx gene by 83.7% and 87.5%, respectively, based on luciferase assays. In addition, dual siRNA molecules were able to significantly reduce the amount of HBV core associated DNA, which is considered as an intracellular replicative intermediate, and the viral DNA in culture supernatant. Therefore, this dual siRNA system provides a more powerful tool for the study of gene function and implicates a potential application in the treatment of viral infection.


title: Overview of preparedness and response for Middle East respiratory syndrome coronavirus (MERS-CoV) in Oman

text: Summary Several countries in the Middle East and around 22 countries worldwide have reported cases of human infection with the Middle East respiratory syndrome coronavirus (MERS-CoV). The exceptionally high fatality rate resulting from MERS-CoV infection in conjunction with the paucity of knowledge about this emerging virus has led to major public and international concern. Within the framework of the national acute respiratory illness surveillance, the Ministry of Health in the Sultanate of Oman has announced two confirmed cases of MERS-CoV to date. The aim of this report is to describe the epidemiological aspects of these two cases and to highlight the importance of public health preparedness and response. The absence of secondary cases among contacts of the reported cases can be seen as evidence of the effectiveness of infection prevention and control precautions as an important pillar of the national preparedness and response plan applied in the health care institutions in Oman.


title: Diagnosing Viral and Atypical Pathogens in the Setting of Community-Acquired Pneumonia

text: The ‘atypical’ pathogens causing pneumonia have long been problematic for physicians because we have had to rely on serologic tests to make a diagnosis. The introduction of polymerase chain reaction techniques revolutionized the diagnosis of respiratory infections and now a new wave of technologies promising faster, cheaper, and more comprehensive testing are becoming available. This review focuses principally on the diagnosis of Legionella, Mycoplasma, and influenza infections, but also covers recent publications on the cutting edge of diagnostic tools likely to transform the field of infectious diseases over the coming decade.


title: Scoring system to triage patients for spine surgery in the setting of limited resources: Application to the COVID-19 pandemic and beyond

text: Abstract Background As of May 04, 2020, the COVID-19 pandemic has affected over 3.5 million people and touched every inhabited continent. Accordingly, it has stressed health systems the world over leading to the cancellation of elective surgical cases and discussions regarding healthcare resource rationing. It is expected that rationing of surgical resources will continue even after the pandemic peak, and may recur with future pandemics, creating a need for a means of triaging emergent and elective spine surgery patients. Methods Using a modified Delphi technique, a cohort of 16 fellowship-trained spine surgeons from 10 academic medical centers constructed a scoring system for the triage and prioritization of emergent and elective spine surgeries. Three separate rounds of videoconferencing and written correspondence were used to reach a final scoring system. Sixteen test cases were used to optimize the scoring system so that it could categorize cases as requiring emergent, urgent, high-priority elective, or low-priority elective scheduling. Results The devised scoring system included 8 independent components: neurological status, underlying spine stability, presentation of a high-risk post-operative complication, patient medical comorbidities, expected hospital course, expected discharge disposition, facility resource limitations, and local disease burden. The resultant calculator was deployed as a freely-available web-based calculator (https://jhuspine3.shinyapps.io/SpineUrgencyCalculator/). Conclusion Here we present the first quantitative urgency scoring system for the triage and prioritizing of spine surgery cases in resource-limited settings. We believe that our scoring system, while not all-encompassing, has potential value as a guide for triaging spine surgical cases during the COVID pandemic and post-COVID period.


title: High incidence of venous thromboembolic events in anticoagulated severe COVID‐19 patients

text: BACKGROUND: Coagulopathy is a common abnormality in patients with COVID‐19. However, the exact incidence of venous thromboembolic event is unknown in anticoagulated, severe COVID‐19 patients. OBJECTIVES: Systematic assessment of venous thromboembolism (VTE) using complete duplex ultrasound (CDU) in anticoagulated COVID‐19 patients. PATIENTS AND METHODS: We performed a retrospective study in 2 French intensive care units (ICU) where CDU is performed as a standard of care. A CDU from thigh to ankle at selected sites with Doppler waveforms and images was performed early during ICU stay in patients admitted with COVID‐19. Anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis. Patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation. Pulmonary embolism was systematically searched in patients with persistent hypoxemia or secondary deterioration. RESULTS: From March 19 to April 11, 2020, 26 consecutive patients with severe COVID‐19 were screened for VTE. Eight patients (31%) were treated with prophylactic anticoagulation, whereas 18 patients (69%) were treated with therapeutic anticoagulation. The overall rate of VTE in patients was 69%. The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with the other group (100% vs 56%, respectively, P = .03). Surprisingly, we found a high rate of thromboembolic events in COVID‐19 patients treated with therapeutic anticoagulation, with 56% of VTE and 6 pulmonary embolisms. CONCLUSION: Our results suggest considering both systematic screening of VTE and early therapeutic anticoagulation in severe ICU COVID‐19 patients.


title: Cell-Penetrating Peptides for Antiviral Drug Development

text: Viral diseases affect hundreds of millions of people worldwide, and the few available drugs to treat these diseases often come with limitations. The key obstacle to the development of new antiviral agents is their delivery into infected cells in vivo. Cell-penetrating peptides (CPPs) are short peptides that can cross the cellular lipid bilayer with the remarkable capability to shuttle conjugated cargoes into cells. CPPs have been successfully utilized to enhance the cellular uptake and intracellular trafficking of antiviral molecules, and thereby increase the inhibitory activity of potential antiviral proteins and oligonucleotide analogues, both in cultured cells and in animal models. This review will address the notable findings of these studies, highlighting some promising results and discussing the challenges CPP technology has to overcome for further clinical applications.


title: Gene expression profiling to identify potentially relevant disease outcomes and support human health risk assessment for carbon black nanoparticle exposure

text: Abstract New approaches are urgently needed to evaluate potential hazards posed by exposure to nanomaterials. Gene expression profiling provides information on potential modes of action and human relevance, and tools have recently become available for pathway-based quantitative risk assessment. The objective of this study was to use toxicogenomics in the context of human health risk assessment. We explore the utility of toxicogenomics in risk assessment, using published gene expression data from C57BL/6 mice exposed to 18, 54 and 162μg Printex 90 carbon black nanoparticles (CBNP). Analysis of CBNP-perturbed pathways, networks and transcription factors revealed concomitant changes in predicted phenotypes (e.g., pulmonary inflammation and genotoxicity), that correlated with dose and time. Benchmark doses (BMDs) for apical endpoints were comparable to minimum BMDs for relevant pathway-specific expression changes. Comparison to inflammatory lung disease models (i.e., allergic airway inflammation, bacterial infection and tissue injury and fibrosis) and human disease profiles revealed that induced gene expression changes in Printex 90 exposed mice were similar to those typical for pulmonary injury and fibrosis. Very similar fibrotic pathways were perturbed in CBNP-exposed mice and human fibrosis disease models. Our synthesis demonstrates how toxicogenomic profiles may be used in human health risk assessment of nanoparticles and constitutes an important step forward in the ultimate recognition of toxicogenomic endpoints in human health risk. As our knowledge of molecular pathways, dose–response characteristics and relevance to human disease continues to grow, we anticipate that toxicogenomics will become increasingly useful in assessing chemical toxicities and in human health risk assessment.


title: Development of a SYBR green I-based quantitative RT-PCR for Ross River virus: Application in vector competence studies and antiviral drug evaluation

text: Abstract Ross River virus (RRV) is an emerging Alphavirus and is presently endemic in many parts of Oceania. Keeping in mind its emergence, we developed a molecular detection system and utilized it to study vector competence and evaluate activity of antiviral compounds against RRV. A SYBR Green I-based quantitative RT-PCR for detection of RRV was developed targeting the E2 gene, with a detection limit of 100 RNA copies/reaction. The specificity was confirmed with closely related Alphaviruses and Flaviviruses. The assay was applied to study the vector competence of Indian Aedes aegypti for RRV, which revealed 100% infection and dissemination rate with 75% transmission rate. Viral RNA was found in saliva as early as 3day post infection (dpi). Further application of the assay in antiviral drug evaluation revealed the superior in vitro activity of ribavirin compared to chloroquine in Vero cells. Successful demonstration of this assay to detect RRV in low titre mosquito samples makes it a sensitive tool in vector surveillance. This study also showed that Indian Ae. aegypti are well competent to transmit RRV highlighting the risk of its introduction to naïve territories across continents. Further validation of this assay, revealed its utility in screening of potential antivirals against RRV.


title: Blocking ELISA for distinguishing infectious bovine rhinotracheitis virus (IBRV)-infected animals from those vaccinated with a gene-deleted marker vaccine

text: Abstract A sensitive and specific blocking enzyme-linked immunosorbent assay (ELISA) was developed to distinguish infectious bovine rhinotracheitis virus (IBRV)-infected animals from those immunized with a glycoprotein gIII deletion mutant, IBRV(NG)dltkdlgIII. For this ELISA, undiluted test sera are used to block the binding of an anti-IBRV gIII monoclonal antibody (mAbgIII)-horseradish peroxidase (HRPO) conjugate to gIII antigen. TMB substrate is used for color development. Negative S/N values (defined as the absorbance at 650 nm of test sera/absorbance at 650 nm of negative control sera) of >0.80 were obtained with immune sera from gnotobiotic cattle immunized with several bovine viruses, with bovine antisera to bovine herpesvirus-2, and vesicular stomatitis virus, with porcine antisera to pseudorabies virus and parvovirus, and with normal sera from heterologous species. Negative S/N values were also obtained with sera from rabbits twice vaccinated with IBRV(NG)dltkdlgIII. However, the S/N values became positive (S/N <0.8) 10 to 17 days after the rabbits were challenge exposed to virulent IBRV(Cooper). Most of 116 sera (84%) from feedlot cattle with virus neutralization (VN) titers of < 1:2 or < 1:4 had negative S/N values >0.8, but 18 sera with negative VN titers had positive S/N values, consistent with observations indicating that an IBRV outbreak was occurring in one of the feedlot herds. Thirty nine sera (98%) from feedlot cattle with VN titers of 1:2 to 1:128 had positive S/N values (<0.8). One serum with a VN titer of 1:2 had a borderline (±) S/N value of 0.81. After immunization with a commercial gIII-positive IBRV vaccine, 115 116 sera with VN titers of 1:2 to 1:256 had positive S/N values (<0.8). One serum with a VN titer of 1:2 had a negative S/N value of 0.83. Serum from one vaccinated animal that failed to seroconvert after vaccination (VN < 1:4) showed a strongly positive ELISA S/N of 0.48.


title: Comparative Research for the Healthcare Budget and Burden of Disease in Perspective Resource Allocation

text: BACKGROUND: Burden of disease can be used to prioritize the healthcare budget allocation. We analyzed the research and development (R&D) budget of the Ministry of Health and Welfare (MOHW) in 2018 and compared the results with those of the 2015 Korean National Burden of Disease (KNBD) study. METHODS: The 2018 MOHW R&D Project integrated implementation plan was used to analyze the R&D budget of the MOHW. The budget was allocated according to the KNBD disease group and according to the budget lines. The allocated budget was compared with the economic burden and the disability adjusted life years (DALYs) in 2015. Also, for budget targets for risk factors, DALYs of attributable risk factors were compared with corresponding budgets. RESULTS: In 2018, the MOHW major R&D budget of USD 435.1 million accounted for 3% of the total government budget. Within the disease specific R&D budget, 35.9% was allocated to communicable disease groups, 64.1% to non-communicable diseases, and 0% to injury and violence. Among level 2 disease groups, neoplasm was ranked first. Among risk factors, climate change and behavioral risk were targeted for R&D. CONCLUSIONS: It would be difficult to say that current R&D allocations focus to minimize the burden of disease. A mismatch was observed between the R&D budget and the burden of disease in terms of economic burden and DALYs. There was a similar finding for risk factors R&D. A novel approach for allocating government R&D funding that is based on the goal of minimizing the disease burden in the Korean population should be considered.


title: Fluorescence based fiber optic and planar waveguide biosensors. A review

text: Abstract The application of optical biosensors, specifically those that use optical fibers and planar waveguides, has escalated throughout the years in many fields, including environmental analysis, food safety and clinical diagnosis. Fluorescence is, without doubt, the most popular transducer signal used in these devices because of its higher selectivity and sensitivity, but most of all due to its wide versatility. This paper focuses on the working principles and configurations of fluorescence-based fiber optic and planar waveguide biosensors and will review biological recognition elements, sensing schemes, as well as some major and recent applications, published in the last ten years. The main goal is to provide the reader a general overview of a field that requires the joint collaboration of researchers of many different areas, including chemistry, physics, biology, engineering, and material science.


title: Establishing research priorities to improve the One Health efficacy of Australian general practitioners and veterinarians with regard to zoonoses: A modified Delphi survey

text: While general medical practitioners (GPs) and veterinarians are often the first line responders in the face of a disease outbreak, pathways to improving the One Health efficacy of these clinicians remain unclear. A two-phase modified Delphi survey of professionals with known expertise in One Health (‘expert panel’) was used to 1) identify key knowledge, attitudes and practices (KAPs) of GPs and veterinarians that would be consistent with a One Health approach to zoonoses; and 2) determine priorities for future surveys with Australian GPs and veterinarians to identify important gaps that impede effective diagnosis and management of zoonoses. A list of 13 topics/sub-topics, as well as a list of 25 specific zoonotic diseases/agents emerged from the first phase of the survey. In the second phase the expert panel identified general knowledge of the clinical aspects and epidemiological aspects of zoonoses, as well as risk management practices, as the most important KAPs and research priorities for both GPs and veterinarians. In terms of diseases, the expert panel regarded knowledge of Hendra virus, Q fever, Australian bat lyssavirus (ABLV), anthrax and Brucella suis most important for veterinarians, whilst for GPs, Q fever, gastrointestinal/foodborne diseases, influenza, ABLV and local vector-borne diseases were found to be most important by the expert panel. Some differences were noted in terms of prioritization of topics/sub-topics and diseases/agents according to expert background (veterinary and non-veterinary). The Delphi survey technique enabled efficient collection of data from a diverse range of One Health ‘experts’/specialists and provided clear priorities for proposed future research, and potentially for educational interventions to improve One Health efficacy of clinicians.


title: Topographical aspects of airborne contamination caused by the use of dental handpieces in the operative environment.

text: ABSTRACT Background The use of dental handpieces produces aerosols containing microbial agents, bacteria and viruses representing a high-risk situation for airborne cross-infections. This study aimed to map and quantify the biological contamination of a dental operatory environment using a biological tracer. Methods Streptococcus mutans suspension was infused into the mouth of a phantom, and an operator performed standardized dental procedures using an air turbine, a contra-angle handpiece or an ultrasonic scaler. The presence of the tracer was measured at 90 sites on the dental unit and the surrounding surfaces of the operatory environment. Results All tested instruments spread the tracer over the entire dental unit and the surrounding environment, including the walls and ceiling. The pattern and degree of contamination were related to the distance from the infection source. The maximum distance of tracer detection was 360 cm for air turbine, 300 cm for contra-angle and 240 cm for scaler (11.8, 9.8 and 7.9 ft, respectively). No surface of the operative environment was free from the tracer after the use of the air turbine. Conclusions Attention should be paid to minimize or avoid the use of rotary and ultrasonic instruments when concerns for the airborne spreading of pandemic disease agents are present. Practical Implications. The present study supports the recommendations of dental associations to avoid treatments generating aerosols, especially during pandemic periods. Guidelines for the management of dental procedures involving aerosols are urgently needed, as well as methods for the aerosols modification aimed to inactivate the infective agent.


title: Live Cell Reporter Systems for Positive-Sense Single Strand RNA Viruses

text: Cell-based reporter systems have facilitated studies of viral replication and pathogenesis, virus detection, and drug susceptibility testing. There are three types of cell-based reporter systems that express certain reporter protein for positive-sense single strand RNA virus infections. The first type is classical reporter system, which relies on recombinant virus, reporter virus particle, or subgenomic replicon. During infection with the recombinant virus or reporter virus particle, the reporter protein is expressed and can be detected in real time in a dose-dependent manner. Using subgenomic replicon, which are genetically engineered viral RNA molecules that are capable of replication but incapable of producing virions, the translation and replication of the replicon could be tracked by the accumulation of reporter protein. The second type of reporter system involves genetically engineered cells bearing virus-specific protease cleavage sequences, which can sense the incoming viral protease. The third type is based on viral replicase, which can report the specific virus infection via detection of the incoming viral replicase. This review specifically focuses on the major technical breakthroughs in the design of cell-based reporter systems and the application of these systems to the further understanding and control of viruses over the past few decades.


title: Virus safety of intravenous immunoglobulin: Future challenges

text: Patients with immunodeficiencies or some types of autoimmune diseases are dependent on safe therapy with intravenous immunoglobulins. State-of-the-art manufacturing processes provide a high safety standard by incorporating virus elimination procedures into the manufacturing process. Based on their mechanism, these procedures are grouped into three classes: partitioning, inactivation, and removal based on size. Because of current socioeconomic and ecological changes, emerging pathogens continue to be expected. Such pathogens may spread very quickly because of increased intercontinental traffic. Severe acute respiratory syndrome-coronavirus and the West Nile virus are recent examples. Currently, it is not possible to predict the impact such a pathogen will have on blood safety because the capacity for a globally coordinated reaction to such a threat is also evolving. The worst-case scenario would be the emergence of a transmissible, small, nonenveloped virus in the blood donor population. Examples of small nonenveloped viruses, which change host and tissue tropism, are discussed, with focus on parvoviridae. Although today’s immunoglobulins are safer than ever, in preparation for future challenges it is a high priority for the plasma industry to proactively investigate such viruses on a molecular and cellular level to identify their vulnerabilities.


title: Early identification of pneumonia patients at increased risk of Middle East respiratory syndrome coronavirus infection in Saudi Arabia

text: Abstract Background The rapid and accurate identification of individuals who are at high risk of Middle East respiratory syndrome coronavirus (MERS-CoV) infection remains a major challenge for the medical and scientific communities. The aim of this study was to develop and validate a risk prediction model for the screening of suspected cases of MERS-CoV infection in patients who have developed pneumonia. Methods A two-center, retrospective case–control study was performed. A total of 360 patients with confirmed pneumonia who were evaluated for MERS-CoV infection by real-time reverse transcription polymerase chain reaction (rRT-PCR) between September 1, 2012 and June 1, 2016 at King Abdulaziz Medical City in Riyadh and King Fahad General Hospital in Jeddah, were included. According to the rRT-PCR results, 135 patients were positive for MERS-CoV and 225 were negative. Demographic characteristics, clinical presentations, and radiological and laboratory findings were collected for each subject. Results A risk prediction model to identify pneumonia patients at increased risk of MERS-CoV was developed. The model included male sex, contact with a sick patient or camel, diabetes, severe illness, low white blood cell (WBC) count, low alanine aminotransferase (ALT), and high aspartate aminotransferase (AST). The model performed well in predicting MERS-CoV infection (area under the receiver operating characteristics curves (AUC) 0.8162), on internal validation (AUC 0.8037), and on a goodness-of-fit test (p =0.592). The risk prediction model, which produced an optimal probability cut-off of 0.33, had a sensitivity of 0.716 and specificity of 0.783. Conclusions This study provides a simple, practical, and valid algorithm to identify pneumonia patients at increased risk of MERS-CoV infection. This risk prediction model could be useful for the early identification of patients at the highest risk of MERS-CoV infection. Further validation of the prediction model on a large prospective cohort of representative patients with pneumonia is necessary.


Corticosteroid use in selected patients with severe Acute Respiratory Distress Syndrome related to Covid-19


title: Epidemiological study of people living in rural North Carolina for novel respiratory viruses

text: During the last 10 years, scientists have grown increasingly aware that emerging respiratory viruses are often zoonotic in their origin. These infections can originate from or be amplified in livestock. Less commonly recognized are instances when humans have transmitted their respiratory pathogens to animals (reverse zoonoses). Even with this knowledge of viral exchange at the human–livestock interface, few studies have been conducted to understand this cross‐over. In this pilot study, we examined persons with influenza‐like illness at an outpatient clinic for evidence of infection with novel zoonotic respiratory pathogens in rural North Carolina where there are dense swine and poultry farming. Environmental air sampling was also conducted. From July 2016 to March 2017, a total of 14 human subjects were enrolled and sampled, and 192 bioaerosol samples were collected. Of the 14 human subject samples molecularly tested, three (21.4%) were positive for influenza A, one (7.1%) for influenza B and one (7.1%) for human enterovirus. Of the 192 bioaerosol samples collected and tested by real‐time RT‐PCR or PCR, three (1.6%) were positive for influenza A and two (1.0%) for adenovirus. No evidence was found for novel zoonotic respiratory viruses.


title: The V5A13.1 envelope glycoprotein deletion mutant of mouse hepatitis virus type-4 is neuroattenuated by its reduced rate of spread in the central nervous system

text: Abstract Following intracerebral inoculation of adult Balb/c Byj mice, the MHV-4 strain of mouse hepatitis virus (MHV) had an LD50 of <0.1 PFU, whereas its monoclonal antibody resistant variant V5A13.1 had an LD50 of 104.2 PFU. To determine the basis for this difference in neurovirulence we have studied the acute central nervous system (CNS) infection of these two viruses by in situ hybridization. Both viruses infected the same, specific neuroanatomical areas, predominantly neurons, and spread via the cerebrospinal fluid, along neuronal pathways and between adjacent cells. The neuronal nuclei infected and the spread of virus within the brain are described. The main difference between the parental and variant viruses was the rate at which the infection spread. MHV-4 spread rapidly, destroying large numbers of neurons and the animals died within 4 days of infection. The variant virus spread to the same areas of the brain but at a slower rate. This difference in the rate of virus spread was also apparent from the brain virus titers. The slower rate of spread of the variant virus appears to allow intervention by the immune response. Consistent with this, the variant virus spread slowly in athymic nu/nu mice, but in the absence of an intact immune response, infection and destruction of neurons eventually reached the same extent as that of the parental virus and the mice died within 6 days of infection. We conclude that the V5A13.1 variant of MHV-4 is neuroattenuated by its slower rate of spread in the CNS.


title: Clinical Characteristics of Patients Who Died of Coronavirus Disease 2019 in China

text: This case series describes the characteristics of a cohort of patients who died of coronavirus disease 2019 in China.


title: Chapter 8 Control of intestinal diseases by dietary supplementation with antibodies

text: Publisher Summary The chapter discusses the control of intestinal diseases by dietary supplementation with antibodies. This chapter presents the most important principles of prophylactic and therapeutic, and oral application of immunoglobulins. Because of the production conditions today about 20–40% of newborn farm animals (cattle, pigs, horses, goats, sheep) exhibit failure of passive transfer (FPT). The direct consequence of this is an increased susceptibility to diseases during the first weeks of life, which necessitates the wide use of antibiotics. As a further consequence, an increasing antibiotic-resistance of diarrheal strains of bacteria has become a fact. An alternative to using antibiotic is oral application of immunoglobulin products in the periods of greatest risk that is within the first days of life and in the postweaning period. Air-dried egg yolk immunoglobulin (IgY), cow colostrum and swine serum, which can be produced on a large scale, provide the greatest chance for mass application. The most important protective role is played by specific antibodies against antigens present in the neonate's environment. The chapter discusses application of xenogenic antibodies. There are several indications for the application of cow colostrum to foals, lambs and kids, such as lack of, or low quality of maternal colostrum, mastitis, twins or multiple fetuses, and so on. Serum produced from the blood of slaughtered swine allows the large-scale production of immunoglobulins. An important problem with oral administration is proteolysis of the immunoglobulins by digestive enzymes, while another problem is caused by inactivation of antibody activity because of low pH.


docid: ziqqalev

title: Design, synthesis and biological evaluation of phosphorodiamidate prodrugs of antiviral and anticancer nucleosides

text: We herein report the application of the phosphorodiamidate phosphate prodrug approach to a series of thirteen nucleoside analogs with antiviral or anticancer activity. Twenty-five symmetrical phosphorodiamidates were synthesized, bearing esterified l-Alanine (and in one case d-alanine) in the prodrug moiety, each as single stereoisomer. The presence of an achiral phosphorus represents a potential advantage over the phosphoramidate ProTide approach, where diastereoisomeric mixtures are routinely obtained, and different biological profiles may be expected from the diastereoisomers. Optimization of the synthetic pathway allowed us to identify two general methods depending on the particular nucleoside analogs. All the compounds were biologically evaluated in antiviral and anticancer assays and several showed improvement of activity compared to their parent nucleosides, as in the case of ddA, d4T, abacavir and acyclovir against HIV-1 and/or HIV-2. The biological results were supported by metabolism studies with carboxypeptidase Y monitored by (31)P NMR to investigate their bioactivation. This work further validates the phosphorodiamidate approach as a monophosphate prodrug motif with broad application in the antiviral and anticancer fields.


title: Association of Digestive Symptoms and Hospitalization in Patients With SARS-CoV-2 Infection

text: INTRODUCTION: High rates of concurrent gastrointestinal manifestations have been noted in patients with corona virus disease 2019 (COVID-19); however, the association between these digestive manifestations and need for hospitalization has not been established. METHODS: This is a retrospective review of consecutive patients diagnosed with COVID-19. A total of 207 patients were identified; 34.5% of patients noted concurrent gastrointestinal symptoms, with 90% of gastrointestinal symptoms being mild. RESULTS: In a multivariate regression model controlled for demographics and disease severity, an increased risk of hospitalization was noted in patients with any digestive symptom (adjusted odds ratio 4.84, 95% confidence interval: 1.68–13.94). DISCUSSION: The presence of digestive symptoms in COVID-19 is associated with a need for hospitalization.


title: Sporadic cases of adult measles: a research article

text: BACKGROUND: Measles caused by a paramyxovirus, characterized by fever, malaise, cough, coryza conjunctivitis, a maculopapular rash is known to result in pneumonia, encephalitis and death. Fatal cases of measles in Sri Lanka are rare after implementation of the National Immunization Programme in 1984. Thereafter 0.1% case fatality rate was observed during October 1999–June 2000 which is a very low figure compared to other regional countries. Immunization guidelines were further revised in 2001, 2011 and in 2012 when additional immunization was recommended to age group 4–21 years; who are likely to have inadequate immunization, in order to achieve elimination of Measles by 2020. However, in 2013–2014, 4690 cases were reported and the majority were children less than 1 year of age. The occurrence in adults is hard to retrieve in published epidemiological reports, however had been 38% (out of 1008 patients) in the 3rd quarter of 2013. During this outbreak 73/101 (72%) reported from the North Central Province of Sri Lanka had been more than 12 years of age with 50% being more than 29 years. 14 Sri lankan adult patients [median age 32 years (range 25–48)] who presented sporadically from June 2014 to March 2016, with confirmed measles infection were enrolled retrospectively after informed consent. Details with regards to their clinical presentation, immunization and other relevant areas were collected using an interviewer administered questionnaire or using patient management records. RESULTS: The patients presented with high fever, headache, severe body aches, sore throat, dry cough, intense tearing, red eyes and posterior cervical lymphadenopathy over 3–5 days duration. Later they developed discrete maculopapular rash helping the diagnosis. They had a variable degree of leucopenia, lymphocytosis, thrombocytopenia and derangements in the liver functions mimicking any other acute febrile illnesses such as dengue, chikungunya, leptospirosis or Zika virus infection. CONCLUSION: At least a 3–5 day delay in the diagnosis was observed (even after the appearance of the rash in some patients), due to non-awareness of its occurrence, unfamiliarity of measles in adults, non-specific nature of the illness and non-availability of rapid diagnostics, risking transmission to the immune-compromised or non-immune staff or patients. Identification of the source of infection in these sporadic adult cases and their virologic surveillance and molecular epidemiology will be important to interrupt the transmission and to achieve the targeted elimination of measles from Sri Lanka by 2020.


title: Polyomaviruses KI and WU in children with respiratory tract infection

text: The polyomaviruses KI (KIPyV) and WU (WUPyV) have recently been discovered in specimens from patients with respiratory tract infections. To analyze the frequency and clinical impact in a cohort of pediatric patients in a German University Children’s Hospital. Nasopharyngeal aspirates or bronchoalveolar lavage specimens of 229 children with acute respiratory tract infection were screened for KIPyV and WUPyV using polymerase chain reaction-based methods. KIPyV was detected in 2 (0.9%) and WUPyV in 1 (0.4%) patients, without co-infections with other respiratory viruses but with co-detection of CMV, EBV and HHV 6 in one immunocompromised patient. Only a very small proportion (1.3%) of positive samples for KIPyV and WUPyV was documented in this study; the clinical relevance of these viruses remains unclear and requires further evaluation.


title: Glass Wool Concentration Optimization for the Detection of Enveloped and Non-enveloped Waterborne Viruses

text: An extremely affordable virus concentration method based on adsorption-elution to glass wool and subsequent reconcentration through polyethylene glycol 6000 (PEG) precipitation was optimized to recover not only non-enveloped viruses but also enveloped viruses. Hepatitis A virus (HAV) and transmissible gastroenteritis virus (TGEV) were employed as surrogates for naked and enveloped viruses, respectively, to set up the methodology. Initial experimentation in small-volume samples showed that both types of particles readily adsorbed to the positively charged glass wool but were poorly detached from it through standard elution with 0.05 M glycine with 3% of beef extract buffer, pH 9.5, with elution efficiencies of 7.2% and 2.6%, for HAV and TGEV, respectively. To improve the recovery of enveloped viruses, several modifications in the elution were assayed: increasing the elution pH, extending glass wool and eluent contact time, adding a detergent, or performing the elution by recirculation or under agitation. Considering practicability and performance, recircularization of the eluent at pH 11.0 for 20 min was the elution procedure of choice, with efficiencies of 25.7% and 18.8% for HAV and TGEV in 50 L of water. Additionally, employing 20% PEG instead of 10% for virus reconcentration improved recoveries up to 47% and 51%, respectively. The optimized procedure was applied to detect naturally occurring HAV and coronaviruses in surface water of Wadi Hanifa, Riyadh. HAV was detected in 38% of the samples, while one sample was positive for an alphacoronavirus. This cheap virus detection system enables the comprehensive surveillance of viruses present in water samples.


title: Innate immune modulation by RNA viruses: emerging insights from functional genomics

text: Although often encoding fewer than a dozen genes, RNA viruses can overcome host antiviral responses and wreak havoc on the cells they infect. Some manage to evade host antiviral defences, whereas others elicit an aberrant or disproportional immune response. Both scenarios can result in the disruption of intracellular signalling pathways and significant pathology in the host. Systems-biology approaches are increasingly being used to study the processes of viral triggering and regulation of host immune responses. By providing a global and integrated view of cellular events, these approaches are beginning to unravel some of the complexities of virus–host interactions and provide new insights into how RNA viruses cause disease.


title: Contactless Vital Signs Measurement System Using RGB-Thermal Image Sensors and Its Clinical Screening Test on Patients with Seasonal Influenza

text: Background: In the last two decades, infrared thermography (IRT) has been applied in quarantine stations for the screening of patients with suspected infectious disease. However, the fever-based screening procedure employing IRT suffers from low sensitivity, because monitoring body temperature alone is insufficient for detecting infected patients. To overcome the drawbacks of fever-based screening, this study aims to develop and evaluate a multiple vital sign (i.e., body temperature, heart rate and respiration rate) measurement system using RGB-thermal image sensors. Methods: The RGB camera measures blood volume pulse (BVP) through variations in the light absorption from human facial areas. IRT is used to estimate the respiration rate by measuring the change in temperature near the nostrils or mouth accompanying respiration. To enable a stable and reliable system, the following image and signal processing methods were proposed and implemented: (1) an RGB-thermal image fusion approach to achieve highly reliable facial region-of-interest tracking, (2) a heart rate estimation method including a tapered window for reducing noise caused by the face tracker, reconstruction of a BVP signal with three RGB channels to optimize a linear function, thereby improving the signal-to-noise ratio and multiple signal classification (MUSIC) algorithm for estimating the pseudo-spectrum from limited time-domain BVP signals within 15 s and (3) a respiration rate estimation method implementing nasal or oral breathing signal selection based on signal quality index for stable measurement and MUSIC algorithm for rapid measurement. We tested the system on 22 healthy subjects and 28 patients with seasonal influenza, using the support vector machine (SVM) classification method. Results: The body temperature, heart rate and respiration rate measured in a non-contact manner were highly similarity to those measured via contact-type reference devices (i.e., thermometer, ECG and respiration belt), with Pearson correlation coefficients of 0.71, 0.87 and 0.87, respectively. Moreover, the optimized SVM model with three vital signs yielded sensitivity and specificity values of 85.7% and 90.1%, respectively. Conclusion: For contactless vital sign measurement, the system achieved a performance similar to that of the reference devices. The multiple vital sign-based screening achieved higher sensitivity than fever-based screening. Thus, this system represents a promising alternative for further quarantine procedures to prevent the spread of infectious diseases.


title: Health Care Associated Middle East Respiratory Syndrome (MERS): A Case from Iran

text: Middle East respiratory syndrome coronavirus (MERS-CoV) Infection, has caused recurrent outbreaks worldwide. It is associated with severe morbidity and mortality, and is not treatable with the currently available antiviral therapies. We present a case of a 43 year-old male healthcare provider, who admitted with productive cough, dyspnea, myalgia, pleuritic chest pain and fever. Computed tomography (CT) showed bilateral ground glass opacities and consolidation. Sputum polymerase chain reaction (PCR) for MERS-coronavirus was positive.


title: Design and biological activities of novel inhibitory peptides for SARS-CoV spike protein and angiotensin-converting enzyme 2 interaction

text: Abstract Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel coronavirus (SARS-CoV). The binding of SARS-CoV spike (S) protein to cellular angiotensin-converting enzyme 2 (ACE2) is the first step in SARS-CoV infection. Therefore, we assayed the inhibitory effects of small peptides derived from S protein on the binding of S protein to ACE2 and on the S-protein-pseudotyped retrovirus infectivity. SP-4 (residues 192–203), SP-8 (residues 483–494), and SP-10 (residues 668–679) significantly blocked the interaction between S protein and ACE2 by biotinylated enzyme-linked immunosorbent assay, with IC50 values of 4.30±2.18, 6.99±0.71, and 1.88±0.52nmol, respectively. Peptide scanning suggested the region spanning residues 660–683 might act as a receptor-binding domain. SP-10 blocked both binding of the S protein and infectivity of S protein-pseudotyped retrovirus to Vero E6 cells. In conclusion, this is the first report of small peptides designed to disrupt the binding of SARS-CoV S protein to ACE2. Our findings suggest that SP-10 may be developed as an anti-SARS-CoV agent for the treatment of SARS-CoV infection.


title: Prognosis of COVID-19 in Patients with Liver and Kidney Diseases: An Early Systematic Review and Meta-Analysis

text: The mortality and severity in COVID-19 is increased in patients with comorbidities. The aim of this study was to evaluate the severity and mortality in COVID-19 patients with underlying kidney and liver diseases. We retrieved data on the clinical features and primary composite end point of COVID-19 patients from Medline and Embase which had been released from inception by the April 16, 2020. The data on two comorbidities, liver diseases and chronic kidney disease, were pooled and statistically analysed to explain the associated severity and mortality rate. One hundred and forty-two abstracts were screened, and 41 full articles were then read. In total, 22 studies including 5595 COVID-19 patients were included in this study with case fatality rate of 16%. The prevalence of liver diseases and chronic kidney disease (CKD) were 3% (95% CI; 2–3%) and 1% (95% CI; 1–2%), respectively. In patients with COVID-19 and underlying liver diseases, 57.33% (43/75) of cases were severe, with 17.65% mortality, while in CKD patients, 83.93% (47/56) of cases were severe and 53.33% (8/15) mortality was reported. This study found an increased risk of severity and mortality in COVID-19 patients with liver diseases or CKD. This will lead to better clinical management and inform the process of implementing more stringent preventative measures for this group of patients.


title: Renyi entropy and mutual information measurement of market expectations and investor fear during the COVID-19 pandemic

text: The COVID-19 pandemic has seriously affected world economies. In this regard, it is expected that information level and sharing between equity, digital currency, and energy markets has been altered due to the pandemic outbreak. Specifically, the resulting twisted risk among markets is presumed to rise during the abnormal state of world economy. The purpose of the current study is twofold. First, by using Renyi entropy, we analyze the multiscale entropy function in the return time series of Bitcoin, S&P500, WTI, Brent, Gas, Gold, Silver, and investor fear index represented by VIX. Second, by estimating mutual information, we analyze the information sharing between these markets. The analyses are conducted before and during the COVID-19 pandemic. The empirical results from Renyi entropy indicate that for all market indices, randomness and disorder are more concentrated in less probable events. The empirical results from mutual information showed that the information sharing network between markets has changed during the COVID-19 pandemic. From a managerial perspective, we conclude that during the pandemic (i) portfolios composed of Bitcoin and Silver, Bitcoin and WTI, Bitcoin and Gold, Bitcoin and Brent, or Bitcoin and S&P500 could be risky, (ii) diversification opportunities exist by investing in portfolios composed of Gas and Silver, Gold and Silver, Gold and Gas, Brent and Silver, Brent and Gold, or Bitcoin and Gas, and that (iii) the VIX exhibited the lowest level of information disorder at all scales before and during the pandemic. Thus, it seems that the pandemic has not influenced the expectations of investors. Our results provide an insight of the response of stocks, cryptocurrencies, energy, precious metal markets, to expectations of investors in the aftermath of the COVID-19 pandemic in terms of information ordering and sharing.


title: Antimicrobial susceptibility of Histophilus somni isolated from clinically affected cattle in Australia

text: Abstract This study investigated antimicrobial resistance traits, clonal relationships and epidemiology of Histophilus somni isolated from clinically affected cattle in Queensland and New South Wales, Australia. Isolates (n = 53) were subjected to antimicrobial susceptibility testing against six antimicrobial agents (ceftiofur, enrofloxacin, florfenicol, tetracycline, tilmicosin and tulathromycin) using disc diffusion and minimum inhibitory concentration (MIC) assays. Clonal relationships were assessed using repetitive sequence PCR and descriptive epidemiological analysis was performed. The H. somni isolates appeared to be geographically clonal, with 27/53 (47%) isolates grouping in one cluster from one Australian state. On the basis of disc diffusion, 34/53 (64%) isolates were susceptible to all antimicrobial agents tested; there was intermediate susceptibility to tulathromycin in 12 isolates, tilmicosin in seven isolates and resistance to tilmicosin in one isolate. Using MIC, all but one isolate was susceptible to all antimicrobial agents tested; the non-susceptible isolate was resistant to tetracycline, but this MIC result could not be compared to disc diffusion, since there are no interpretative guidelines for disc diffusion for H. somni against tetracycline. In this study, there was little evidence of antimicrobial resistance in H. somni isolates from Australian cattle. Disc diffusion susceptibility testing results were comparable to MIC results for most antimicrobial agents tested; however, results for isolates with intermediate susceptibility or resistance to tilmicosin and tulathromycin on disc diffusion should be interpreted with caution in the absence of MIC results.


title: Chapter 19 Orthomyxoviruses of Fish

text: Abstract The family Orthomyxoviridae is well known for containing influenza viruses with a segmented RNA genome that is prone to gene reassortment in mixed infections (known as antigenic shift) resulting in new virus subtypes that cause pandemics, and cumulative mutations (known as antigenic drift), resulting in new virus strains that cause epidemics. This family also contains infectious salmon anemia virus (ISAV) and tilapia lake virus (TiLV), which are a unique orthomyxoviruses that infect fish and is unable to replicate above room temperature (24°C). This chapter describes the comparative virology of members in the family Orthomyxoviridae in general, helping to understand the emergent teleost orthomyxoviruses, ISAV and TiLV. The most current information on virus–host interactions of the fish orthomyxoviruses, particularly ISAV, as they relate to variations in virus structure, virulence, persistence, host range and immunological aspects is presented in detail.


title: Antibiotics in acute bronchitis: a meta-analysis

text: Abstract PURPOSE: Most patients with acute bronchitis who seek medical care are treated with antibiotics, although the effectiveness of this intervention is uncertain. We performed a meta-analysis of randomized, controlled trials to estimate the effectiveness of antibiotics in the treatment of acute bronchitis. SUBJECTS AND METHODS: English-language studies published January 1966 to April 1998 were retrieved using MEDLINE, bibliographies, and consultation with experts. Only randomized trials that enrolled otherwise healthy patients with a diagnosis of acute bronchitis, used an antibiotic in the treatment group and a placebo in the control group, and provided sufficient data to calculate an effect size were included. RESULTS: We identified eight randomized controlled trials that satisfied all inclusion criteria. These studies used one of three antibiotics (erythromycin, doxycycline, trimethoprim/sulfamethoxazole). The use of antibiotics decreased the duration of cough and sputum production by approximately one-half day (summary effect size 0.21; 95% CI, 0.05 to 0.36). For specific symptoms, there were nonsignificant trends favoring the use of antibiotics: a decrease of 0.4 days of purulent sputum (95% CI, −0.1 to 0.8), a decrease of 0.5 days of cough (95% CI, −0.1 to 1.1), and a decrease of 0.3 days lost from work (95% CI, −0.6 to 1.1). CONCLUSION: This meta-analysis suggests a small benefit from the use of the antibiotics erythromycin, doxycycline, or trimethoprim/sulfamethoxazole in the treatment of acute bronchitis in otherwise healthy patients. As this small benefit must be weighed against the risk of side effects and the societal cost of increasing antibiotic resistance, we believe that the use of antibiotics is not justified in these patients.


title: Assessment of synthetic peptides of severe acute respiratory syndrome coronavirus recognized by long‐lasting immunity

text: Abstract: In order to determine highly immunogenic severe acute respiratory syndrome coronavirus (SARS‐CoV) epitope peptides capable of inducing long‐lasting immunity, we first screened immunoglobulin‐G (IgG) antibodies reactive to 197 different overlapping 15‐mers from the SARS‐CoV proteins in the sera of three infected patients. Forty‐two peptides among them were reactive to the sera from all three patients. Consequently, we tested for the reactivity of these 42 peptides to patients' sera (n = 45) at 6‐month post‐infection. The significantly higher levels of IgG antibodies specific to three (S791, M207 and N161) of 42 peptides were detectable in the post‐infection sera from 23 (51%), 27 (60%) and 19 (42%) of 45 patients, respectively. These three peptides, recognized by their long‐lasting immunity, may provide a better understanding of the immunogenicity of SARS‐CoV.


title: Sea Turtles: Old Viruses and New Tricks

text: Abstract Recent years have seen an inexplicable increase in the frequency of an appalling disease in sea turtles: fibropapillomatosis, which is likely caused by a herpesvirus and causes tumors to grow throughout the turtle's body. New research has led to the disturbing conclusion that recent, human-induced environmental changes are responsible.


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title: New Respiratory Viruses and the Elderly

text: The diagnostics of respiratory viral infections has improved markedly during the last 15 years with the development of PCR techniques. Since 1997, several new respiratory viruses and their subgroups have been discovered: influenza A viruses H5N1 and H1N1, human metapneumovirus, coronaviruses SARS, NL63 and HKU1, human bocavirus, human rhinoviruses C and D and potential respiratory pathogens, the KI and WU polyomaviruses and the torque teno virus. The detection of previously known viruses has also improved. Currently, a viral cause of respiratory illness is almost exclusively identifiable in children, but in the elderly, the detection rates of a viral etiology are below 40%, and this holds also true for exacerbations of chronic respiratory illnesses. The new viruses cause respiratory symptoms like the common cold, cough, bronchitis, bronchiolitis, exacerbations of asthma and chronic obstructive pulmonary disease and pneumonia. Acute respiratory failure may occur. These viruses are distributed throughout the globe and affect people of all ages. Data regarding these viruses and the elderly are scarce. This review introduces these new viruses and reviews their clinical significance, especially with regard to the elderly population.


title: European Society for Neurogastroenterology and Motility (ESNM) recommendations for conducting gastrointestinal motility and function testing in the recovery phase of the COVID‐19 pandemic

text: BACKGROUND: During the peak of the COronaVIrus Disease 2019 (COVID‐19) pandemic, care for patients with gastrointestinal motility and functional disorders was largely suspended. In the recovery phases of the pandemic, non‐urgent medical care is resumed, but there is a lack of guidance for restarting and safely conducting motility and function testing. Breath tests and insertion of manometry and pH monitoring probes carry a risk for SARS‐CoV‐2 spread through droplet formation. METHODS: A panel of experts from the European Society for Neurogastroenterology and Motility (ESNM) evaluated emerging national and single center recommendations to provide the best current evidence and a pragmatic approach to ensure the safe conduct of motility and function testing for both healthcare professionals and patients. RESULTS: At a general level, this involves evaluation of the urgency of the procedure, evaluation of the infectious risk associated with the patient, the investigation and the health care professional(s) involved, provision of the test planning and test units, education and training of staff and use of personnel protection equipment. Additional guidance is provided for specific procedures such as esophageal manometry, pH monitoring and breath tests. CONCLUSIONS AND INFERENCES: The ESNM guidelines provide pragmatic and appropriate guidance for the safe conduct of motility and function testing in the COVID‐19 pandemic and early recovery phase.


title: Assessing air quality changes in large cities during COVID-19 lockdowns: The impacts of traffic-free urban conditions in Almaty, Kazakhstan

text: Abstract Number of cities worlwide experienced air quality improvements during COVID-19 lockdowns; however, such changes may have been different in places with major contributions from nontraffic related sources. In Almaty, a city-scale quarantine came into force on March 19, 2020, which was a week after the first COVID-19 case was registered in Kazakhstan. This study aims to analyze the effect of the lockdown from March 19 to April 14, 2020 (27 days), on the concentrations of air pollutants in Almaty. Daily concentrations of PM2.5, NO2, SO2, CO, O3, and BTEX were compared between the periods before and during the lockdown. During the lockdown, the PM2.5 concentration was reduced by 21% with spatial variations of 6–34% compared to the average on the same days in 2018–2019, and still, it exceeded WHO daily limit values for 18 days. There were also substantial reductions in CO and NO2 concentrations by 49% and 35%, respectively, but an increase in O3 levels by 15% compared to the prior 17 days before the lockdown. The concentrations of benzene and toluene were 2–3 times higher than those during in the same seasons of 2015–2019. The temporal reductions may not be directly attributed to the lockdown due to favorable meteorological variations during the period, but the spatial effects of the quarantine on the pollution levels are evidenced. The results demonstrate the impact of traffic on the complex nature of air pollution in Almaty, which is substantially contributed by various nontraffic related sources, mainly coal-fired combined heat and power plants and household heating systems, as well as possible small irregular sources such as garbage burning and bathhouses.


title: Clinical characteristics of COVID-19 in children compared with adults in Shandong Province, China

text: AIMS AND BACKGROUND: The COVID-19 outbreak spread in China and is a threat to the world. We reported on the epidemiological, clinical, laboratory, and radiological characteristics of children cases to help health workers better understand and provide timely diagnosis and treatment. METHODS: Retrospectively, two research centers’ case series of 67 consecutive hospitalized cases including 53 adult and 14 children cases with COVID-19 between 23 Jan 2020 and 15 Feb 2020 from Jinan and Rizhao were enrolled in this study. Epidemiological, clinical, laboratory, and radiological characteristics of children and adults were analyzed and compared. RESULTS: Most cases in children were mild (21.4%) and conventional cases (78.6%), with mild clinical signs and symptoms, and all cases were of family clusters. Fever (35.7%) and dry cough (21.4%) were described as clinical manifestations in children cases. Dry cough and phlegm were not the most common symptoms in children compared with adults (p = 0.03). In the early stages of the disease, lymphocyte counts did not significantly decline but neutrophils count did in children compared with adults (p = 0.02). There was a lower level of CRP (p = 0.00) in children compared with adults. There were 8 (57.1%) asymptomatic cases and 6 (42.9%) symptomatic cases among the 14 children cases. The age of asymptomatic patients was younger than that of symptomatic patients (p = 0.03). Even among asymptomatic patients, 5 (62.5%) cases had lung injuries including 3 (60%) cases with bilateral involvement, which was not different compared with that of symptomatic cases (p = 0.58, p = 0.74). CONCLUSIONS: The clinical symptoms of children are mild, there is substantial lung injury even among children, but that there is less clinical disease, perhaps because of a less pronounced inflammatory response, and that the occurrence of this pattern appears to inversely correlate with age.


title: Pathogenic murine coronaviruses II. Characterization of virus-specific proteins of murine coronaviruses JHMV and A59V

text: Abstract We have identified nine intracellular virus-specific proteins in cells infected with JHMV or A59V. Seven virus-specific proteins were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and two additional virus-specific proteins were detected by two-dimensional gel electrophoresis. The A59V- and JHMV-specific proteins differ slightly in molecular weight. Four of the nine proteins are structural proteins. The synthesis of the nine virus-specific proteins is noncoordinate with respect to time.


title: Cathepsin L Helps to Defend Mice from Infection with Influenza A

text: Host-derived proteases can augment or help to clear infections. This dichotomy is exemplified by cathepsin L (CTSL), which helps Hendra virus and SARS coronavirus to invade cells, but is essential for survival in mice with mycoplasma pneumonia. The present study tested the hypothesis that CTSL protects mice from serious consequences of infection by the orthomyxovirus influenza A, which is thought to be activated by host-supplied proteases other than CTSL. Ctsl(-/-) mice infected with influenza A/Puerto Rico/8/34(H1N1) had larger lung viral loads and higher mortality than infected Ctsl(+/+) mice. Lung inflammation in surviving infected mice peaked 14 days after initial infection, accompanied marked focal distal airway bronchiolization and epithelial metaplasia followed by desquamation and fibrotic interstitial remodeling, and persisted for at least 6 weeks. Most deaths occurred during the second week of infection in both groups of mice. In contrast to mycoplasma pneumonia, infiltrating cells were predominantly mononuclear rather than polymorphonuclear. The histopathology of lung inflammation and remodeling in survivors was similar in Ctsl(-/-) and Ctsl(+/+) mice, although Ctsl(+/+) mice cleared immunoreactive virus sooner. Furthermore, Ctsl(-/-) mice had profound deficits in CD4+ lymphocytes before and after infection and weaker production of pathogen-specific IgG. Thus, CTSL appears to support innate as well as adaptive responses, which confer a survival advantage on mice infected with the orthomyxovirus influenza A.


title: Management of newborns exposed to mothers with confirmed or suspected COVID-19

text: There is limited information about newborns with confirmed or suspected COVID-19. Particularly in the hospital after delivery, clinicians have refined practices in order to prevent secondary infection. While guidance from international associations is continuously being updated, all facets of care of neonates born to women with confirmed or suspected COVID-19 are center-specific, given local customs, building infrastructure constraints, and availability of protective equipment. Based on anecdotal reports from institutions in the epicenter of the COVID-19 pandemic close to our hospital, together with our limited experience, in anticipation of increasing numbers of exposed newborns, we have developed a triage algorithm at the Penn State Hospital at Milton S. Hershey Medical Center that may be useful for other centers anticipating a similar surge. We discuss several care practices that have changed in the COVID-19 era including the use of antenatal steroids, delayed cord clamping (DCC), mother–newborn separation, and breastfeeding. Moreover, this paper provides comprehensive guidance on the most suitable respiratory support for newborns during the COVID-19 pandemic. We also present detailed recommendations about the discharge process and beyond, including providing scales and home phototherapy to families, parental teaching via telehealth and in-person education at the doors of the hospital, and telehealth newborn follow-up.


title: CORONAVIRUS – COVID 19: Más allá de la enfermedad pulmonar, qué es y qué sabemos del vínculo con el sistema cardiovascular

text: Resumen La infección por SARS-CoV2 es una pandemia. Se creía que el primer caso de esta enfermedad ocurrió el 8 de diciembre de 2019 en la provincia de Hubei en China, aunque posteriormente se indicó que el primer caso confirmado por laboratorio ocurrió el 1.º de diciembre de 2019 ante la presencia de un brote de neumonía en 59 pacientes sospechosos en un mercado local de mariscos en Wuhan. No solo produce patología respiratoria, con frecuencia compremete el sistema cardiovascular ya que produce lesión miocárdica, miocarditis, y, con cierta frecuencia, aumenta la descompensación de enfermedades cardiovasculares preestablecidas. En este artículo se trata de dilucidar el componente cardiovascular hasta ahora existente en la literatura y se sugieren algunos pasos a seguir en pacientes con estas enfermedades, acorde con la evidencia actual. Abstract Infection due to SARS-CoV2 is a pandemic. It is believed that the first case occurred on 8 December 2019 in Hubei province in China, although it was later indicated that the first laboratory-confirmed case occurred on 1 December 2019 due to the presence of an outbreak of suspected pneumonia in 59 patients in a shellfish market in Wuhan. It not only caused a respiratory disease, it often compromised the cardiovascular system since it produces a myocardial lesion, myocarditis, and, less often, increased the decompensation of pre-established cardiovascular diseases. An attempt is made in this article to elucidate the cardiovascular component presented in the current literature, and to suggest some steps to follow in patients with these diseases in accordance with the current evidence.


The Human Genome and Advances in Medicine: Limits and Future Prospects


title: Inhibitory effect of flavonoids against NS2B-NS3 protease of ZIKA virus and their structure activity relationship

text: OBJECTIVES: To determine the inhibitory activities of flavonoids against NS2B-NS3 protease of ZIKA virus (ZIKV NS2B-NS3(pro)) expressed in Escherichia coli BL21 (DE3) and their structure activity relationship. RESULTS: ZIKV NS2B-NS3(pro) was expressed in E. coli BL21(DE3) as a 35 kDa protein. It had a K (m) of 26 µM with the fluorogenic peptide Dabcyl-KTSAVLQSGFRKME-Edan. The purified ZIKV NS2B-NS3(pro) was used for inhibition and kinetic assays to determine the activities of 22 polyphenol compounds. These polyphenol compounds at 100 µM inhibited the activity of ZIKV NS2B-NS3(pro) by 6.2–88%. Seven polyphenol compounds had IC(50) ranging from 22 ± 0.2 to 112 ± 5.5 µM. Myricetin showed a mixed type inhibitory pattern against ZIKV NS2B-NS3(pro) protease. Its IC(50) value was 22 ± 0.2 µM with a K (i) value of 8.9 ± 1.9 µM. CONCLUSION: The chemical structure of a polyphenol compound and its inhibitory activity against ZIKV NS2B-NS3(pro) can be explored to develop highly selective inhibitors against ZIKV NS2B-NS3(pro). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10529-016-2261-6) contains supplementary material, which is available to authorized users.


title: A cluster of patients with severe acute respiratory syndrome in a chest ward in southern Taiwan

text: OBJECTIVE: Severe acute respiratory syndrome (SARS) is an emerging and easily clustering infectious disease. We describe an outbreak of SARS in a chest ward of a medical center in southern Taiwan and seek to identify the risk factors of those SARS patients who required mechanical ventilation. We focus on previous health patients. DESIGN: This retrospective case series was collected during the SARS outbreak. Degrees of severity were established, based on whether intubation and mechanical ventilation was necessary. SETTING: A 2500-bed medical center in southern Taiwan. PATIENTS: Forty-four patients exhibited symptoms that met the modified World Health Organization (WHO) definition of SARS. These included of three subgroups: health-care workers (n=16), relatives (n=14), and patients already admitted for other ailments (n=14). Of these, 20 eventually required mechanical ventilation. MEASUREMENTS AND RESULTS: Laboratory analyses showed statistically significant differences between intubated and nonintubated patients in white blood cell count, neutrophil percentage, and C-reactive protein level as well as in age and underlying malignancy. Risk factors for SARS patients who had been healthy prior to their illness included old age, high peak fever grade, increased neutrophil count, increased neutrophil percentage, and close or prolonged contact with a SARS patient. CONCLUSIONS: Old age, high white blood cell counts, high peak grade fever, and close or prolonged contact with a SARS patient increase the risk of intubation in previous healthy SARS patients.


title: Why Isn’t Latvia the “Next” Crimea? Reconsidering Ethnic Integration

text: Abstract In the aftermath of Russia's military incursion in Ukraine and the annexation of Crimea in 2014, a flurry of articles predicted the next territorial conquest of President Vladimir Putin's Russian revanchism. High on the list were the Baltic countries, which sit precariously on the edge of Europe and historically have been the “bloodlands” between East and West in author Timothy Snyder's phrasing. More specifically, journalists and analysts pointed to the “Russian enclaves” in northeastern Estonia and southeastern Latvia, where, by many accounts, large ethnic Russian populations were prepared to rise up against Baltic governments with a bit of provocation from across the eastern border. However, six years on, there is little indication that Russian speakers in the Baltic countries are on the brink of causing an internal uprising. While there are multiple factors that can help explain the Baltic “dog that didn’t bark,” this essay considers an often overlooked variable in the equation: the depth of civic and cultural integration among Russian speakers in Latvia.


title: Investigation of effective climatology parameters on COVID-19 outbreak in Iran

text: Abstract SARS CoV-2 (COVID-19) Coronavirus cases are confirmed throughout the world and millions of people are being put into quarantine. A better understanding of the effective parameters in infection spreading can bring about a logical measurement toward COVID-19. The effect of climatic factors on spreading of COVID-19 can play an important role in the new Coronavirus outbreak. In this study, the main parameters, including the number of infected people with COVID-19, population density, intra-provincial movement, and infection days to end of the study period, average temperature, average precipitation, humidity, wind speed, and average solar radiation investigated to understand how can these parameters effects on COVID-19 spreading in Iran? The Partial correlation coefficient (PCC) and Sobol’-Jansen methods are used for analyzing the effect and correlation of variables with the COVID-19 spreading rate. The result of sensitivity analysis shows that the population density, intra-provincial movement have a direct relationship with the infection outbreak. Conversely, areas with low values of wind speed, humidity, and solar radiation exposure to a high rate of infection that support the virus's survival. The provinces such as Tehran, Mazandaran, Alborz, Gilan, and Qom are more susceptible to infection because of high population density, intra-provincial movements and high humidity rate in comparison with Southern provinces.


Comments to the predecessor of human SARS coronavirus in 2003–2004 epidemic


title: Targeting the Linear Ubiquitin Assembly Complex to Modulate the Host Response and Improve Influenza A Virus Induced Lung Injury

text: Abstract Influenza virus infection is characterized by symptoms ranging from mild congestion and body aches to severe pulmonary edema and respiratory failure. While the majority of those exposed have minor symptoms and recover with little morbidity, an estimated 500,000 people succumb to IAV-related complications each year worldwide. In these severe cases, an exaggerated inflammatory response, known as “cytokine storm”, occurs which results in damage to the respiratory epithelial barrier and development of acute respiratory distress syndrome (ARDS). Data from retrospective human studies as well as experimental animal models of influenza virus infection highlight the fine line between an excessive and an inadequate immune response, where the host response must balance viral clearance with exuberant inflammation. Current pharmacological modulators of inflammation, including corticosteroids and statins, have not been successful in improving outcomes during influenza virus infection. We have reported that the amplitude of the inflammatory response is regulated by Linear Ubiquitin Assembly Complex (LUBAC) activity and that dampening of LUBAC activity is protective during severe influenza virus infection. Therapeutic modulation of LUBAC activity may be crucial to improve outcomes during severe influenza virus infection, as it functions as a molecular rheostat of the host response. Here we review the evidence for modulating inflammation to ameliorate influenza virus infection-induced lung injury, data on current anti-inflammatory strategies, and potential new avenues to target viral inflammation and improve outcomes.


title: Navigating the jungles of tropical infectious gastrointestinal pathology: a pattern-based approach to the endoscopic biopsy

text: International travels and global human migration have had the unforeseen consequence of increasing the exposure of histopathologists in developed countries to the pathology of tropical infectious disease. The gastrointestinal tract (GIT) is often the primary site of infection due to the faecal-oral route of transmission and the high risk of exposure to contaminated water, food or soil when travelling to these regions. Whilst current microbiologic techniques are far more sensitive than histology in detecting infectious pathogens, the histopathologist nonetheless retains a pivotal role in diagnosing tropical GIT disease. This role entails evaluating endoscopic biopsies for any characteristic inflammatory pattern, identifying pathogens which may be present and excluding other look-alike pathologies. Recent advances in commercially available diagnostic modalities, including molecular techniques, have further broadened the scope of the histopathologist’s armamentarium. This review outlines a practical pattern-based approach to diagnosing tropical GIT infections in endoscopic material, so as to assist pathologists less familiar with this spectrum of pathology.


title: New emergence pattern with variant porcine epidemic diarrhea viruses, South Korea, 2012–2015

text: Abstract Since outbreaks of porcine epidemic diarrhea virus (PEDV) in the United States in 2013, explosive outbreaks of PED in South Korea have infected all age groups of pigs in 2014–2015year. This study analyzed a large collection of the Spike protein coding gene to infer the spatial-temporal diffusion history of PEDV. The studying results suggested that PEDVs in Korea belonged to different genogroups. While classical G1 was continuingly circulating between provinces of Korea, the pandemic G2a were recently introduced from China and USA. By the application of Bayesian phylogeographical analysis, this study demonstrated the spatial-temporal transmission of PEDVs within Korea. Of the recent emerged G2a viruses, J3142 strains showed potential recombination breakpoint (376–2,143nt) of S1 gene between KNU1303_Korea strain_G2a (KJ451046) and 45RWVCF0712_Thailand strain_G2b (KF724935). The pandemic G2a virus was partial neutralized by the antibodies invoked by the G1- based PED vaccine virus.


So geht Wiederbelebung in Corona-Zeiten


title: The neuroinvasive potential of SARS‐CoV2 may play a role in the respiratory failure of COVID‐19 patients

text: Following the severe acute respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome coronavirus (MERS‐CoV), another highly pathogenic coronavirus named SARS‐CoV‐2 (previously known as 2019‐nCoV) emerged in December 2019 in Wuhan, China, and rapidly spreads around the world. This virus shares highly homological sequence with SARS‐CoV, and causes acute, highly lethal pneumonia coronavirus disease 2019 (COVID‐19) with clinical symptoms similar to those reported for SARS‐CoV and MERS‐CoV. The most characteristic symptom of patients with COVID‐19 is respiratory distress, and most of the patients admitted to the intensive care could not breathe spontaneously. Additionally, some patients with COVID‐19 also showed neurologic signs, such as headache, nausea, and vomiting. Increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system inducing neurological diseases. The infection of SARS‐CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Furthermore, some coronaviruses have been demonstrated able to spread via a synapse‐connected route to the medullary cardiorespiratory center from the mechanoreceptors and chemoreceptors in the lung and lower respiratory airways. Considering the high similarity between SARS‐CoV and SARS‐CoV2, it remains to make clear whether the potential invasion of SARS‐CoV2 is partially responsible for the acute respiratory failure of patients with COVID‐19. Awareness of this may have a guiding significance for the prevention and treatment of the SARS‐CoV‐2‐induced respiratory failure.


title: Rapid generation of neutralizing antibody responses in COVID-19 patients

text: Summary SARS-CoV-2, the virus responsible for COVID-19, is causing a devastating global pandemic and there is a pressing need to understand the development, specificity, and neutralizing potency of humoral immune responses during acute infection. We report a cross-sectional study of antibody responses to the receptor-binding domain (RBD) of the spike protein and virus neutralization activity in a cohort of 44 hospitalized COVID-19 patients. RBD-specific IgG responses are detectable in all patients 6 days after PCR confirmation. Isotype switching to IgG occurs rapidly, primarily to IgG1 and IgG3. Using a clinical SARS-CoV-2 isolate, neutralizing antibody titers are detectable in all patients by 6 days after PCR confirmation and correlate with RBD-specific binding IgG titers. The RBD-specific binding data were further validated in a clinical setting with 231 PCR-confirmed COVID-19 patient samples. These findings have implications for understanding protective immunity against SARS-CoV-2, therapeutic use of immune plasma, and development of much-needed vaccines.


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title: Enhancement of anti-murine colon cancer immunity by fusion of a SARS fragment to a low-immunogenic carcinoembryonic antigen

text: BACKGROUND: It is widely understood that tumor cells express tumor-associated antigens (TAAs), of which many are usually in low immunogenicity; for example, carcinoembryonic antigen (CEA) is specifically expressed on human colon cancer cells and is viewed as a low-immunogenic TAA. How to activate host immunity against specific TAAs and to suppress tumor growth therefore becomes important in cancer therapy development. RESULTS: To enhance the immune efficiency of CEA in mice that received, we fused a partial CEA gene with exogenous SARS-CoV fragments. Oral vaccination of an attenuated Salmonella typhimurium strain transformed with plasmids encoding CEA-SARS-CoV fusion gene into BALB/c mice elicited significant increases in TNF-α and IL-10 in the serum. In addition, a smaller tumor volume was observed in CT26/CEA-bearing mice who received CEA-SARS-CoV gene therapy in comparison with those administered CEA alone. CONCLUSION: The administration of fusing CEA-SARS-CoV fragments may provide a promising strategy for strengthening the anti-tumor efficacy against low-immunogenic endogenous tumor antigens.


title: Updated diagnosis, treatment and prevention of COVID-19 in children: experts’ consensus statement (condensed version of the second edition)

text: In the early February, 2020, we called up an experts’ committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.


title: Cooperativity Enables Non-neutralizing Antibodies to Neutralize Ebolavirus

text: Drug combinations are synergistic when their combined efficacy exceeds the sum of the individual actions, but they rarely include ineffective drugs that become effective only in combination. We identified several ‘‘enabling pairs’’ of neutralizing and non-neutralizing anti-ebolavirus monoclonal antibodies, whose combination exhibited new functional profiles, including transforming a non-neutralizing antibody to a neutralizer. Sub-neutralizing concentrations of antibodies 2G4 or m8C4 enabled non-neutralizing antibody FVM09 (IC(50) >1 mM) to exhibit potent neutralization (IC(50) 1–10 nM). While FVM09 or m8C4 alone failed to protect Ebola-virus-infected mice, a combination of the two antibodies provided 100% protection. Furthermore, non-neutralizers FVM09 and FVM02 exponentially enhanced the potency of two neu-tralizing antibodies against both Ebola and Sudan viruses. We identified a hotspot for the binding of these enabling antibody pairs near the interface of the glycan cap and GP2. Enabling cooperativity may be an underappreciated phenomenon for viruses, with implications for the design and development of immunotherapeutics and vaccines.


The UK Public Health Association and Congress of the World Federation of Public Health Associations (WFPHA) conference—plenary session presentations


title: Seroprevalence of antibody to pandemic influenza A (H1N1) 2009 among healthcare workers after the first wave in Hong Kong

text: Summary During the first wave of an influenza pandemic prior to the availability of an effective vaccine, healthcare workers (HCWs) may be at particular risk of infection with the novel influenza strain. We conducted a cross-sectional study of the prevalence of antibody to pandemic influenza A (H1N1) 2009 (pH1N1) among HCWs in Hong Kong in February–March 2010 following the first pandemic wave. Sera collected from HCWs were tested for antibody to pH1N1 influenza virus by viral neutralisation (VN). We assessed factors associated with higher antibody titres, and we compared antibody titres in HCWs with those in a separate community study. In total we enrolled 703 HCWs. Among 599 HCWs who did not report receipt of pH1N1 vaccine, 12% had antibody titre ≥1:40 by VN. There were no significant differences in the age-specific proportions of unvaccinated HCWs with antibody titre ≥1:40 compared with the general community following the first wave of pH1N1. Under good adherence to infection control guidelines, potential occupational exposures in the hospital setting did not appear to be associated with any substantial excess risk of pH1N1 infection in HCWs. Most HCWs had low antibody titres following the first pandemic wave.