title: COVID‐19 in recent heart transplant recipients: Clinicopathologic features and early outcomes

text: BACKGROUND: The impact of COVID‐19 on heart transplant (HTx) recipients remains unclear, particularly in the early post‐transplant period. METHODS: We share novel insights from our experience in five HTx patients with COVID‐19 (three within 2 months post‐transplant) from our institution at the epicenter of the pandemic. Results: All five exhibited moderate (requiring hospitalization, n = 3) or severe (requiring ICU and/or mechanical ventilation, n = 2) illness. Both cases with severe illness were transplanted approximately 6 weeks before presentation and acquired COVID‐19 through community spread. All five patients were on immunosuppressive therapy with mycophenolate mofetil (MMF) and tacrolimus, and three that were transplanted within the prior 2 months were additionally on prednisone. The two cases with severe illness had profound lymphopenia with markedly elevated C‐reactive protein, procalcitonin, and ferritin. All had bilateral ground‐glass opacities on chest imaging. MMF was discontinued in all five, and both severe cases received convalescent plasma. All three recent transplants underwent routine endomyocardial biopsies, revealing mild (n = 1) or no acute cellular rejection (n = 2), and no visible viral particles on electron microscopy. Within 30 days of admission, the two cases with severe illness remain hospitalized but have clinically improved, while the other three have been discharged. CONCLUSIONS: COVID‐19 appears to negatively impact outcomes early after heart transplantation.


title: Early Intervention Can Improve Clinical Outcome of Acute Interstitial Pneumonia

text: Study objectives: To report on our experience with acute interstitial pneumonia (AIP) in which patients underwent early diagnostic procedures and received mechanical ventilation with a “lung-protective” strategy and early institution of immunosuppressive therapy. Design: A retrospective chart review. Setting: A tertiary referral hospital. Participants: Ten patients with AIP who presented with idiopathic ARDS and showed diffuse alveolar damage on surgical lung biopsy specimens from July 1995 to March 2004. Measurements and results: The median age of patients was 65.5 years (age range, 38 to 73 years). Patients presented with a median duration of severe dyspnea of 9.5 days (range, 2 to 34 days) at the hospital visit. All patients required mechanical ventilation beginning at median time of hospital day 1 (range, hospital day 0 to 5), which continued for a median duration of 9.5 days (range, 4 to 98 days). Patients received ventilation in the pressure assist-control mode with a median tidal volume of 6.97 mL/kg (range, 6.05 to 8.86 mL/kg) and median positive end-expiratory pressure of 11 cm H2O (range, 8 to 16 cm H2O). An aggressive diagnostic workup for respiratory infection, including BAL at a median time of hospital day 2 (range, hospital day 1 to 5) was performed. High-dose steroid pulse therapy was initiated on median hospital day 3.5 (range, hospital day 1 to 8), while surgical lung biopsy was performed on median hospital day 4 (range, hospital day 2 to 7). Eight patients (80%) survived to hospital discharge. Conclusion: Earlier intervention, such as an aggressive diagnostic approach, mechanical ventilation with lung-protective strategy, and the early institution of immunosuppressive may improve clinical outcome in patients with AIP.


title: Use of Dipstick Assay and Rapid PCR-DNA Analysis of Nasal Secretions for Diagnosis of Bacterial Sinusitis in Children With Chronic Cough

text: BACKGROUND: Chronic cough in children is a diagnostic challenge. OBJECTIVE: To discover the utility of nasal dipsticks and polymerase chain reaction (PCR)-DNA analysis in differentiating bacterial sinusitis from other causes of chronic cough and identifying pathogens from the nasal cavity. METHOD: We recruited 22 patients under 15 years of age with cough lasting longer than 4 weeks (group 1), 7 controls with allergic rhinitis (group 2), and 10 controls without respiratory symptoms (group 3). Based on symptoms, the results of nasal secretion assays, and nasal endoscopy, a diagnosis of clinical bacterial sinusitis was made. We identified potential pathogens by quantitative PCR of nasal secretions. RESULTS: Group 1A (cough with clinical bacterial sinusitis n = 10): Eight (80%) patients had bacterial sinusitis associated with dominant potential pathogenic bacteria (PPB): Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Group 1B (cough without clinical bacterial sinusitis n = 12): None had dominant PPB. Group 2 (allergic rhinitis n = 7): None had dominant PPB. Group 3 (asymptomatic n = 10): None had dominant PPB. Twenty to 57% of all groups were colonized with Staphylococcus aureus. Fifty to 70% were colonized with Staphylococcus epidermidis, Corynebacterium pseudodiphtheriticum, and Dolosigranulum pigrum. CONCLUSION: In children with chronic cough, clinicians can utilize a simple and inexpensive nasal secretion dipstick assay for rapid diagnosis of sinusitis and identify PPB by DNA-PCR test for specific antibiotic treatment.


title: Beyond Disaster Preparedness: Building a Resilience-Oriented Workforce for the Future

text: Enhancing citizens’ and communities’ resilience is critical to adapt successfully to ongoing challenges faced by communities, as well as acute shocks resulting from disasters. While significant progress has been made in this area, several research and practice gaps remain. A crucial next step to advance resilience is the development of a resilience-oriented workforce. This narrative review examines existing literature to determine key components of a resilience-oriented workforce, with a focus on organizational structures, training and education, and leadership models. Reviewed articles spanned a variety of study types, including needs assessments of existing workforce, program evaluations, and reviews/commentaries. A resilience-oriented workforce spans many disciplines and training programs will need to reflect that. It requires a collaborative organizational model that promotes information sharing structures. Leadership models should foster a balance between workforce autonomy and operation as a collective entity. Optimal strategies to develop a resilience-oriented workforce have yet to be realized and future research will need to collect and synthesize data to promote and evaluate the growth of this field.


title: Mesenchymal stem cells and management of COVID-19 pneumonia

text: Abstract Human coronavirus, hCoV-19, is highly pathogenic with severe pneumonia associated with rapid virus replication. Arising in Wuhan China December 2019, the current COVID-19 epidemic has rapidly grown with person-to-person infection expanding to become a global health emergency now on pandemic scale. Governments will not be able to minimise both deaths from COVID-19 and the economic impact of viral spread in mitigation of this current COVID-19 pandemic, according to Anderson et al. 2020 [1], Keeping mortality as low as possible will be the highest priority for individuals; hence governments must put in place measures to ameliorate the inevitable economic downturn. The current global picture shows small chains of transmission in many countries and large chains resulting in extensive spread in a few countries, such as Italy, Iran, South Korea, and Japan. Most countries are likely to have spread of COVID-19, at least in the early stages, before any mitigation measures have an impact. The scale of the problem is massive. Here I consider new approaches to improve patient's biological resistance to COVID-19 using stem cells, and how benefit might be scaled and simplified using synthetic stem cells to meet logistical needs within a short time frame.


Address COVID‐19 Issues With Volunteers


title: SARS-CoV spike protein-expressing recombinant vaccinia virus efficiently induces neutralizing antibodies in rabbits pre-immunized with vaccinia virus

text: A vaccine for severe acute respiratory syndrome (SARS) is being intensively pursued against its re-emergence. We generated a SARS coronavirus (SARS-CoV) spike protein-expressing recombinant vaccinia virus (RVV-S) using highly attenuated strain LC16m8. Intradermal administration of RVV-S into rabbits induced neutralizing (NT) antibodies against SARS-CoV 1 week after administration and the NT titer reached 1:1000 after boost immunization with RVV-S. Significantly, NT antibodies against SARS-CoV were induced by administration of RVV-S to rabbits that had been pre-immunized with LC16m8. RVV-S can induce NT antibodies against SARS-CoV despite the presence of NT antibodies against VV. These results suggest that RVV-S may be a powerful SARS vaccine, including in patients previously immunized with the smallpox vaccine.


title: Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health implications

text: Summary Background Since the first case of Middle East respiratory syndrome coronavirus (MERS-CoV) in South Korea was reported on 20th May 2015, there have been 186 confirmed cases, 38 deaths and 16,752 suspected cases. Previously published research on South Korea's MERS outbreak was limited to the early stages, when few data were available. Now that the outbreak has ended, albeit unofficially, a more comprehensive review is appropriate. Methods Data were obtained through the MERS portal by the Ministry for Health and Welfare (MOHW) and Korea Centres for Disease Control and Prevention, press releases by MOHW, and reports by the MERS Policy Committee of the Korean Medical Association. Cases were analysed for general characteristics, exposure source, timeline and infection generation. Sex, age and underlying diseases were analysed for the 38 deaths. Findings Beginning with the index case that infected 28 others, an in-depth analysis was conducted. The average age was 55 years, which was a little higher than the global average of 50 years. As in most other countries, more men than women were affected. The case fatality rate was 19.9%, which was lower than the global rate of 38.7% and the rate in Saudi Arabia (36.5%). In total, 184 patients were infected nosocomially and there were no community-acquired infections. The main underlying diseases were respiratory diseases, cancer and hypertension. The main contributors to the outbreak were late diagnosis, quarantine failure of ‘super spreaders’, familial care-giving and visiting, non-disclosure by patients, poor communication by the South Korean Government, inadequate hospital infection management, and ‘doctor shopping’. The outbreak was entirely nosocomial, and was largely attributable to infection management and policy failures, rather than biomedical factors.


title: Histidine-rich Modification of a Scorpion-derived Peptide Improves Bioavailability and Inhibitory Activity against HSV-1

text: Rationale: HSV is one of the most widespread human viral pathogens. HSV-1 infects a large portion of the human population and causes severe diseases. The current clinical treatment for HSV-1 is based on nucleoside analogues, the use of which is limited due to drug resistance, side effects and poor bioavailability. AMPs have been identified as potential antiviral agents that may overcome these limitations. Therefore, we screened anti-HSV-1 peptides from a scorpion-derived AMP library and engineered one candidate into a histidine-rich peptide with significantly improved antiviral activity and development potential. Methods: A venomous gland cDNA library was constructed from the scorpion Euscorpiops validus in the Yunnan Province of China. Six putative AMPs were characterized from this cDNA library, and the synthesized peptides were screened via plaque-forming assays to determine their virucidal potential. Time of addition experiments according to the infection progress of HSV-1 were used to identify the modes of action for peptides of interest. The histidine-rich modification was designed based on structural analysis of peptides by a helical wheel model and CD spectroscopy. Peptide cellular uptake and distribution were measured by flow cytometry and confocal microscopy, respectively. Results: The peptide Eval418 was found to have high clearance activity in an HSV-1 plaque reduction assay. Eval418 exhibited dose-dependent and time-dependent inactivation of HSV-1 and dose-dependent inhibition of HSV-1 attachment to host cells. However, Eval418 scarcely suppressed an established HSV-1 infection due to poor cellular uptake. We further designed and modified Eval418 into four histidine-rich derivative peptides with enhanced antiviral activities and lower cytotoxicities. All of the derivative peptides suppressed established HSV-1 infections. One of these peptides, Eval418-FH5, not only had strong viral inactivation activity and enhanced attachment inhibitory activity but also had high inhibitory activity against intracellular HSV-1, which was consistent with its improved intracellular uptake and distribution as confirmed by confocal microscopy and flow cytometry. Conclusion: We successfully identified an anti-HSV-1 peptide, Eval418, from a scorpion venom peptide library and designed a histidine-rich Eval418 derivative with significantly improved potential for further development as an anti-HSV-1 drug. This successful modification can provide a design strategy to improve the bioavailability, cellular distribution and antiviral activity of peptide agents.


title: Interaction of the innate immune system with positive-strand RNA virus replication organelles

text: Abstract The potential health risks associated with (re-)emerging positive-strand RNA (+RNA) viruses emphasizes the need for understanding host-pathogen interactions for these viruses. The innate immune system forms the first line of defense against pathogenic organisms like these and is responsible for detecting pathogen-associated molecular patterns (PAMPs). Viral RNA is a potent inducer of antiviral innate immune signaling, provoking an antiviral state by directing expression of interferons (IFNs) and pro-inflammatory cytokines. However, +RNA viruses developed various methods to avoid detection and downstream signaling, including isolation of viral RNA replication in membranous viral replication organelles (ROs). These structures therefore play a central role in infection, and consequently, loss of RO integrity might simultaneously result in impaired viral replication and enhanced antiviral signaling. This review summarizes the first indications that the innate immune system indeed has tools to disrupt viral ROs and other non- or aberrant-self membrane structures, and may do this by marking these membranes with proteins such as microtubule-associated protein 1A/1B-light chain 3 (LC3) and ubiquitin, resulting in the recruitment of IFN-inducible GTPases. Further studies should evaluate whether this process forms a general effector mechanism in +RNA virus infection, thereby creating the opportunity for development of novel antiviral therapies.


Carbon dioxide gas leaks during transanal minimally invasive surgery


title: Socioeconomic marginalization and opioid-related overdose: A systematic review

text: BACKGROUND: Socioeconomic marginalization (SEM) is an important but under-explored determinant of opioid overdose with important implications for health equity and associated public policy initiatives. This systematic review synthesizes evidence on the role of SEM in both fatal and non-fatal overdose among people who use opioids. METHODS: Studies published between January 1, 2000 and March 31, 2018 were identified through searching electronic databases, citations, and by contacting experts. The titles, abstracts, citation information, and descriptor terms of citations were screened by two team members. Data were synthesized using the lumping technique. RESULTS: A total of 37 studies met inclusion criteria and were included in the review, with 34 of 37 finding a significant association between at least one socioeconomic factor and overdose. The included studies contained variables related to eight socioeconomic factors: criminal justice system involvement, income, employment, social support, health insurance, housing/homelessness, education, and composite measures of socio-economic status. Most studies found associations in the hypothesized direction, whereby increased SEM was associated with a higher rate or increased likelihood of the overdose outcome measured. The review revealed an underdeveloped evidence base. CONCLUSIONS: Nearly all reviewed studies found a connection between a socioeconomic variable and overdose, but more research is needed with an explicit focus on SEM, using robust and nuanced measures that capture multiple dimensions of disadvantage, and collect data over time to better inform decision making around opioid overdose.


title: Colchicina: una herramienta terapéutica potencial frente a COVID-19. Experiencia en 5 pacientes

text: Resumen COVID-19 es una enfermedad de aparición reciente, que se ha convertido en un reto global de salud pública. Debido a la falta de conocimiento acerca del virus, se ha propuesto un número significativo de objetivos potenciales para utilizar un fármaco en particular. Presentamos aquí cinco casos con historia clínica de biopolímeros en la región glútea, que desarrollaron alogenosis iatrogénica (AI). A los 5 casos se les administró tratamiento de colchicina debido a crisis de AI, no teniendo síntomas específicos (cefalea, tos sin disnea, y artralgias), con resultado positivo en el test de SARS-CoV-2. Sus contactos cercanos tenían síntomas de leves a graves, y tres de ellos fallecieron. En la infección por SARS-CoV-2 se alteran diferentes rutas inflamatorias, en las que la colchicina reduce los niveles de citocinas y la activación de macrófagos, neutrófilos e inflamasoma. Revisamos también en este artículo los posibles mecanismos que puede utilizar colchicina para prevenir el síndrome de distrés respiratorio agudo (SDRA) en pacientes con COVID-19. Abstract COVID-19 is a newly emerged disease that has become a global public health challenge. Due to a lack of knowledge about the virus, a significant number of potential targets for using a particular drug have been proposed. Five cases with a clinical history of biopolymers in the gluteal region that developed iatrogenic allogenosis (IA) are presented here. The 5 cases were put under colchicine treatment for IA crisis and had non-specific symptoms (headache, cough without dyspnoea, and arthralgias) with a positive SARS-CoV-2 test. Their close contacts had mild to severe symptoms and three of them died. In the SARS-CoV-2 infection different inflammatory pathways are altered where colchicine reduces cytokine levels as well as the activation of macrophages, neutrophils, and the inflammasome. The possible mechanisms that colchicine may use to prevent acute respiratory distress syndrome (ARDS) in patients with COVID-19 infection are also reviewed in this article.


title: Chapter 16 Passive Monoclonal and Polyclonal Antibody Therapies

text: Abstract Passive antibody therapies have a long history of use. In the 19th century, antibodies from xenographic sources of polyclonal antibodies were used to treat infections (diphtheria). They were used often as protection from infectious agents and toxins. Complications related to their use involved development of immune complexes and severe allergic reactions. As a result, human source plasma for polyclonal antibodies became the preferential source for antibodies. They are used to treat infection, remove toxins, prevent hemolytic disease of the newborn, modify inflammatory reactions, and control autoimmune diseases. Continued improvements in processing decreased the transfusion/infusion transmission of infections. In the late 20th century (∼1986), monoclonal antibodies were developed. The first monoclonal antibodies were of xenographic source and were wrought with problems of immunogenicity. These forms of antibodies did not gain favor until chimerization took pace in the mid-1990s and in 1998 two monoclonal antibodies were approved one to treat respiratory syncytial virus and the other for breast cancers. Further development of humanized and then fully human monoclonal antibodies has led to an evolution of therapies with these agents. Monoclonal antibodies are being researched or approved to treat a multitude of diseases to include oncologic, inflammatory, autoimmune, cardiovascular, respiratory, neurologic, allergic, benign hematologic, infections, orthopedic, coagulopathy, metabolic and to decrease morbidity of disease (diminution of pain), modify disease progression, and potentially anatomic development. In this chapter, we will review the history of use of these passive antibody therapies, their mechanism of action, pharmacologic-therapeutic classification, particular medical indication, adverse reactions, and potential future use of these medications.


title: The Promise of Proteomics for the Study of ADP-Ribosylation

text: ADP-ribosylation is a post-translational modification where single units (mono-ADP-ribosylation) or polymeric chains (poly-ADP-ribosylation) of ADP-ribose are conjugated to proteins by ADP-ribosyltransferases. This post-translational modification and the ADP-ribosyltransferases (also known as PARPs) responsible for its synthesis have been found to play a role in nearly all major cellular processes, including DNA repair, transcription, translation, cell signaling, and cell death. Furthermore, dysregulation of ADP-ribosylation has been linked to diseases including cancers, diabetes, neurodegenerative disorders, and heart failure, leading to the development of therapeutic PARP inhibitors, many of which are currently in clinical trials. The study of this therapeutically important modification has recently been bolstered by the application of mass spectrometry-based proteomics, arguably the most powerful tool for the unbiased analysis of protein modifications. Unfortunately, progress has been hampered by the inherent challenges that stem from the physicochemical properties of ADP-ribose, which as a post-translational modification is highly charged, heterogeneous (linear or branched polymers, as well as monomers), labile, and found on a wide range of amino acid acceptors. In this Perspective, we discuss the progress that has been made in addressing these challenges, including the recent breakthroughs in proteomics techniques to identify ADP-ribosylation sites, and future developments to provide a proteome-wide view of the many cellular processes regulated by ADP-ribosylation.


title: Les vaccins de demain

text: Vaccination represents one of the major advances in the field of health. The first vaccines were produced on a rather empirical concept based on the so-called 3I strategy: isolation, inactivation, injection. More recently, protein vaccines have emerged. However, the emergence of new pathogens, the inefficiency of these vaccine strategies to protect against several infections, the need to be able to develop new vaccines quickly and at low cost have led to the development of new types of vaccines. In this context vaccines based on the use of the nucleic acid coding sequences of the antigens of interest (viral vectors, DNA vaccines, RNA vaccines) have been developed in order to improve the efficiency of the currently available vaccines and to propose generic platforms potentially usable against a large number of different pathogens. In addition to the use of these new vaccines, ongoing vaccine research is benefiting from technological developments aimed at optimally delivering vaccines, targeting, for example, dendritic cells, and better characterizing the antigens of interest through the use of vaccines of reverse vaccinology.


Oncologist's perspective: when cancer encounters COVID‐19


title: Rapid detection and differentiation of avian infectious bronchitis virus: an application of Mass genotype by melting temperature analysis in RT-qPCR using SYBR Green I

text: A method based on Melting Temperature analysis of Hypervariable regions (HVR) of S1 gene within a RT-qPCR was developed to detect different genotypes of avian infectious bronchitis virus (IBV) and identify the Mass genotype. The method was able to rapidly identify the Mass genotype among IBV field isolates, vaccine attenuated strains and reference M41 strain in allantoic liquid and also directly in tissues. The RT-qPCR developed detected the virus in both tracheal and pulmonary samples from M41-infected or H120-infected birds, in a larger post-infection period compared to detection by standard method of virus isolation. RT-qPCR method tested provided a sensitivity and rapid approach for screening on IBV detection and Mass genotyping from IBV isolates.


Stronger national public health institutes for global health


Development of Different Animal Models for Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) Infection


title: Plasticity of PDZ domains in ligand recognition and signaling

text: The PDZ domain is a protein–protein interacting module that plays an important role in the organization of signaling complexes. The recognition of short intrinsically disordered C-terminal peptide motifs is the archetypical PDZ function, but the functional repertoire of this versatile module also includes recognition of internal peptide sequences, dimerization and phospholipid binding. The PDZ function can be tuned by various means such as allosteric effects, changes of physiological buffer conditions and phosphorylation of PDZ domains and/or ligands, which poses PDZ domains as dynamic regulators of cell signaling. This review is focused on the plasticity of the PDZ interactions.


title: Viral vaccines and their manufacturing cell substrates: New trends and designs in modern vaccinology

text: Vaccination is one of the most effective interventions in global health. The worldwide vaccination programs significantly reduced the number of deaths caused by infectious agents. A successful example was the eradication of smallpox in 1979 after two centuries of vaccination campaigns. Since the first variolation administrations until today, the knowledge on immunology has increased substantially. This knowledge combined with the introduction of cell culture and DNA recombinant technologies revolutionized vaccine design. This review will focus on vaccines against human viral pathogens, recent developments on vaccine design and cell substrates used for their manufacture. While the production of attenuated and inactivated vaccines requires the use of the respective permissible cell substrates, the production of recombinant antigens, virus‐like particles, vectored vaccines and chimeric vaccines requires the use – and often the development – of specific cell lines. Indeed, the development of novel modern viral vaccine designs combined with, the stringent safety requirements for manufacture, and the better understanding on animal cell metabolism and physiology are increasing the awareness on the importance of cell line development and engineering areas. A new era of modern vaccinology is arriving, offering an extensive toolbox to materialize novel and creative ideas in vaccine design and its manufacture.


title: Clinical and magnetic resonance imaging findings in 92 cats with clinical signs of spinal cord disease

text: Medical records of 92 cats presented with clinical signs of spinal cord disease, which had undergone magnetic resonance imaging (MRI), were reviewed. The cats were grouped into seven categories based upon the diagnosis suggested by results of MRI, cerebrospinal fluid analysis and other diagnostic procedures: neoplastic (n =25), inflammatory or infectious (n =13), traumatic (n =8), vascular (n =6), degenerative (n =5), anomalous (n =3) and those with an unremarkable MRI (n =32). There were two independent predictors of abnormal MRI findings: severity of clinical signs and presence of spinal pain. Abnormal MRI findings and speed of onset of disease were significantly associated with survival. For the 32 cats with unremarkable MRI findings, only nine died due to spinal disease and, therefore, the median survival time (MST) was not reached (lower 95% confidence interval (CI)=970 days). For the 60 cats with abnormal MRI findings, 37 died due to their disease and the MST was 138 days (95% CI: 7–807).


title: Doubtful precipitation of hemolysis by hydroxychloroquine in glucose‐6‐phosphate dehydrogenase deficient patient with COVID‐19 infection

text: We read with great interest the recent article by Beauverd et al.(1) on an interesting case of severe hemolysis in a patient with COVID‐19 treated with hydroxychloroquine. The authors concluded that COVID‐19 infection was possibly the initial trigger for hemolysis. However, the article also suggested that hydroxychloroquine possibly worsened the hemolysis, and further cautioned the use of hydroxychloroquine in glucose‐6‐phosphate dehydrogenase (G6PD)‐deficient patients. We would like to comment on the authors’ attribution of accentuated hemolysis to the use of hydroxychloroquine.


title: A complex minuet: behaviour change at the large scale Sara E Davies

text: Unknown


title: Attaching-effacing Bacteria in Animals

text: Summary Enteric bacteria with a demonstrable or potential ability to form attaching-effacing lesions, so-called attaching-effacing (AE) bacteria, have been found in the intestinal tracts of a wide variety of warm-blooded animal species, including man. In some host species, for example cattle, pigs, rabbits and human beings, attaching-effacing Escherichia coli (AEEC) have an established role as enteropathogens. In other host species, AE bacteria are of less certain significance. With continuing advances in the detection and typing of AE strains, the importance of these bacteria for many hosts is likely to become clearer. The pathogenic effects of AE bacteria result from adhesion to the intestinal mucosa by a variety of mechanisms, culminating in the formation of the characteristic intimate adhesion of the AE lesion. The ability to induce AE lesions is mediated by the co-ordinated expression of some 40 bacterial genes organized within a so-called pathogenicity island, known as the “Locus for Enterocyte Effacement”. It is also believed that the production of bacterial toxins, principally Vero toxins, is a significant virulence factor for some AEEC strains. Recent areas of research into AE bacteria include: the use of Citrobacter rodentium to model human AEEC disease; quorum-sensing mechanisms used by AEEC to modulate virulence gene expression; and the potential role of adhesion in the persistent colonization of the intestine by AE bacteria. This review of AE bacteria covers their molecular biology, their occurrence in various animal species, and the diagnosis, pathology and clinical aspects of animal diseases with which they are associated. Reference is made to human pathogens where appropriate. The focus is mainly on natural colonization and disease, but complementary experimental data are also included.


title: In silico Design of novel Multi-epitope recombinant Vaccine based on Coronavirus surface glycoprotein

text: It is of special significance to find a safe and effective vaccine against coronavirus disease 2019 (COVID-19) that can induce T cell and B cell -mediated immune responses. There is currently no vaccine to prevent COVID-19. In this project, a novel multi-epitope vaccine for COVID-19 virus based on surface glycoprotein was designed through application of bioinformatics methods. At the first, seventeen potent linear B-cell and T-cell binding epitopes from surface glycoprotein were predicted in silico, then the epitopes were joined together via different linkers. The ability of the selected epitopes to induce interferon-gamma was evaluate using IFNepitope web server. One final vaccine was constructed which composed of 398 amino acids and attached to 50S ribosomal protein L7/L12 as adjuvant. Physicochemical properties, as well as antigenicity in the proposed vaccines, were checked for defining the vaccine stability and its ability to induce cell-mediated immune responses. Three-dimensional structure of the mentioned vaccine was subjected to the molecular docking studies with MHC-I and MHC-II molecules. The results proposed that the multi-epitope vaccine with 50S ribosomal protein L7/L12 was a stable construct with high aliphatic content and high antigenicity.


title: Deploying Elemental Iodine in a Vapor Form to Disinfect Water and to Clear Biofilms

text: Traditionally, iodine has been delivered as a solution, tablet or resin to disinfect water. In this study we evaluated the “I(2) vapor infusion” (I(2)VP) technology which passes an airstream through a matrix containing elemental iodine (I(2)) to produce I(2) vapor as an innovative method of iodine delivery for water disinfection. Pressured air was provided either by a compressor or hand pump. Testing was performed with water inoculated with either Gram-negative (Escherichia, Salmonella) or Gram-positive (Enterococcus) bacteria or with pre-formed Acinetobacter or Staphylococcus biofilms. Bacterial colony forming units were used to assess efficacy of the device. In distilled water all bacteria and biofilms were eliminated after brief exposures (<90 s). Culturable bacteria were also eliminated from pond and municipal sewer water, but the technology was mostly ineffective against dairy lagoon water with high turbidity and organic particulate. Longer duration infusion and higher air volumes used to overcome interference from organic matter were also associated with higher concentrations of residual iodine. We conclude that I(2) vapor infusion has the potential to be useful for emergency water treatment and potentially for reducing microbiological contamination of some waste streams.


title: Studying up harm reduction policy: The office as an assemblage

text: Abstract Background By recounting the making of the office that contributed to the implementation of the harm reduction policy in Taiwan, this paper aims to answer two questions: Who and what assembled to make this policy possible? Which conceptual tool works best to understand what this policy-making was all about? Methods The research was designed as a multi-sited qualitative study whose materials were collected through archival research, in-depth interviews, and direct field observation. The data were analysed on the basis of the constructivist version of grounded theory. Result Formulating the office as an assemblage with heterogeneous components and shifting territories, the present work endeavours to show how it was constituted by way of guanxi, or webs of social relationship that blur the boundary between the private and the public, the governmental and the social. Conclusion This “studying up” approach is hoped to elicit more research on the office in which harm reduction policies are made into the backdrop of drug users on the street.


title: Chronic enterocyte infection with coronavirus: One possible cause of the syndrome of tropical sprue?

text: A man with a gastrojejunostomy and intestinal malabsorption was found to be excreting large numbers of coronavirus-like particles in his stools over a period of at least eight months. Coronavirus-like particles were found in vesicles in degenerating jejunal enterocytes in all of five jejunal biopsies. In a review of electron micrographs, similar structures were found in biopsies from three of 12 patients with classical chronic tropical sprue and in one patient with a sprue-like syndrome associated with agammaglobulinaemia. The hypothesis is advanced that infection with this virus may produce enterocyte damage and may be one cause of the syndrome of tropical sprue.


title: Polyprotein cleavage mechanism of SARS CoV M(pro) and chemical modification of the octapeptide

text: The cleavage mechanism of severe acute respiratory syndrome (SARS) coronavirus main proteinase (M(pro) or 3CL(pro)) for the octapeptide AVLQSGFR is studied using molecular mechanics (MM) and quantum mechanics (QM). The catalytic dyad His-41 and Cys-145 in the active pocket between domain I and II seem to polarize the π-electron density of the peptide bond between Gln and Ser in the octapeptide, leading to an increase of positive charge on C(CO) of Gln and negative charge on N(NH) of Ser. The possibility of enhancing the chemical bond between Gln and Ser based on the “distorted key” theory [Anal. Biochem. 233 (1996) 1] is examined. The scissile peptide bond between Gln and Ser is found to be solidified through “hybrid peptide bond” by changing the carbonyl group CO of Gln to CH(2) or CF(2). This leads to a break of the π-bond system for the peptide bond, making the octapeptide (AVLQSGFR) a “distorted key” and a potential starting system for the design of anti SARS drugs.


title: An overview of coronaviruses including the SARS-2 coronavirus – Molecular biology, epidemiology and clinical implications

text: Abstract Coronavirus infections have emerged as epidemic and pandemic threats in last two decades. After the H1N1 influenza pandemic in 2009, recently diagnosed novel betacoronavirus or severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has spread across 203 countries and territories in all 5 major continents. World Health Organization (WHO) declared this as a public health emergency of international concern on January 30, 2020. Subsequently on February 11, 2020 a new name was given to this disease i.e. COVID-19 by an expert group from WHO. As of April 12, 2020, 10:00 CET, GMT+2:00, 1,696,588 confirmed cases and 105,952 confirmed deaths have been reported to the WHO. (Coronavirus disease 2019, situation report 83). It possibly originated from a small animal market in Wuhan, China. A cluster of patients were admitted with unusual pneumonia not responding to treatment in various hospitals. Epidemiological, genomic analysis and correlation with other coronaviruses led to the isolation of new coronavirus, closely resembling the bat coronaviruses, from such patients in Wuhan. They were identified as the SARS-CoV-2. This virus infection presents as influenza like illness in the affected people. Fever, cough, respiratory distress with fatigue, diarrhea, nausea and vomiting are common symptoms seen in adults. This may progress on to respiratory distress, hypoxia, need for oxygen supplementation and ventilator support as seen in patients in the SARS-CoV-1 epidemic (2003) in Guangdong, China. The transmissibility of SARS-CoV-1 was less as compared to SARS-CoV-2 infection, and it was well controlled with good public health efforts. The present COVID-19 epidemic is still in the acceleration phase of 3 and 4 in various countries. Without any effective antiviral agents available at present, the need of the hour is early case detection, isolation of cases, use of good preventive care measures by the household contacts and in the hospital set up. The results of ongoing clinical trials on hydroxychloroquine, azithromycin alone or in combination and a new antiviral agent remdesivir may help to treat some of the infections. A need for effective vaccine is being seen an as good preventive strategy in this pandemic. However the results of clinical trials and incorporation of vaccines in public health programs is a long way to go.


title: Peptide-conjugated morpholino oligomers inhibit porcine reproductive and respiratory syndrome virus replication

text: Abstract Porcine reproductive and respiratory syndrome (PRRS) has been devastating the global swine industry for more than a decade, and current strategies to control PRRS are inadequate. In this study we characterized the inhibition of PRRS virus (PRRSV) replication by antisense phosphorodiamidate morpholino oligomers (PMO). Of 12 peptide-conjugated PMO (PPMO), four were found to be highly effective at inhibiting PRRSV replication in cell culture in a dose-dependant and sequence-specific manner. PPMO 5UP2 and 5HP are complementary to sequence in the 5′ end of the PRRSV genome, and 6P1 and 7P1 to sequence in the translation initiation regions of ORF6 and ORF7, respectively. Treatment of cells with 5UP2 or 5HP caused a 4.5log10 reduction in PRRSV yield, compared to a control PPMO. Combination of 6P1 and 7P1 led to higher level reduction than 6P1 or 7P1 alone. 5UP2, 5HP, and a combination of 6P1 and 7P1 inhibited PRRSV replication in porcine alveolar macrophages and protected the cells from PRRSV-induced cytopathic effect. Northern blot and real-time RT-PCR results demonstrated that the effective PPMO led to a reduction of PRRSV RNA level. 5UP2 and 5HP inhibited virus replication of 10 other strains of PRRSV. Results from this study suggest potential applications of PPMO for PRRS control.


title: Surveillance and Monitoring of Hepatocellular Carcinoma During the COVID-19 Pandemic

text: Abstract The Coronavirus disease 2019 (COVID-19) pandemic is expected to have a long-lasting impact on the approach to care for patients at risk for and with hepatocellular carcinoma (HCC) due to the risks from potential exposure and resource reallocation. The goal of this document is to provide recommendations on HCC surveillance and monitoring, including strategies to limit unnecessary exposure while continuing to provide high-quality care for patients. Publications and guidelines pertaining to the management of HCC during COVID-19 were reviewed for recommendations related to surveillance and monitoring practices, and any available guidance was referenced to support the authors’ recommendations when applicable. Existing HCC risk stratification models should be utilized to prioritize imaging resources to those patients at highest risk of incident HCC and recurrence following therapy though surveillance can likely continue as before in settings where COVID-19 prevalence is low and adequate protections are in place. Waitlisted patients who will benefit from urgent LT should be prioritized for surveillance whereas it would be reasonable to extend surveillance interval by a short period in HCC patients with lower risk tumor features and those more than 2 years since their last treatment. For patients eligible for systemic therapy, the treatment regimen should be dictated by the risk of COVID-19 associated with route of administration, monitoring and treatment of adverse events, within the context of relative treatment efficacy.


title: Is Returning to Work during the COVID-19 Pandemic Stressful? A Study on Immediate Mental Health Status and Psychoneuroimmunity Prevention Measures of Chinese Workforce

text: Abstract This study aimed to quantify the immediate psychological effects and psychoneuroimmunity prevention measures of a workforce returning to work during the COVID-19 epidemic. Workforce returning to work was invited to complete an online questionnaire regarding their attitude toward the COVID-19 epidemic and return-to-work along with psychological parameters including the Impact of Event Scale-Revised, Depression, Anxiety, Stress Scale- 21 (DASS-21) and Insomnia Severity Index (ISI). Psychoneuroimmunity prevention measures include precautions at personal and organization levels. From 673 valid questionnaires, we found that 10.8% of respondents met the diagnosis of post-traumatic stress disorder (PTSD) after returning to work. The respondents reported a low prevalence of anxiety (3.8%), depression (3.7%), stress (1.5%) and insomnia (2.3%). There were no significant differences in the severity of psychiatric symptoms between workers/technicians and executives/managers. More than 95% reported psychoneuroimmunity prevention measures including good ventilation in the workplace and wore a face mask as protective. Factors that were associated with the severity of psychiatric symptoms in the workforce were marital status, presence of physical symptom, poor physical health and viewing return to work as a health hazard (p<0.05). In contrast, personal psychoneuroimmunity prevention measures including hand hygiene and wearing face masks as well as organizational measures including significant improvement of workplace hygiene and concerns from the company were associated with less severe psychiatric symptoms (p<0.05). Contrary to expectations, returning to work had not caused a high level of psychiatric symptoms in the workforce. The low prevalence of psychiatric symptoms could be due to confidence instilled by psychoneuroimmunity prevention measures before the resumption of work. Our findings would provide information for other countries during the COVID-19 pandemic.


title: Wann dürfen Sportler mit COVID-19 wieder trainieren?

text: Neue Empfehlungen -- Infektionen mit SARS-CoV-2 können das Myokard schädigen. US-amerikanische Kardiologen haben daher Empfehlungen entwickelt, was bei der Rückkehr von COVID-19-Patienten zum Sport zu beachten ist.


COVID-19 in patients with diabetes: risk factors that increase morbidity


title: A method to identify respiratory virus infections in clinical samples using next-generation sequencing

text: Respiratory virus infections are very common. Such infections impose an enormous economic burden and occasionally lead to death. Furthermore, every few decades, respiratory virus pandemics emerge, putting the entire world population at risk. Thus, there is an urgent need to quickly and precisely identify the infecting agent in a clinical setting. However, in many patients with influenza-like symptoms (ILS) the identity of the underlying pathogen remains unknown. In addition, it takes time and effort to individually identify the virus responsible for the ILS. Here, we present a new next-generation sequencing (NGS)-based method that enables rapid and robust identification of pathogens in a pool of clinical samples without the need for specific primers. The method is aimed at rapidly uncovering a potentially common pathogen affecting many samples with an unidentified source of disease.


title: Hypochlorous acid – a review

text: The surgeon needs to have an inexpensive, available, non-toxic, and practical disinfectant that is effective in sanitizing against the CoVID-19 virus. The purpose of this paper is to review the evidence for using hypochlorous acid (HOCl) in the office setting on a daily basis. The methods used to assemble recommendations were to review the literature including evidence for this solution when used in different locations and industries other than the oral-maxillofacial clinic facility. The results indicate that this material can be used with a high predictability for disinfecting against the CoVID-19 virus.


title: Implications of COVID-19 in pediatric rheumatology

text: COVID-19 (coronavirus disease 2019) pandemic caused by SARS-CoV-2, is a global public health issue threatening millions of lives worldwide. Although the infection is mild in most of the affected individuals, it may cause severe clinical manifestations such as acute respiratory distress syndrome or cytokine storm leading to death. Children are affected less, and most experience a milder disease. As rheumatologists, we deal with the uncontrolled response of the immune system, and most of the drugs we use are either immune modulators or immunosuppressants. Thus, the rheumatologists participate in the multidisciplinary management of COVID-19 patients. On the other hand, our patients with rheumatic diseases constitute a vulnerable group in this pandemic. In this review, a systematic literature search was conducted utilizing MEDLINE/PubMed and Scopus databases, and 231 COVID-19 patients with rheumatic diseases have been identified. Only one of these patients was a child. Among these, 9 (3.9%) died due to COVID-19. In light of the current data, the aspects of COVID-19 resembling rheumatic diseases, the possible reasons for why children are affected less severely, the hypothetic role of available vaccines in preventing COVID-19, the unique position of patients with rheumatic diseases in this pandemic, and the use of anti-rheumatic drugs in COVID-19 treatment are discussed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00296-020-04612-6) contains supplementary material, which is available to authorized users.


title: Analysis on stability of an autonomous dynamics system for sars epidemic

text: An extended dynamic model for SARS epidemic was deduced on the basis of the K-M infection model with taking the density constraint of susceptible population and the cure and death rates of patients into consideration. It is shown that the infection-free equilibrium is the global asymptotic stability under given conditions, and endemic equilibrium is not the asymptotic stability. It comes to the conclusion that the epidemic system is the permanent persistence existence under appropriate conditions.


title: (18)F-FDG PET/CT and Serial Chest CT Findings in a COVID-19 Patient With Dynamic Clinical Characteristics in Different Period

text: Neurological symptoms and gastrointestinal symptoms were rare at onset in COVID-19. Here we report a 37-year-old man with vertigo, fever, and diarrhea symptoms as the first manifestation. (18)F-FDG PET/CT spotted multiple ground glass opacity (GGO) lesions in the lungs, with increased tracer uptake in both lung GGOs and the whole colon. Serial CT examinations showed the emersion and dissipation of lung GGOs. We illustrate the symptoms initiation, the laboratory test results, the imaging examination, and the treatment strategy in the duration of COVID-19 with a timeline chart.


Inflammatory bowel disease management during the COVID-19 outbreak: a survey from the European Crohn’s and Colitis Organization (ECCO)


title: 19 Xenogenic Adenoviral Vectors

text: Abstract Many nonhuman adenoviruses (AdVs) of simian, bovine, porcine, canine, ovine, murine, and fowl origin are being developed as gene delivery systems for recombinant vaccines and gene therapy applications. In addition to circumventing preexisting human AdV (HAdV) immunity, nonhuman AdV vectors utilize coxsackievirus-adenovirus receptor or other receptors for vector internalization, thereby expanding the range of cell types that can be targeted. Nonhuman AdV vectors also provide excellent platforms for veterinary vaccines. A specific nonhuman AdV vector when used in its species of origin could provide an excellent animal model for evaluating the vector efficacy and pathogenesis. These vectors are useful in prime–boost approaches with other AdV vectors or with other gene delivery systems including DNA immunization and viral or bacterial vectors. When multiple vector inoculations are required, nonhuman AdV vectors could supplement HAdV or other viral vectors.


title: Bioaerosol sampling optimization for community exposure assessment in cities with poor sanitation: A one health cross-sectional study

text: Abstract Evidence of exposure to enteric pathogens through the air and associated risk of infection is scarce in the literature outside of animal- or human-waste handling settings. Cities with poor sanitation are important locations to investigate this aerial exposure pathway as their rapid growth will pose unprecedented challenges in waste management. To address this issue, simple surveillance methods are needed. Therefore, the objectives of this study were to optimize a community exposure bioaerosol surveillance strategy for urban outdoor locations with poor sanitation, and to determine which bioaerosols could contribute to exposure. Passive and active bioaerosol sampling methods were used to characterize the fate and transport of sanitation-related bioaerosols during the rainy and dry seasons in La Paz, Bolivia. Median coliform bacteria fluxes were 71 CFU/(m2 × h) during the rainy season and 64 CFU/(m2 × h) during the dry season, with 38% of the dry season samples testing positive for E. coli. Wind speed, relative humidity and UVB irradiance were identified as significant covariates to consider in bioaerosol transport models in La Paz. Active sampling yielded one positive sample (10%) for human adenovirus (HadV) and one sample (10%) for influenza A virus during the rainy season. HadV was detected at the site with the highest bacterial flux. Four samples (8%) were positive for influenza A virus in the dry season. These findings suggest that aerosols can contribute to community exposure to potentially pathogenic microorganisms in cities with poor sanitation. The use of passive sampling, despite its limitations, can provide quantitative data on microorganisms' viability within realistic timeframes of personal exposure.


title: High-Throughput Transcription-mediated amplification on the Hologic Panther is a highly sensitive method of detection for SARS-CoV-2

text: BACKGROUND: As the demand for laboratory testing for SARS-CoV-2 increases, additional varieties of testing methodologies are being considered. While real time polymerase chain reaction (RT-PCR) has performed as the main method for virus detection, other methods are becoming available, including transcription mediated amplification (TMA). The Hologic Aptima SARS-CoV-2 Assay utilizes TMA as a target amplification mechanism, and it has only recently received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA). OBJECTIVES: We sought to compare the sensitivity and specificity of the Aptima SARS-CoV-2 Assay to RTPCR as a means of SARS-CoV-2 detection in a diagnostic setting. STUDY DESIGN: We performed a limit-of-detection study (LoD) to assess the analytical sensitivity of TMA and RT-PCR. This preceded a comparison of the methods using previously evaluated clinical specimens (nasopharyngeal swabs) using 116 human specimens tested by both methodologies. Specimens included sixty-one (61) specimens found reactive by real-time PCR, fifty-one (51) found non-reactive, and four (4) deemed inconclusive. RESULTS: The Aptima SARS-CoV-2 Assay showed a markedly higher analytical sensitivity than RT-PCR by LoD study. Evaluation of clinical specimens resulted in fewer inconclusive results by the SARS-CoV-2 assay, leading to potentially higher clinical sensitivity. CONCLUSIONS: The higher analytical sensitivity may explain the assay’s ability to ascertain for the presence of SARS-CoV-2 genome in human specimens deemed inconclusive by real-time PCR. TMA provides an effective, highly sensitive means of detection of SARS-CoV-2 in nasopharyngeal specimens.


title: COVID‐19 leads to jump in people seeking MH help in NYC

text: It's a stressful time to be a New Yorker. People are stuck at home, worrying about their health, their family and their paycheck, Spectrum News New York 1 reported April 13. “We are seeing a lot of calls related to anxiety and stress that people are experiencing today,” said Matt Kudish, executive director of the National Alliance on Mental Illness of New York City. The organization says the number of callers seeking help has jumped 60% over the last few weeks, and that conversations now last about 15 minutes longer than average. The city says it's also seeing an increase in demand. Web sessions to its NYC Well service jumped 185% last month to more than 81,000. “We're hearing from people who are worried about their own physical health, they're worried about their mental health being forced to stay socially distant from other people,” Kudish said. Health care providers predict that even when the COVID‐19 crisis ends, the mental health crisis will continue. They say people will continue to be anxious — this time about leaving home and being convinced it's safe to be outside.


title: Viral dynamics in asymptomatic patients with COVID-19

text: Abstract Data are limited on the viral load, viral shedding patterns and potential infectivity of asymptomatic patients (APs) with coronavirus disease 2019 (COVID-19). We included 31 adult patients who were virologically confirmed to have COVID-19 but were asymptomatic on admission. Among these 31 patients, 22 presented symptoms after admission and were defined as asymptomatic patients in incubation period (APIs); the other 9 patients remained asymptomatic during hospitalization and were defined as asymptomatic patients (APs). The cycle threshold (Ct) values of APs (39.0, IQR 37.5-39.5) was significantly higher than those of APIs (34.5, IQR 32.2-37.0), which indicated a lower viral load in APs, but the duration of viral shedding remained similar between the two groups (7 days IQR 5-14 vs. 8 days IQR 5-16). The study findings demonstrated that although they have a lower viral load, APs with COVID-19 still have certain period of viral shedding, which suggests the possibility of transmission during their asymptomatic period. Further longitudinal surveillance of these asymptomatic cases via virus nucleic acid tests are warranted.


title: Gut microbes as future therapeutics in treating inflammatory and infectious diseases: Lessons from recent findings

text: Abstract The human gut microbiota has been the interest of extensive research in recent years and our knowledge on using the potential capacity of these microbes are growing rapidly. Microorganisms colonized throughout the gastrointestinal tract of human are coevolved through symbiotic relationship and can influence physiology, metabolism, nutrition and immune functions of an individual. The gut microbes are directly involved in conferring protection against pathogen colonization by inducing direct killing, competing with nutrients and enhancing the response of the gut-associated immune repertoire. Damage in the microbiome (dysbiosis) is linked with several life-threatening outcomes viz. inflammatory bowel disease, cancer, obesity, allergy, and auto-immune disorders. Therefore, the manipulation of human gut microbiota came out as a potential choice for therapeutic intervention of the several human diseases. Herein, we review significant studies emphasizing the influence of the gut microbiota on the regulation of host responses in combating infectious and inflammatory diseases alongside describing the promises of gut microbes as future therapeutics.


title: Activation of the Antiviral Kinase PKR and Viral Countermeasures

text: The interferon-induced double-stranded (ds)RNA-dependent protein kinase (PKR) limits viral replication by an eIF2α-mediated block of translation. Although many negative-strand RNA viruses activate PKR, the responsible RNAs have long remained elusive, as dsRNA, the canonical activator of PKR, has not been detected in cells infected with such viruses. In this review we focus on the activating RNA molecules of different virus families, in particular the negative-strand RNA viruses. We discuss the recently identified non-canonical activators 5′-triphosphate RNA and the vRNP of influenza virus and give an update on strategies of selected RNA and DNA viruses to prevent activation of PKR.


The impact of COVID-19 on the neurosurgery practice in the North of Jordan


title: COVID-19 and the cancer care workforce: From doctors to ancillary staff

text: The COVID-19 pandemic poses daily challenges to the entire oncology workforce. Staff members must absorb multiple executive briefings, adapt to escalating scenario modelling, and seamlessly execute ever-changing operational modes in real-time. The unique threat of looming re-deployment and rationing care add to the uncertainty. We highlight the need for qualitative research to understand the psychosocial impact of these challenges. We posit that the perspective of all team members should be explored: from doctors to ancillary staff.


title: Enhanced MERS Coronavirus Surveillance of Travelers from the Middle East to England

text: During the first year of enhanced MERS coronavirus surveillance in England, 77 persons traveling from the Middle East had acute respiratory illness and were tested for the virus. Infection was confirmed in 2 travelers with acute respiratory distress syndrome and 2 of their contacts. Patients with less severe manifestations tested negative.


title: Diarrhées aiguës de l’enfant

text: La diarrhée aiguë est toujours potentiellement grave chez l’enfant, mais les variations des tableaux cliniques sont importantes. De nombreuses recommandations existent, mais on ne peut définir des indications thérapeutiques applicables à tous les cas. L’analyse clinique et l’évaluation de la déshydratation sont cruciales. Les solutions de réhydratation par voie orale sont d’utilisation systématique chez le jeune enfant. Le traitement antibiotique est réservé à certaines étiologies. Les médicaments antidiarrhéiques sont utiles, toujours en complément de la réhydratation par voie orale. La réalimentation précoce est systématique. Le processus diarrhéique peut durer quelques jours, comme par exemple lors d’une infection à rotavirus, cause la plus fréquente des diarrhées. Toute persistance exagérée doit faire rechercher un risque de passage à la chronicité, source de dénutrition qu’il faut savoir prévenir.


Impact of Emerging, Re-Emerging and Zoonotic Viral Infectious Diseases, in a Virologist’s Perspective


title: Neutrophil Diversity in Health and Disease

text: New evidence has challenged the outdated dogma that neutrophils are a homogeneous population of short-lived cells. Although neutrophil subpopulations with distinct functions have been reported under homeostatic and pathological conditions, a full understanding of neutrophil heterogeneity and plasticity is currently lacking. We review here current knowledge of neutrophil heterogeneity and diversity, highlighting the need for deep genomic, phenotypic, and functional profiling of the identified neutrophil subpopulations to determine whether these cells truly represent bona fide novel neutrophil subsets. We suggest that progress in understanding neutrophil heterogeneity will allow the identification of clinically relevant neutrophil subpopulations that may be used in the diagnosis of specific diseases and lead to the development of new therapeutic approaches.


title: Glycosylated hemoglobin is associated with systemic inflammation, hypercoagulability, and prognosis of COVID-19 patients

text: BACKGROUND: Diabetes is a risk factor for the progression and prognosis of coronavirus disease (COVID-19), but the relationship between glycosylated hemoglobin (HbA1c) level, inflammation, and prognosis of COVID-19 patients has not been explored. METHODS: This was a retrospective study of COVID-19 patients who underwent an HbA1c test. Their demographic data, medical history, signs and symptoms of COVID-19, laboratory test results, and final outcomes of COVID-19 treatment were collected and analyzed. RESULTS: A total of 132 patients were included and divided into three groups based on their blood glucose status. There were significant differences in SaO(2), serum ferritin level, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen (Fbg) level, and IL6 level among the three groups. A pairwise comparison of the groups showed that groups B and C were significantly different from group A in terms of CRP, ESR, and Fbg, IL6, and serum ferritin levels (P < 0.05). Correlation analysis showed that there was a linear negative correlation between SaO(2) and HbA1c (r = −0.22, P = 0.01), while there was a linear positive correlation between serum ferritin, CRP, Fbg, and ESR levels and HbA1c (P < 0.05). CONCLUSIONS: High HbA1c level is associated with inflammation, hypercoagulability, and low SaO(2) in COVID-19 patients, and the mortality rate (27.7%) is higher in patients with diabetes. Determining HbA1c level after hospital admission is thus helpful assessing inflammation, hypercoagulability, and prognosis of COVID-19 patients.


title: Recent successes in therapeutics for Ebola virus disease: no time for complacency

text: The PALM trial in the Democratic Republic of the Congo identified a statistically significant survival benefit for two monoclonal antibody-based therapeutics in the treatment of acute Ebola virus disease; however, substantial gaps remain in improving the outcomes of acute Ebola virus disease and for the survivors. Ongoing efforts are needed to develop more effective strategies, particularly for individuals with severe disease, for prevention and treatment of viral persistence in immune-privileged sites, for optimisation of post-exposure prophylaxis, and to increase therapeutic breadth. As antibody-based approaches are identified and advanced, promising small-molecule antivirals currently in clinical stage development should continue to be evaluated for filovirus diseases, with consideration of their added value in combination approaches with bundled supportive care, their penetration in tissues of interest, the absence of interaction with glycoprotein-based vaccines, and filoviral breadth.


title: Endothelial Targeting of Cowpea Mosaic Virus (CPMV) via Surface Vimentin

text: Cowpea mosaic virus (CPMV) is a plant comovirus in the picornavirus superfamily, and is used for a wide variety of biomedical and material science applications. Although its replication is restricted to plants, CPMV binds to and enters mammalian cells, including endothelial cells and particularly tumor neovascular endothelium in vivo. This natural capacity has lead to the use of CPMV as a sensor for intravital imaging of vascular development. Binding of CPMV to endothelial cells occurs via interaction with a 54 kD cell-surface protein, but this protein has not previously been identified. Here we identify the CPMV binding protein as a cell-surface form of the intermediate filament vimentin. The CPMV-vimentin interaction was established using proteomic screens and confirmed by direct interaction of CPMV with purified vimentin, as well as inhibition in a vimentin-knockout cell line. Vimentin and CPMV were also co-localized in vascular endothelium of mouse and rat in vivo. Together these studies indicate that surface vimentin mediates binding and may lead to internalization of CPMV in vivo, establishing surface vimentin as an important vascular endothelial ligand for nanoparticle targeting to tumors. These results also establish vimentin as a ligand for picornaviruses in both the plant and animal kingdoms of life. Since bacterial pathogens and several other classes of viruses also bind to surface vimentin, these studies suggest a common role for surface vimentin in pathogen transmission.


title: Nonprofit Service Continuity and Responses in the Pandemic: Disruptions, Ambiguity, Innovation and Challenges

text: This Viewpoint essay examines the service delivery responses of nonprofit organizations that offer homeless support services amid the COVID‐19 pandemic. Government mandates and severe human needs have forced nonprofits to adapt quickly. Literature reviews provide little information about how nonprofits should manage service continuity under pandemics. Data collected from websites and interviews with nonprofits executives provide an understanding of adaptions and innovations. The study uses a crisis response model: “Disruptions‐Ambiguities‐Innovations‐Challenges” (DAIC) to demonstrate how social service nonprofits are responding to challenges under COVID‐19. Lessons learned are useful for scholars and practitioners to understand ways nonprofits have remained agile and innovative. This article is protected by copyright. All rights reserved.


title: Avian Influenza: A New Pandemic Threat?

text: In December 2003, the largest outbreak of highly pathogenic avian influenza H5N1 occurred among poultry in 8 Asian countries. A limited number of human H5N1 infections have been reported from Vietnam and Thailand, with a mortality rate approaching 70%. Deaths have occurred in otherwise healthy young individuals, which is reminiscent of the 1918 Spanish influenza pandemic. The main presenting features were fever, pneumonitis, lymphopenia, and diarrhea. Notably, sore throat, conjunctivitis, and coryza were absent. The H5N1 strains are resistant to amantadine and rimantadine but are susceptible to neuraminidase inhibitors, which can be used for treatment and prophylaxis. The widespread epidemic of avian influenza in domestic birds increases the likelihood for mutational events and genetic reassortment. The threat of a future pandemic from avian influenza is real. Adequate surveillance, development of vaccines, outbreak preparedness, and pandemic influenza planning are important. This article summarizes the current knowledge on avian influenza, including the virology, epidemiology, diagnosis, and management of this emerging disease.


title: Isolation of a Coronavirus from Kidney Biopsies of Endemic Balkan Nephropathy Patients

text: Endemic Balkan nephropathy (EBN) is a kidney disease of unknown etiology limited to Bulgaria, Rumania and former Yugoslavia. Primary kidney tissue cultures were established as explants from tissue obtained at operations from 5 EBN patients with urinary tract tumors. Four out of the five biopsy specimens on extended culture incubation at 33°C yielded a coronavirus virus (EBNV) which was cytopathogenic for human fibroblast and Vero cells. In cells inoculated with EBNV, cytoplasmic immunofluorescence was found using antisera for human coronaviruses OC43 and 229E as well as the porcine transmissible gastroenteric virus and avian (chicken) bronchitis virus. In neutralization tests, EBNV failed to react with antisera to these viruses. Using hyperimmune serum raised with EBNV, positive cytoplasmic immunofluorescence was seen with cells infected with OC43, 229E, TGV and significantly with the kidney tissue of the biopsy specimens from the EBN patients. A screen for neutralizing antibody using the EBN virus revealed that 87.2% of EBN patients on dialysis were positive, also 74% of people from an endemic area were also positive, while only 13.5% from outside were positive. It is suggested that a coronavirus is involved in the etiology of the disease and that humans are an incidental host of a coronavirus zoonosis.


title: A case of successful treatment of severe COVID‐19 pneumonia with favipiravir and tocilizumab in post–kidney transplant recipient

text: We report a case of COVID‐19 in kidney transplant patient in Thailand. A 58‐year‐old 2 years post–kidney transplant recipient, with maintenance immunosuppression of tacrolimus, mycophenolate mofetil (MMF), and prednisolone, presented with acute diarrhea which followed by fever on day 12. Symptoms of pneumonia together with lymphopenia from complete blood count were developed on day 7 after onset of fever with the x‐ray finding of bilateral multifocal patchy infiltration. COVID‐19 infection has been confirmed by reverse real‐time polymerase chain reaction (PCR) in nasal swab as well as found in stool. Darunavir together with ritonavir, hydroxychloroquine, azithromycin, and favipiravir was initiated on the first day of admission at primary hospital. Patient has been transferred to our hospital on day 2 of admission in which tacrolimus together with MMF was discontinued. High‐flow nasal cannula oxygen therapy was required on days 4‐5 of hospitalization. Tocilizumab was administered after rising of serum IL‐6 level. Symptoms of pneumonia were improved in which no oxygen treatment required from day 10 of hospitalization. Drug interaction between tacrolimus and anti‐viral treatment leads to severely high level of tacrolimus which caused reversible acute kidney injury (AKI) after supportive treatment.


title: The changing patter of COVID-19 in China: A tempo-geographic analysis of the SARS-CoV-2 epidemic

text: BACKGROUND: Evaluating whether an infectious disease has reached a turning point is important for planning additional intervention efforts. This study aimed to analyze the changing patterns and the tempo-geographic features of the COVID-19 epidemic, to provide further evidence for real-time responses. METHODS: Daily data on COVID-2019 cases between 31(st) Dec. 2019 and 26(th) Feb. 2020 were collected and analyzed for Hubei and non-Hubei regions. Observed trends for new and cumulative cases were analyzed through joint-point regressions. Spatial analysis was applied to show the geographic distribution and changing pattern of the epidemic. RESULTS: By 26(th) Feb. 2020, 78,630 confirmed COVID-19 cases had been reported in China. In Hubei, an increasing trend (slope=221) was observed for new cases between 24(th) Jan. and February 7(th) Feb. 2020, after which a decline commenced (slope=-868). However, as the diagnosis criteria changed, a sudden increase (slope=5530) was observed on 12(th) Feb., which sharply decreased afterward (slope=-4898). In non-Hubei regions, the number of new cases increased from 20(th) Jan. to 3(rd) Feb. and started to decline afterward (slope=-53). The spatial analysis identified Chongqing, Guangzhou, Shenzhen, Changsha, Nanchang, Wenzhou, Shanghai, Xinyang, Jining, and Beijing as the hotspots outside of Hubei province in China. CONCLUSION AND RELEVANCE: The joint-point regression analysis indicated that the epidemic might have been under control in China, especially for regions outside of Hubei province. Further improvement in the response strategies based on these new patterns is needed.


Mayo Clinic Strategies for COVID-19 Introduction


title: High Rate of Viral Identification and Coinfections in Infants with Acute Bronchiolitis

text: OBJECTIVES: To determine the viruses and risk factors associated with hospital and intensive care unit (ICU) admissions in infants with acute bronchiolitis. INTRODUCTION: Bronchiolitis is a major cause of morbidity in infants. Widespread use of molecular-based methods has yielded new insights about its etiology, but the impact of viral etiologies on early outcomes is still unclear. METHODS: Seventy-seven infants with bronchiolitis who were under two years of age and visited an emergency unit were included. Using molecular-based methods, samples were tested for 12 different respiratory viruses. Logistic regression models were used to identify clinical and virological variables associated with the main endpoints: hospital admission and ICU admission. RESULTS: We identified at least one virus in 93.5% of patients, and coinfections were found in nearly 40% of patients. RSV was the most common pathogen (63.6%), followed by rhinovirus (39%). Identification of RSV was only associated with an increased risk of hospital admission in the univariate model. Younger age and enterovirus infection were associated with an increased risk of hospital admission, while atopy of a first-degree relative showed a protective effect. Prematurity was associated with an increased risk of admission to the ICU. Coinfections were not associated with worse outcomes. CONCLUSIONS: Molecular-based methods resulted in high rates of viral identification but did not change the significant role of RSV in acute bronchiolitis. Younger age and enterovirus infection were risk factors for hospital admission, while prematurity appeared to be a significant risk factor for admission to the ICU in acute viral bronchiolitis.


title: Respiratory syncytial virus bronchiolitis, weather conditions and air pollution in an Italian urban area: An observational study

text: Abstract Background In this study we sought to evaluate the association between viral bronchiolitis, weather conditions, and air pollution in an urban area in Italy. Methods We included infants hospitalized for acute bronchiolitis from 2004 to 2014. All infants underwent a nasal washing for virus detection. A regional agency network collected meteorological data (mean temperature, relative humidity and wind velocity) and the following air pollutants: sulfur dioxide, nitrogen oxide, carbon monoxide, ozone, benzene and suspended particulate matter measuring less than 10 µm (PM10) and less than 2.5 µm (PM2.5) in aerodynamic diameter. We obtained mean weekly concentration data for the day of admission, from the urban background monitoring sites nearest to each child's home address. Overdispersed Poisson regression model was fitted and adjusted for seasonality of the respiratory syncytial virus (RSV) infection, to evaluate the impact of individual characteristics and environmental factors on the probability of a being positive RSV. Results Of the 723 nasal washings from the infants enrolled, 266 (68%) contained RSV, 63 (16.1%) rhinovirus, 26 (6.6%) human bocavirus, 20 (5.1%) human metapneumovirus, and 16 (2.2%) other viruses. The number of RSV-positive infants correlated negatively with temperature (p < 0.001), and positively with relative humidity (p < 0.001). Air pollutant concentrations differed significantly during the peak RSV months and the other months. Benzene concentration was independently associated with RSV incidence (p = 0.0124). Conclusions Seasonal weather conditions and concentration of air pollutants seem to influence RSV-related bronchiolitis epidemics in an Italian urban area.


title: BRCA testing in a genomic diagnostics referral center during the COVID-19 pandemic

text: The first person-to-person transmission of the 2019-novel coronavirus in Italy on 21 February 2020 led to an infection chain that represents one of the largest known COVID-19 outbreaks outside Asia. Hospitals have been forced to reorganized their units in response to prepare for an unforeseen healthcare emergency. In this context, our laboratory (Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS) re-modulated its priorities by temporarily interrupting most of the molecular tests guaranteeing only those considered “urgent” and not postponable. In particular, this paper details changes regarding the execution of germline BRCA (gBRCA) testing in our laboratory. A substantial reduction in gBRCA testing (about 60%) compared to the first 2 months of the current year was registered, but the requests have not been reset. The requesting physicians were mainly gynaecologists and oncologists. These evidences further emphasize the new era of gBRCA testing in the management of cancer patients and confirms definitively the integration of gBRCA testing/Next Generation Sequencing (NGS) into clinical oncology. Finally, a re-organization of gBRCA testing in our Unit, mainly related to delayed and reduced arrival of tests was necessary, ensuring, however, a high-quality standard and reliability, mandatory for gBRCA testing in a clinical setting.


title: How do we leave lockdown?

text: With more than a third of the world living under covid-19 restrictions, it is time to decide what happens next, reports Graham Lawton


title: Serum cytokines and clinical features in patients with fever and thrombocytopenia syndrome

text: Abstract Purpose To explore the clinical, microbiological and immunological features of patients with fever and thrombocytopenia. Methods Patients with unexplained fever and thrombocytopenia were enrolled. Viruses were detected using real-time PCR, and bacteria were measured by culturing methods. Serum cytokines, platelet antibody IgG (PA-IgG) and Helicobacter pylori (HP) were detected using ELISA. Results Pathogens were detected in 74.68% of patients, which included single fungal/viral/bacterial infection and multiple infection. The pathogens could not be unidentified in 25.32% of cases. Cytokines including Interleukin (IL)-6, IL-10, interferon-γ(IFN-γ), platelet activating factor (PAF) and PA-IgG were significantly higher in patients as compared to healthy controls (P < .01 or P < .05). Principal component analyses extracted four groups of parameters that have a strong positive predicting value, revealing that disease status evaluation would be more accurate if we combined the platelet parameters and inflammatory biomarkers. While event-free survival (EFS) that indicates the time of platelet elevated after therapy was the highest in patients with single bacterial or fungal infection, EFS was affected by the levels of cytokines and PA-IgG. Conclusions Differences in immune function may be the main factors affecting the prognosis of patients with fever and thrombocytopenia, while treatment based on precise etiological diagnosis is important for therapeutic efficacy.


title: Comparison of tissue sample processing methods for harvesting the viral metagenome and a snapshot of the RNA viral community in a turkey gut

text: Abstract RNA viruses have been associated with enteritis in poultry and have been isolated from diseased birds. The same viral agents have also been detected in healthy flocks bringing into question their role in health and disease. In order to understand better eukaryotic viruses in the gut, this project focused on evaluating alternative methods to purify and concentrate viral particles, which do not involve the use of density gradients, for generating viral metagenome data. In this study, the sequence outcomes of three tissue processing methods have been evaluated and a data analysis pipeline has been established for RNA viruses from the gastrointestinal tract. In addition, with the use of the best method and increased sequencing depth, a glimpse of the RNA viral community in the gastrointestinal tract of a clinically normal 5-week old turkey is presented. The viruses from the Reoviridae and Astroviridae families together accounted for 76.3% of total viruses identified. The rarefaction curve at the species level further indicated that majority of the species diversity was included with the increased sequencing depth, implying that viruses from other viral families were present in very low abundance.


Renin–angiotensin–aldosterone system dysregulation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection


title: Characterisation of the faecal virome of captive and wild Tasmanian devils using virus-like particles metagenomics and meta-transcriptomics

text: The Tasmanian devil is an endangered carnivorous marsupial threatened by devil facial tumour disease (DFTD). While research on DFTD has been extensive, little is known about the viruses present in devils, and whether any of these are of potential conservation relevance for this endangered species. Using both metagenomics based on virus-like particle (VLP) enrichment and sequence-independent amplification (VLP metagenomics), and meta-transcriptomics based on bulk RNA sequencing, we characterised and compared the faecal viromes of captive and wild Tasmanian devils. A total of 54 devil faecal samples collected from captive (n = 2) and wild (n = 4) populations were processed for virome characterisation using both approaches. We detected many novel, highly divergent viruses, including vertebrate viruses, bacteriophage and other dietary associated plant and insect viruses. In total, 18 new vertebrate viruses, including novel sapelovirus, astroviruses, bocaviruses, papillomaviruses and gammaherpesvirus were identified, as well as known mammalian pathogens including rabbit haemorrhagic disease virus 2 (RHDV2). Captive devils showed significantly lower levels of viral diversity than wild devils. Comparison of the two methodological approaches revealed substantial differences in the number and types of viruses detected, with meta-transcriptomics mainly identifying RNA viruses, and VLP metagenomics largely identifying DNA viruses. This study has greatly expanded our knowledge of eukaryotic viruses in the Tasmanian devil and provides important baseline information that will contribute to the conservation and captive management of this endangered species. In addition, our results showed that a combination of VLP metagenomics and meta-transcriptomics may be a more comprehensive approach to virome characterisation than either method alone.


title: A model of tripeptidyl-peptidase I (CLN2), a ubiquitous and highly conserved member of the sedolisin family of serine-carboxyl peptidases

text: BACKGROUND: Tripeptidyl-peptidase I, also known as CLN2, is a member of the family of sedolisins (serine-carboxyl peptidases). In humans, defects in expression of this enzyme lead to a fatal neurodegenerative disease, classical late-infantile neuronal ceroid lipofuscinosis. Similar enzymes have been found in the genomic sequences of several species, but neither systematic analyses of their distribution nor modeling of their structures have been previously attempted. RESULTS: We have analyzed the presence of orthologs of human CLN2 in the genomic sequences of a number of eukaryotic species. Enzymes with sequences sharing over 80% identity have been found in the genomes of macaque, mouse, rat, dog, and cow. Closely related, although clearly distinct, enzymes are present in fish (fugu and zebra), as well as in frogs (Xenopus tropicalis). A three-dimensional model of human CLN2 was built based mainly on the homology with Pseudomonas sp. 101 sedolisin. CONCLUSION: CLN2 is very highly conserved and widely distributed among higher organisms and may play an important role in their life cycles. The model presented here indicates a very open and accessible active site that is almost completely conserved among all known CLN2 enzymes. This result is somehow surprising for a tripeptidase where the presence of a more constrained binding pocket was anticipated. This structural model should be useful in the search for the physiological substrates of these enzymes and in the design of more specific inhibitors of CLN2.


title: Synthetic studies towards anti-SARS agents: application of an indium-mediated allylation of α-aminoaldehydes as the key step towards an intermediate

text: Abstract AG7088 was identified as a good starting point for modification, leading to an efficient and bio-available inhibitor for the SARS coronavirus main proteinase (SARS-CoV Mpro). Synthesis of intermediate 1 and analogues proceeded via a highly diastereoselective indium-mediated allylation of α-aminoaldehydes.


title: Evaluation of the Anticipated Burden of COVID-19 on Hospital-Based Healthcare Services Across the United States

text: Background: Coronavirus disease-19 (COVID-19) is a global pandemic, with the potential to infect nearly 60% of the population. The anticipated spread of the virus requires an urgent appraisal of the capacity of US healthcare services and the identification of states most vulnerable to exceeding their capacity Methods: In the American Hospital Association survey for 2018, a database of US community hospitals, we identified total inpatient beds, adult intensive care unit (ICU) beds, and airborne isolation rooms across all hospitals in each state of continental US. The burden of COVID-19 hospitalizations was estimated based on a median hospitalization duration of 12 days and was evaluated for a 30-day reporting period. Results: At 5155 US community hospitals across 48 states in the contiguous US and Washington DC, there were a total of 788,032 inpatient beds, 68,280 adult ICU beds, and 44,222 isolation rooms. The median daily bed occupancy was 62.8% (IQR 58.1%, 66.6%) across states. Nationally, for every 10,000 individuals, there are 24.2 inpatient beds, 2.8 adult ICU beds, and 1.4 isolation beds. There is a 3-fold variation in the number of inpatient beds available across the US, ranging from 16.4 per 10,000 in Oregon to 47 per 10,000 in South Dakota. There was also a similar 3-fold variation in available or non-occupied beds, ranging from 4.7 per 10,000 in Connecticut through 18.3 per 10,000 in North Dakota. The availability of ICU beds is low nationally, ranging from 1.4 per 10,000 in Nevada to 4.7 per 10000 in Washington DC. Hospitalizations for COVID-19 in a median 0.2% (IQR 0.2 %, 0.3%) of state population, or 1.4% of state's older adults (1.0%, 1.9%) will require all non-occupied beds. Further, a median 0.6% (0.5%, 0.8%) of state population, or 3.9% (3.1%, 4.6%) of older individuals would require 100% of inpatient beds. Conclusion: The COVID-19 pandemic is likely to overwhelm the limited number of inpatient and ICU beds for the US population. Hospitals in half of US states would exceed capacity if less than 0.2% of the state population requires hospitalization in any given month.


title: CLEC4M-positive and CD81-negative Huh7 cells are not susceptible to JFH-1 HCVcc infection but mediate transinfection

text: C-type lectin domain family 4, member M (CLEC4M), a trans-membrane protein specifically expressed in liver sinusoidal endothelial cells, is considered a candidate receptor for hepatotropism of hepatitis C virus (HCV). CLEC4M was previously reported to capture artificial HCVpp (pseudoparticle) and transmit it to hepatocytes (transinfection) via CLEC4M-positive cells. It is still not known whether CLEC4M acts as a receptor for HCVcc (cell-culture-produced HCV) transinfection or whether CLEC4M is an entry receptor for HCVcc. Initially, we established stably CLEC4M-positive and HCV-replication-permissive cell lines by introducing a CLEC4M expression vector into Huh7-25 cells (Huh7-25-CLEC4M) by transfection. Huh7-25 is a mutant cell line that is resistant to JFH-1 HCVcc due to the lack of expression of CD81 but permissive for replication of JFH1 HCV RNA. When Huh7-25-CLEC4M cells were infected with HCVcc and cultured for 6 days, none were positive for infection. Next, to examine whether CLEC4M functions as a receptor for transinfection, Huh7-25-CLEC4M cells were inoculated with HCVcc and thereafter co-cultured with Huh7-it cells, which are susceptible to HCV infection. The amount of HCV RNA was increased in Huh7-it cells co-cultured with Huh7-25-CLEC4M cells, and the transinfection was inhibited in the presence of anti-CLEC4M antibody during inoculation. Thus, CLEC4M cannot substitute for CD81 as an entry receptor for JFH-1 HCVcc. It just mediates transinfection without internalization of HCVcc. CD81 is still crucial for HCV entry into hepatocytes, and CLEC4M in liver sinusoidal endothelial cells may be responsible for hepatotropism of HCV infection by trapping circulating HCV to transmit it to adjacent hepatocytes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-014-2150-z) contains supplementary material, which is available to authorized users.


title: New aspects of p38 mitogen activated protein kinase (MAPK) biology in lung inflammation

text: Lung inflammation features in asthma, chronic obstructive airways disease (COPD), acute respiratory distress syndrome (ARDS), cystic fibrosis (CF) and others. Whilst in asthma anti-inflammatory glucocorticosteroids are generally effective, certain individuals are steroid resistant and in COPD, ARDS and CF, as well as disease exacerbations caused by infection, there seems little benefit. We summarise recent advances in p38 mitogen activated protein kinase (MAPK) biology and document beneficial and possibly detrimental effects in respect of lung inflammation. Section editors: Maria Belvisi – Imperial College School of Medicine, London, UK Stuart Farrow – GlaxoSmithKline, Stevenage, UK


title: One-Pot Reverse Transcriptional Loop-Mediated Isothermal Amplification (RT-LAMP) for Detecting MERS-CoV

text: Due to the limitation of rapid development of specific antiviral drug or vaccine for novel emerging viruses, an accurate and rapid diagnosis is a key to manage the virus spread. We developed an efficient and rapid method with high specificity for the Middle East Respiratory Syndrome coronavirus (MERS-CoV), based on one-pot reverse transcription loop-mediated isothermal amplification (one-pot RT-LAMP). A set of six LAMP primers [F3, B3, FIP, BIP, LF (Loop-F), and LB (Loop-B)] were designed using the sequence of nucleocapsid (N) gene with optimized RT-LAMP enzyme conditions: 100 U M-MLV RTase and 4 U Bst polymerase, implying that the reaction was able to detect four infectious viral genome copies of MERS-CoV within a 60 min reaction time period. Significantly, EvaGreen dye has better signal read-out properties in one-pot RT-LAMP reaction and is more compatible with DNA polymerase than SYBR green I. Isothermally amplified specific N genes were further evaluated using field-deployable microchamber devices, leading to the specific identification of as few as 0.4 infectious viral genome copies, with no cross-reaction to the other acute respiratory disease viruses, including influenza type A (H1N1 and H3N2), type B, human coronavirus 229E, and human metapneumovirus. This sensitive, specific and feasible method provides a large-scale technical support in emergencies, and is also applied as a sample-to-detection module in Point of Care Testing devices.


title: Subacute Thyroiditis After Sars-COV-2 Infection

text: CONTEXT: Subacute thyroiditis (SAT) is a thyroid disease of viral or postviral origin. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that began in Wuhan, China, has spread rapidly worldwide and Italy has been severely affected by this outbreak. OBJECTIVES: The objective of this work is to report the first case of SAT related to SARS-CoV-2 infection. METHODS: We describe the clinical, laboratory, and imaging features of an 18-year-old woman who came to our attention for fever, neck pain radiated to the jaw, and palpitations occurring 15 days after a SARS-CoV-2–positive oropharyngeal swab. Coronavirus disease 2019 (COVID-19) had been mild and the patient had completely recovered in a few days. RESULTS: At physical examination the patient presented with a slightly increased heart rate and a painful and enlarged thyroid on palpation. At laboratory exams free thyroxine and free triiodothyronine were high, thyrotropin undetectable, and inflammatory markers and white blood cell count elevated. Bilateral and diffuse hypoechoic areas were detected at neck ultrasound. One month earlier, thyroid function and imaging both were normal. We diagnosed SAT and the patient started prednisone. Neck pain and fever recovered within 2 days and the remaining symptoms within 1 week. Thyroid function and inflammatory markers normalized in 40 days. CONCLUSIONS: We report the first case of SAT after a SARS-CoV-2 infection. We alert clinicians to additional and unreported clinical manifestations associated with COVID-19.


title: [Comment] Treatment strategies to fight the new coronavirus SARS-CoV-2: A challenge for a Rubik's Cube solver

text: SARS-coronavirus-2 (SARS-CoV-2), the etiologic agent of the new lung disease COVID-19 is closely related to SARS-CoV, and together with MERS-CoV are three new human coronaviruses that emerged in the last 20 years. The COVID-19 outbreak is a rapidly evolving situation with higher transmissibility and infectivity compared with SARS and MERS. Clinical presentations range from asymptomatic or mild symptoms to severe illness. The prevalent cause of mortality is pneumonia that progresses to ARDS. The ongoing pandemic has already resulted in more than 135,000 deaths and an unprecedented burden on national health systems worldwide. Pending the availability of a vaccine, there is a critical need to identify effective treatments and a number of clinical trials have been implemented worldwide. Trials are based on repurposed drugs that are already approved for other infections, have acceptable safety profiles or have performed well in animal studies against the other two deadly coronaviruses. Supportive care remains the mainstay of therapy at present, as it is still unclear how well these data can be extrapolated to SARS-CoV-2. Most of those emerging re-introduced drugs are administered to patients in the context of clinical trials. In this review, we summarize the strategies currently employed in the treatment of COVID-19.


title: Organ Transplantation, Risks

text: Viruses are among the most common causes of opportunistic infection after solid organ and hematopoietic stem cell transplantation (SOT and HSCT). Viral infection is associated with both direct (invasive disease) and indirect (immune modulation) effects affecting susceptibility to other infections and promoting allograft rejection. The transplantation recipient is susceptible to a broad array of viral pathogens. Some may be transmitted with the allograft as donor-derived infections, while others result from exposure, either soon after the transplant or from more distant exposures when infection is latent and reactivates in the setting of immune suppression. Simultaneous infections with multiple viral or viral and nonviral pathogens are common. The risk for viral infection is a function of the intensity of exposure and virulence of the specific virus, the intensity of immune suppression used to prevent graft rejection or graft-versus-host disease, underlying immune deficits, and factors affecting host susceptibility. Studies of viral latency, reactivation, and of the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections. This article covers specific issues relating to viral infection in SOT and HSCT; additional details regarding these viral infections are also found elsewhere in this text.


title: Non-overt coagulopathy in non-icu patients with mild to moderate COVID-19 pneumonia

text: Introduction: Aim of the study is to assess the occurrence of early stage coagulopathy and disseminated intravascular coagulation (DIC) in patients with mild to moderate respiratory distress secondary to SARS-CoV-2 infection. Materials and methods: Data of patients hospitalized from 18 March 2020 to 20 April 2020 were retrospectively reviewed. Two scores for the screening of coagulopathy (SIC and non-overt DIC scores) were calculated. The occurrence of thrombotic complication, death, and worsening respiratory function requiring non-invasive ventilation (NIV) or admission to ICU were recorded, and these outcomes were correlated with the results of each score. Chi-square test, receiver-operating characteristic curve, and logistic regression analysis were used as appropriate. p Values < 0.05 were considered statistically significant. Results: Data of 32 patients were analyzed. Overt-DIC was diagnosed in two patients (6.2%), while 26 (81.2%) met the criteria for non-overt DIC. Non-overt DIC score values ≥4 significantly correlated with the need of NIV/ICU (p = 0.02) and with the occurrence of thrombotic complications (p = 0.04). A score ≥4 was the optimal cut-off value, performing better than SIC score (p = 0.0018). Values ≥4 in patients with thrombotic complications were predictive of death (p = 0.03). Conclusions: Overt DIC occurred in 6.2% of non-ICU patients hospitalized for a mild to moderate COVID-19 respiratory distress, while 81.2% fulfilled the criteria for non-overt DIC. The non-overt DIC score performed better than the SIC score in predicting the need of NIV/ICU and the occurrence of thrombotic complications, as well as in predicting mortality in patients with thrombotic complications, with a score ≥4 being detected as the optimal cut-off.