title: A mathematical model reveals the influence of population heterogeneity on herd immunity to SARS-CoV-2

text: Despite various levels of preventive measures, in 2020 many countries have suffered severely from the coronavirus 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. We show that population heterogeneity can significantly impact disease-induced immunity as the proportion infected in groups with the highest contact rates is greater than in groups with low contact rates. We estimate that if R(0) = 2.5 in an age-structured community with mixing rates fitted to social activity then the disease-induced herd immunity level can be around 43%, which is substantially less than the classical herd immunity level of 60% obtained through homogeneous immunization of the population. Our estimates should be interpreted as an illustration of how population heterogeneity affects herd immunity, rather than an exact value or even a best estimate.


title: A Predictive Model for the Evolution of COVID-19

text: We predict the evolution of the COVID-19 pandemic in several countries using a logistic model. The model uses a regression analysis based on the least-squares fitting. In particular, the growth rate of the infection has been fitted as an exponential decay, as compared to a linear decay, reported previously in logistic models. The model has been validated with the data of China and South Korea, where the pandemic is nearing to its end. The data of Italy, Germany, Spain, and Sweden show that the peak of the infection has been reached, i.e. a time when the new infections will start to decrease as compared to the previous day. The model predicts the approximate number of total infections at the end of the outbreak. The possible peak date and the total number of infections for different countries are predicted using the data available. The total number of infections in the USA is estimated to be around 4 million. The model prediction of Brazil shows that the peak will reach on 5 July 2020 and total infections will be 3.2 million. The reported data of India show a large initial scatter in the growth rate. The total number of infections in India is estimated to be around 2.4 million by the model and the predicted peak date is 3 August 2020. The predictions of India are discussed in the context of restricted movement of population, i.e. lock-down imposed by the government.


title: Anti-Influenza A Virus Activity of Rhamnan Sulfate from Green Algae Monostroma nitidum in Mice with Normal and Compromised Immunity

text: Influenza viruses cause a significant public health burden each year despite the availability of anti-influenza drugs and vaccines. Therefore, new anti-influenza virus agents are needed. Rhamnan sulfate (RS) is a sulfated polysaccharide derived from the green alga Monostroma nitidum. Here, we aimed to demonstrate the antiviral activity of RS, especially against influenza A virus (IFV) infection, in vitro and in vivo. RS showed inhibitory effects on viral proliferation of enveloped viruses in vitro. Evaluation of the anti-IFV activity of RS in vitro showed that it inhibited both virus adsorption and entry steps. The oral administration of RS in IFV-infected immunocompetent and immunocompromised mice suppressed viral proliferation in both mouse types. The oral administration of RS also had stimulatory effects on neutralizing antibody production. Fluorescent analysis showed that RS colocalized with M cells in Peyer’s patches, suggesting that RS bound to the M cells and may be incorporated into the Peyer’s patches, which are essential to intestinal immunity. In summary, RS inhibits influenza virus infection and promotes antibody production, suggesting that RS is a potential candidate for the treatment of influenza virus infections.


title: The Urban-Rural Disparity in the Status and Risk Factors of Health Literacy: A Cross-Sectional Survey in Central China

text: Health literacy is the ability of individuals to access, process, and understand health information to make decisions regarding treatment and their health on the whole; it is critical to maintain and improve public health. However, the health literacy of urban and rural populations in China has been little known. Thus, this study aims to assess the status of health literacy and explore the differences of its possible determinants (e.g., socio-economic factors) among urban and rural populations in Henan, China. A cross-sectional study, 78,646 participants were recruited from a populous province in central China with a multi-stage random sampling design. The Chinese Resident Health Literacy Scale was adopted to measure the health literacy of the respondents. In the participants, the level of health literacy (10.21%) in central China was significantly lower than the national average, and a big gap was identified between urban and rural populations (16.92% vs. 8.09%). A noticeable difference was reported in different aspects and health issues of health literacy between urban and rural populations. The health literacy level was lower in those with lower levels of education, and a significant difference was identified in the level of health literacy among people of different ages and occupations in both urban and rural areas. Note that in rural areas, as long as residents educated, they all had higher odds to exhibit basic health literacy than those uneducated; in rural areas, compared with those aged 15 to 24 years, residents aged 45 to 54 years (OR = 0.846,95% CI (0.730, 0.981)), 55 to 64 years (OR = 0.716,95% CI (0.614, 0.836)) and above 65 years (OR = 0.679, 95% CI (0.567, 0.812)) were 84.6%, 71.6%, and 67.9%, respectively, less likely to exhibit basic health literacy. Considering the lower health literacy among rural residents compared with their urban counterparts, a reorientation of the health policy-making for Chinese rural areas is recommended. This study suggests that urban–rural disparity about health literacy risk factors should be considered when implementing health literacy promotion intervention.


title: Trade credit research before and after the global financial crisis of 2008 – A bibliometric overview

text: Abstract This study presents an overview of the state-of-the-art in trade credit research by examining 1191 publications between 1955 and 2019. Applying bibliometric and econometric tools, this study presents a comparative analysis of the extant research across the three sub-domains of banking and finance, production and operations, and accounting. Findings suggest that the financial emergency in the global market had resulted in a watershed moment in trade credit research. About 69 % of the literature was found to have emerged after the global economic crisis of 2008. A network analysis grouped the trade credit articles into four major and four minor clusters. The banking and financing cluster exhibited the highest growth followed by the production and operation cluster while the perspectives of accounting are yet to gain traction. Conversely, reputation of the publishing hub, empirical studies, and the production and operational dimensions of the research positively and significantly influence citations. Alongside thorough introspection, the study also provides new areas to direct the course of future research.


title: On Tuberculosis and COVID-19 co-infection

text: COVID-19 may boost tuberculosis given infection and mortality, further studies are needed


COVID-19 pandemic and cardiovascular complications: what have we learned so far?


title: Risk factors for severe bronchiolitis caused by respiratory virus infections among Mexican children in an emergency department

text: Severe bronchiolitis is the most common reason for hospitalization among children younger than 2 years. This study analyzed the prevalence of community-acquired respiratory virus infection and the risk factors for hospitalization of Mexican children with severe bronchiolitis treated in an Emergency department. This retrospective study included 134 children 2 years or younger with severe viral bronchiolitis, and 134 healthy age-matched controls. The study period was September 2012 to January 2015. We determined the viral etiology and coinfections with multiple viruses and compared the risk factors detected in children with severe viral bronchiolitis with those in the control group. A total of 153 respiratory viruses in these 134 patients, single or mixed infections, were identified: respiratory syncytial virus (RSV) type A or B was the most frequently detected (23.6% and 17.6%, respectively), followed by rhinovirus (RV; 16.3%) and parainfluenza virus (PIV) type 3 (12.4%). Coinfections of 2 respiratory viruses were found in 14.2% of cases; all cases had either RSV type A or B with another virus, the most common being parainfluenza virus or rhinovirus. Exposure to cigarette smoking was independently associated with hospitalization for severe bronchiolitis (OR, 3.5; 95% CI, 1.99–6.18; P = .0001), and having completed the vaccination schedule for their age was a protective factor against adverse outcome (OR, 0.55; 95% CI, 0.35–0.87; P = .010). RSV is a common infection among young children with severe bronchiolitis; thus, developing a vaccine against RSV is essential. Campaigns to reinforce the importance of avoiding childhood exposure to cigarette smoke are also needed.


Histological–ultrasonographical correlation of pulmonary involvement in severe COVID-19


title: Containment of future waves of COVID-19: simulating the impact of different policies and testing capacities for contact tracing, testing, and isolation

text: We used multi-agent simulations to estimate the testing capacity required to find and isolate a number of infections sufficient to break the chain of transmission of SARS-CoV-2. Depending on the mitigation policies in place, a daily capacity between 0.7 to 3.6 tests per thousand was required to contain the disease. However, if contact tracing and testing efficacy dropped below 60% (e.g. due to false negatives or reduced tracing capability), the number of infections kept growing exponentially, irrespective of any testing capacity. Under these conditions, the population’s geographical distribution and travel behaviour could inform sampling policies to aid a successful containment.


title: Carrageenan nasal spray in virus confirmed common cold: individual patient data analysis of two randomized controlled trials

text: BACKGROUND: Clinical trials applying iota-carrageenan nasal spray have previously shown to reduce duration of virus-confirmed common cold. The present study pooled data of two similar clinical trials to provide further evidence for the antiviral effectiveness of carrageenan. METHODS: Individual patient data were analyzed from two randomized double blind placebo controlled trials assessing the therapeutic effectiveness of carrageenan nasal spray in acute common cold. Patients with virus-confirmed common cold (n = 254, verum 126, placebo 128) were included and the following parameters were appraised: duration of disease, number of patients with relapses, number of respiratory viruses and viral titers at inclusion (visit 1) compared to days 3–5 (visit 2). RESULTS: Carrageenan treated patients showed a significant reduction in duration of disease of almost 2 days (p < 0.05) as well as significantly fewer relapses during 21 days of observation period (p < 0.05). The virus clearance between visit 1 and visit 2 was significantly more pronounced in the carrageenan group (p < 0.05). In both studies, virus-confirmed common cold was caused by three main virus subtypes: human rhinovirus (46%), human coronavirus (25%) and influenza A (14%) virus. Carrageenan nasal spray showed significant antiviral efficacy in all three virus subgroups, the highest effectiveness was observed in human corona virus-infected patients. The reduced duration of disease was 3 days (p < 0.01) and the number of relapses was three times less (p < 0.01) in carrageenan treated corona-virus-infected patients compared to control patients. CONCLUSIONS: Administration of carrageenan nasal spray in children as well as in adults suffering from virus-confirmed common cold reduced duration of disease, increased viral clearance and reduced relapses of symptoms. Carrageenan nasal spray appeared as an effective treatment of common cold in children and adults. TRIAL REGISTRATION: Pooled data from ISRCTN52519535 and ISRCTN80148028


title: Virulence, pathology, and pathogenesis of Pteropine orthoreovirus (PRV) in BALB/c mice: Development of an animal infection model for PRV

text: BACKGROUND: Cases of acute respiratory tract infection caused by Pteropine orthoreovirus (PRV) of the genus Orthoreovirus (family: Reoviridae) have been reported in Southeast Asia, where it was isolated from humans and bats. It is possible that PRV-associated respiratory infections might be prevalent in Southeast Asia. The clinical course of PRV is not fully elucidated. METHODS: The virulence, pathology, and pathogenesis of two PRV strains, a human-borne PRV strain (isolated from a patient, who returned to Japan from Bali, Indonesia in 2007) and a bat-borne PRV (isolated from a bat [Eonycteris spelaea] in the Philippines in 2013) were investigated in BALB/c mice using virological, pathological, and immunological study methods. RESULTS: The intranasal inoculation of BALB/c mice with human-borne PRV caused respiratory infection. In addition, all mice with immunity induced by pre-inoculation with a non-lethal dose of PRV were completely protected against lethal PRV infection. Mice treated with antiserum with neutralizing antibody activity after inoculation with a lethal dose of PRV showed a reduced fatality rate. In this mouse model, bat-borne PRV caused respiratory infection similar to human-borne PRV. PRV caused lethal respiratory disease in an animal model of PRV infection, in which BALB/c mice were used. CONCLUSIONS: The BALB/c mouse model might help to accelerate research on the virulence of PRV and be useful for evaluating the efficacy of therapeutic agents and vaccines for the treatment and prevention of PRV infection. PRV was shown for the first time to be a causative virus of respiratory disease on the basis of Koch’s postulations by the additional demonstration that PRV caused respiratory disease in mice through their intranasal inoculation with PRV.


Report of Acute Adaptive Policies to Maximize the Educational Efficacy of the Clinical Hospital Ward during COVID-19 Pandemia


Critical Care during the Coronavirus Crisis – challenges and considerations for the cardiothoracic and vascular anesthesia community


title: Repurposing Quaternary Ammonium Compounds as Potential Treatments for COVID-19

text: The COVID-19 pandemic has highlighted an important role for drug repurposing. Quaternary ammonium compounds such as ammonium chloride, cetylpyridinium and miramistin represent widely accessible antiseptic molecules with well-known broad-spectrum antiviral activities and represent a repurposing opportunity as therapeutics against SARS-CoV-2. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11095-020-02842-8) contains supplementary material, which is available to authorized users.


title: Human metapneumovirus genotypes and severity of disease in young children (n = 100) during a 7‐year study in Dijon hospital, France

text: Human metapneumovirus is a cause of respiratory tract infections at all ages. Our objectives were to analyze the distribution of the A and B genotypes over 7 years in Dijon and to investigate a possible association between hMPV genotypes and disease severity. During 2002–2009, we genotyped the 100 isolates from children <3 years old with hMPV. Phylogenetic analysis indicated a change in the distribution of hMPV genotype over the years. Severity was then measured by detailed clinical evaluation. The hospitalization rate was greater when genotype B was involved 72.5% versus 53.3% (P = 0.054). Those infected with genotype B tended to have a higher clinical score, as measured by Vicente et al. 2006 (P = 0.07). We showed that, although clinical severity is not clearly associated with hMPV genotype in this study, pathological signs on chest X‐ray were observed more often in B subgroup (P < 0.01). J. Med. Virol. 82:1782–1789, 2010. © 2010 Wiley‐Liss, Inc.


title: The European Union Current Asylum Policy: Selected Problems in the Shadow of COVID-19

text: Recent years in Europe have generated situations requiring the European Union to take extra-coordinated action in the field of asylum policy. The sudden and growing influx of refugees to Europe in 2015 and 2016 has caused the collapse of the previous common European asylum system. The European Union has taken a number of measures to resolve this crisis situation. When the situation seemed to be under control, a new challenge emerged in early 2020. The first COVID-19 infectious disease case was reported in Europe, and on 13 March 2020 the WHO reported that Europe had become the epicentre of the coronavirus pandemic. The measures taken by individual countries and the European Union to limit the spread of the virus have had a significant impact on many spheres of state and individual functioning, including the situation of persons seeking international protection. This publication consists of three parts. The first part discusses actions taken by the European Union in the face of the migration and refugee crisis that emerged in 2015 and 2016. The second part presents one of the limitations introduced in connection with preventing the spread of COVID-19, which has a huge impact on persons wishing to seek international protection, i.e., changes in the regime of crossing borders and entering the territory of particular countries. The third one points out selected problems experienced by persons seeking protection who already stay in the territory of EU Member States.


title: “Management of Community-Acquired Pneumonia in Immunocompromised Adults: A Consensus Statement Regarding Initial Strategies”

text: Abstract Background Community-acquired pneumonia (CAP) guidelines have improved the management and outcomes of patients with CAP, primarily by standardization of initial empiric therapy. But current society-published guidelines exclude immunocompromised patients. Research Question There is no concensus regarding the initial management of immunocompromised patients with suspected CAP. Study Design and Methods This consensus document was created by a multidisciplinary panel of 45 physicians with experience in the management of CAP in immunocompromised patients. The Delphi survey methodology was used to reach consensus. Results The panel focused on 21 questions addressing initial management strategies. The panel achieved consensus in defining the population, site of care, likely pathogens, microbiological work-up, general principles of empiric therapy, and empiric therapy for specific pathogens. Interpretation This document offer general suggestions for the initial management of the immunocompromised patient who arrives at the hospital with pneumonia.


title: Chapter 57 Potential of Cupressus sempervirens (Mediterranean Cypress) in Health

text: Abstract Cupressus sempervirens L. (Cupressaceae), known as Mediterranean cypress, is a medicinal and aromatic plant with decorative uses. It is widely distributed throughout the Mediterranean region, including Syria, Turkey, Cyprus, Lebanon, Palestine, and some Greek Islands, as well as the southern coasts of the Caspian Sea in Iran. The plant has a long history of utilization in folk medicine in many countries, mainly for cough and flu treatment, and the research has consistently shown that C. sempervirens has antimicrobial, antiviral, insecticidal, antihyperlipidemic, cytotoxic, antioxidant, antiplatelet, hepatoprotective, and neurobiological activities to varying extents. The mentioned biological activities of the plant are strongly associated with its phytochemical content, which is particularly rich in phenolic constituents and essential oils that could be responsible for most of its antimicrobial, antioxidant, and antiviral activities. This chapter covers botanical information, brief phytochemistry, and pharmacological activities related to C. sempervirens.


title: INHIBITORY EFFECT OF EMODIN ON RAW 264.7 ACTIVATED WITH DOUBLE STRANDED RNA ANALOGUE POLY I:C

text: BACKGROUND: Emodin (3-methyl-1, 6, 8-trihydroxyanthraquinone) is a compound which can be found in Polygoni Multiflori Radix (PMR). PMR is the root of Polygonum multiflorum. PMR is used to treat dizziness, spermatorrhea, sores, and scrofula as well as chronic malaria traditionally in China and Korea. The anti-tumor property of emodin was already reported. However, anti-viral activity of emodin on macrophages are not fully reported. MATERIALS AND METHODS: Effects of emodin on RAW 264.7 mouse macrophages induced by polyinosinic-polycytidylic acid (poly I:C), a synthetic analog of double-stranded RNA, were evaluated. RESULTS: Emodin restored the cell viability in poly I: C-induced RAW 264.7 at concentrations of up to 50 μM. Emodin significantly inhibited the production of nitric oxide, IL-1α, IL-Ιβ, IL-6, GM-CSF, G-CSF, M-CSF, MCP-1, MIP-1a, MIP-Ιβ, MIP-2, RANTES, and IP-10 as well as calcium release and mRNA expression of signal transducer and activated transcription 1 (STAT1) in poly I:C-induced RAW 264.7 (P < 0.05). CONCLUSION: This study shows the inhibitory effect of emodin on poly I: C-induced RAW 264.7 via calcium-STAT pathway.


title: Regional Diversification of Influenza Activity in Poland During the 2015/16 Epidemic Season

text: The National Influenza Center (NIC) at the Department of Influenza Research of the National Institute for Public Health–National Institute of Hygiene (NIPH-NIH) participates in the Global Influenza Surveillance and Response System (GISRS) and continuously coordinates epidemiological and virological surveillance of influenza in Poland. The aim of this study was to determine the regional differences of influenza activity in Poland in the 2015/16 epidemic season. The influenza surveillance involved 16 administrative districts in which there are Voivodeship (province) Sanitary Epidemiological Stations set up to report influenza and influenza-like illness among the Polish population. Over 8000 specimens were tested in the season with regard to the respiratory viral infections in all regions investigated. The circulation of influenza viruses A and B was confirmed, with the subtype A/H1N1/pdm09 being predominant in the Pomerania, Podlaskie, Subcarpathian, Lubuskie, Silesian, and Warmian-Masuria provinces. The influenza-like virus occurred in individual cases, except for respiratory syncytial virus that also was detected in the Greater Poland and Warmia-Masuria provinces. The highest incidence of cases and suspected cases of influenza was recorded in Pomerania and the lowest one in Lubuskie provinces. The knowledge of regional differences in influenza activity is important for streamlining the distribution of preventive, therapeutic, and economic resources to combat the epidemic.


CHAPTER 31 Exercise and Immunity: Clinical Studies


title: Contemporary resuscitation of hemorrhagic shock: What will the future hold?

text: Resuscitation of the critically ill patient with fluid and blood products is one of the most widespread interventions in medicine. This is especially relevant for trauma patients, as hemorrhagic shock remains the most common cause of preventable death after injury. Consequently, the study of the ideal resuscitative product for patients in shock has become an area of great scientific interest and investigation. Recently, the pendulum has swung towards increased utilization of blood products for resuscitation. However, pathogens, immune reactions and the limited availability of this resource remain a challenge for clinicians. Technologic advances in pathogen reduction and innovations in blood product processing will allow us to increase the safety profile and efficacy of blood products, ultimately to the benefit of patients. The purpose of this article is to review the current state of blood product based resuscitative strategies as well as technologic advancements that may lead to safer resuscitation.


title: Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein

text: Most neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) target the receptor-binding domain (RBD) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). The epitopes and mechanisms of mAbs targeting non-RBD regions have not been well characterized yet. Here we report the monoclonal antibody 7D10 that binds to the N-terminal domain (NTD) of the spike glycoprotein and inhibits the cell entry of MERS-CoV with high potency. Structure determination and mutagenesis experiments reveal the epitope and critical residues on the NTD for 7D10 binding and neutralization. Further experiments indicate that the neutralization by 7D10 is not solely dependent on the inhibition of DPP4 binding, but also acts after viral cell attachment, inhibiting the pre-fusion to post-fusion conformational change of the spike. These properties give 7D10 a wide neutralization breadth and help explain its synergistic effects with several RBD-targeting antibodies.


title: Cancer Patients Have a Higher Risk Regarding COVID-19 - and Vice Versa?

text: The world is currently suffering from a pandemic which has claimed the lives of over 230,000 people to date The responsible virus is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and causes the coronavirus disease 2019 (COVID-19), which is mainly characterized by fever, cough and shortness of breath In severe cases, the disease can lead to respiratory distress syndrome and septic shock, which are mostly fatal for the patient The severity of disease progression was hypothesized to be related to an overshooting immune response and was correlated with age and comorbidities, including cancer A lot of research has lately been focused on the pathogenesis and acute consequences of COVID-19 However, the possibility of long-term consequences caused by viral infections which has been shown for other viruses are not to be neglected In this regard, this opinion discusses the interplay of SARS-CoV-2 infection and cancer with special focus on the inflammatory immune response and tissue damage caused by infection We summarize the available literature on COVID-19 suggesting an increased risk for severe disease progression in cancer patients, and we discuss the possibility that SARS-CoV-2 could contribute to cancer development We offer lines of thought to provide ideas for urgently needed studies on the potential long-term effects of SARS-CoV-2 infection


Kawasaki disease or Kawasaki syndrome?


title: Coronavirus induction of class I major histocompatibility complex expression in murine astrocytes is virus strain specific

text: Neurotropic strains of mouse hepatitis viruses (MHV) such as MHV-A59 (A59) and MHV-4 (JHMV) cause acute and chronic encephalomyelitis and demyelination in susceptible strains of mice and rats. They are widely used as models of human demyelinating diseases such as multiple sclerosis (MS), in which immune mechanisms are thought to participate in the development of lesions in the central nervous system (CNS). The effects of MHV infection on target cell functions in the CNS are not well understood, but A59 has been shown to induce the expression of MHC class I molecules in glial cells after in vivo and in vitro infection. Changes in class I expression in infected cells may contribute to the immunopathogenesis of MHV infection in the CNS. In this communication, a large panel of MHV strains was tested for their ability to stimulate class I expression in primary astrocytes in vitro. The data show that the more hepatotropic strains, such as MHV-A59, MHV-1, MHV-2, MHV-3, MHV-D, MHV-K, and MHV-NuU, were potent inducers of class I expression in astrocytes during acute infection, measured by radioimmunoassay. The Kb molecule was preferentially expressed over Db. By contrast, JHMV and several viral strains derived from it did not stimulate the expression of class I molecules. Assays of virus infectivity indicated that the class I-inducing activity did not correlate with the ability of the individual viral strain to replicate in astrocytes. However, exposure of the viruses or the supernatants from infected astrocytes to ultraviolet light abolished the class I-inducing activity, indicating that infectious virus is required for class I expression. These data also suggest that class I expression was induced directly by virus infection, and not by the secretion of a soluble substance into the medium by infected astrocytes. Finally, analyses of A59/JHMV recombinant viral strains suggest that class I-inducing activity resides in one of the A59 structural genes.


title: Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center’s observational study

text: BACKGROUND: An outbreak of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was first detected in Wuhan, Hubei, China. People of all ages are susceptible to SARS-CoV-2 infection. No information on severe pediatric patients with COVID-19 has been reported. We aimed to describe the clinical features of severe pediatric patients with COVID-19. METHODS: We included eight severe or critically ill patients with COVID-19 who were treated at the Intensive Care Unit (ICU), Wuhan Children’s Hospital from January 24 to February 24. We collected information including demographic data, symptoms, imaging data, laboratory findings, treatments and clinical outcomes of the patients with severe COVID-19. RESULTS: The onset age of the eight patients ranged from 2 months to 15 years; six were boys. The most common symptoms were polypnea (8/8), followed by fever (6/8) and cough (6/8). Chest imaging showed multiple patch-like shadows in seven patients and ground-glass opacity in six. Laboratory findings revealed normal or increased whole blood counts (7/8), increased C-reactive protein, procalcitonin and lactate dehydrogenase (6/8), and abnormal liver function (4/8). Other findings included decreased CD16 + CD56 (4/8) and Th/Ts*(1/8), increased CD3 (2/8), CD4 (4/8) and CD8 (1/8), IL-6 (2/8), IL-10 (5/8) and IFN-γ (2/8). Treatment modalities were focused on symptomatic and respiratory support. Two critically ill patients underwent invasive mechanical ventilation. Up to February 24, 2020, three patients remained under treatment in ICU, the other five recovered and were discharged home. CONCLUSIONS: In this series of severe pediatric patients in Wuhan, polypnea was the most common symptom, followed by fever and cough. Common imaging changes included multiple patch-like shadows and ground-glass opacity; and a cytokine storm was found in these patients, which appeared more serious in critically ill patients.


title: Severe respiratory syndromes: Travel history matters

text: Summary History of travel or contact is an important clue to emerging infections. Common and novel respiratory viruses can occasionally cause epidemics of viral pneumonitis with severe acute respiratory symptoms (sars). In 2003, World Health Organisation (WHO) coined the word SARS for Severe Acute Respiratory Syndrome in patients with a relevant travel/contact history and sars. The WHO case definition of suspected SARS was fever, respiratory symptoms and close contact with SARS patients or travel history to an epidemic area. The clinical features are essentially the same as for any respiratory viral infections or pneumonitis. Since 2003, many new surveillance guidelines and confusing abbreviations appeared in the city of Hong Kong. In 2012, another outbreak of coronavirus pneumonitis occurred in the Middle-East. More case definitions such as MERS (Middle East Respiratory Syndrome) and SARI (Severe Acute Respiratory Infections) were coined for the viral pneumonitis. In medicine, a definition or syndrome representing “a constellation of symptomatology seen in association” should stand the trial of time after it is coined. Health organisations should provide consistent definitions for index surveillance, epidemiological and prognostication studies. Travel or contact history is pivotal in formulating management protocol during any outbreak when the pathogen is not initially clear.


title: A late onset widespread skin rash in a previous Covid‐19 infected patient: viral or multidrug effect?

text: in the end of 2019, a series of pneumonia cases emerged in China, with clinical presentations greatly resembling viral pneumonia, caused by Covid‐19 o SARS‐CoV‐2. Currently, several clinicians described an increasingly cases of coronavirus‐positive patients reporting skin problems, either in early stage of infection or as late onset manifestation. Recently, Dr. Sebastiano Recalcati analyzed the cutaneous involvement in 148 COVID‐19 patients hospitalized in the Lecco Hospital, Lombardy, Italy.


title: Killing Two Birds with One Stone? Green Dead Ends and Ways Out of the COVID-19 Crisis

text: The coronavirus crisis has opened up a window of opportunity for transformation. This should be used without getting off the regulatory track. Green recovery programs must not be reduced to a mere competition for green subsidies. Abandoning barriers to green investments and imposing a carbon price are equally important. Where economically sensible, green subsidies should contribute both to stabilizing the economy and mitigating climate change. Moreover, smart green recovery programs may contribute to raising revenues for the additionally necessary public expenditures.


title: Porcine aminopeptidase N binds to F4(+) enterotoxigenic Escherichia coli fimbriae

text: F4(+) enterotoxigenic Escherichia coli (ETEC) strains cause diarrheal disease in neonatal and post-weaned piglets. Several different host receptors for F4 fimbriae have been described, with porcine aminopeptidase N (APN) reported most recently. The FaeG subunit is essential for the binding of the three F4 variants to host cells. Here we show in both yeast two-hybrid and pulldown assays that APN binds directly to FaeG, the major subunit of F4 fimbriae, from three serotypes of F4(+) ETEC. Modulating APN gene expression in IPEC-J2 cells affected ETEC adherence. Antibodies raised against APN or F4 fimbriae both reduced ETEC adherence. Thus, APN mediates the attachment of F4(+)E. coli to intestinal epithelial cells.


title: Reverse transcription loop-mediated isothermal amplification assay for rapid detection of Bovine Rotavirus

text: BACKGROUND: Bovine rotavirus (BRV) infection is common in young calves. This viral infection causes acute diarrhea leading to death. Rapid identification of infected calves is essential to control BRV successfully. Therefore development of simple, highly specific, and sensitive detection method for BRV is needed. RESULTS: A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed and optimized for rapid detection of BRV. Specific primer sets were designed to target the sequences of the VP6 gene of the neonatal calf diarrhea virus (NCDV) strain of BRV. The RT-LAMP assay was performed in a water bath for 60 minutes at 63°C, and the amplification products were visualized either directly or under ultraviolet light. This BRV specific RT-LAMP assay could detect 3.32 copies of subtype A BRV. No cross-reactions were detected with other bovine pathogens. The ability of RT-LAMP to detect bovine rotavirus was further evaluated with 88 bovine rectal swab samples. Twenty-nine of these samples were found to be positive for BRV using RT-LAMP. The BRV-specific-RT-LAMP results were also confirmed by real-time RT-PCR assay. CONCLUSIONS: The bovine rotavirus-specific RT-LAMP assay was highly sensitive and holds promise as a prompt and simple diagnostic method for the detection of group A bovine rotavirus infection in young calves.


title: Co-circulation of three clusters of 793/B-like avian infectious bronchitis virus genotypes in Iranian chicken flocks

text: Avian infectious bronchitis (IB) is an acute and highly contagious viral disease causing severe economic losses in the poultry industry. The 793/B IB virus is an important infectious bronchitis virus (IBV) genotype currently circulating in several countries, including Iran. One hundred confirmed IBV samples (between 2014 and 2015; from 15 provinces in Iran) were selected for genotyping based on S1 sequencing. After phylogenetic analysis, it was found that 30% of the IBV isolates belonged to the 793/B genotype. Results showed that the Iranian 793/B-like IBV isolates could be divided in to three clusters: 4/91-like (50%), 1/96-like (40%), and IB88-like (10%). The sequence similarity between Iranian 793/B-like IBV isolates is 87.69%–100%. The highest identity is between the 4/91 and IB88 clusters (96.38%), and the lowest similarity is between the 1/96 and IB88 clusters (87.62%). This study provides a comprehensive analysis of 793/B-type IBV in Iran and characterization of IBV molecular epidemiology in the country.


title: COVID‐19 and ABO blood group: another viewpoint

text: Juyi Li et al. [1] have recently published "an association between ABO blood groups and risk of SARS-CoV-2 pneumonia", an observation already reported a few weeks ago as a MedRxiv preprint by Jiao Zhao et al. [2] and which had a certain impact in the press.


title: Synthesis of a bacteriophage MB78 late protein by novel ribosomal frameshifting

text: Abstract MB78 is a virulent phage of Salmonella typhimurium that possesses a number of interesting features, making it a suitable organism to study the regulation of gene expression. A detailed physical map of this phage genome has been constructed and is being extensively studied at the molecular level. Here, we demonstrate the expression of two late proteins of bacteriophage MB78 derived from the same gene as a result of possible ribosomal frameshifting. In vitro transcription-translation yields a major protein that migrates as 28kDa, whereas in vivo expression using pET expression vectors yields two equally expressed proteins of molecular sizes 28 and 26kDa. A putative slippery sequence TTTAAAG and a pseudoknot structure, two essential cis elements required for the classical ribosomal frameshifting, are identified in the reading frame. Mutations created at the slippery sequence resulted in a single 28kDa protein and completely abolished the expression of 26kDa protein. Thus, we have produced the first evidence that ribosomal frameshifting occurs in bacteriophage MB78 of Salmonella typhimurium.


title: Single reaction, real time RT-PCR detection of all known avian and human metapneumoviruses

text: Abstract Current molecular methods for the detection of avian and human metapneumovirus (AMPV, HMPV) are specifically targeted towards each virus species or individual subgroups of these. Here a broad range SYBR Green I real time RT-PCR was developed which amplified a highly conserved fragment of sequence in the N open reading frame. This method was sufficiently efficient and specific in detecting all MPVs. Its validation according to the NF U47-600 norm for the four AMPV subgroups estimated low limits of detection between 1000 and 10copies/μL, similar with detection levels described previously for real time RT-PCRs targeting specific subgroups. RNA viruses present a challenge for the design of durable molecular diagnostic test due to the rate of change in their genome sequences which can vary substantially in different areas and over time. The fact that the regions of sequence for primer hybridization in the described method have remained sufficiently conserved since the AMPV and HMPV diverged, should give the best chance of continued detection of current subgroups and of potential unknown or future emerging MPV strains.


title: Food safety issues related to wildlife have not been taken seriously from SARS to COVID-19

text: Abstract 17 years after the outbreak of SARS, the 2019-nCoV broke out in December 2019. It's an unprecedented huge challenge and disaster for people all over the world. According to Web of Science database, The author found that 95,724 virology papers have been published in the past 17 years, 68,632 of which are supported by fund (71.7%). Meanwhile, 50,567 papers related to food safety have been published in the past 17 years, 28,165 of which are supported by fund (55.7%%). It seems that people's safety and global stability are greatly guaranteed. However, whether SARS or 2019-nCoV, scientists were targeting wildlife, the author found that only 515 studies on food safety related to wildlife have been published worldwide in the past 17 years. After SARS, the whole world did not pay enough attention to food safety related to wildlife.


title: Clinical Features of Patients Infected with the 2019 Novel Coronavirus (COVID-19) in Shanghai, China

text: Background: Since mid-December 2019, a cluster of pneumonia-like diseases caused by a novel coronavirus, now designated COVID-19 by the WHO, emerged in Wuhan city and rapidly spread throughout China. Here we identify the clinical characteristics of COVID-19 in a cohort of patients in Shanghai. Methods: Cases were confirmed by real-time RT-PCR and were analysed for demographic, clinical, laboratory and radiological features. Results: Of 198 patients, the median duration from disease onset to hospital admission was 4 days. The mean age of the patients was 50.1 years, and 51.0% patients were male. The most common symptom was fever. Less than half of the patients presented with respiratory systems including cough, sputum production, itchy or sore throat, shortness of breath, and chest congestion. 5.6% patients had diarrhoea. On admission, T lymphocytes were decreased in 45.8% patients. Ground glass opacity was the most common radiological finding on chest computed tomography. 9.6% were admitted to the ICU because of the development of organ dysfunction. Compared with patients not treated in ICU, patients treated in the ICU were older, had longer waiting time to admission, fever over 38.5o C, dyspnoea, reduced T lymphocytes, elevated neutrophils and organ failure. Conclusions: In this single centre cohort of COVID-19 patients, the most common symptom was fever, and the most common laboratory abnormality was decreased blood T cell counts. Older age, male, fever over 38.5oC, symptoms of dyspnoea, and underlying comorbidity, were the risk factors most associated with severity of disease. Key words: 2019 novel coronavirus; acute respiratory infection; risk factors for disease severity


Lu pour vous


title: Xylitol for the prevention of acute otitis media episodes in children aged 2–4 years: protocol for a pragmatic randomised controlled trial

text: INTRODUCTION: Xylitol (or ‘birch sugar’) is a naturally occurring sugar with antibacterial properties that has been used as a natural non-sugar sweetener in chewing gums, confectionery, toothpaste and medicines. In this preventative randomised trial, xylitol will be tested for the prevention of acute otitis media (AOM), a common and costly condition in young children. The primary outcome will be the incidence of AOM. Secondary outcomes will include upper respiratory tract infections (URTIs) and dental caries. METHODS AND ANALYSIS: This study will be a pragmatic, blinded (participant and parents, practitioners and analyst), two-armed superiority, placebo-controlled randomised trial with 1:1 allocation, stratified by clinical site. The trial will be conducted in the 11 primary care group practices participating in the TARGet Kids! research network in Canada. Eligible participants between the ages of 2–4 years will be randomly assigned to the intervention arm of regular xylitol syrup use or the control arm of regular sorbitol use for 6 months. We expect to recruit 236 participants, per treatment arm, to detect a 20% relative risk reduction in AOM episodes. AOM will be identified through chart review. The secondary outcomes of URTIs and dental caries will be identified through monthly phone calls with specified questions. ETHICS AND DISSEMINATION: Ethics approval from the Research Ethics Boards at the Hospital for Sick Children and St. Michael’s Hospital has been obtained for this study and also for the TARGet Kids! research network. Results will be submitted for publication to a peer-reviewed journal and will be discussed with decision makers. TRIAL REGISTRATION NUMBER: NCT03055091; Pre-results.


title: Telehealth as a Bright Spot of the COVID-19 Pandemic: Recommendations From the Virtual Frontlines ("Frontweb")

text: The coronavirus disease (COVID-19) pandemic has accelerated the telehealth tipping point in the practice of family medicine and primary care in the United States, making telehealth not just a novel approach to care but also a necessary one for public health safety. Social distancing requirements and stay-at-home orders have shifted patient care from face-to-face consultations in primary care offices to virtual care from clinicians’ homes or offices, moving to a new frontline, which we call the “frontweb.” Our telehealth workgroup employed the Clinical Transformation in Technology implementation framework to accelerate telehealth expansion and to develop a consensus document for clinician recommendations in providing remote virtual care during the pandemic. In a few weeks, telehealth went from under 5% of patient visits to almost 93%, while maintaining high levels of patient satisfaction. In this paper, we share clinician recommendations and guidance gleaned from this transition to the frontweb and offer a systematic approach for ensuring “webside” success.


DE UCI HEPÁTICA A UCI COVID: HISTORIA DE UNA TRANSFORMACIÓN


title: The role of the urologist, BCG vaccine administration, and SARS‐CoV‐2: An overview

text: OBJECTIVES: To summarize the available literature regarding bacillus Calmette‐Guerin (BCG) administration, severe acute respiratory syndrome conoravirus‐2 (SARS‐CoV‐2), and the resulting clinical condition coronavirus disease (COVID‐19) in light of recent epidemiologic work suggesting decreased infection severity in BCG immunized populations while highlighting the potential role of the urologist in clinical trials and ongoing research efforts. MATERIALS AND METHODS: We reviewed the available literature regarding COVID‐19 and BCG vaccination. Specifically, the epidemiologic evidence for decreased COVID‐19 morbidity in countries with BCG vaccination programs, current clinical trials for BCG vaccination to protect against COVID‐19, potential mechanisms and rationale for this protection, and the role of the urologist and urology clinic in providing support and/or leading ongoing efforts. RESULTS: Epidemiologic evidence suggests that the crude case fatality rates are lower for countries with BCG vaccination compared to those without such programs. Four prospective, randomized clinical trials for BCG vaccination were identified including NCT04348370 (BADAS), NCT04327206 (BRACE), NCT04328441 (BCG‐CORONA), and NCT04350931. BCG administration may contribute to innate and adaptive immune priming with several opportunities for translational research. CONCLUSIONS: The urologist’s expertise with BCG and the infrastructure of urologic clinics may afford several opportunities for collaboration and leadership to evaluate and understand the potential role of BCG in the current COVID‐19 pandemic.


title: Chronic obstructive pulmonary disease

text: Acute exacerbations of underlying COPD are a common cause of respiratory deterioration. Developments have been made in preventive measures, but admission to hospital for acute exacerbations can be expected to remain common. Several expert consensus guidelines have been published to define the appropriate management of COPD patients. These consensus guidelines generally agree, but all acknowledge a lack of large well-controlled clinical studies, especially studies focusing on the management of acute exacerbations. Consequently, many potential controversies exist about the details of managing patients with acute exacerbations. Although studies of many fundamental aspects of management are still needed, the results of controlled clinical trials are sufficient to emphasise the importance of a careful clinical assessment, supplemental oxygen, inhaled bronchodilators to partially improve airway obstruction, corticosteroids to decrease the likelihood of treatment failures and to speed recovery, antibiotics, especially in severe patients, and non-invasive positive-pressure ventilation for treatment of acute ventilatory failure in selected patients.


title: Signal Transduction in SARS‐CoV‐Infected Cells

text: abstract: Severe acute respiratory syndrome (SARS) is a newly found infectious disease that is caused by a novel human coronavirus, SARS coronavirus (SARS‐CoV). Because the mortality rate of SARS patients is very high, understanding the pathological mechanisms of SARS not only in vivo but in vitro is important for the prevention of SARS. Activation of signaling pathways caused by SARS‐CoV infection leads to the phosphorylation and activation of downstream molecules. Two conflicting cellular programs, apoptosis to eliminate virus‐infected cells and survival to delay apoptosis by producing antiviral cytokines, occur in SARS patients. Recent studies regarding SARS and SARS‐CoV have clarified that activation of mitogen‐activated protein kinases (MAPKs) plays important roles in upregulation of cytokine expression and apoptosis both in vitro and in vivo. Both Akt and p38 MAPK are keys for determination of cell survival or death in SARS‐CoV‐infected cells in vitro. Agents being developed to target these signaling cascades may be important for the design of anti‐SARS‐CoV drugs. This review highlights recent progress regarding SARS‐CoV biology, especially signal transduction in SARS‐CoV‐infected cells.


title: Chapter 15 Microbially synthesized nanoparticles as next generation antimicrobials: scope and applications

text: Abstract The development of multidrug resistant (MDR) pathogens at an alarming rate has created a great health concern worldwide. Nanotechnology today provides hope as an alternative to antibiotics, in the field of antimicrobial therapy. The diverse structures and small size make the nanoparticles (NPs) exhibit unique and remarkable properties, drastically different from its bulk counterparts. Various microorganisms such as actinomycetes, algae, yeast, fungi, and bacteria synthesize inorganic nanoparticles enzymatically, either extracellularly or intracellularly. Various metallic NPs, for example, magnesium, titanium, copper, silver, and gold, are well reported for their antimicrobial, antiviral, and antifungal properties. The antimicrobial properties of these NPs may be attributed to its ability to disorganize membrane structure, form pores in the bacterial cell wall, inhibit or disruption biofilm, etc. Most metal oxide nanoparticles like ZnO-NPs, exhibit bactericidal properties by generating reactive oxygen species (ROS). However, other NPs like MgO-NPs are effective due to their peculiar physical structure. Nanoparticles can also be fabricated with various bioactive entities. Due to their small and controllable size, functionalized nanoparticles can deliver drugs precisely and safely to the target sites. Thus, microbial mediated production of nanoparticles is gaining substantial interest as a potential solution to the growing need for the development of eco-friendly ways to fight microbial resistance and control diseases.


title: The changing face of healthcare worker perceptions on powered air‐purifying respirators during the SARS outbreak

text: Objectives: Before the advent of severe acute respiratory syndrome (SARS), use of the powered air‐purifying respirator (PAPR) in the setting of pulmonary tuberculosis has been controversial. Data regarding health care worker (HCW) perceptions and problems encountered with the use of the PAPRs were lacking. Methodology: A questionnaire‐based survey was conducted of HCWs who had used the PAPR in clinical practice during the SARS outbreak, when use of the PAPR was mandatory and widespread. Evaluations of the question of whether HCWs were receptive to the use of the PAPR and their perceptions of common problems that were encountered were made. Perceptions of comfort, ease of use, visual, hearing, breathing and speech impairment, perceived protection against SARS and usage preferences were recorded. Results: Only a minority of respondents found the PAPR uncomfortable, despite some interference with communication. Despite its much higher cost, the majority (84%) preferred to use the PAPR rather than the N‐95 respirator when treating suspected SARS patients. However, opinions were equally divided regarding its use when treating patients with pulmonary tuberculosis; with 51% being in favour. Conclusions: With the advent of highly contagious diseases that pose a major occupational hazard to HCWs, the use of the PAPR has become more acceptable in clinical practice.


title: COVID‐19 comorbidities, associated pro‐coagulant extracellular vesicles and venous thromboembolisms: a possible link with ethnicity?

text: Several comorbidities predict mortality in patients with COVID‐19, some of which are more prevalent in Black Asian and Minority Ethnic (BAME) groups. Extracellular vesicles (EVs) released from cells are nano‐sized membrane‐bound vesicles that carry nucleic acids and proteins and mediate intercellular communication. In COVID‐19 associated comorbidities including diabetes, CVD and risk factors such as hypertension, elevated angiotensin II and obesity, levels of circulating EVs are raised and their cargo modified. Importantly, EVs released from damaged endothelial cells are known to be procoagulant. EVs in Black and White populations differentially express phosphorylated insulin signalling proteins, associated with impaired insulin signalling, insulin resistance and an increased risk of venous thromboembolism; these EV proteins are also associated with clinical mortality risk markers. If plasma EV levels are raised, and cargo modified in comorbidities associated with COVID‐19 such as diabetes, and account for excess deaths in BAME patients, this raises the possibility for important roles of EVs, also relating to ethnicity. This places EVs as hitherto understudied key factors, filling the current knowledge gap in COVID‐19, amongst BAME patients.


title: A simple model for COVID-19

text: Abstract An S L 1 L 2 I 1 I 2 A 1 A 2 R epidemic model is formulated that describes the spread of an epidemic in a population. The model incorporates an Erlang distribution of times of sojourn in incubating, symptomatically and asymptomatically infectious compartments. Basic properties of the model are explored, with focus on properties important in the context of current COVID-19 pandemic.


title: Evaluation of biosecurity measures to prevent indirect transmission of porcine epidemic diarrhea virus

text: BACKGROUND: The effectiveness of biosecurity methods to mitigate the transmission of porcine epidemic diarrhea virus (PEDV) via farm personnel or contaminated fomites is poorly understood. This study was undertaken to evaluate the effectiveness of biosecurity procedures directed at minimizing transmission via personnel following different biosecurity protocols using a controlled experimental setting. RESULTS: PEDV RNA was detected from rectal swabs of experimentally infected (INF) and sentinel pigs by real-time reverse transcription polymerase chain reaction (rRT-PCR). Virus shedding in INF pigs peaked at 1 day post infection (dpi) and viral RNA levels remained elevated through 19 dpi. Sentinel pigs in the low biosecurity group (LB) became PEDV positive after the first movement of study personnel from the INF group. However, rectal swabs from pigs in the medium biosecurity (MB) and high biosecurity (HB) groups were negative during the 10 consecutive days of movements and remained negative through 24 days post movement (dpm) when the first trial was terminated. Viral RNA was detected at 1 dpm through 3 dpm from the personal protective equipment (PPE) of LB personnel. In addition, at 1 dpm, 2 hair/face swabs from MB personnel were positive; however, transmission of virus was not detected. All swabs of fomite from the HB study personnel were negative. CONCLUSIONS: These results indicate that indirect PEDV transmission through contaminated PPE occurs rapidly (within 24 h) under modeled conditions. Biosecurity procedures such as changing PPE, washing exposed skin areas, or taking a shower are recommended for pig production systems and appear to be an effective option for lowering the risk of PEDV transmission between groups of pigs.


title: Should I get an antibody test?

text: Antibody testing can reveal if you have had covid-19. Michael Le Page asks if it is worth paying for a test


title: Continuity of Care and Outpatient Management for Patients with and at High Risk for Cardiovascular Disease during the COVID-19 Pandemic: A Scientific Statement from the American Society for Preventive Cardiology

text: Abstract The coronavirus disease 2019 (COVID-19) pandemic has consumed our healthcare system, with immediate resource focus on the management of high numbers of critically ill patients. Those that fare poorly with COVID-19 infection more commonly have cardiovascular disease (CVD), hypertension and diabetes. There are also several other conditions that raise concern for the welfare of patients with and at high risk for CVD during this pandemic. Traditional ambulatory care is disrupted and many patients are delaying or deferring necessary care, including preventive care. New impediments to medication access and adherence have arisen. Social distancing measures can increase social isolation and alter physical activity and nutrition patterns. Virtually all facility based cardiac rehabilitation programs have temporarily closed. If not promptly addressed, these changes may result in delayed waves of vulnerable patients presenting for urgent and preventable CVD events. Here, we provide several recommendations to mitigate the adverse effects of these disruptions in outpatient care. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers should be continued in patients already taking these medications. Where possible, it is strongly preferred to continue visits via telehealth, and patients should be counselled about promptly reporting new symptoms. Barriers to medication access should be reviewed with patients at every contact, with implementation of strategies to ensure ongoing provision of medications. Team-based care should be leveraged to enhance the continuity of care and adherence to lifestyle recommendations. Patient encounters should include discussion of safe physical activity options and access to healthy food choices. Implementation of adaptive strategies for cardiac rehabilitation is recommended, including home based cardiac rehab, to ensure continuity of this essential service. While the practical implementation of these strategies will vary by local situation, there are a broad range of strategies available to ensure ongoing continuity of care and health preservation for those at higher risk of CVD during the COVID-19 pandemic.


title: Identification of γδT lymphocyte subsets that populate calf ileal mucosa after birth

text: Abstract Ileal intraepithelial and lamina propria lymphocytes from newborn, 1.5-week-old, and 3-week-old calves were compared to determine to what extent the mucosa becomes populated after birth. Single and dual fluorescence flow cytometry were used with monoclonal antibodies to bovine (Bo) CD molecules to identify lymphocyte subpopulations. Few ileal mucosal lymphocytes were present in calves at birth. However, by 1.5 weeks of age, the villi were populated with large numbers of lymphocytes, and by 3 weeks of age, the numbers had increased further. These included a prominent subpopulation of γδT cells. Several subsets of γδT cells populated ileal mucosa after birth. The predominant subset coexpressed BoCD2, and a smaller subset coexpressed BoCD8. WC1+ γδT cells comprised the smallest subset. All γδT cell subsets coexpressed ACT2, a molecule expressed on activated WC1+ and WC1− γδT cells from cattle.


title: Detection of Novel Coronavirus on the Surface of Environmental Materials Contaminated by COVID-19 Patients in the Republic of Korea

text: This study aimed to determine the presence of SARS-CoV-2 on surfaces frequently touched by COVID-19 patients, and assess the scope of contamination and transmissibility in facilities where the outbreaks occurred. In the course of this epidemiological investigation, a total of 80 environmental specimens were collected from 6 hospitals (68 specimens) and 2 “mass facilities” (6 specimens from a rehabilitation center and 6 specimens from an apartment building complex). Specific reverse transcriptase-polymerase chain reaction targeting of RNA-dependent RNA polymerase, and envelope genes, were used to identify the presence of this novel coronavirus. The 68 specimens from 6 hospitals (A, B, C, D, E, and G), where prior disinfection/cleaning had been performed before environmental sampling, tested negative for SARS-CoV-2. However, 2 out of 12 specimens (16.7%) from 2 “mass facilities” (F and H), where prior disinfection/cleaning had not taken place, were positive for SARS-CoV-2 RNA polymerase, and envelope genes. These results suggest that prompt disinfection and cleaning of potentially contaminated surfaces is an effective infection control measure. By inactivating SARS-CoV-2 with disinfection/cleaning the infectivity and transmission of the virus is blocked. This investigation of environmental sampling may help in the understanding of risk assessment of the COVID-19 outbreak in “mass facilities” and provide guidance in using effective disinfectants on contaminated surfaces.


title: Biosynthesis, structure, and biological activities of envelope protein gp65 of murine coronavirus

text: Abstract We have previously shown that gp65 (E3) is a virion structural protein which varies widely in quantity among different strains of mouse hepatitis virus (MHV). In this study, the biosynthetic pathway and possible biological activities of this protein were examined. The glycosylation of gp65 in virus-infected cells was inhibited by tunicamycin but not by monensin, suggesting that it contains an N-glycosidic linkage. Glycosylation is cotranslational and appears to be complete before the glycoprotein reaches the Golgi complex. Pulse-chase experiments showed that this protein decreased in size after 30 min of chase, suggesting that the carbohydrate chains of gp65 undergo trimming during its transport across the Golgi. This interpretation is supported by the endoglycosidase treatment of gp65, which showed that the peptide backbone of gp65 did not decrease in size after pulse-chase periods. This maturation pathway is distinct from that of the E1 or E2 glycoproteins. Partial endoglycosidase treatment indicated that gp65 contains 9 to 10 carbohydrate side chains; thus, almost all of the potential glycosylation sites of gp65 were glycosylated. In vitro translation studies coupled with protease digestion suggest that gp65 is an integral membrane protein. The presence of gp65 in the virion is correlated with the presence of an acetylesterase activity. No hemagglutinin activity was detected.


title: Facing highly infectious diseases: new trends and current concepts

text: A highly infectious disease (HID) that is transmissible from person to person causes life-threatening illness and presents a serious hazard in the healthcare setting and in the community that requires specific control measures. Due to environmental factors, changes in lifestyle and many other unknown factors, the emergence of such HIDs is becoming more and more likely. As has already been demonstrated during the SARS outbreak, healthcare facilities are likely to be the origin of future HID outbreaks. Preparedness planning will be essential in helping facilities manage future outbreaks of emerging or resurgent infectious diseases. Guidelines have been developed by national and international institutions. To avoid contamination of healthcare workers, the care of HID patients should follow the same infection control rules that are applied to laboratory workers exposed to similar agents. Here, the current knowledge concerning the clinical care of patients with HIDs is reviewed, and specific aspects of the management of such diseases are introduced.


title: Airborne SARS-CoV-2 is Rapidly Inactivated by Simulated Sunlight

text: Aerosols represent a potential route of transmission of COVID-19. This study examined the effect of simulated sunlight, relative humidity, and suspension matrix on the stability of SARS-CoV-2 in aerosols. Both simulated sunlight and matrix significantly affected the decay rate of the virus. Relative humidity alone did not affect the decay rate; however, minor interactions between relative humidity and the other factors were observed. Decay rates in simulated saliva, under simulated sunlight levels representative of late winter/early fall and summer were 0.121±0.017 min(-1) (90% loss: 19 minutes) and 0.379±0.072 min(-1) (90% loss: 6 minutes), respectively. The mean decay rate without simulated sunlight across all relative humidity levels was 0.008±0.011 min(-1) (90% loss: 125 minutes). These results suggest that the potential for aerosol transmission of SARS-CoV-2 may be dependent on environmental conditions, particularly sunlight. These data may be useful to inform mitigation strategies to minimize the potential for aerosol transmission.


title: A chemical cocktail during the COVID-19 outbreak in Beijing, China: Insights from six-year aerosol particle composition measurements during the Chinese New Year holiday

text: The rapidly spread coronavirus disease (COVID-19) has limited people's outdoor activities and hence caused substantial reductions in anthropogenic emissions around the world. However, the air quality in some megacities has not been improved as expected due to the complex responses of aerosol chemistry to the changes in precursors and meteorology. Here we demonstrate the responses of primary and secondary aerosol species to the changes in anthropogenic emissions during the COVID-19 outbreak in Beijing, China along with the Chinese New Year (CNY) holiday effects on air pollution by using six-year aerosol particle composition measurements. Our results showed large reductions in primary aerosol species associated with traffic, cooking and coal combustion emissions by 30–50% on average during the CNY, while the decreases in secondary aerosol species were much small (5–12%). These results point towards a future challenge in mitigating secondary air pollution because the reduced gaseous precursors may not suppress secondary aerosol formation efficiently under stagnant meteorological conditions. By analyzing the long-term measurements from 2012 to 2020, we found considerable increases in the ratios of nitrate to sulfate, secondary to primary OA, and sulfur and nitrogen oxidation capacity despite the overall decreasing trends in mass concentrations of most aerosol species, suggesting that the decreases in anthropogenic emissions have facilitated secondary formation processes during the last decade. Therefore, a better understanding of the mechanisms driving the chemical responses of secondary aerosol to the changes in anthropogenic emissions under complex meteorological environment is essential for future mitigation of air pollution in China.


title: COVID-19 Q&A: Keeping a cancer core going

text: Jennifer Koblinski explains how the Cancer Mouse Models Core at Virginia Commonwealth University (VCU) Massey Cancer Center (MCC) has kept its facility up and running in the face of the ongoing coronavirus pandemic.


COVID‐19 pandemic impact on gynaecological cancers: a perspective


Has loneliness increased during COVID-19? Comment on “Loneliness: A signature mental health concern in the era of COVID-19”


title: Emergency department evaluation of the febrile traveler

text: Summary The emergency department evaluation of the febrile traveler presents the emergency physician with a set of unique and often challenging circumstances. In addition to evaluating and managing the usual array of community-acquired infections, the clinician must be prepared to diagnose and treat a host of uncommon and potentially life-threatening pathogens. This diseases range from widespread tropical diseases such as malaria to the more exotic and lethal viral hemorrhagic fevers. A thoughtful approach guided by geographic patterns of illness offers a reliable method for determining the most likely sources of fever in the returned traveler as well as a focused diagnostic and treatment strategy.


title: Primary percutaneous coronary intervention in a COVID-19 patient with ST-segment elevation myocardial infarction after lung transplantation: a case report

text: 本文首次报告了重症新型冠状病毒肺炎(COVID-19)感染接受肺移植并行急症冠脉介入治疗的病 例。通过对多学科协作成功救治的总结, 为重症 COVID-19 救治提供经验。我们发现, 重症 COVID-19 感染在肺移植术后可能出现多种危险 因素诱发心肌梗死, 急症冠脉介入治疗是救治此 类患者的重要手段。


title: COVID-19 pandemic, socioeconomic crisis and human stress in resource-limited settings: A case from Bangladesh

text: Considering the population density, healthcare capacity, limited resources and existing poverty, environmental factors, social structure, cultural norms, and already more than 18,863 people infected, the community transmission of COVID-19 is happening fast. These exacerbated a complex fear among the public. The aim of this article is, therefore, to understand the public perception of socioeconomic crisis and human stress in resource-limited settings of Bangladesh during the COVID-19 outbreak. The sample comprised of 1066 Bangladeshi participants. Principal component analysis (PCA) was considered to design a standardized scale to measure the mental stress and socioeconomic crisis, one-way ANOVA and t-test were conducted to perceive different demographic risk groups; multiple linear regression was applied to estimate the statistically significant association between each component, and classical test theory (CTT) analysis was applied to examine the reliability of each item according to the components to develop a composite score. Without safeguarding the fundamental needs for the vulnerable ultra-poor group can undeniably cause the socioeconomic crisis and mental stress due to the COVID-19 lockdown. It has further created unemployment, deprivation, hunger, and social conflicts. The weak governance in the fragile healthcare system exacerbates the general public's anxiety as the COVID-19 testing facilities are centered around in the urban areas, a long serial to be tested, minimum or no treatment facilities in the dedicated hospital units for COVID-19 patients are the chief observations hampered along with the disruption of other critical healthcare services. One-way ANOVA and t-test confirmed food and nutritional deficiency among the vulnerable poorest section due to loss of livelihood. Also, different emergency service provider professions such as doctors, healthcare staff, police forces, volunteer organizations at the frontline, and bankers are at higher risk of infection and subsequently mentally stressed. Proper risk assessment of the pandemic and dependable risk communications to risk groups, multi-sectoral management taskforce development, transparency, and good governance with inter-ministerial coordination is required along with strengthening healthcare capacity was suggested to reduce mental and social stress causing a socioeconomic crisis of COVID-19 outbreak. Moreover, relief for the low-income population, proper biomedical waste management through incineration, and preparation for the possible natural disasters such as flood, cyclones, and another infectious disease such as dengue was suggested. Finally, this assessment process could help the government and policymakers to judge the public perceptions to deal with COVID-19 pandemic in densely populated lower-middle-income and limited-resource countries like Bangladesh.


title: Dilated Cardiomyopathy Risk in Patients with Coronavirus Disease 2019: How to Identify and Characterise it Early?

text: Multiple lines of evidence have shown that elevated blood troponin is strongly associated with poor prognosis in patients with the novel coronavirus disease 2019 (COVID-19). Possible mechanisms of myocardial injury in COVID-19 include ischaemia due to circulatory and respiratory failure, epicardial or intramyocardial small coronary artery thrombotic obstruction due to increased coagulability, and myocarditis caused by systemic inflammation or direct binding of the virus to its receptor, angiotensin-converting enzyme-2 (ACE2), which is abundantly expressed in the heart. It is postulated that persistent immune activation upon viral infection increases the risk of developing dilated cardiomyopathy in COVID-19 patients.


title: New variants of porcine epidemic diarrhea virus with large deletions in the spike protein, identified in the United States, 2016-2017

text: Four types of porcine epidemic diarrhea virus (PEDV) variants with a large deletion in the spike protein were detected, together with the original US PEDV, from pig fecal and oral fluid samples collected during 2016-2017 in the US. Two of the variants are similar to those identified in Japan: one contains a 194-aa deletion, the same as PEDV variant TTR-2/JPN/2014, while the other contains a 204-aa deletion, the same as PEDV variant JKa-292/CS1de204. Two new S1 NTD-del PEDV variants were found: one contains a 201-aa deletion located at residues 30-230 and the other contains a 202-aa deletion located at residues 24-225 of the S protein. This is the first report on coinfection of S1 NTD-del PEDV variants and the original US PEDV strain in US pigs, indicating that PEDV continues to evolve in pigs and might be responsible for disease pattern changes.


title: Tropical viral infections

text: Travel into subtropical and tropical areas is increasing, with a corresponding increase in the number of suspected viral infections acquired while travelling. In addition, legal and illegal immigrants may enter with overseas-acquired infections. Some of these infections are endemic to Australia, but are seen more often in returned travellers because they are more common overseas. These include hepatitis A, hepatitis B, HIV, seasonal influenza, measles, mumps and rubella. In addition there are number of infectious agents that are exotic or uncommon within Australia and are a particular diagnostic concern in people recently arrived from overseas. The most important of these are dengue virus infections, which have been increasing internationally in recent decades. Other arboviruses such as chikungunya and Japanese encephalitis virus also require consideration. Other important but rare viruses include Nipah virus, hantaviruses, rabies virus and the viruses causing viral haemorrhagic fever. Also it is important to consider new pathogens, as Asia has seen the emergence of SARS coronavirus, avian influenza virus, Nipah virus and others in recent years. This talk will focus on the exotic viruses and the diagnostic approach to potential overseas-acquired viral illnesses.


Enterovirus D68–Associated Severe Pneumonia, China, 2014


title: Glucocorticoid therapy delays the clearance of SARS‐CoV‐2 RNA in an asymptomatic COVID‐19 patient

text: The outbreak of severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2) started in Wuhan China, has become a global health concern. At present, glucocorticoid therapy is one of the most typically controversial treatments with COVID‐19 patients. Here, we reported an asymptomatic COVID‐19 patient with persistent positive detection of SARS‐CoV‐2 for 3 weeks and proposed that glucocorticoid therapy delays the clearance of SARS‐CoV‐2 RNA. Therefore, more attention must be paid to the COVID‐19 patients receiving glucocorticoid therapy. This article is protected by copyright. All rights reserved.


COVID‐19 in Australian health care workers: early experience of the Royal Melbourne Hospital emphasises the importance of community acquisition


title: Innate antiviral defenses in body fluids and tissues

text: Abstract Innate, non-specific, resistance mechanisms are important barriers to pathogens, particularly delaying virus multiplication at the onset of infections. These innate defense mechanisms include a series of mechanical barriers, pre-existing inhibitory molecules, and cellular responses with antimicrobial activity. The antiviral activities of these innate inhibitors reside in a variety of partly characterized substances. This review presents the innate antiviral inhibitors in cell cultures, urine, serum, the gastrointestinal tract, the nervous system, tissues of crustaceans, and saliva. Medical adaptation of the innate antiviral defense mechanisms may be useful for prevention and treatment of viral infections.


title: Tissue and cellular tropism of the coronavirus associated with severe acute respiratory syndrome: an in‐situ hybridization study of fatal cases

text: Severe acute respiratory syndrome (SARS) is a new human infectious disease with significant morbidity and mortality. The disease has been shown to be associated with a new coronavirus (SARS‐CoV). The clinical and epidemiological aspects of SARS have been described. Moreover, the viral genome of SARS‐CoV has been fully sequenced. However, much of the biological behaviour of the virus is not known and data on the tissue and cellular tropism of SARS‐CoV are limited. In this study, six fatal cases of SARS were investigated for the tissue and cellular tropism of SARS‐CoV using an in‐situ hybridization (ISH) technique. Among all the tissues studied, positive signals were seen in pneumocytes in the lungs and surface enterocytes in the small bowel. Infected pneumocytes were further confirmed by immunofluorescence–fluorescence in‐situ hybridization (FISH) analysis. These results provide important information concerning the tissue tropism of SARS‐CoV, which is distinct from previously identified human coronaviruses, and suggest the possible involvement of novel receptors in this infection. Whereas the lung pathology was dominated by diffuse alveolar damage, the gut was relatively intact. These findings indicated that tissue responses to SARS‐CoV infection are distinct in different organs. Copyright © 2004 John Wiley & Sons, Ltd.


Perioperative planning in the COVID-19 pandemic: Vascular issues.


title: The role of small RNAs in human diseases: Potential troublemaker and therapeutic tools

text: Small RNAs, including short interfering RNAs (siRNAs) and microRNAs (miRNAs), are ubiquitous, versatile repressors of gene expression in plants, animals, and many fungi. They can trigger destruction of homologous mRNA or inhibition of cognate mRNA translation and play an important role in maintaining the stable state of chromosome structure and regulating the expression of protein‐coding genes. Furthermore, the recent research showed that there exists close relationship between small RNAs and human diseases. Several human diseases have surfaced in which miRNAs or their machinery might be implicated, such as some neurological diseases and cancers. The specificity and potency of small RNAs suggest that they might be promising as therapeutic agents. This article will review the role of small RNAs in some human diseases etiology and investigations of taking siRNAs as therapeutic tools for treating viral infection, cancer, and other diseases. We also discuss the potential of miRNAs in gene therapy. © 2004 Wiley Periodicals, Inc.


title: Comparison of viral and epidemiological profiles of hospitalized children with severe acute respiratory infection in Beijing and Shanghai, China

text: BACKGROUND: No comparison data have been reported on viral and epidemiological profiles of hospitalized children with severe acute respiratory infection (SARI) in Beijing or Shanghai, China. METHODS: We collected 700 nasopharyngeal aspirates (NPA) from hospitalized children with SARI in Beijing (northern China) and Shanghai (southern China). Multiple respiratory viruses (including 15 common viruses) were screened by validated polymerase chain reaction (PCR) or real-time reverse transcription-PCR assays and confirmed by sequencing. Demographic data and the distribution of viral infections were also examined. RESULTS: Of 700 samples, 547 (78.1%) tested positive for viral infections. The picornaviruses (PIC), which included rhinovirus (RV) and enterovirus (EV), were the most common (34.0%), followed by respiratory syncytial virus (RSV) (28.3%), human bocavirus (HBoV) (19.1%), adenovirus (ADV) (13.7%), human coronaviruses (HCoV) (10.7%), influenza A and B (8.9%), parainfluenza virus (PIV 1–3) (7.9%), and human metapneumovirus (HMPV) (5.0%). PIC (RV/EV) and RSV were the most prevalent etiological agents of SARI in both cities. The total and age-matched prevalence of RSV, HCoV, and hMPV among SARI children under 5 years old were significantly higher in Beijing than in Shanghai. Different age and seasonal distribution patterns of the viral infections were found between Beijing and Shanghai. CONCLUSIONS: Viral infection was tested and shown to be the most prevalent etiological agent among children with SARI in either the Beijing or the Shanghai area, while showing different patterns of viral and epidemiological profiles. Our findings provide a better understanding of the roles of geographic location and climate in respiratory viral infections in hospitalized children with SARI.


title: Identification and genotyping of feline infectious peritonitis-associated single nucleotide polymorphisms in the feline interferon-γ gene

text: Feline infectious peritonitis (FIP) is an immune-mediated, highly lethal disease caused by feline coronavirus (FCoV) infection. Currently, no protective vaccine or effective treatment for the disease is available. Studies have found that some cats survive the challenge of virulent FCoV isolates. Since cellular immunity is thought to be critical in preventing FIP and because diseased cats often show a significant decrease in interferon-γ (IFN-γ) production, we investigated whether single nucleotide polymorphisms (SNP) in the feline IFN-γ gene (fIFNG) are associated with the outcome of infection. A total of 82 asymptomatic and 63 FIP cats were analyzed, and 16 SNP were identified in intron 1 of fIFNG. Among these SNP, the fFING + 428 T allele was shown to be a FIP-resistant allele (p = 0.03), and the heterozygous genotypes 01C/T and +408C/T were found to be FIP-susceptible factors (p = 0.004). Furthermore, an fIFNG + 428 resistant allele also showed a clear correlation with the plasma level of IFN-γ in FIP cats. For the identification of these three FIP-related SNP, genotyping methods were established using amplification refractory mutation system PCR (ARMS-PCR) and restriction fragment length polymorphisms (RFLP), and the different genotypes could easily be identified without sequencing. The identification of additional FIP-related SNP will allow the selection of resistant cats and decrease the morbidity of the cat population to FIP.


Nuevos tiempos, nuevas prioridades


title: Longer incubation period of coronavirus disease 2019 (COVID‐19) in older adults

text: OBJECTIVE: The aim of this study was to explore any age‐related change in the incubation period of COVID‐19, specifically any difference between older (aged ≥65 years) and younger adults. METHODS: Based on online data released officially by 21 Chinese cities from January 22 to February 15, 2020, the incubation period of COVID‐19 patients who had travelled to Hubei was studied according to age. Previous studies were reviewed and compared. RESULTS: The study recruited 136 COVID‐19 patients who had travelled to Hubei during January 5‐31, 2020, stayed for 1‐2 days, and returned with symptom onset during January 10‐February 6, 2020. The median age was 50.5 years (range 1‐86 years), and 22 patients (16.2%) were aged ≥65 years. The age‐stratified incubation period was U‐shaped with higher values at extremes of age. The median COVID‐19 incubation period was 8.3 (90% confidence interval [CI], 7.4‐9.2) days for all patients, 7.6 (90% CI, 6.7‐8.6) days for younger adults, and 11.2 (90% CI, 9.0‐13.5) days for older adults. The 5th/25th/75th/90th percentiles were 2.3/5.3/11.3/14.2 days for all, 2.0/5.0/10.5/13.2 days for younger adults, and 3.1/7.8/14.4/17.0 days for older adults. There were 11 published studies on COVID‐19 incubation periods up to March 30, 2020, reporting means of 1.8‐7.2 days, and medians of 4‐7.5 days, but there was no specific study on the effect of age on incubation period. One study showed that severe COVID‐19 cases, which included more elderly patients, had longer incubation periods. CONCLUSION: Based on 136 patients with a travel history to Hubei, the epicenter of COVID‐19, the COVID‐19 incubation period was found to be longer in older adults. This finding has important implications for diagnosis, prevention, and control of COVID‐19.


title: Elective surgery cancellations due to the COVID‐19 pandemic: global predictive modelling to inform surgical recovery plans

text: BACKGROUND: The COVID‐19 pandemic has disrupted routine hospital services globally. This study estimated the total number of adult elective operations that would be cancelled worldwide during the 12 weeks of peak disruption due to COVID‐19. METHODS: A global expert‐response study was conducted to elicit projections for the proportion of elective surgery that would be cancelled or postponed during the 12 weeks of peak disruption. A Bayesian beta‐regression model was used to estimate 12‐week cancellation rates for 190 countries. Elective surgical case‐mix data, stratified by specialty and indication (cancer versus benign surgery), was determined. This case‐mix was applied to country‐level surgical volumes. The 12‐week cancellation rates were then applied to these figures to calculate total cancelled operations. RESULTS: The best estimate was that 28,404,603 operations would be cancelled or postponed during the peak 12 weeks of disruption due to COVID‐19 (2,367,050 operations per week). Most would be operations for benign disease (90.2%, 25,638,922/28,404,603). The overall 12‐week cancellation rate would be 72.3%. Globally, 81.7% (25,638,921/31,378,062) of benign surgery, 37.7% (2,324,069/6,162,311) of cancer surgery, and 25.4% (441,611/1,735,483) of elective Caesarean sections would be cancelled or postponed. If countries increase their normal surgical volume by 20% post‐pandemic, it would take a median 45 weeks to clear the backlog of operations resulting from COVID‐19 disruption. CONCLUSIONS: A very large number of operations will be cancelled or postponed due to disruption caused by COVID‐19. Governments should mitigate against this major burden on patients by developing recovery plans and implementing strategies to safely restore surgical activity. This article is protected by copyright. All rights reserved.


title: Virus inoculation and treatment regimens for evaluating anti-filovirus monoclonal antibody efficacy in vivo

text: The development of monoclonal antibodies to treat disease caused by filoviruses, particularly Ebola virus, has risen steeply in recent years thanks to several key studies demonstrating their remarkable therapeutic potential. The increased drive to develop new and better monoclonal antibodies has necessarily seen an increase in animal model efficacy testing, which is critical to the pre-clinical development of any novel countermeasure. Primary and secondary efficacy testing against filoviruses typically makes use of one or more rodent models (mice, guinea pigs, and occasionally hamsters) or the more recently described ferret model, although the exact choice of model depends on the specific filovirus being evaluated. Indeed, no single small animal model exists for all filoviruses, and the use of any given model must consider the nature of that model as well as the nature of the therapeutic and the experimental objectives. Confirmatory evaluation, on the other hand, is performed in nonhuman primates (rhesus or cynomolgus macaques) regardless of the filovirus. In light of the number of different animal models that are currently used in monoclonal antibody efficacy testing, we sought to better understand how these efficacy tests are being performed by numerous different laboratories around the world. To this end, we review the animal models that are being used for antibody efficacy testing against filoviruses, and we highlight the challenge doses and routes of infection that are used. We also describe the various antibody treatment regimens, including antibody dose, route, and schedule of administration, that are used in these model systems. We do not identify any single best model or treatment regimen, and we do not advocate for field-wide protocol standardization. Instead, we hope to provide a comprehensive resource that will facilitate and enhance the continued pre-clinical development of novel monoclonal antibody therapeutics.


title: Global health goals: lessons from the worldwide effort to eradicate poliomyelitis

text: Summary The Global Polio Eradication Initiative was launched in 1988. Assessment of the politics, production, financing, and economics of this international effort has suggested six lessons that might be pertinent to the pursuit of other global health goals. First, such goals should be based on technically sound strategies with proven operational feasibility in a large geographical area. Second, before launching an initiative, an informed collective decision must be negotiated and agreed in an appropriate international forum to keep to a minimum long-term risks in financing and implementation. Third, if substantial community engagement is envisaged, efficient deployment of sufficient resources at that level necessitates a defined, time-limited input by the community within a properly managed partnership. Fourth, although the so-called fair-share concept is arguably the best way to finance such goals, its limitations must be recognised early and alternative strategies developed for settings where it does not work. Fifth, international health goals must be designed and pursued within existing health systems if they are to secure and sustain broad support. Finally, countries, regions, or populations most likely to delay the achievement of a global health goal should be identified at the outset to ensure provision of sufficient resources and attention. The greatest threats to poliomyelitis eradication are a financing gap of US$210 million and difficulties in strategy implementation in at most five countries.


title: Structure-based antigen design: a strategy for next generation vaccines

text: Vaccine design is progressing from empiricism towards the increasingly rational presentation of the targets of protective immunity. Nevertheless, most current vaccine antigens are essentially the native macromolecules of pathogens. These molecules are adapted to evade, not induce, immunity. High resolution structures reveal the electrostatic surfaces recognized by neutralizing antibodies and the architectures underlying these surfaces, thereby identifying which substructures must be left intact and which can be changed to optimize biochemical and immunologic performance. Armed with detailed structural information, we can engineer optimized antigens that are more stable, homogeneous, and efficiently produced, making immunization more practical and affordable. Understanding the structural basis for immunogenicity and immunodominance will allow us to improve vaccine efficacy and broaden the range of vaccine-preventable diseases.


title: Negative Nasopharyngeal and Oropharyngeal Swabs Do Not Rule Out COVID-19

text: Coronavirus Disease 19 (COVID-19), has become the Public Health Emergency of International Concern.….


title: Association between ages and clinical characteristics and outcomes of coronavirus disease 2019

text: Age significantly determined the clinical features and prognosis of the disease. The prognosis was worse in patients older than 60 years, calling for clinicians to pay more attention to patients on this special age. https://bit.ly/34DTI05


title: Novel single-stranded, circular DNA virus identified in cats in Japan

text: We detected a novel feline stool-associated circular DNA virus (FeSCV) in fecal samples from cats with diarrhea using consensus primers matching those of circovirus and cyclovirus. FeSCV is a circular DNA virus containing a genome with a total length of 2,046 nt encoding 2 open reading frames. Phylogenetic analyses indicated that FeSCV is classified into a clade different from that of circovirus and cyclovirus. Since the FeSCVs detected in several cats in the same household had genetically similar genomes, these viruses are most likely derived from the same origin. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-018-4020-6) contains supplementary material, which is available to authorized users.


title: Cross-Reactivity of TCR Repertoire: Current Concepts, Challenges, and Implication for Allotransplantation

text: Being able to track donor reactive T cells during the course of organ transplantation is a key to improve the graft survival, to prevent graft dysfunction, and to adapt the immunosuppressive regimen. The attempts of transplant immunologists have been for long hampered by the large size of the alloreactive T cell repertoire. Understanding how self-TCR can interact with allogeneic MHC is a key to critically appraise the different assays available to analyze the TCR Vβ repertoire usage. In this report, we will review conceptually and experimentally the process of cross-reactivity. We will then highlight what can be learned from allotransplantation, a situation of artificial cross-reactivity. Finally, the low- and high-resolution techniques to characterize the TCR Vβ repertoire usage in transplantation will be critically discussed.


title: Dual Respiratory Virus Infections

text: We retrospectively reviewed eight prospective epidemiological studies conducted between 1991 and 1995 for dual respiratory virus infection (DRVI) to determine the frequency, associated comorbid conditions, clinical presentations, and morbidity related to DRVI among immunocompetent persons. Two viruses were identified as the cause of 67 (5.0%) of 1,341 acute respiratory virus infections. DRVI was detected in patients from <1 year to 79 years of age, in both sexes, and in many races. Forty-two percent of patients with DRVI were ⩽4 years old. Fifty-eight percent of patients with DRVI had underlying chronic lung disease. DRVI was associated with upper respiratory tract illness; lower respiratory tract illness, including pneumonia; systemic influenza-like illnesses; and exacerbations of asthma or chronic obstructive pulmonary disease. All of the common acute respiratory viruses were identified; picornaviruses and influenzavirus A were the most common. The rate of DRVI (11.6%) was highest in the epidemiological studies in which cell culture, serology, and polymerase chain reaction were used together. Patients with DRVI were hospitalized significantly more often than those with respiratory infection due to a single virus (46.3% vs. 21.7%; P < .01). The percentage of DRVIs increased proportionally with the number of diagnostic methods used.


title: Pseudoknots: RNA Structures with Diverse Functions

text: Just as proteins form distinct structural motifs, certain structures are commonly adopted by RNA molecules. Amongst the most prevalent is the RNA pseudoknot.


title: Inclusion of MERS-spike protein ELISA in algorithm to determine serologic evidence of MERS-CoV infection

text: The Centers for Disease Control and Prevention (CDC) algorithm for detecting presence of serum antibodies against Middle East Respiratory Syndrome coronavirus (MERS-CoV) in subjects with potential infections with the virus has included screening by indirect ELISA against recombinant nucleocapsid (N) protein and confirmation by immunofluorescent staining of infected monolayers and/or micro-neutralization titration. Other international groups include indirect ELISA assays using the spike (S) protein, as part of their serological determinations. In the current study, we describe development and validation of an indirect MERS-CoV S ELISA to be used as part of our serological determination for evidence of previous exposure to the virus.


title: Existing bitter medicines for fighting 2019‐nCoV‐associated infectious diseases

text: The sudden outbreak of COVID‐19 has led to more than seven thousand deaths. Unfortunately, there are no specific drugs available to cure this disease. Type 2 taste receptors (TAS2Rs) may play an important role in host defense mechanisms. Based on the idea of host‐directed therapy (HDT), we performed a negative co‐expression analysis using big data of 60 000 Affymetrix expression arrays and 5000 TCGA data sets to determine the functions of TAS2R10, which can be activated by numerous bitter substances. Excitingly, we found that the main functions of TAS2R10 involved controlling infectious diseases caused by bacteria, viruses, and parasites, suggesting that TAS2R10 is a key trigger of host defense pathways. To quickly guide the clinical treatment of 2019‐nCoV, we searched currently available drugs that are agonists of TAS2Rs. We identified many cheap, available, and safe medicines, such as diphenidol, quinine, chloroquine, artemisinin, chlorpheniramine, yohimbine, and dextromethorphan, which may target the most common symptoms caused by 2019‐nCoV. We suggest that a cocktail‐like recipe of existing bitter drugs may help doctors to fight this catastrophic disease and that the general public may drink or eat bitter substances, such as coffee, tea, or bitter vegetables, to reduce the risk of infection.