title: Genetic analysis of calicivirus genomes detected in intestinal contents of piglets in Japan

text: Enteric caliciviruses, noroviruses, and sapoviruses are emerging path- ogens responsible for diarrhea or gastroenteritis in their respective hosts. In this study, swine enteric caliciviruses were detected in ten samples of intestinal contents from 24 piglets in Japan by reverse transcription-polymerase chain reaction using a broadly reactive primer pair (P290/289) that targeted the highly conserved RNA polymerase regions of the enteric caliciviruses. From the positive samples, the entire viral genome of strain K7/JP and 3′-end parts of the genomes of strains K5/JP and K10/JP were cloned and sequenced. K7/JP had an RNA genome of 7144 bases, excluding its 3′ poly (A) tail. The K7/JP genome possessed two open reading frames and characteristics common to sapoviruses. In phylogenetic analysis using amino acid sequences of VP1, K5/JP was demonstrated to be close to the noroviruses previously detected in pigs, and K7/JP and K10/JP were considered to be classified as a new genogroup of sapoviruses.


title: Molecular characterization of a novel Muscovy duck parvovirus isolate: evidence of recombination between classical MDPV and goose parvovirus strains

text: BACKGROUND: Muscovy duck parvovirus (MDPV) and Goose parvovirus (GPV) are important etiological agents for Muscovy duck parvoviral disease and Derzsy’s disease, respectively; both of which can cause substantial economic losses in waterfowl industry. In contrast to GPV, the complete genomic sequence data of MDPV isolates are still limited and their phylogenetic relationships largely remain unknown. In this study, the entire genome of a pathogenic MDPV strain ZW, which was isolated from a deceased Muscovy duckling in 2006 in China, was cloned, sequenced, and compared with that of other classical MDPV and GPV strains. RESULTS: The genome of strain ZW comprises of 5071 nucleotides; this genome was shorter than that of the pathogenic MDPV strain YY (5075 nt). All the four deleted nucleotides produced in strain ZW are located at the base-pairing positions in the palindromic stem of inverted terminal repeats (ITR) without influencing the formation of a hairpin structure. Recombination analysis revealed that strain ZW originated from genetic recombination between the classical MDPV and GPV strain. The YY strain of MDPV acts as the major parent, whereas the virulent strains YZ99–6 and B and the vaccine strain SYG61v of GPV act as the minor parents in varying degrees. Two recombination sites were detected in strain ZW, with the small recombination site surrounding the P9 promoter, and the large recombination site situated in the middle of the VP3 gene. The SYG61V strain is a vaccine strain used for preventing goose parvoviral disease. This strain was found to be solely involved in the recombination event detected in the P9 promoter region. Phylogenetic analyses between strain ZW and other classical strains of MDPV and GPV were performed. The results supported the in silico recombination analysis conclusion. CONCLUSIONS: MDPV Strain ZW is a novel recombinant parvovirus, and the bulk of its genome originates from the classical MDPV strain. Two virulent strains and a vaccine strain of GPV were involved in the recombination process in varying degrees.


title: Macrolide-Resistant Mycoplasma pneumoniae, United States

text: Macrolide-resistant Mycoplasma pneumoniae (MRMP) is highly prevalent in Asia and is now being reported from Europe. Few data on MRMP are available in the United States. Using genotypic and phenotypic methods, we detected high-level MRMP in 13.2% of 91 M. pneumoniae–positive specimens from 6 US locations.


title: Chapter 12 Synthesis

text: Abstract The preceding chapters have described in detail specific examples of viruses that have emerged or re-emerged from animal sources. Most, although not all, are zoonotic and have caused significant human morbidity and mortality. This final chapter will attempt to bring together a number of the common themes raised by these examples. These include the role of historical events in shaping the emergence of viruses in the present, the ability to retrospectively test samples to trace the emergence of disease and the technologies used to detect viruses. Technologies such as the polymerase chain reaction and mass sequencing have revolutionized virus detection and enabled the rapid identification and characterization of viruses. The application of these methods has led to the identification of new groups of viruses in samples obtained from a range of animal species without the need for invasive sampling or the recovery of live virus. However, with the detection of such a large range of viruses that exist asymptomatically with other species, the challenge now becomes the identification of those with the potential to become pathogenic for humans.


(90)Y Radioembolization: Telemedicine During COVID-19 Outbreak, Opportunity for Prime Time


title: Side effects of ruxolitinib in patients with SARS-CoV-2 infection: two case reports

text: • Innovative drugs are not always available in emergency settings; • Use of ruxolitinib in patients with COVID-19 has given unsatisfactory results; • Janus kinase (JAK) inhibitors may be associated with a major incidence of side effects in COVID-19 patients.


title: Public image and governance of epidemics: Comparing HIV/AIDS and SARS

text: Abstract A comparative analysis of the 2002–2003 infectious disease outbreak, severe acute respiratory syndrome (SARS), and the HIV/AIDS epidemic that has affected the world over the past two decades reveals the significant role of socio-cultural beliefs and attitudes in the shaping of people's lifestyles and approaches to the control and prevention of epidemics. The main research question is: what can we learn from the SARS experience about effective prevention of HIV/AIDS? The sources of data include population figures on the development of these epidemics and findings from two sociological studies of representative samples of Singapore's multi-ethnic population. The comparative study illustrates the impact of cultural beliefs and attitudes in shaping the public image of these two different infectious diseases; the relevance of public image of the disease for effective prevention and control of epidemics.


title: Skin fragility syndrome in a cat with feline infectious peritonitis and hepatic lipidosis

text: A 6‐year‐old spayed female domestic shorthair cat with a 3‐week history of inappetence, weight loss, and hiding was examined. A palpable abdominal fluid wave, dehydration, and a small tear on the left flank were noted during initial examination. When the cat was gently restrained for blood sampling, the skin on the dorsal neck tore, leaving a 15 cm × 7 cm flap of skin. Clinicopathological abnormalities included nonregenerative anaemia, hypoalbuminaemia, increased globulin concentration, and mildly elevated aspartate aminotransferase and alkaline phosphatase activities. Abdominal fluid was viscous and had a total protein of 5.3 g dL(−1) with 316 cells µL(−1), consistent with a modified transudate. Cytology of the abdominal fluid revealed 86% nondegenerate neutrophils, 13% macrophages, and 1% small lymphocytes. Histopathological evaluation and indirect immunohistochemistry confirmed a diagnosis of feline infectious peritonitis, hepatic lipidosis and feline skin fragility syndrome. Feline skin fragility syndrome has not previously been reported in association with feline infectious peritonitis (FIP). Its inclusion as a clinical sign associated with FIP may facilitate a diagnosis.


title: Old Enemies, Still with Us after All These Years

text: Although some previously common infections, such as Sendai virus and Mycoplasma pulmonis, have become rare in laboratory rodents in North American research facilities, others continue to plague researchers and those responsible for providing biomedical scientists with animals free of adventitious disease. Long-recognized agents that remain in research facilities in the 21(st) century include parvoviruses of rats and mice, mouse rotavirus, Theiler's murine encephalomyelitis virus (TMEV), mouse hepatitis virus (MHV), and pinworms. The reasons for their persistence vary with the agent. The resilience of parvoviruses, for example, is due to their resistance to inactivation, their prolonged shedding, and difficulties with detection, especially in C57BL/6 mice. Rotavirus also has marked environmental resistance, but periodic reintroduction into facilities, possibly on bags of feed, bedding, or other supplies or equipment, also seems likely. TMEV is characterized by resistance to inactivation, periodic reintroduction, and relatively long shedding periods. Although MHV remains active in the environment at most a few days, currently prevalent strains are shed in massive quantities and likely transmitted by fomites. Pinworm infestations continue because of prolonged infections, inefficient diagnosis, and the survivability of eggs of some species in the environment. For all of these agents, increases in both interinstitutional shipping and the use of immunodeficient or genetically modified rodents of unknown immune status may contribute to the problem, as might incursions by wild or feral rodents. Elimination of these old enemies will require improved detection, strict adherence to protocols designed to limit the spread of infections, and comprehensive eradication programs.


title: On mothering and being mothered: a personal reflection on women's productivity during Covid‐19

text: This is a personal reflection, as a female academic during Covid‐19, on how women's academic productivity seems primarily to be discussed in relation to a different kind of productivity–motherhood. A recent procedure in a maternity hospital, evoked feelings and associations of mothering and being mothered, and how these associations hover over relationships regardless of whether wombs are productive or not. My hope in writing this piece, is that every woman's fear and anxiety may be productively contained (regardless of how she is seen from the outside or momentarily construed from within) during this time of extraordinary turmoil.


title: Clinical Epidemiology of Bocavirus, Rhinovirus, Two Polyomaviruses and Four Coronaviruses in HIV-Infected and HIV-Uninfected South African Children

text: BACKGROUND: Advances in molecular diagnostics have implicated newly-discovered respiratory viruses in the pathogenesis of pneumonia. We aimed to determine the prevalence and clinical characteristics of human bocavirus (hBoV), human rhinovirus (hRV), polyomavirus-WU (WUPyV) and –KI (KIPyV) and human coronaviruses (CoV)-OC43, -NL63, -HKU1 and -229E among children hospitalized with lower respiratory tract infections (LRTI). METHODS: Multiplex real-time reverse-transcriptase polymerase chain reaction was undertaken on archived nasopharyngeal aspirates from HIV-infected and –uninfected children (<2 years age) hospitalized for LRTI, who had been previously investigated for respiratory syncytial virus, human metapneumovirus, parainfluenza I–III, adenovirus and influenza A/B. RESULTS: At least one of these viruses were identified in 274 (53.0%) of 517 and in 509 (54.0%) of 943 LRTI-episodes in HIV-infected and -uninfected children, respectively. Human rhinovirus was the most prevalent in HIV-infected (31.7%) and –uninfected children (32.0%), followed by CoV-OC43 (12.2%) and hBoV (9.5%) in HIV-infected; and by hBoV (13.3%) and WUPyV (11.9%) in HIV-uninfected children. Polyomavirus-KI (8.9% vs. 4.8%; p = 0.002) and CoV-OC43 (12.2% vs. 3.6%; p<0.001) were more prevalent in HIV-infected than –uninfected children. Combined with previously-tested viruses, respiratory viruses were identified in 60.9% of HIV-infected and 78.3% of HIV-uninfected children. The newly tested viruses were detected at high frequency in association with other respiratory viruses, including previously-investigated viruses (22.8% in HIV-infected and 28.5% in HIV–uninfected children). CONCLUSIONS: We established that combined with previously-investigated viruses, at least one respiratory virus was identified in the majority of HIV-infected and HIV-uninfected children hospitalized for LRTI. The high frequency of viral co-infections illustrates the complexities in attributing causality to specific viruses in the aetiology of LRTI and may indicate a synergetic role of viral co-infections in the pathogenesis of childhood LRTI.


title: The contagion effects of the COVID-19 pandemic: Evidence from Gold and Cryptocurrencies

text: Abstract At the beginning of the 2020 global COVID-2019 pandemic, Chinese financial markets acted as the epicentre of both physical and financial contagion. Our results indicate that a number of characteristics expected during a ”flight to safety” were present during the period analysed. The volatility relationship between the main Chinese stock markets and Bitcoin evolved significantly during this period of enormous financial stress. We provide a number of observations as to why this situation occurred. Such dynamic correlations during periods of stress present further evidence to cautiously support the validity of the development of this new financial product within mainstream portfolio design through the diversification benefits provided.


title: The workplace integration of veterans: Applying diversity and fit perspectives

text: Abstract Military veterans are a valuable part of the human capital resource pool. Nonetheless, veterans often struggle with their transition into civilian life and workplaces. This problem often limits the extent to which work organizations utilize their talents. Here, we briefly review relevant work from outside the management field and nascent work within the field to build a conceptual model for understanding the integration of veterans into the workplace. We do this by applying diversity and person-environment fit perspectives. A diversity standpoint helps us to understand veterans as a social group and their inclusion in the workplace, while the person-environment fit perspective helps us describe veterans’ compatibility with their work environments in terms of organizational demands and veterans’ needs. We intend for this conceptual model to guide future empirical research on veterans as human capital and their transition into civilian organizations as part of their societal reintegration, career development, and personal well-being.


title: MERS-CoV Infection in a Pregnant Woman in Korea

text: Middle East respiratory syndrome (MERS) is a lethal respiratory disease — caused by MERS-coronavirus (MERS-CoV) which was first identified in 2012. Especially, pregnant women can be expected as highly vulnerable candidates for this viral infection. In May 2015, this virus was spread in Korea and a pregnant woman was confirmed with positive result of MERS-CoV polymerase chain reaction (PCR). Her condition was improved only with conservative treatment. After a full recovery of MERS, the patient manifested abrupt vaginal bleeding with rupture of membrane. Under an impression of placenta abruption, an emergent cesarean section was performed. Our team performed many laboratory tests related to MERS-CoV and all results were negative. We report the first case of MERS-CoV infection during pregnancy occurred outside of the Middle East. Also, this case showed relatively benign maternal course which resulted in full recovery with subsequent healthy full-term delivery without MERS-CoV transmission.


title: Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3

text: Middle East respiratory syndrome coronavirus (MERS-CoV) infection has claimed hundreds of lives and has become a global threat since its emergence in Saudi Arabia in 2012. The ability of MERS-CoV to evade the host innate antiviral response may contribute to its severe pathogenesis. Many MERS-CoV-encoded proteins were identified to have interferon (IFN)-antagonizing properties, which correlates well with the reduced IFN levels observed in infected patients and ex vivo models. In this study, we fully characterized the IFN-antagonizing property of the MERS-CoV M protein. Expression of MERS-CoV M protein suppressed type I IFN expression in response to Sendai virus infection or poly(I:C) induction. This suppressive effect was found to be specific for the activation of IFN regulatory factor 3 (IRF3) but not nuclear factor-κB. MERS-CoV M protein interacted with TRAF3 and disrupted TRAF3–TBK1 association leading to reduced IRF3 activation. M proteins from MERS-CoV and SARS-CoV have three highly similar conserved N-terminal transmembrane domains and a C-terminal region. Using chimeric and truncation mutants, the N-terminal transmembrane domains of the MERS-CoV M protein were found to be sufficient for its inhibitory effect on IFN expression, whereas the C-terminal domain was unable to induce this suppression. Collectively, our findings suggest a common and conserved mechanism through which highly pathogenic MERS-CoV and SARS-CoV harness their M proteins to suppress type I IFN expression at the level of TBK1-dependent phosphorylation and activation of IRF3 resulting in evasion of the host innate antiviral response.


title: COVID-19 Cardiac Injury: Implications for Long-Term Surveillance and Outcomes in Survivors

text: Up to 20-30% of patients hospitalized with coronavirus disease (COVID-19) have evidence of myocardial involvement. Acute cardiac injury in patients hospitalized with COVID-19 is associated with higher morbidity and mortality. There are no data on how acute treatment for COVID-19 may affect convalescent phase or long-term cardiac recovery and function. Myocarditis from other viral pathogens can evolve into overt or subclinical myocardial dysfunction, and sudden death has been described in the convalescent phase of viral myocarditis. This raises concerns for patients recovering from COVID-19. Some patients will have subclinical and possibly overt cardiovascular abnormalities. Patients with ostensibly recovered cardiac function may still be at risk for cardiomyopathy and cardiac arrhythmias. Screening for residual cardiac involvement in the convalescent phase for patients recovered from COVID-19 associated cardiac injury is needed. The type of testing, and therapies for post COVID-19 myocardial dysfunction will need to be determined. Therefore, now is the time to plan for appropriate registries and clinical trials to properly assess these issues and prepare for long-term sequelae of “post-COVID-19 Cardiac Syndrome”


title: Pathogenesis of Murine Coronavirus in the Central Nervous System

text: Murine coronavirus (mouse hepatitis virus, MHV) is a collection of strains that induce disease in several organ systems of mice. Infection with neurotropic strains JHM and A59 causes acute encephalitis, and in survivors, chronic demyelination, the latter of which serves as an animal model for multiple sclerosis. The MHV receptor is a carcinoembryonic antigen-related cell adhesion molecule, CEACAM1a; paradoxically, CEACAM1a is poorly expressed in the central nervous system (CNS), leading to speculation of an additional receptor. Comparison of highly neurovirulent JHM isolates with less virulent variants and the weakly neurovirulent A59 strain, combined with the use of reverse genetics, has allowed mapping of pathogenic properties to individual viral genes. The spike protein, responsible for viral entry, is a major determinant of tropism and virulence. Other viral proteins, both structural and nonstructural, also contribute to pathogenesis in the CNS. Studies of host responses to MHV indicate that both innate and adaptive responses are crucial to antiviral defense. Type I interferon is essential to prevent very early mortality after infection. CD8 T cells, with the help of CD4 T cells, are crucial for viral clearance during acute disease and persist in the CNS during chronic disease. B cells are necessary to prevent reactivation of virus in the CNS following clearance of acute infection. Despite advances in understanding of coronavirus pathogenesis, questions remain regarding the mechanisms of viral entry and spread in cell types expressing low levels of receptor, as well as the unique interplay between virus and the host immune system during acute and chronic disease.


title: Isozyme characterization of cattle (Bos taurus) and American buffalo (Bison bison) cell cultures

text: Four Bovidae cell lines (BEK‐1, MDBK, Bu and EBTr) were characterized by means of enzymatic biochemical markers. Out of 15 enzymatic systems, 3 — adenosine dea‐minase [Ada), phosphoglucomutase (Pgm) and nucleoside phosphorylase (Np) —were found to be polymorphic and quite suitable for biochemical identification of each cell line. The Bu cell line has shown a Np phenotypic pattern which could be distinctive of the Bison bison species.


Vitamin D, virus etiology, and atopy in first‐time wheezing children in Finland


title: Protective Effects of Cell-Free Supernatant and Live Lactic Acid Bacteria Isolated from Thai Pigs Against a Pandemic Strain of Porcine Epidemic Diarrhea Virus

text: Porcine epidemic diarrhea virus (PEDV) is a coronavirus which causes severe diarrhea and fatal dehydration in piglets. In general, probiotic supplements could enhance recovery and protect piglets against enteric pathogens. Seven local lactic acid bacteria (LAB), (Ent. faecium 79N and 40N, Lact. plantarum 22F, 25F and 31F, Ped. acidilactici 72N and Ped. pentosaceus 77F) from pig feces were well-characterized as high potential probiotics. Cell-free supernatants (CFS) and live LAB were evaluated for antiviral activities by co-incubation on Vero cells and challenged with a pandemic strain of PEDV isolated from pigs in Thailand. Cell survival and viral inhibition were determined by cytopathic effect (CPE) reduction assay and confirmed by immunofluorescence. At 1:16, CFS dilution (pH 6.3–6.8) showed no cytotoxicity in Vero cells and was therefore used as the dilution for antiviral assays. The diluted CFS of all Lact. plantarum showed the antiviral effect against PEDV; however, the same antiviral effect could not be observed in Ent. faecium and Pediococcus strains. In competitive experiment, only live Lact. plantarum 25F and Ped. pentosaceus 77F showed CPE reduction in the viral infected cells to <50% observed field area. This study concluded that the CFS of all tested lactobacilli, and live Lact. plantarum (22F and 25F) and Pediococcus strains 72N and 77F could reduce infectivity of the pandemic strain of PEDV from pigs in Thailand on the target Vero cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12602-017-9281-y) contains supplementary material, which is available to authorized users.


title: Food Intake and Nutrition During Pregnancy, Lactation and Weaning in the Dam and Offspring

text: In mammalian species, the connection between reproduction and nutrition is undeniable and illustrated by numerous publications: its role concerning regulation of hormonal secretions, fertility, pregnancy outcome, lactation and neonatal development indeed retains the attention of the scientific community. The interest on the influence of nutrition in dog and cat reproductive physiology is growing. Awareness on the key aspects of feeding during critical periods like pregnancy, lactation and weaning is essential to optimize the reproductive performances in these species.


title: Adenovirus inactivation by in situ photocatalytically and photoelectrocatalytically generated halogen viricides

text: Abstract This study investigates and compares the virucidal performances of photocatalytic (PC) and photoelectrocatalytic (PEC) treatments in the presence and absence of halides, such as Br− and Cl−, under comparable experimental conditions. The results confirm that the PC virucidal efficiency can be enhanced in the presence of low halide concentrations (e.g., X=Br− or Cl−) and further enhanced by applying potential bias onto the photoanode in a PEC system. The PEC treatment in the presence of 1.0mM Br (PEC-Br) shows the highest virucidal efficiency, enabling complete inactivation of a ∼1000 TCID50 replication-deficient recombinant adenovirus (RDRADS) population within 31.7s. The superior virucidal performances of PEC-X treatments can be attributed to the increased production of active oxygen species and additional viricides resulting from the PEC halide oxidation, as well as prolonged lifetime of photoholes (h+ ) for direct inactivation. The findings of this work confirm that new forms of active species generated in situ via a PC or PEC process are effective for viruses.


title: Chapter 9 Edible Vaccines

text: Abstract Vaccines are considered primary tools for health intervention in both humans and animals. Vaccines can be used more widely, especially in developing countries, if their cost of production can be reduced and they can be preserved without refrigeration. In developing countries certain limitations, like vaccine affordability, the need for “cold chains” from the producer to the site of use of the vaccine, and the dependence on injection, are barriers to health care services. Plant-derived vaccines do not face such limitations. Research under way is dedicated to solving these limitations by finding ways to produce oral (edible) vaccines from transgenic plants. Plant-derived vaccines offer increased safety, envisage low-cost programs for mass vaccination, and propose a wider use of vaccination for veterinary use.


title: An observational study of febrile seizures: the importance of viral infection and immunization

text: BACKGROUND: Febrile seizures are common in young children. Annual peaks in incidence mirror increased respiratory virus activity during winter. Limited virological data are available using modern diagnostic techniques for children with febrile seizures. We aimed to determine the frequency of detection of specific viral pathogens in children with febrile seizures, to describe risk factors including recent vaccination and clinical features associated with specific etiologies. METHODS: An observational study was performed. Children aged 6 months to 5 years presenting to the Emergency Department of a tertiary children’s hospital in Western Australia with febrile seizures were enrolled between March 2012 and October 2013. Demographic, clinical data and vaccination history were collected, and virological testing was performed on per-nasal and per-rectal samples. RESULTS: One hundred fifty one patients (72 female; median age 1.7y; range 6 m-4y9m) were enrolled. Virological testing was completed for 143/151 (95%). At least one virus was detected in 102/143 patients (71%). The most commonly identified were rhinoviruses (31/143, 22%), adenovirus (30/151, 21%), enteroviruses, (28/143, 20%), influenza (19/143, 13%) and HHV6 (17/143, 12%). More than one virus was found in 48/143 (34%). No significant clinical differences were observed when children with a pathogen identified were compared with those with no pathogen detected. Febrile seizures occurred within 14 days of vaccine administration in 16/151 (11%). CONCLUSION: At least one virus was detected in over two thirds of cases tested (commonly picornaviruses, adenovirus and influenza). Viral co-infections were frequently identified. Febrile seizures occurred infrequently following immunization.


title: Predisposition or Protection? COVID-19 in a Patient on LVAD Support with HIV/AIDS

text: Abstract There is a desperate search to discover effective therapies against COVID-19. Patients with HIV/AIDS comprise a unique population whose clinical course may provide insights into the effects of ART on COVID-19. We describe the case of a patient with HIV/AIDS on LVAD support who was hospitalized and recovered from COVID-19.


The Federal Trade Commission’s response to the COVID-19 pandemic


title: Influenza and SARS-Coronavirus Activating Proteases TMPRSS2 and HAT Are Expressed at Multiple Sites in Human Respiratory and Gastrointestinal Tracts

text: The type II transmembrane serine proteases TMPRSS2 and HAT activate influenza viruses and the SARS-coronavirus (TMPRSS2) in cell culture and may play an important role in viral spread and pathogenesis in the infected host. However, it is at present largely unclear to what extent these proteases are expressed in viral target cells in human tissues. Here, we show that both HAT and TMPRSS2 are coexpressed with 2,6-linked sialic acids, the major receptor determinant of human influenza viruses, throughout the human respiratory tract. Similarly, coexpression of ACE2, the SARS-coronavirus receptor, and TMPRSS2 was frequently found in the upper and lower aerodigestive tract, with the exception of the vocal folds, epiglottis and trachea. Finally, activation of influenza virus was conserved between human, avian and porcine TMPRSS2, suggesting that this protease might activate influenza virus in reservoir-, intermediate- and human hosts. In sum, our results show that TMPRSS2 and HAT are expressed by important influenza and SARS-coronavirus target cells and could thus support viral spread in the human host.


title: Development and Evaluation of an Enterovirus D68 Real-Time Reverse Transcriptase PCR Assay

text: We have developed and evaluated a real-time reverse transcriptase PCR (RT-PCR) assay for the detection of human enterovirus D68 (EV-D68) in clinical specimens. This assay was developed in response to the unprecedented 2014 nationwide EV-D68 outbreak in the United States associated with severe respiratory illness. As part of our evaluation of the outbreak, we sequenced and published the genome sequence of the EV-D68 virus circulating in St. Louis, MO. This sequence, along with other GenBank sequences from past EV-D68 occurrences, was used to computationally select a region of EV-D68 appropriate for targeting in a strain-specific RT-PCR assay. The RT-PCR assay amplifies a segment of the VP1 gene, with an analytic limit of detection of 4 copies per reaction, and it was more sensitive than commercially available assays that detect enteroviruses and rhinoviruses without distinguishing between the two, including three multiplex respiratory panels approved for clinical use by the FDA. The assay did not detect any other enteroviruses or rhinoviruses tested and did detect divergent strains of EV-D68, including the first EV-D68 strain (Fermon) identified in California in 1962. This assay should be useful for identifying and studying current and future outbreaks of EV-D68 viruses.


title: Morphology Remodeling and Selective Autophagy of Intracellular Organelles during Viral Infections

text: Viruses have evolved different strategies to hijack subcellular organelles during their life cycle to produce robust infectious progeny. Successful viral reproduction requires the precise assembly of progeny virions from viral genomes, structural proteins, and membrane components. Such spatial and temporal separation of assembly reactions depends on accurate coordination among intracellular compartmentalization in multiple organelles. Here, we overview the rearrangement and morphology remodeling of virus-triggered intracellular organelles. Focus is given to the quality control of intracellular organelles, the hijacking of the modified organelle membranes by viruses, morphology remodeling for viral replication, and degradation of intracellular organelles by virus-triggered selective autophagy. Understanding the functional reprogram and morphological remodeling in the virus-organelle interplay can provide new insights into the development of broad-spectrum antiviral strategies.


Covid-19 management with Inflammation Resolving Mediators? Perspectives and Potential


title: Middle East Respiratory Syndrome Coronavirus in Bats, Saudi Arabia

text: The source of human infection with Middle East respiratory syndrome coronavirus remains unknown. Molecular investigation indicated that bats in Saudi Arabia are infected with several alphacoronaviruses and betacoronaviruses. Virus from 1 bat showed 100% nucleotide identity to virus from the human index case-patient. Bats might play a role in human infection.


Comment on: “Acral findings during the COVID-19 outbreak: Chilblain-like lesions should be preferred to acro-ischemic lesions”


title: Job loss at home: children’s school performance during the Great Recession

text: This paper studies the intergenerational impact of parental job loss on school performance during the Great Recession in Spain. Collecting data through parental surveys in a school in the province of Barcelona, I obtain information about the parental labour market status before and after the Great Recession. I can then link this information to repeated information on their children’s school performance, for a sample of over 300 students. Using individual fixed effects, the estimates show a negative and significant decrease on average grades of around 15% of a standard deviation after father’s job loss. These results are mainly driven by those students whose fathers suffer long unemployment spells. In contrast, the average impact of mother’s job loss on school performance is close to zero and non-significant. The decline in school performance during the Great Recession after father’s job loss, particularly among disadvantaged students, could result in detrimental long-term effects that might contribute to increased inequality. This could be an important and underemphasised cost of recessions.


title: RNA interference: An emerging generation of biologicals

text: RNA interference (RNAi) is a mechanism displayed by most eukaryotic cells to rid themselves of foreign double‐stranded RNA molecules. RNAi has now been demonstrated to function in mammalian cells to alter gene expression, and has been used as a means for genetic discovery as well as a possible strategy for genetic correction. RNAi was first described in animal cells by Fire and colleagues in the nematode, Caenorhabditis elegans. Knowledge of RNAi mechanism in mammalian cell in 2001 brought a storm in the field of drug discovery. During the past few years scientists all over the world are focusing on exploiting the therapeutic potential of RNAi for identifying a new class of therapeutics. The applications of RNAi in medicine are unlimited because all cells possess RNAi machinery and hence all genes can be potential targets for therapy. RNAi can be developed as an endogenous host defense mechanism against many infections and diseases. Several studies have demonstrated therapeutic benefits of small interfering RNAs and micro RNAs in animal models. This has led to the rapid advancement of the technique from research discovery to clinical trials.


title: Metabolite identification of arbidol in human urine by the study of CID fragmentation pathways using HPLC coupled with ion trap mass spectrometry

text: The metabolism of arbidol in humans was studied using liquid chromatography‐electrospray ionization (ESI) ion trap mass spectrometry (ITMS) after an oral dose of 300‐mg arbidol. A total of 17 metabolites were identified including the glucuronide arbidol and the glucuronide sulfinylarbidol as the major metabolites. Arbidol and its metabolites have some common fragmentation patterns as a result of a homolytic bond cleavage. This cleavage will form odd‐electron ions with the loss of a radical. The arbidol fragmentation sequence is first to lose dimethylamine (45 Da), followed by the loss of acetaldehyde (44 Da), and then the phenylthio radical (109 Da). This fragmentation sequence is also observed from N‐demethylarbidol, sulfonylarbidol, and N‐demethylsulfonylarbidol. However, for sulfinylarbidol and N‐demethylsulfinylarbidol, the fragmentation sequence is reversed so that the phenylsulfiny radical (125 Da) was lost first, followed by the loss of dimethylamine (45 Da), and then acetaldehyde (44 Da). The exact masses for arbidol and sulfinylarbidol fragment ions were determined by a quadrupole/time‐of‐flight mass spectrometer (Q‐TOF MS). The phase II metabolites, such as sulfate and glucuronide conjugates of arbidol, N‐demethylarbidol, sulfonylarbidol, and N‐demethylsulfonylarbidol were identified by observing the neutral loss of 80 Da (SO(3)) or 176 Da (glucuronic acid) from the MS(2) spectra. The sulfate and glucuronide conjugates such as sulfinylarbidol and N‐demethylsulfinylarbidol had an unusual fragmentation pattern, in which the phenylsulfinyl radical (125 Da) was lost before the loss of SO(3) group (80 Da) or glucuronic acid (176 Da) occurred. Copyright © 2008 John Wiley & Sons, Ltd.


title: Clinical characteristics and outcomes of human rhinovirus positivity in hospitalized children

text: BACKGROUND: The clinical relevance of positive human rhinovirus (HRV) in hospitalized patients is unclear. Our objective was to describe the clinical characteristics and outcomes of HRV positivity in a heterogeneous population of hospitalized children, compared to those positive for another respiratory virus and those where no respiratory virus was detected. METHODS: A retrospective case–control study of children hospitalized between January 2014 to April 2015 who had a respiratory viral specimen collected. Clinical and laboratory data were collected, and baseline characteristics and clinical variables were compared. RESULTS: During the study period, there were 671 specimens obtained from 577 patients that were processed for the respiratory viral polymerase chain reaction assay, of which 198 were positive for HRV, 167 positive for another respiratory virus, and 306 where no respiratory virus was detected. A history of asthma was significantly associated with HRV-positive patients (odds ratio [OR] 3.71; P < 0.001). On multivariate analysis, HRV-positive patients had a higher requirement for mechanical ventilation (OR 1.44), lower rates of readmission (OR 0.53), and lower mortality (OR 0.35) compared to patients with no respiratory virus isolated; however, none were statistically significant. HRV-positive patients did have a significantly shorter length of stay (LOS) compared with patients with no respiratory virus isolated (difference–0.35; P = 0.001). Similar outcomes were seen in patients positive for other respiratory viruses. CONCLUSIONS: HRV-positive hospitalized pediatric patients with a heterogeneous set of clinical diagnoses had higher association with asthma compared to patients who had another, or no, respiratory virus isolated. HRV-positive patients had shorter LOS compared to patients who had no respiratory viruses isolated. These findings suggest that HRV positivity in hospitalized pediatric patients may not lead to adverse clinical outcomes, although asthma is a risk factor regardless of clinical comorbidities and diagnoses. Further research is warranted to understand the predisposition of asthma to HRV positivity.


title: Estimation of the secondary attack rate of COVID-19 using proportional meta-analysis of nationwide contact tracing data in Taiwan

text: Abstract Crude secondary attack rate (SAR) of COVID-19 in Taiwan was 0.84% using nationwide contact-tracing data till April 8, 2020. The random-effect Bayesian metaanalysis yielded 95% credible intervals of 0.42%-1.69% and 0.08%-8.32%, respectively, for estimated SAR pooling from 15 case series and for predicted SAR in the future if pandemic continues.


title: A Simple Method for Detection of a Novel Coronavirus (SARS‐CoV‐2) using One‐step RT‐PCR followed by Restriction Fragment Length Polymorphism

text: BACKGROUND: A novel coronavirus associated with acute respiratory disease (named SARS‐CoV‐2) is recently identified in Wuhan city, China, spread rapidly worldwide. An early identification of this novel coronavirus by molecular tools is critical for surveillance and control of the epidemic outbreak. OBJECTIVES: We aimed to establish a simple method for detection of SARS‐CoV‐2 in differentiating with SARS‐CoV. STUDY DESIGN: Primers of our in‐house RT‐PCR assays were designed to target conserved regions of the RdRP gene and E gene, selected restriction enzymes EcoRI, Tsp45I and AluI to distinguish between SARS‐CoV‐2 and SARS‐CoV. RESULTS AND DISCUSSIONS: In this report, a 396 bp fragment of the RdRp gene and 345 bp fragment of the E gene were amplified by one‐step RT‐PCR. Enzyme Tsp45I cuts the RdRP amplified product of SARS‐CoV‐2 generating 3 fragments of 45, 154 and 197 bp, but it did not cut the amplicon of SARS‐CoV. In contrast, the amplified product of SARS‐CoV was digested with EcoRI producing 2 fragments of 76 and 320 bp, whereas, the amplicon of SARS‐CoV‐2 was undigested by Tsp45I help to distinguish clearly SARS‐CoV‐2 from SARS‐CoV on gel electrophoresis. In addition, AluI cut the amplicon of the E gene of SARS‐CoV‐2 generating 2 fragments of 248 and 97 bp without cutting to SARS‐CoV. Accuracy of assay was confirmed by sequencing and phylogenetic analysis. When evaluated on clinical samples showed a high sensitivity of 95%, specificity of our assay was 100% and clinical performance for detection of SARS‐CoV‐2 in comparison with other reference assays. In conclusion, the present study, we successfully developed a simple method for molecular detection of SARS‐CoV‐2 in differentiating with SARS‐CoV. This article is protected by copyright. All rights reserved.


title: High isolation rate of adenovirus serotype 7 from South Korean military recruits with mild acute respiratory disease

text: Adenovirus is a major cause of acute respiratory disease (ARD) in military recruits. When South Korean military recruits with ARD were surveyed, adenovirus was identified in 122 (61.0%) of the 200 recruits studied. Moreover, all cases of ARD involving adenovirus were caused by serotype 7.


National action plan to eliminate central line-associated bloodstream infections in Taiwan


title: Human bocavirus (HBoV) in children with respiratory tract infection by enzyme linked immunosorbent assay (ELISA) and qualitative polymerase chain reaction (PCR)

text: BACKGROUND: Human bocavirus (HBoV) is a recently discovered parvovirus associated with mild to severe lower respiratory tract infections in children, the aim of the work was determination of human bocavirus in nasopharyngeal aspirate (NPA) of infants by qualitative PCR and determination of acute human bocavirus infection by estimation of immunoglobulin M (IgM) antibodies in serum by enzyme linked immunosorbent assay. RESULTS: Twenty two (22%) out of the 100 NPA specimens of the patients with respiratory manifestations were positive for HBoV by qualitative PCR, while ELISA revealed positive HBoV IgM antibodies in 18 (18%) patients who were also positive by PCR. Non of the controls were positive by both techniques. The correlation study between ELISA and PCR revealed high significant association, (p < 0.001, X(2 )= 36 and agreement = 96%). Also PCR detected 4 (18.1%) NPA samples as HBoV positive cases among the patients that were not identified by ELISA. This could be due to high sensitivity and efficacy of PCR. ELISA being less sensitive than RT-PCR, sensitivity was (81.8% vs 100%), the efficacy was 97.7% in ELISA versus 99.7% for RT-PCR. CONCLUSION: HBoV infections could be diagnosed in NPA of children by conventional PCR as a rapid and sensitive technique. While ELISA was a reliable serologic analysis for diagnosis of acute HBoV infection by estimation IgM antibodies in serum.


title: Chapter 1 Introduction to virus origins and their role in biological evolution

text: Abstract Viruses are diverse parasites of cells and extremely abundant. They might have arisen during an early phase of the evolution of life on Earth dominated by ribonucleic acid or RNA-like macromolecules, or when a cellular world was already well established. The theories of the origin of life on Earth shed light on the possible origin of primitive viruses or virus-like genetic elements in our biosphere. Some features of present-day viruses, notably error-prone replication, might be a consequence of the selective forces that mediated their ancestral origin. Two views on the role of viruses in our biosphere predominate; viruses considered as opportunistic, selfish elements, and viruses considered as active participants in the construction of the cellular world via the lateral transfer of genes. These two models have a bearing on viruses being considered predominantly as disease agents or predominantly as cooperators in the shaping of differentiated cellular organisms.


title: Internet-based self-help intervention aimed at increasing social self-efficacy among internal migrants in Poland: Study protocol for a randomized controlled trial

text: Abstract Background Migration is a challenging life transition that may be a source of various problems related to well-being and mental health. However, the psychological adaptation of migrants may be potentially facilitated by social self-efficacy—the beliefs in one's ability to initiate and maintain interpersonal relationships. Previous research suggests that social self-efficacy is positively related to adjustment and negatively related to loneliness, depression, and psychological distress. Research also confirms that self-efficacy beliefs can be effectively enhanced using Internet-based interventions. These results served as a background for creating the New in Town, a self-help Internet-based intervention for internal migrants in Poland that aims at increasing social self-efficacy. Exercises in the intervention are based on the principles of Cognitive Behavioral Therapy and relate to sources of self-efficacy beliefs: mastery experiences, vicarious experiences, verbal persuasions, and emotional and physiological states. Users complete increasingly challenging tasks that encourage them to interact with their environment. The aim of this trial was to investigate the efficacy of the New in Town intervention. Methods The efficacy of the New in Town intervention will be tested in a two-arm randomized controlled trial with a waitlist control group. Social self-efficacy will be the primary outcome. Secondary outcomes will include loneliness, perceived social support, and satisfaction with life. Additionally, we will measure user experience among participants allocated to the experimental group. We aim to recruit a total of N = 280 participants aged at least 18 years who have changed their place of residence in the last 6 months and have an Internet connection. Participants will be assessed at baseline, 3-week post-test, and 8-week follow-up. Discussion The trial will provide insights into the efficacy of Internet-based self-help interventions in increasing social self-efficacy. Given that the intervention works, New in Town could provide an easily accessible support option for internal migrants in Poland. Trial registration The trial was registered with ClinicalTrials.gov (identifier: NCT04088487) on 11th September 2019.


title: The incidence of the novel coronavirus SARS-CoV-2 among asymptomatic patients: a systematic review

text: BACKGROUND: the recent outbreak of the coronavirus disease 2019 (COVID‐19) has quickly spread globally since its discovery in Wuhan, China, in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, and clinical treatment is urgently needed to win the battle against COVID-19. Recently, numerous studies reported the incidence of SARS-CoV-2 in asymptomatic patients. Yet, the incidence and viral transmission from the asymptomatic cases are not apparent yet. AIM: this study aims to systematically review the published literature on SARS-CoV-2 in the asymptomatic patients to estimate the incidence of COVID-19 among asymptomatic cases, as well as describe its epidemiological and clinical significance. METHOD: the literature was searched through four scientific databases: PubMed, Web of Science, Scopus, and Science Direct. RESULTS: a total of 63 studies satisfied the inclusion criteria where the majority of the reported studies were from China. However, there was a lack of SARS-CoV-2 epidemiological studies from several countries worldwide, tracing the actual incidence of COVID-19, especially in asymptomatic patients. Studies with a large sample size (n>1000) estimated that percentage of people contracting SARS-CoV-2 and are likely to be asymptomatic ranges from 1.2-12.9%. However, the other studies with a smaller sample size reported a much higher incidence and indicated that up to 87.9% of COVID-19 infected individuals could be asymptomatic. Most of these studies indicated that asymptopatics are a potential source of infection to the community. CONCLUSION: this review highlighted the need for more robust and well-designed studies to better estimate COVID-19 incidence among asymptomatic patients worldwide. The early identification of the asymptomatic cases, as well as monitoring and tracing close contact, could help in mitigating the spread of COVID-19.


title: Anti-inflammatory effects of Lactococcus lactis NCDO 2118 during the remission period of chemically induced colitis

text: BACKGROUND: Many probiotic bacteria have been described as promising tools for the treatment and prevention of inflammatory bowel diseases (IBDs). Most of these bacteria are lactic acid bacteria, which are part of the healthy human microbiota. However, little is known about the effects of transient bacteria present in normal diets, including Lactococcus lactis. METHODS: In the present study, we analysed the immunomodulatory effects of three L. lactis strains in vitro using intestinal epithelial cells. L. lactis NCDO 2118 was administered for 4 days to C57BL/6 mice during the remission period of colitis induced by dextran sodium sulphate (DSS). RESULTS: Only one strain, L. lactis NCDO 2118, was able to reduce IL-1β-induced IL-8 secretion in Caco-2 cells, suggesting a potential anti-inflammatory effect. Oral treatment using L. lactis NCDO 2118 resulted in a milder form of recurrent colitis than that observed in control diseased mice. This protective effect was not attributable to changes in secretory IgA (sIgA); however, NCDO 2118 administration was associated with an early increase in IL-6 production and sustained IL-10 production in colonic tissue. Mice fed L. lactis NCDO 2118 had an increased number of regulatory CD4(+) T cells (Tregs) bearing surface TGF-β in its latent form (Latency-associated peptide-LAP) in the mesenteric lymph nodes and spleen. CONCLUSIONS: Here, we identified a new probiotic strain with a potential role in the treatment of IBD, and we elucidated some of the mechanisms underlying its anti-inflammatory effect.


title: Development of a Social Contact Survey Instrument Relevant to the Spread of Infectious Disease and Its Application in a Pilot Study Among Korean Adults

text: OBJECTIVES: This study aimed to develop a valid social contact survey instrument and to verify its feasibility for use among Korean adults. METHODS: The Delphi technique was used to develop an instrument to assess social contacts, which was then applied in a cross-sectional pilot study. A panel of 15 medical professionals reviewed the feasibility and validity of each item. The minimum content validity ratio was 0.49. Thirty participants used the developed measure to record contacts during a 24-hour period. RESULTS: After a systematic review, the survey instrument (parts I and II) was developed. Part I assessed social contact patterns over a 24-hour period, and part II assessed perceptions of contacts in daily life and preventive behaviors (hand hygiene and coughing etiquette). High validity and feasibility were found. In the pilot study, the 30 participants had a combined total of 198 contacts (mean, 6.6 daily contacts per person). The participants’ age (p=0.012), occupation (p<0.001), household size (p<0.001), education (p<0.001), personal income (p=0.003), and household income (p<0.001) were significantly associated with the number of contacts. Contacts at home, of long duration, and of daily frequency were relatively likely to be physical. Assortative mixing was observed between individuals in their 20s and 50s. Contact type differed by location, duration, and frequency (p<0.001). CONCLUSIONS: The developed social contact survey instrument demonstrated high validity and feasibility, suggesting that it is viable for implementation.


title: Manipulation of the Coronavirus Genome Using Targeted RNA Recombination with Interspecies Chimeric Coronaviruses

text: Targeted RNA recombination has proven to be a powerful tool for the genetic engineering of the coronavirus genome, particularly in its 3′ part. Here we describe procedures for the generation of recombinant and mutant mouse hepatitis virus and feline infectious peritonitis virus. Key to the two-step method is the efficient selection of recombinant viruses based on host cell switching. The first step consists of the preparation—using this selection principle—of an interspecies chimeric coronavirus. In this virus the ectodomain of the spike glycoprotein is replaced by that of a coronavirus with a different species tropism. In the second step this chimeric virus is used as the recipient for recombination with synthetic donor RNA carrying the original spike gene. Recombinant viruses are then isolated on the basis of their regained natural (e.g., murine or feline) cell tropism. Additional mutations created in the donor RNA can be co-incorporated into the recombinant virus in order to generate mutant viruses.


title: Targeted Immunosuppression Distinguishes COVID-19 from Influenza in Moderate and Severe Disease

text: Coronavirus disease 2019 (COVID-19) is characterized by a high incidence of acute respiratory failure. The underlying immunopathology of that failure and how it compares to other causes of severe respiratory distress, such as influenza virus infection, are not fully understood. Here we addressed this by developing a prospective observational cohort of COVID-19 and influenza subjects with varying degrees of disease severity and assessing the quality and magnitude of their immune responses at the cellular and protein level. Additionally, we performed single-cell RNA transcriptional profiling of peripheral blood mononuclear cells from select subjects. The cohort consists of 79 COVID-19 subjects, 26 influenza subjects, and 15 control subjects, including 35 COVID-19 and 7 influenza subjects with acute respiratory failure. While COVID-19 subjects exhibited largely equivalent or greater activated lymphocyte counts compared to influenza subjects, they had fewer monocytes and lower surface HLA-class II expression on monocytes compared to influenza subjects and controls. At least two distinct immune profiles were observed by cytokine levels in severe COVID-19 patients: 3 of 71 patients were characterized by extreme inflammation, with greater than or equal to ~50% of the 35 cytokines measured greater than 2 standard deviations from the mean level of other severe patients (both influenza and COVID-19); the other immune profile, which characterized 68 of 71 subjects, had a mixed inflammatory signature, where 28 of 35 cytokines in COVID-19 patients had lower mean cytokine levels, though not all were statistically significant. Only 2 cytokines were higher in COVID-19 subjects compared to influenza subjects (IL-6 and IL-8). Influenza and COVID-19 patients could be distinguished statistically based on cytokine module expression, particularly after controlling for the significant effects of age on cytokine expression, but again with lower levels of most cytokines in COVID-19 subjects. Further, high circulating levels of IL-1RA and IL-6 were associated with increased odds of intubation in the combined influenza and COVID-19 cohort [OR = 3.93 and 4.30, respectively] as well as among only COVID-19 patients. Single cell transcriptional profiling of COVID-19 and influenza subjects with respiratory failure identified profound suppression in type I and type II interferon signaling in COVID-19 patients across multiple clusters. In contrast, COVID-19 cell clusters were enriched for alterations in metabolic, stress, and apoptotic pathways. These alterations were consistent with an increased glucocorticoid response in COVID-19 patients compared to influenza. When considered across the spectrum of innate and adaptive immune profiles, the immune pathologies underlying severe influenza and COVID-19 are substantially distinct. The majority of COVID-19 patients with acute respiratory failure do not have a cytokine storm phenotype but instead exhibit profound type I and type II IFN immunosuppression when compared to patients with acute influenza. Upregulation of a small number of inflammatory mediators, including IL-6, predicts acute respiratory failure in both COVID-19 and influenza patients.


title: Dynamic changes of peripheral blood lymphocytes subsets in adult patients with COVID-19

text: Abstract Introduction Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been widely spread. We aim to investigate the dynamic changes of peripheral blood lymphocytes subsets in adult patients with COVID-19. Methods Electronic medical records including demographics, clinical manifestation, comorbidities, laboratory data, and radiological materials of 435 hospitalized COVID-19 patients, with confirmed result of SARS-CoV-2 viral infection, were extracted and retrospectively analyzed. The counts of lymphocyte subsets at each week after the onset of the illness were compared with other weeks of illness and with those from normal individuals. Results The various lymphocyte subsets (CD3 +, CD4 +, CD8 +, CD19 +and CD16/56 +) were below the normal ranges at the first week after the onset of the illness, reaching a nadir during the second week, which increased gradually in the third week and returned to normal levels in the fifth week, but was still lower than the healthy controls. The CD3+, CD4+ and CD8+ counts were significantly lower in those with severe disease compared to those with non-severe disease, and in those patients that died compared to those who recovered. Discussion our research indicates that the levels of peripheral blood lymphocyte subsets (CD3 +, CD4 +, and CD8 +) are associated with disease progression, severity, and prognosis in patients with COVID-19. Dynamic monitoring of human immune function is one of the indicators for evaluating the severity and prognosis of COVID-19 patients, and it is helpful to formulate appropriate treatment strategies.


title: The impact of different COVID-19 containment measures on electricity consumption in Europe

text: As of March 13, 2020, the director general of the World Health Organization (WHO) considered Europe as the centre of the global COVID-19 outbreak. All countries within Europe had a confirmed case of COVID-19 by March 17. In response to the pandemic, different European countries took different approaches. This paper compares the impact of different containment measures taken by European countries in response to COVID-19 on their electricity consumption profiles. The comparisons are made for Spain, Italy, Belgium and the UK as countries with severe restrictions, and for the Netherlands and Sweden as countries with less restrictive measures. The results show that the consumption profiles reflect the difference in peoples’ activities in different countries using various measures.


title: What has COVID‐19 taken from us and brought instead?

text: The outbreak of the novel corona virus had dramatic impact throughout the World. It was completely unexpected for most of us and we were not prepared at all to change our daily routines. When the first cases of deaths due to the novel corona virus were announced, the first reaction was an acute interest followed by some degree of ignorance and many people thought that the situation was being exaggerated. In a very short time, the novel corona virus became extremely popular in the media and sat right at the centre of attraction.


title: Engineered hepatitis B virus surface antigen L protein particles for in vivo active targeting of splenic dendritic cells

text: Dendritic cells (DCs) are key regulators of adaptive T-cell responses. By capturing exogenous antigens and presenting antigen-derived peptides via major histocompatibility complex molecules to naïve T cells, DCs induce antigen-specific immune responses in vivo. In order to induce effective host immune responses, active delivery of exogenous antigens to DCs is considered important for future vaccine development. We recently generated bionanocapsules (BNCs) consisting of hepatitis B virus surface antigens that mediate stringent in vivo cell targeting and efficient endosomal escape, and after the fusion with liposomes (LP) containing therapeutic materials, the BNC-LP complexes deliver them to human liver-derived tissues in vivo. BNCs were further modified to present the immunoglobulin G (IgG) Fc-interacting domain (Z domain) derived from Staphylococcus aureus protein A in tandem. When mixed with IgGs, modified BNCs (ZZ-BNCs) displayed the IgG Fv regions outwardly for efficient binding to antigens in an oriented-immobilization manner. Due to the affinity of the displayed IgGs, the IgG-ZZ-BNC complexes accumulated in specific cells and tissues in vitro and in vivo. After mixing ZZ-BNCs with antibodies against DCs, we used immunocytochemistry to examine which antibodies delivered ZZ-BNCs to mouse splenic DCs following intravenous injection of the ZZ-BNCs. ZZ-BNCs displaying anti-CD11c monoclonal antibodies (α-CD11c-ZZ-BNCs) were found to accumulate with approximately 62% of splenic DCs, and reside within some of them. After the fusion with liposomes containing antigens, the α-CD11c-ZZ-BNCs could elicit the respective antibodies more efficiently than other nontargeting control vaccines, suggesting that this DC-specific nanocarrier is promising for future vaccines.


title: Oxalate contents of commonly used Chinese medicinal herbs

text: Abstract Objective To assess the total and soluble oxalate contents of commonly used Chinese medicinal herbs. Methods Twenty-two Chinese medicinal herbs were extracted in both acid and water prior to determination of total and soluble oxalate, respectively. Oxalate was assayed in herbal extracts using a well-established enzymatic procedure. Results Among the 22 medicinal herbs, there was significant variation in oxalate content; Houttuynia cordata contained the highest amount of soluble oxalate (2146 mg/100 g) and Selaginella doederleinii contained the lowest amount (71 mg/100 g). Conclusion The results indicated that different Chinese medicinal herbs, even from the same family, contain significantly different amounts of oxalate. In susceptible individuals, the use of medicinal herbs with the highest oxalate contents could increase risk of kidney stone formation.


title: Regulation of cell death during infection by the severe acute respiratory syndrome coronavirus and other coronaviruses

text: Both apoptosis and necrosis have been observed in cells infected by various coronaviruses, suggesting that the regulation of cell death is important for viral replication and/or pathogenesis. Expeditious research on the severe acute respiratory syndrome (SARS) coronavirus, one of the latest discovered coronaviruses that infect humans, has provided valuable insights into the molecular aspects of cell‐death regulation during infection. Apoptosis was observed in vitro, while both apoptosis and necrosis were observed in tissues obtained from SARS patients. Viral proteins that can regulate apoptosis have been identified, and many of these also have the abilities to interfere with cellular functions. Occurrence of cell death in host cells during infection by other coronaviruses, such as the mouse hepatitis virus and transmissible porcine gastroenteritis virus, has also being extensively studied. The diverse cellular responses to infection revealed the complex manner by which coronaviruses affect cellular homeostasis and modulate cell death. As a result of the complex interplay between virus and host, infection of different cell types by the same virus does not necessarily activate the same cell‐death pathway. Continuing research will lead to a better understanding of the regulation of cell death during viral infection and the identification of novel antiviral targets.


title: Recombinant vesicular stomatitis virus as an HIV-1 vaccine vector

text: Recombinant vesicular stomatitis virus (rVSV) is currently under evaluation as a human immunodeficiency virus (HIV)-1 vaccine vector. The most compelling reasons to develop rVSV as a vaccine vector include a very low seroprevalence in humans, the ability to infect and robustly express foreign antigens in a broad range of cells, and vigorous growth in continuous cell lines used for vaccine manufacture. Numerous preclinical studies with rVSV vectors expressing antigens from a variety of human pathogens have demonstrated the versatility, flexibility, and potential efficacy of the rVSV vaccine platform. When administered to nonhuman primates (NHPs), rVSV vectors expressing HIV-1 Gag and Env elicited robust HIV-1-specific cellular and humoral immune responses, and animals immunized with rVSV vectors expressing simian immunodeficiency virus (SIV) Gag and HIV Env were protected from AIDS after challenge with a pathogenic SIV/HIV recombinant. However, results from an exploratory neurovirulence study in NHPs indicated that these prototypic rVSV vectors might not be adequately attenuated for widespread use in human populations. To address this safety concern, a variety of different attenuation strategies, designed to produce a range of further attenuated rVSV vectors, are currently under investigation. Additional modifications of further attenuated rVSV vectors to upregulate expression of HIV-1 antigens and coexpress molecular adjuvants are also being developed in an effort to balance immunogenicity and attenuation.


title: Virus émergents ou menaces à répétition

text: Résumé Les virus émergents ont défrayé la chronique durant les années 2003 et 2004. À cette occasion sont réapparues les peurs antiques concernant l’apparition d’un agent infectieux hautement pathogène, pouvant provoquer des épidémies associées à une mortalité élevée. Ces phénomènes sont clairement des menaces à répétition. L’analyse des mécanismes ayant permis l’apparition de ces virus montre que pour chaque virus émergent décrit, il ne s’agit en aucun cas de phénomènes purement aléatoires, mais bien de l’accumulation de facteurs qui permettent à ces agents infectieux de diffuser de l’animal vers l’homme. Différents modes d’infection existent, soit par transmission directe, soit par l’intermédiaire des vecteurs (moustiques, tiques ou autres animaux). La conjonction de facteurs écologiques, économiques et épidémiologiques font que ces épidémies naissent et éventuellement diffusent. Grâce au développement des réseaux de surveillance et à l’amélioration des techniques diagnostiques, les virus responsables de ces épidémies sont mieux identifiés. Les expériences récentes du SRAS et de la grippe aviaire en sont les meilleurs exemples. Abstract Emergent viruses have attracted attention during years 2003 and 2004. Ancient fears have reappeared regarding pathogenic agents, capable to result in epidemics with high mortality rates. Such events constitute really repeated threats. The analysis of mechanisms permitting emergence of these viruses has shown that they are not random phenomenons, but they result from accumulated factors leading to transmission from animals to men. Several modes of transmission of infection include: either direct transmission, or by intermediate vectors (mosquitoes, ticks and other (mammals) animals). Convergence of ecologic, economic and epidemiologic factors confer to the epidemics potential ability do spread widely. With the development of surveillance networks and improvement in diagnostic technologies, these “new” viruses are better identified. Recent occurrence of SARS and of the avian influenza are best examples of such experiences.


Les phases de l’épidémie du COVID-19: critères, défis et enjeux pour le future*


title: Clinical development of monoclonal antibody-based drugs in HIV and HCV diseases

text: Today there are many licensed antiviral drugs, but the emergence of drug resistant strains sometimes invalidates the effects of the current therapies used in the treatment of infectious diseases. Compared to conventional antiviral drugs, monoclonal antibodies (mAbs) used as pharmacological molecules have particular physical characteristics and modes of action, and, therefore, they should be considered as a distinct therapeutic class. Despite being historically validated, antibodies may represent a novel tool for combatting infectious diseases. The current high cost of mAbs' production, storage and administration (by injection only) and the consequent obstacles to development are outweighed by mAbs' clinical advantages. These are related to a low toxicity combined with high specificity and versatility, which allows a specific antibody to mediate various biological effects, ranging from the virus neutralization mechanisms to the modulation of immune responses. This review briefly summarizes the recent technological advances in the field of immunoglobulin research, and the current status of mAb-based drugs in clinical trials for HIV and HCV diseases. For each clinical trial the available data are reported and the emerging conceptual problems of the employed mAbs are highlighted. This overview helps to give a clear picture of the efficacy and challenges of the mAbs in the field of these two infectious diseases which have such a global impact.


title: Trends in parameterization, economics and host behaviour in influenza pandemic modelling: a review and reporting protocol

text: BACKGROUND: The volume of influenza pandemic modelling studies has increased dramatically in the last decade. Many models incorporate now sophisticated parameterization and validation techniques, economic analyses and the behaviour of individuals. METHODS: We reviewed trends in these aspects in models for influenza pandemic preparedness that aimed to generate policy insights for epidemic management and were published from 2000 to September 2011, i.e. before and after the 2009 pandemic. RESULTS: We find that many influenza pandemics models rely on parameters from previous modelling studies, models are rarely validated using observed data and are seldom applied to low-income countries. Mechanisms for international data sharing would be necessary to facilitate a wider adoption of model validation. The variety of modelling decisions makes it difficult to compare and evaluate models systematically. CONCLUSIONS: We propose a model Characteristics, Construction, Parameterization and Validation aspects protocol (CCPV protocol) to contribute to the systematisation of the reporting of models with an emphasis on the incorporation of economic aspects and host behaviour. Model reporting, as already exists in many other fields of modelling, would increase confidence in model results, and transparency in their assessment and comparison.


title: Antibody responses against SARS‐CoV‐2 in COVID‐19 patients

text: The emerging coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has become a global pandemic, and brings formidable challenges to public health, society and the economy worldwide. Currently, the antibody responses against SARS‐CoV‐2 remains largely unknown. We herein estimated the longevity of specific antibodies against SARS‐CoV‐2, and reported that antibodies waned over substantially in COVID‐19 patients after recovery. This article is protected by copyright. All rights reserved.


title: Hyperinflammation with Covid-19: the key to patient deterioration?()()

text: BACKGROUND: The potential risk of cytokine storm in patients with coronavirus disease 2019 (Covid-19) has been described(1); we write to share our experience treating a 17-year-old male with haemophagocytic lymphohistiocytosis (HLH) secondary to Covid-19 infection. CASE REPORT: This patient presented with cough, sore throat, anorexia and pyrexia. On examination, he had gross cervical lymphadenopathy and palpable splenomegaly. Nose and throat swab for SARS-CoV-2 was positive and blood tests revealed pancytopaenia with very high ferritin, triglyceride and d-dimer levels. The patient’s HScore(2) was calculated at 220, suggesting probability of HLH of 93-96%. Considering Russell and colleagues’(3) comments about potential harm of corticosteroid use in patients with Covid-19 infection, the patient was commenced on treatment with the selective IL-1 receptor antagonist drug, Anakinra, and a two day course of intravenous immunoglobulin. RESULTS: The patient responded rapidly to treatment, becoming apyrexial after 24 hours. His lymph nodes and spleen began to normalise after the first 48 hours, at which time point the ferritin also started to decrease. He was discharged after 11 days feeling fit and well. CONCLUSION: This case certainly illustrates the importance of hyperinflammation syndromes in Covid-19. It also raises the question – is the severe pneumonitis seen in patients with Covid-19 an immunological phenomenon? We know that the viral load of patients with Covid-19 seems to peak in the early stages of illness(4, 5), however patients deteriorate later in the disease course, at around days 10-14. This patient, who had risk factors for deterioration (male, pancytopaenic), did not develop an oxygen requirement and clinically and biochemically improved rapidly on Anakinra with no adverse events. We might suggest Anakinra to the scientific community as a treatment option in Covid-19 infection.


title: Supportive care for patient with respiratory diseases: An umbrella review

text: Background: Supportive treatment is an important and effective part of the management for patients with life-threatening diseases This study aims to identify and evaluate the forms of supportive care for patients with respiratory diseases Methods: An umbrella review of supportive care for patient with respiratory diseases was undertaken We comprehensively searched the following databases: Medline, EMBASE, Web of Science, CNKI (China National Knowledge Infrastructure), Wanfang Data and CBM (SinoMed) from their inception to 31 March 2020, and other sources to identify systematic reviews and meta-analyses related to supportive treatments for patient with respiratory diseases including Coronavirus Disease 2019 (COVID-19), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and influenza We assessed the methodological quality using the AMSTAR score and the quality of the evidence for the primary outcomes of each included systematic review and meta-analysis Results: We included 18 systematic reviews and meta-analyses in this study Most studies focused on the respiratory and circulatory support Ten studies were of high methodological quality, five studies of medium quality, and three studies of low quality According to four studies extracorporeal membrane oxygenation did not reduce mortality in adults [odds ratio/relative risk (OR/RR) ranging from 0 71 to 1 28], but two studies reported significantly lower mortality in patients receiving venovenous extracorporeal membrane oxygenation than in the control group (OR/RR ranging from 0 38 to 0 73) Besides, monitoring of vital signs and increasing the number of medical staff may also reduce the mortality in patients with respiratory diseases Conclusions: Our overview suggests that supportive care may reduce the mortality of patients with respiratory diseases to some extent However, the quality of evidence for the primary outcomes in the included studies was low to moderate Further systematic reviews and meta-analyses are needed to address the evidence gap regarding the supportive care for SARS, MERS and COVID-19


ACE2 Expression in Pancreas May Cause Pancreatic Damage After SARS-CoV-2 Infection


title: In Silico Prediction of Intestinal Permeability by Hierarchical Support Vector Regression

text: The vast majority of marketed drugs are orally administrated. As such, drug absorption is one of the important drug metabolism and pharmacokinetics parameters that should be assessed in the process of drug discovery and development. A nonlinear quantitative structure–activity relationship (QSAR) model was constructed in this investigation using the novel machine learning-based hierarchical support vector regression (HSVR) scheme to render the extremely complicated relationships between descriptors and intestinal permeability that can take place through various passive diffusion and carrier-mediated active transport routes. The predictions by HSVR were found to be in good agreement with the observed values for the molecules in the training set (n = 53, r(2) = 0.93, [Formula: see text] = 0.84, RMSE = 0.17, s = 0.08), test set (n = 13, q(2) = 0.75–0.89, RMSE = 0.26, s = 0.14), and even outlier set (n = 8, q(2) = 0.78–0.92, RMSE = 0.19, s = 0.09). The built HSVR model consistently met the most stringent criteria when subjected to various statistical assessments. A mock test also assured the predictivity of HSVR. Consequently, this HSVR model can be adopted to facilitate drug discovery and development.


title: Caspase-1 Promotes Epstein-Barr Virus Replication by Targeting the Large Tegument Protein Deneddylase to the Nucleus of Productively Infected Cells

text: The large tegument proteins of herpesviruses contain N-terminal cysteine proteases with potent ubiquitin and NEDD8-specific deconjugase activities, but the function of the enzymes during virus replication remains largely unknown. Using as model BPLF1, the homologue encoded by Epstein-Barr virus (EBV), we found that induction of the productive virus cycle does not affect the total level of ubiquitin-conjugation but is accompanied by a BPLF1-dependent decrease of NEDD8-adducts and accumulation of free NEDD8. Expression of BPLF1 promotes cullin degradation and the stabilization of cullin-RING ligases (CRLs) substrates in the nucleus, while cytoplasmic CRLs and their substrates are not affected. The inactivation of nuclear CRLs is reversed by the N-terminus of CAND1, which inhibits the binding of BPLF1 to cullins and prevents efficient viral DNA replication. Targeting of the deneddylase activity to the nucleus is dependent on processing of the catalytic N-terminus by caspase-1. Inhibition of caspase-1 severely impairs viral DNA synthesis and the release of infectious virus, pointing a previously unrecognized role of the cellular response to danger signals triggered by EBV reactivation in promoting virus replication.


title: Cell‐surface receptors on macrophages and dendritic cells for attachment and entry of influenza virus

text: Airway MΦ and DCs are important components of innate host defense and can play a critical role in limiting the severity of influenza virus infection. Although it has been well established that cell‐surface SA acts as a primary attachment receptor for IAV, the particular receptor(s) or coreceptor(s) that mediate IAV entry into any cell, including MΦ and DC, have not been clearly defined. Identifying which receptors are involved in attachment and entry of IAV into immune cells may have important implications in regard to understanding IAV tropism and pathogenesis. Recent evidence suggests that specialized receptors on MΦ and DCs, namely CLRs, can act as capture and/or entry receptors for many viral pathogens, including IAV. Herein, we review the early stages of infection of MΦ and DC by IAV. Specifically, we examine the potential role of CLRs expressed on MΦ and DC to act as attachment and/or entry receptors for IAV.


title: Hospitalized COVID-19 patients treated with Convalescent Plasma in a mid-size city in the midwest

text: Background SARS-CoV-2 and its associated disease, COVID-19, has infected over seven million people world-wide, including two million people in the United States. While many people recover from the virus uneventfully, a subset of patients will require hospital admission, some with intensive care needs including intubation, and mechanical ventilation. To date there is no cure and no vaccine is available. Passive immunotherapy by the transfusion of convalescent plasma donated by COVID-19 recovered patients might be an effective option to combat the virus, especially if used early in the course of disease. Here we report our experience of using convalescent plasma at a tertiary care center in a mid-size, midwestern city that did not experience an overwhelming patient surge. Methods Hospitalized COVID-19 patients categorized as having Severe or Life-Threatening disease according to the Mayo Clinic Emergency Access Protocol were screened, consented, and treated with convalescent plasma collected from local donors recovered from COVID-19 infection. Clinical data and outcomes were collected retrospectively. Results 31 patients were treated, 16 severe patients and 15 life-threatened patients. Overall mortality was 27% (4/31) but only patients with life-threatening disease died. 94% of transfused patients with severe disease avoided escalation to ICU care and mechanical ventilation. 67% of patients with life-threatening disease were able to be extubated. Most transfused patients had a rapid decrease in their respiratory support requirements on or about day 7 following convalescent plasma transfusion. Conclusion Our results demonstrate that convalescent plasma is associated with reducing ventilatory requirements in patients with both severe and life-threatening disease, but appears to be most beneficial when administered early in the course of disease when patients meet the criteria for severe illness.


title: Real-Time Surveillance for Respiratory Disease Outbreaks, Ontario, Canada

text: To validate the utility of a chief complaint–based emergency department surveillance system, we compared it with respiratory diagnostic data and calls to Telehealth Ontario about respiratory disease. This local syndromic surveillance system accurately monitored status of respiratory diseases in the community and contributed to early detection of respiratory disease outbreaks.


title: Inhibition of HBV gene expression and replication by stably expressed interferon‐α1 via adeno‐associated viral vectors

text: BACKGROUND: Interferon‐α2 (IFNα2) is routinely used for anti‐hepatitis B virus (HBV) treatment. However, the therapeutic efficiency is unsatisfactory, particularly in East Asia. Such inefficiency might be a result of the short half‐life, relatively low local concentration and strong side‐effects of interferons. Frequent and repeated injection is also a big burden for patients. In the present study, a single dose of vector‐delivered IFNα1 was tested for its anti‐HBV effects. METHODS: Adeno‐associated viral vector (AAV‐IFNα1) was generated to deliver the IFNα1 gene into hepatocytes. IFNα1, hepatitis B surface (HBsAg) and e (HBeAg) antigens were measured by enzyme‐linked immunosorbent assay and/or western blotting. The level of viral DNA was measured by quantitative real‐time polymerase chain reaction. RESULTS: AAV‐IFNα1 effectively transduced HBV‐producing cells (HepAD38) and mouse hepatocytes, where IFNα1 was expressed in a stable manner. Both intracellular and extracellular HBsAg and HBeAg were significantly reduced in vitro. In the HBV‐producing mice, the concentration of IFNα1 in the liver was eight‐fold higher than that in plasma. Compared with control groups, HBeAg/HBsAg antigen levels were reduced by more than ten‐fold from day 1–5, and dropped to an undetectable level on day 9 in the AAV‐IFNα1 group. Concurrently, the level of viral DNA decreased over 30‐fold for several weeks. CONCLUSIONS: A single dose administration of AAV‐IFNα1 viral vector displayed prolonged transgene expression and superior antiviral effects both in vitro and in vivo. Therefore, the use of AAV‐IFNα1 might be a potential alternative strategy for anti‐HBV therapy. Copyright © 2008 John Wiley & Sons, Ltd.


Editorial overview: Viral pathogenesis: dealing with complexity in virus-induced disease


title: Molecular isothermal techniques for combating infectious diseases: towards low-cost point-of-care diagnostics

text: Nucleic acid amplification techniques such as PCR have facilitated rapid and accurate diagnosis in central laboratories over the past years. PCR-based amplifications require high-precision instruments to perform thermal cycling reactions. Such equipment is bulky, expensive and complex to operate. Progressive advances in isothermal amplification chemistries, microfluidics and detectors miniaturisation are paving the way for the introduction and use of compact ‘sample in-results out’ diagnostic devices. However, this paradigm shift towards decentralised testing poses diverse technological, economic and organizational challenges both in industrialized and developing countries. This review describes the landscape of molecular isothermal diagnostic techniques for infectious diseases, their characteristics, current state of development, and available products, with a focus on new directions towards point-of-care applications.


title: One month of the novel coronavirus 2019 outbreak: Is it still a threat?

text: The novel coronavirus 2019 disease (COVID-19) is now in an outbreak not only in China but also around the world, suspected to be originated from a wet market in Wuhan, Hubei province, China. The flare-up of COVID-19, it has already been infected 78,811 people with 2462 fatalities in 1 month window. The most alarming issue is the virus can transmit from host to host and still asymptomatic. Currently, 24 counties with 505 confirmed cases have been reported. Presently, there is no specific treatment or vaccine but physicians are battling with the use of antibiotics, steroid, anti-viral and anti-HIV drugs and some of the infected cases are testified improved. WHO and China National health Commission are cooperatively striving to come up with elucidation but it will take a minimum of 3 to 4 months at least to undergo a phase-1 trial. However, the soaring rates of spreading each day has become much stable which might even improve within the next few weeks in China but not for some other countries. Healthy peoples are instructed to avoid public gathering, always wearing the mask and frequently wash hands. Currently, China has able to hold up more than 97.7% infection within China but a scientific breakthrough is crucial before it’s too late.


title: COVID-19: Emergence, Spread, Possible Treatments, and Global Burden

text: The Coronavirus (CoV) is a large family of viruses known to cause illnesses ranging from the common cold to acute respiratory tract infection. The severity of the infection may be visible as pneumonia, acute respiratory syndrome, and even death. Until the outbreak of SARS, this group of viruses was greatly overlooked. However, since the SARS and MERS outbreaks, these viruses have been studied in greater detail, propelling the vaccine research. On December 31, 2019, mysterious cases of pneumonia were detected in the city of Wuhan in China's Hubei Province. On January 7, 2020, the causative agent was identified as a new coronavirus (2019-nCoV), and the disease was later named as COVID-19 by the WHO. The virus spread extensively in the Wuhan region of China and has gained entry to over 210 countries and territories. Though experts suspected that the virus is transmitted from animals to humans, there are mixed reports on the origin of the virus. There are no treatment options available for the virus as such, limited to the use of anti-HIV drugs and/or other antivirals such as Remdesivir and Galidesivir. For the containment of the virus, it is recommended to quarantine the infected and to follow good hygiene practices. The virus has had a significant socio-economic impact globally. Economically, China is likely to experience a greater setback than other countries from the pandemic due to added trade war pressure, which have been discussed in this paper.


title: Systematic assessment of venous thromboembolism in COVID-19 patients receiving thromboprophylaxis: incidence and role of D-dimer as predictive factors

text: Coagulopathy in COVID-19 is a burning issue and strategies to prevent thromboembolic events are debated and highly heterogeneous. The objective was to determine incidence and risk factors of venous thromboembolism (VTE) in COVID-19 inpatients receiving thromboprophylaxis. In this retrospective French cohort study, patients hospitalized in medical wards non-ICU with confirmed COVID-19 and adequate thromboprophylaxis were included. A systematic low limb venous duplex ultrasonography was performed at hospital discharge or earlier if deep venous thrombosis (DVT) was clinically suspected. Chest angio-CT scan was performed when pulmonary embolism (PE) was suspected. Of 71 patients, 16 developed VTE (22.5%) and 7 PE (10%) despite adequate thromboprophylaxis. D-dimers at baseline were significantly higher in patients with DVT (p < 0.001). Demographics, comorbidities, disease manifestations, severity score, and other biological parameters, including inflammatory markers, were similar in patients with and without VTE. The negative predictive value of a baseline D-dimer level < 1.0 µg/ml was 90% for VTE and 98% for PE. The positive predictive value for VTE was 44% and 67% for D-dimer level ≥ 1.0 µg/ml and ≥ 3 µg/ml, respectively. The association between D-dimer level and VTE risk increased by taking into account the latest available D-dimer level prior to venous duplex ultrasonography for the patients with monitoring of D-dimer. Despite thromboprophylaxis, the risk of VTE is high in COVID-19 non-ICU inpatients. Increased D-dimer concentrations of more than 1.0 μg/ml predict the risk of venous thromboembolism. D-dimer level-guided aggressive thromboprophylaxis regimens using higher doses of heparin should be evaluated in prospective studies.


title: Characterization of Uncultivable Bat Influenza Virus Using a Replicative Synthetic Virus

text: Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV). Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1). This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2) showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses.


title: COVID-19 pandemic: The role of community pharmacists in chronic kidney disease management supportive care

text: The COVID-19 pandemic is putting enormous pressure on healthcare systems worldwide and various countries are struggling to flatten the curve to prevent their healthcare system from becoming overwhelmed. Studies have shown that people with chronic kidney disease (CKD) are at increased risk of COVID-19 infection and mortality. However, the interruption of routine care and support due to the current challenges with healthcare providers, facilities, and essential medicines due to this pandemic is adversely affecting people with CKD. This is because poor management of this disease leads to negative health outcomes. In order to maintain good health, this vulnerable group of patients relied heavily on the extended role of the community pharmacists in chronic disease management. This paper highlights the extended role of the community pharmacists in CKD supportive care during the COVID-19 pandemic.


title: Emerging Advances in Rapid Diagnostics of Respiratory Infections

text: Recent developments in rapid diagnostics for respiratory infections have mostly occurred in the areas of antigen and nucleic acid detection. Nucleic acid amplification tests have improved the ability to identify respiratory viruses in clinical specimens and have played pivotal roles in the rapid characterization of new viral pathogens. Antigen-detection assays in immunochromatographic or similar formats are most easily developed as near-patient tests, although they have been developed commercially only for a limited range of respiratory pathogens. New approaches for respiratory pathogen detection are needed, and breath analysis is an exciting area with enormous potential.


Bats and Viruses: Friend or Foe?


title: Roles of N‐Myc and STAT interactor in cancer: From initiation to dissemination

text: N‐myc & STAT Interactor, NMI, is a protein that has mostly been studied for its physical interactions with transcription factors that play critical roles in tumor growth, progression and metastasis. NMI is an inducible protein, thus its intracellular levels and location can vary dramatically, influencing a diverse array of cellular functions in a context‐dependent manner. The physical interactions of NMI with its binding partners have been linked to many aspects of tumor biology including DNA damage response, cell death, epithelial‐to‐mesenchymal transition and stemness. Thus, discovering more details about the function(s) of NMI could reveal key insights into how transcription factors like c‐Myc, STATs and BRCA1 are contextually regulated. Although a normal, physiological function of NMI has not yet been discovered, it has potential roles in pathologies ranging from viral infection to cancer. This review provides a timely perspective of the unfolding roles of NMI with specific focus on cancer progression and metastasis.


title: ITRACONAZOLE INHIBITS ENTEROVIRUS REPLICATION BY TARGETING THE OXYSTEROL-BINDING PROTEIN

text: Itraconazole (ITZ) is a well-known antifungal agent that also has anti-cancer activity. In this study, we identified ITZ as a broad-spectrum inhibitor of enteroviruses (e.g. poliovirus, coxsackievirus, enterovirus-71, rhinovirus). We demonstrate that ITZ inhibits viral RNA replication by targeting oxysterol-binding protein (OSBP) and OSBP-related protein 4 (ORP4). Consistently, OSW-1, a specific OSBP/ORP4 antagonist, also inhibits enterovirus replication. Knockdown of OSBP inhibits virus replication whereas overexpression of OSBP or ORP4 counteracts the antiviral effects of ITZ and OSW-1. ITZ binds OSBP and inhibits its function, i.e. shuttling of cholesterol and phosphatidylinositol-4-phosphate between membranes, thereby likely perturbing the virus-induced membrane alterations essential for viral replication organelle formation. ITZ also inhibits hepatitis C virus replication, which also relies on OSBP. Together, these data implicate OSBP/ORP4 as novel molecular targets of ITZ and point to an essential role of OSBP/ORP4-mediated lipid exchange in virus replication that can be targeted by antiviral drugs.


title: Sialic Acid Binding Properties of Soluble Coronavirus Spike (S1) Proteins: Differences between Infectious Bronchitis Virus and Transmissible Gastroenteritis Virus

text: The spike proteins of a number of coronaviruses are able to bind to sialic acids present on the cell surface. The importance of this sialic acid binding ability during infection is, however, quite different. We compared the spike protein of transmissible gastroenteritis virus (TGEV) and the spike protein of infectious bronchitis virus (IBV). Whereas sialic acid is the only receptor determinant known so far for IBV, TGEV requires interaction with its receptor aminopeptidase N to initiate infection of cells. Binding tests with soluble spike proteins carrying an IgG Fc-tag revealed pronounced differences between these two viral proteins. Binding of the IBV spike protein to host cells was in all experiments sialic acid dependent, whereas the soluble TGEV spike showed binding to APN but had no detectable sialic acid binding activity. Our results underline the different ways in which binding to sialoglycoconjugates is mediated by coronavirus spike proteins.


title: Crisis management of SARS in a hospital

text: Abstract Introduction: A large general hospital was suddenly disabled by an in-hospital outbreak of Severe Acute Respiratory Distress Syndrome (SARS). Method: The crisis was successfully managed by a Standard Operation Procedure (SOP) that included: (a) containment of SARS patients on a special floor and evacuation of the patients from the infected and near-around floors; (b) sorting of the hospital into areas and floors to avoid cross contact of people; (c) triage of patients into groups according to risks; (d) closure of the emergency room and outpatient clinics; and (e) set up of an outdoor fever screening station and emergency service. Results: The situation was quickly controlled after the implementation of these procedures. The central argument in this case is that crisis managerial behavior is the result of how managers channel and distribute the attention of their crisis sense. Impact on industry: What managers should do depends on what risk issues and actions related to risk independency, efficiency, safety priority, and transparency they take. What risk issues and actions they take depends on the crisis sense and on how management responds to leadership, resource, and execution.


title: Complete Genome Sequence Analysis of a Reassortant Strain of Bluetongue Virus Serotype 16 from Italy

text: The complete genome sequence of a reassortant field strain of bluetongue virus serotype 16 (BTV-16), isolated from cattle in the Apulia region of Italy in 2002, has been determined by Illumina sequencing. Sequence comparisons of segment 1 (Seg-1) to Seg-10, except Seg-5, show that BTV-16 strain ITL2002 belongs to the major eastern topotype of BTV.