title: Egg forensics: An appraisal of DNA sequencing to assist in species identification of illegally smuggled eggs

text: Abstract Psittaciformes (parrots and cockatoos) are charismatic birds, their plumage and capacity for learning make them highly sought after pets. The illegal trade in parrots and cockatoos poses a serious threat to the viability of native populations; in addition, species transported to non-endemic areas may potentially vector disease and genetically ‘pollute’ local native avifauna. To reduce the logistical difficulties associated with trafficking live birds, smugglers often transport eggs. This creates a problem for authorities in elucidating accurate species identification without the laborious task of incubation and hand rearing until a morphological identification can be made. Here, we use 99 avian eggs seized from carriers coming into and within Australia, as a result of suspected illegal trade. We investigate and evaluate the use of mitochondrial DNA (mtDNA) to accurately identify eggs to family, genus or species level. However, Identification of a species based on percentage mtDNA similarities is difficult without good representations of the inter- and intra-levels of species variation. Based on the available reference database, we were able to identify 52% of the eggs to species level. Of those, 10 species from eight genera were detected, all of which belong to the parrot (Psittacidae) and cockatoo (Cacatuidae) families. Of the remaining 48%, a further 36% of eggs were identified to genus level, and 12% identified to family level using our assignment criteria. Clearly the lack of validated DNA reference sequences is hindering our ability to accurately assign a species identity, and accordingly, we advocate that more attention needs to be paid to establishing validated, multi locus mtDNA reference databases for exotic birds that can both assist in genetic identifications and withstand legal scrutiny.


title: Isolation and characterization of a Korean porcine epidemic diarrhea virus strain KNU-141112

text: Abstract Severe outbreaks of porcine epidemic diarrhea virus (PEDV) have re-emerged in Korea and rapidly swept across the country, causing tremendous economic losses to producers and customers. Despite the availability of PEDV vaccines in the domestic market, the disease continues to plague the Korean pork industry, raising issues regarding their protective efficacy and new vaccine development. Therefore, PEDV isolation in cell culture is urgently needed to develop efficacious vaccines and diagnostic assays and to conduct further studies on the virus biology. In the present study, one Korean PEDV strain, KOR/KNU-141112/2014, was successfully isolated and serially propagated in Vero cells for over 30 passages. The in vitro and in vivo characteristics of the Korean PEDV isolate were investigated. Virus production in cell culture was confirmed by cytopathology, immunofluorescence, and real-time RT-PCR. The infectious virus titers of the viruses during the first 30 passages ranged from 105.1 to 108.2 TCID50 per ml. The inactivated KNU-141112 virus was found to mediate potent neutralizing antibody responses in immunized guinea pigs. Animal studies showed that KNU-141112 virus causes severe diarrhea and vomiting, fecal shedding, and acute atrophic enteritis, indicating that strain KNU-141112 is highly enteropathogenic in the natural host. In addition, the entire genomes or complete S genes of KNU-141112 viruses at selected cell culture passages were sequenced to assess the genetic stability and relatedness. Our genomic analyses indicated that the Korean isolate KNU-141112 is genetically stable during the first 30 passages in cell culture and is grouped within subgroup G2b together with the recent re-emergent Korean strains.


title: SARS-CoV2 Testing: The Limit of Detection Matters

text: Resolving the COVID-19 pandemic requires diagnostic testing to determine which individuals are infected and which are not. The current gold standard is to perform RT-PCR on nasopharyngeal samples. Best-in-class assays demonstrate a limit of detection (LoD) of ~100 copies of viral RNA per milliliter of transport media. However, LoDs of currently approved assays vary over 10,000-fold. Assays with higher LoDs will miss more infected patients, resulting in more false negatives. However, the false-negative rate for a given LoD remains unknown. Here we address this question using over 27,500 test results for patients from across our healthcare network tested using the Abbott RealTime SARS-CoV-2 EUA. These results suggest that each 10-fold increase in LoD is expected to increase the false negative rate by 13%, missing an additional one in eight infected patients. The highest LoDs on the market will miss a majority of infected patients, with false negative rates as high as 70%. These results suggest that choice of assay has meaningful clinical and epidemiological consequences. The limit of detection matters.


title: Epidemiology and clinical impact of viral, atypical, and fungal respiratory pathogens in symptomatic immunocompromised patients: a two-center study using a multi-parameter customized respiratory Taqman® array card

text: The prevalence of respiratory viruses in immunocompromised adult patients and the association with clinical outcomes is still underexplored. Our goal was to assess the epidemiology and the potential clinical impact of respiratory viral infections in a high-risk patient population. Two large hospitals performed a respiratory Taqman array card (TAC), targeting 24 viruses, 8 bacteria, and 2 fungi simultaneously, on 435 samples from 397 symptomatic immunocompromised patients. Clinical details were collected retrospectively using a structured case report form. An overall positivity rate of 68% was found (51% mono- and 17% co-infections). Pathogen distribution was as follows: influenza A (20.7%), rhinoviruses (15.2%), coronaviruses (7.8%), Pneumocystis jirovecii (7.4%), RSV (7.1%), and CMV (6.0%) were the most frequently encountered, followed by HSV (5.5%), hMPV (4.4%), parainfluenza viruses (3.9%), influenza B (3.7%), and Aspergillus species (3.7%). Other pathogens were not detected or detected only in ≤ 1% of samples. Hospital and ICU admission rates were 84% and 11%, respectively. The presence of a pathogen was strongly associated with higher need for supplemental oxygen (p = 0.001), but it had no impact on ICU admission, mechanical ventilation requirement, antibacterial therapy, or mortality. In conclusion, our study described the epidemiology of respiratory pathogens in a large group of symptomatic immunocompromised patients and provides evidence of a relationship between pathogen detection and the need for supplemental oxygen. This association was still found after the exclusion of the results positive for influenza viruses, suggesting that non-influenza viruses contribute to severe respiratory illness in patients with compromised immunity.


title: Flow cytometric detection and serotyping of enterovirus for the clinical laboratory

text: Abstract Culture and serotyping of human enteroviruses by fluorescence microscopy are time-consuming and labor-intensive. Flow cytometry has the potential of being more rapid, sensitive, and objective but has not been used for these purposes in a clinical laboratory. Primary rhesus monkey kidney (PMK) cells were inoculated with several enterovirus serotypes and stained with enterovirus-specific antibodies for flow cytometry and indirect fluorescence antibody testing (IFA). Kinetic studies of coxsackievirus B1 and echovirus 30 infection of PMK cells were performed on days 1–4 after inoculation. Flow cytometry results for echovirus 6, 9, 11, and 30 and coxsackievirus B1 correlated with IFA in all cases. Coxsackievirus B1 and echovirus 30 infections were detected 1 day earlier by flow cytometry than IFA. Flow cytometry can be effectively used for detecting enterovirus-infected cells in a clinical laboratory with the advantages of better quantitation of low levels of infection and earlier detection of virally infected cells in culture systems.


title: Polyproteins in structural biology

text: Polyproteins are chains of covalently conjoined smaller proteins that occur in nature as versatile means to organize the proteome of viruses including HIV. During maturation, viral polyproteins are typically cleaved into the constituent proteins with different biological functions by highly specific proteases, and structural analyses at defined stages of this maturation process can provide clues for antiviral intervention strategies. Recombinant polyproteins that use similar mechanisms are emerging as powerful tools for producing hitherto inaccessible protein targets such as the influenza polymerase, for high-resolution structure determination by X-ray crystallography. Conversely, covalent linking of individual protein subunits into single polypeptide chains are exploited to overcome sample preparation bottlenecks. Moreover, synthetic polyproteins provide a promising tool to dissect dynamic folding of polypeptide chains into three-dimensional architectures in single-molecule structure analysis by atomic force microscopy (AFM). The recent use of natural and synthetic polyproteins in structural biology and major achievements are highlighted in this contribution.


title: Re-evaluation of the evolution of influenza H1 viruses using direct PCA

text: The history of influenza H1 virus was re-evaluated by applying a new methodology to sequencing data; this objective method enables comparisons among viral types. The approach led to the segregation of all segments of swine and human viruses into three distinct groups: two of them included the pandemic 1977 and 2009 human viruses, and the remaining group may be new in humans. These three groups might have originated from avian viruses and drifted out independently. Genome shifts occurred occasionally among swine viruses; however, distances between avian and swine/human viruses negated the existence of direct shifts from avian viruses. In humans, only one or two viruses appeared each year, which suggests the presence of competition among viruses that migrated freely. All segments drifted continuously under certain rules and constant velocity. Viruses that had caused an outbreak did not appear again over subsequent decades, which may mean populations had become immune to such viruses. In contrast, the viruses in livestock were rather conserved and maintained unique strains in small, separate areas. Such collections of swine strains included human segments, which could become an epidemic in the future.


title: Entry of Scotophilus Bat Coronavirus-512 and Severe Acute Respiratory Syndrome Coronavirus in Human and Multiple Animal Cells

text: Bats are natural reservoirs of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV). Scotophilus bat CoV-512 demonstrates potential for cross-species transmission because its viral RNA and specific antibodies have been detected in three bat species of Taiwan. Understanding the cell tropism of Scotophilus bat CoV-512 is the first step for studying the mechanism of cross-species transmission. In this study, a lentivirus-based pseudovirus was produced using the spike (S) protein of Scotophilus bat CoV-512 or SARS-CoV as a surface protein to test the interaction between coronaviral S protein and its cell receptor on 11 different cells. Susceptible cells expressed red fluorescence protein (RFP) after the entry of RFP-bound green fluorescence protein (GFP)-fused S protein of Scotophilus bat CoV-512 (RFP-Sco-S-eGFP) or RFP-SARS-S pseudovirus, and firefly luciferase (FLuc) activity expressed by cells infected with FLuc-Sco-S-eGFP or FLuc-SARS-S pseudovirus was quantified. Scotophilus bat CoV-512 pseudovirus had significantly higher entry efficiencies in Madin Darby dog kidney epithelial cells (MDCK), black flying fox brain cells (Pabr), and rat small intestine epithelial cells (IEC-6). SARS-CoV pseudovirus had significantly higher entry efficiencies in human embryonic kidney epithelial cells (HEK-293T), pig kidney epithelial cells (PK15), and MDCK cells. These findings demonstrated that Scotophilus bat CoV-512 had a broad host range for cross-species transmission like SARS-CoV.


title: Cystatins in Immune System

text: Cystatins comprise a large superfamily of related proteins with diverse biological activities. They were initially characterised as inhibitors of lysosomal cysteine proteases, however, in recent years some alternative functions for cystatins have been proposed. Cystatins possessing inhibitory function are members of three families, family I (stefins), family II (cystatins) and family III (kininogens). Stefin A is often linked to neoplastic changes in epithelium while another family I cystatin, stefin B is supposed to have a specific role in neuredegenerative diseases. Cystatin C, a typical type II cystatin, is expressed in a variety of human tissues and cells. On the other hand, expression of other type II cystatins is more specific. Cystatin F is an endo/lysosome targeted protease inhibitor, selectively expressed in immune cells, suggesting its role in processes related to immune response. Our recent work points on its role in regulation of dendritic cell maturation and in natural killer cells functional inactivation that may enhance tumor survival. Cystatin E/M expression is mainly restricted to the epithelia of the skin which emphasizes its prominent role in cutaneous biology. Here, we review the current knowledge on type I (stefins A and B) and type II cystatins (cystatins C, F and E/M) in pathologies, with particular emphasis on their suppressive vs. promotional function in the tumorigenesis and metastasis. We proposed that an imbalance between cathepsins and cystatins may attenuate immune cell functions and facilitate tumor cell invasion.


title: Hand Hygiene, Mask-Wearing Behaviors and Its Associated Factors during the COVID-19 Epidemic: A Cross-Sectional Study among Primary School Students in Wuhan, China

text: Although the emphasis on behaviors of hand-washing and mask-wearing was repeated during the pandemic of Coronavirus Disease 2019 (COVID-19), not everyone paid enough attention to this. A descriptive statistic was used to make sense of the status of hand hygiene and mask-wearing among primary school students in Wuhan, China. A binary logistic regression analysis was conducted to identify the risk factors affecting the behaviors of hand-washing and mask-wearing. p < 0.05 (two-sides) was considered as significant at statistics. 42.05% of the primary school students showed a good behavior of hand-washing, while 51.60% had a good behavior of mask-wearing. Gender, grade, out-going history, father’s occupation, mother’s educational background, and the time filling out the survey were significantly associated with hand hygiene, whereas grade, mother’s educational background, and residence were associated with mask-wearing. The behaviors of hand-washing and mask-wearing among primary school students were influenced by gender, grade, shady is back tell a friendand other factors, therefore, parents should make efforts of behavior guidance whereas governments should enlarge medium publicity.


Roles of the Chinese clinical pharmacist during the COVID‐19 pandemic


title: Use of a Safe, Reproducible, and Rapid Aerosol Delivery Method to Study Infection by Burkholderia pseudomallei and Burkholderia mallei in Mice

text: Burkholderia pseudomallei, the etiologic agent of melioidosis, is a saprophytic bacterium readily isolated from wet soils of countries bordering the equator. Burkholderia mallei is a host-adapted clone of B. pseudomallei that does not persist outside of its equine reservoir and causes the zoonosis glanders, which is endemic in Asia, Africa, the Middle East and South America. Infection by these organisms typically occurs via percutaneous inoculation or inhalation of aerosols, and the most common manifestation is severe pneumonia leading to fatal bacteremia. Glanders and melioidosis are difficult to diagnose and require prolonged antibiotic therapy with low success rates. There are no vaccines available to protect against either Burkholderia species, and there is concern regarding their use as biological warfare agents given that B. mallei has previously been utilized in this manner. Hence, experiments were performed to establish a mouse model of aerosol infection to study the organisms and develop countermeasures. Using a hand-held aerosolizer, BALB/c mice were inoculated intratracheally with strains B. pseudomallei 1026b and B. mallei ATCC23344 and growth of the agents in the lungs, as well as dissemination to the spleen, were examined. Mice infected with 10(2), 10(3) and 10(4) organisms were unable to control growth of B. mallei in the lungs and bacteria rapidly disseminated to the spleen. Though similar results were observed in mice inoculated with 10(3) and 10(4) B. pseudomallei cells, animals infected with 10(2) organisms controlled bacterial replication in the lungs, dissemination to the spleen, and the extent of bacteremia. Analysis of sera from mice surviving acute infection revealed that animals produced antibodies against antigens known to be targets of the immune response in humans. Taken together, these data show that small volume aerosol inoculation of mice results in acute disease, dose-dependent chronic infection, and immune responses that correlate with those seen in human infections.


title: Purification, crystallization and preliminary X-ray analysis of nonstructural protein 2 (nsp2) from avian infectious bronchitis virus

text: Avian infectious bronchitis virus (IBV) is a member of the group III coronaviruses, which differ from the other groups of coronaviruses in that they do not encode the essential pathogenic factor nonstructural protein 1 (nsp1) and instead start with nsp2. IBV nsp2 is one of the first replicase proteins to be translated and processed in the viral life cycle; however, it has an entirely unknown function. In order to better understand the structural details and functional mechanism of IBV nsp2, the recombinant protein was cloned, overexpressed in Escherichia coli, purified and crystallized. The crystals diffracted to 2.8 Å resolution and belonged to space group P2(1), with unit-cell parameters a = 57.0, b = 192.3, c = 105.7 Å, β = 90.8°. Two molecules were found in the asymmetric unit; the Matthews coefficient was 3.9 Å(3) Da(−1), corresponding to a solvent content of 68.2%.


title: Three cases of idiopathic eosinophilic enteritis with chronic obstinate diarrhea in Japanese Black fattening cattle

text: Eosinophilic enteritis (EOE) is a type of inflammatory bowel disease and is characterized clinically by chronic obstinate diarrhea. Three Japanese Black (JB) fattening cattle (2 males and 1 female) on different cattle farms presented with chronic episodic diarrhea without fever or dehydration. Soft reddish spherical carneous tissues (1−3 cm) were occasionally excreted within the diarrheic feces. Administration of antibiotics, antidiarrheal drugs and vermicides had no therapeutic effect, but dexamethasone improved the fecal characteristics. The symptoms persisted until the animals were slaughtered at 27–30 months of age. Histopathological examination of the intestines revealed marked eosinophilic infiltration in the lamina propria and submucosa. From these findings, we diagnosed these cattle as the first cases of EOE in JB cattle.


title: Coagulopathy in COVID-19 infection: a case of acute upper limb ischemia

text: Coagulation abnormalities and thrombosis have been recently identified as sequelae of severe infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report a case of severe coagulopathy manifesting with right upper limb arterial and deep vein thrombosis in an 80-year-old male patient with severe COVID-19 associated pneumonia. He clinically deteriorated and received care in the intensive care unit where he was intubated. At that point, his coagulation laboratory tests were deranged, and he eventually developed dry gangrene in his right thumb and index finger, as well as a deep venous thromboembolism in his right axillary vein. Despite receiving treatment dose anticoagulation and undergoing arterial embolectomy, revascularization was unsuccessful. Amputation of the right arm at the level of the elbow was considered, but the patient died from respiratory failure.


A Carton-Made Protective Shield for Suspicious/Confirmed COVID-19 Intubation and Extubation During Surgery


title: Immunité et vaccinations antivirales : exemple de la muqueuse respiratoire

text: Rèsumè Objectifs Les surfaces muqueuses de l’arbre respiratoire constituant une porte d’entrée très importante pour de nombreux agents pathogènes, bactériens ou viraux, elles apparaissent comme un site critique pour la réponse immune. Ainsi, des vaccins stimulant cette immunité locale sembleraient constituer une approche intéressante dans la prévention de ces infections. Après avoir détaillé les différents mécanismes mis en jeu dans cette immunité muqueuse, cette étude a pour but d’analyser le principe d’une telle vaccination et les différents vaccins administrables par voie respiratoire. Immunité muqueuse Les principaux anticorps sécrétés localement appartiennent à l’isotype IgA (S-IgA), les anticorps de type IgM (S-IgM) et IgG (S-IgG) ayant un rôle encore largement discuté. Les cellules effectrices qui dominent au niveau de la muqueuse ne sont pas des cellules IgA de type B, mais des lymphocytes T qui peuvent représenter jusqu’à 80 % de la totalité des populations lymphocytaires de la muqueuse. Immunoprophylaxie par voie respiratoire Des immunoglobulines spécifiques administrées localement peuvent prévenir des infections virales comme cela a été démontré pour le VRS ; mais les quantités d’anticorps nécessaires pour être actives sont très importantes et difficiles à obtenir. Parmi les facteurs susceptibles d’induire une réponse immune muqueuse et une immunité à médiation cellulaire, on retrouve la voie orale ou respiratoire et des virus réplicatifs. À ce jour, très peu de vaccins antiviraux muqueux ont vu le jour et le seul exemple pour les virus respiratoires reste le vaccin grippal atténué administré par voie nasale. D’autres vaccins commercialisés par voie parentérale ont été utilisés expérimentalement par voie nasale. Qu’il s’agisse de vaccins vivants (varicelle, rougeole) ou inactivés (grippe injectable), ils n’induisent par cette voie inhabituelle qu’une réponse locale modérée. Conclusion Il apparaît donc dans l’état actuel de nos connaissances et des vaccins disponibles que la voie muqueuse ne constitue pas une voie essentielle et incontournable pour élaborer un vaccin actif contre des virus respiratoires. Mais l’exemple du vaccin grippe atténué administré par voie nasale est à lui seul prometteur pour l’avenir de la vaccination par voie muqueuse et d’autres approches plus sophistiquées pourraient voir le jour dans les années à venir. Abstract Objective As the mucosal surfaces of the respiratory tract represent a major portal of entry for most human viruses and many bacteria, they seem to be a critical component of the mammalian immunologic repertoire. Thus, vaccines stimulating this local immunity could represent an interesting approach to prevent these infections. After detailing the different mechanisms implied in this mucosal immunity, the aim of this study is to analyze the basis of such a vaccination and the different vaccines available to mucosal respiratory tract use. Mucosal immunity The major antibody isotype in external secretions is secretory immunoglobin A (S-IgA); the role of IgM (S-IgM) and IgG (S-IgG) are actually questionned. It is, however, interesting that the major effector cells in the mucosal surfaces are not IgA B cells, but T lymphocytes that may represent up to 80% of the entire mucosal lymphoid cell population. Immunoprophylaxis by the mucosal route Passive antibodies were shown to protect against mucosal viral infections, such as those caused by RSV, but very high quantities of passive antibodies are needed to restrict virus replication on mucosal surface. In general, factors which favor development of mucosal antibody and cell mediated immune responses include the oral or respiratory immunization and the replicating nature of the vaccine agents. However, to date only a few vaccines have become available to mucosal respiratory tract use, and cold-adapted influenza virus vaccines is the only one available using nasal route. Other parenteral licensed vaccines have not been recommended for mucosal administration. Some of them have been experimentally used with nasal administration of replicating agents (varicella and measles vaccines) or non replicating agents (influenza inactivated vaccine), but have been found to induce a very low mucosal response. Conclusion Based on the experience with existing vaccines, the development of mucosal immunity or administration of vaccines via the mucosal route is clearly not a prerequisite today for control or prevention of most viral infectious respiratory diseases or diseases with respiratory tract as a route of contamination. But the example of live attenuated intranasal influenza vaccine inducing both systemic and local immune response without immunopathology, is promising for the future of the mucosal immunization against respiratory viral infections.


Excretion of Sars-Cov-2 in human breastmilk samples


title: 2018 recommendations for the management of community acquired pneumonia

text: Community-acquired pneumonia (CAP) is the leading cause of death worldwide. Despite the vast diversity of respiratory microbiota, Streptococcus pneumoniae remains the most prevalent pathogen among etiologic agents. Despite the significant decrease in the mortality rates for lower respiratory tract infections in recent decades, CAP ranks third as a cause of death in Brazil. Since the latest Guidelines on CAP from the Sociedade Brasileira de Pneumologia e Tisiologia (SBPT, Brazilian Thoracic Association) were published (2009), there have been major advances in the application of imaging tests, in etiologic investigation, in risk stratification at admission and prognostic score stratification, in the use of biomarkers, and in the recommendations for antibiotic therapy (and its duration) and prevention through vaccination. To review these topics, the SBPT Committee on Respiratory Infections summoned 13 members with recognized experience in CAP in Brazil who identified issues relevant to clinical practice that require updates given the publication of new epidemiological and scientific evidence. Twelve topics concerning diagnostic, prognostic, therapeutic, and preventive issues were developed. The topics were divided among the authors, who conducted a nonsystematic review of the literature, but giving priority to major publications in the specific areas, including original articles, review articles, and systematic reviews. All authors had the opportunity to review and comment on all questions, producing a single final document that was approved by consensus.


title: Norovirus disease: changing epidemiology and host susceptibility factors

text: Abstract Noroviruses cause the majority of acute viral gastroenteritis cases that occur worldwide. The increased recognition of noroviruses as the cause of outbreaks and sporadic disease is due to the recent availability of improved norovirus-specific diagnostics. Transmission of these viruses is facilitated by their high prevalence in the community, shedding of infectious virus particles from asymptomatic individuals and the high stability of the virus in the environment. Currently, the spectrum of clinical disease and the understanding of host susceptibility factors are changing. Cases of chronic norovirus gastroenteritis have been observed in transplant recipients and unusual clinical presentations have been recognized in otherwise healthy adults that are under physical stress. Recently, noroviruses were found to bind to gut-expressed carbohydrates, leading to a correlation between a person's genetically determined carbohydrate expression and their susceptibility to Norwalk virus infection. Greater community surveillance and further investigation of carbohydrate receptor-binding properties could provide further insights into norovirus transmission, susceptibility and pathogenesis, and should aid in developing vaccines and antiviral therapies for this common viral disease.


title: Strategies for Rational Use of Personal Protective Equipment (PPE) Among Healthcare Providers During the COVID-19 Crisis

text: As the coronavirus 2019 (COVID-19) began spreading globally with no clear treatment in sight, prevention became a major part of controlling the disease and its effects. COVID-19 spreads from the aerosols of an infected individual whether they are showing any symptoms or not. Therefore, it becomes nearly impossible to point exactly where the patient is. This is where personal protective equipment (PPE) comes in. These are masks, respirators, gloves, and in hospitals where the contact with the infected and confirmed patient is direct, also gowns or body covers. The PPEs play a major role in the prevention and control of the COVID-19. The PPE is able to prevent any invasion of the virus particles into the system of an individual which is why it is an essential item to have for healthcare workers. Due to the high demand for PPEs all around the world, it is important to optimize the use of protective gear and ration the supplies so that the demand are met. However, there are guidelines recommended by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) to maintain the supply in the wake of this increased demand of PPE, how the manufacturers should track their supplies, and how the recipients should manage them. Various strategies can be used to increase the re-use of PPEs during the COVID-19 pandemic that has modified the donning and doffing procedure.


title: Targeting the Heme-Heme Oxygenase System to Prevent Severe Complications Following COVID-19 Infections

text: SARS-CoV-2 is causing a pandemic resulting in high morbidity and mortality. COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) are often critically ill and show lung injury and hemolysis. Heme is a prosthetic moiety crucial for the function of a wide variety of heme-proteins, including hemoglobin and cytochromes. However, injury-derived free heme promotes adhesion molecule expression, leukocyte recruitment, vascular permeabilization, platelet activation, complement activation, thrombosis, and fibrosis. Heme can be degraded by the anti-inflammatory enzyme heme oxygenase (HO) generating biliverdin/bilirubin, iron/ferritin, and carbon monoxide. We therefore postulate that free heme contributes to many of the inflammatory phenomena witnessed in critically ill COVID-19 patients, whilst induction of HO-1 or harnessing heme may provide protection. HO-activity not only degrades injurious heme, but its effector molecules possess also potent salutary anti-oxidative and anti-inflammatory properties. Until a vaccine against SARS-CoV-2 becomes available, we need to explore novel strategies to attenuate the pro-inflammatory, pro-thrombotic, and pro-fibrotic consequences of SARS-CoV-2 leading to morbidity and mortality. The heme-HO system represents an interesting target for novel “proof of concept” studies in the context of COVID-19.


title: Emojis in public health and how they might be used for hand hygiene and infection prevention and control

text: Emojis are frequently used picture characters known as possible surrogates for non-verbal aspects of behavior. Considering the ability of emojis to enhance and facilitate communication, there has been a growing interest in studying their effects in scientific and health-related topics over the past few years. Infection prevention and control (IPC) is a field of medicine that is directly associated with specific behaviors. These include hand hygiene, which is the cornerstone of the prevention of healthcare-associated infections, and essential in stemming the spread of antimicrobial resistance. This paper aims to provide an overview of how emojis have been used in the medical and public health literature and proposes their possible use in IPC and hand hygiene to put forth a vision for the future research.


title: New Vaccine Technologies to Combat Outbreak Situations

text: Ever since the development of the first vaccine more than 200 years ago, vaccinations have greatly decreased the burden of infectious diseases worldwide, famously leading to the eradication of small pox and allowing the restriction of diseases such as polio, tetanus, diphtheria, and measles. A multitude of research efforts focuses on the improvement of established and the discovery of new vaccines such as the HPV (human papilloma virus) vaccine in 2006. However, radical changes in the density, age distribution and traveling habits of the population worldwide as well as the changing climate favor the emergence of old and new pathogens that bear the risk of becoming pandemic threats. In recent years, the rapid spread of severe infections such as HIV, SARS, Ebola, and Zika have highlighted the dire need for global preparedness for pandemics, which necessitates the extremely rapid development and comprehensive distribution of vaccines against potentially previously unknown pathogens. What is more, the emergence of antibiotic resistant bacteria calls for new approaches to prevent infections. Given these changes, established methods for the identification of new vaccine candidates are no longer sufficient to ensure global protection. Hence, new vaccine technologies able to achieve rapid development as well as large scale production are of pivotal importance. This review will discuss viral vector and nucleic acid-based vaccines (DNA and mRNA vaccines) as new approaches that might be able to tackle these challenges to global health.


title: Data Sharing in a Humanitarian Organization: The Experience of Médecins Sans Frontières

text: Unni Karunakara and colleagues discuss how Médecins Sans Frontières decided to adopt a data sharing policy for routinely collected clinical and research data in humanitarian settings and its aspirations to create a truly open data set with the first step being managed access. Please see later in the article for the Editors' Summary


title: Protection from lethal coronavirus infection by affinity-purified spike glycoprotein of murine hepatitis virus, strain A59

text: Abstract Murine hepatitis viruses provide excellent animal models for the study of virus-induced diseases of the central nervous system and gastrointestinal tract. Several studies have indirectly provided evidence that the spike glycoprotein (S) of these coronaviruses bears determinants for pathogenesis and the induction of protective immunity. In order to directly evaluate the immunogenicity of this protein, it was purified by affinity chromatography with an in vitro neutralizing and in vivo protective monoclonal antibody which immunoprecipitated the 180-kDa spike glycoprotein of the neurotropic A59 strain of murine hepatitis virus (MHV-A59). Mice immunized twice with approximately 1 μg of purified S in Freund's adjuvant developed high titers of neutralizing and fusion inhibiting antibodies, even though the protein was at least partially denaturated after elution from the affinity column. Moreover, these mice were protected from lethal encephalitis when challenged intracerebrally with 10 LD50 of MHV-A59. This study provides a direct demonstration of the importance of the coronavirus spike glycoprotein in the induction of a protective immune response.


title: Emerging Respiratory Viruses Other than Influenza

text: Non-influenza respiratory virus infections are common worldwide and contribute to morbidity and mortality in all age groups. The recently identified Middle East respiratory syndrome coronavirus has been associated with rapidly progressive pneumonia and high mortality rate. Adenovirus 14 has been increasingly recognized in severe acute respiratory illness in both military and civilian individuals. Rhinovirus C and human bocavirus type 1 have been commonly detected in infants and young children with respiratory tract infection and studies have shown a positive correlation between respiratory illness and high viral loads, mono-infection, viremia, and/or serologically-confirmed primary infection.


title: Ebola virus disease: a highly fatal infectious disease reemerging in West Africa

text: Abstract Ebolavirus can cause a highly fatal and panic-generating human disease which may jump from bats to other mammals and human. High viral loads in body fluids allow efficient transmission by contact. Lack of effective antivirals, vaccines and public health infrastructures in parts of Africa make it difficult to health workers to contain the outbreak.


title: Cytokine systems approach demonstrates differences in innate and pro-inflammatory host responses between genetically distinct MERS-CoV isolates

text: BACKGROUND: The recent emergence of a novel coronavirus in the Middle East (designated MERS-CoV) is a reminder of the zoonotic and pathogenic potential of emerging coronaviruses in humans. Clinical features of Middle East respiratory syndrome (MERS) include atypical pneumonia and progressive respiratory failure that is highly reminiscent of severe acute respiratory syndrome (SARS) caused by SARS-CoV. The host response is a key component of highly pathogenic respiratory virus infection. Here, we computationally analyzed gene expression changes in a human airway epithelial cell line infected with two genetically distinct MERS-CoV strains obtained from human patients, MERS-CoV SA 1 and MERS-CoV Eng 1. RESULTS: Using topological techniques, including persistence homology and filtered clustering, we performed a comparative transcriptional analysis of human Calu-3 cell host responses to the different MERS-CoV strains, with MERS-CoV Eng 1 inducing early kinetic changes, between 3 and 12 hours post infection, compared to MERS-CoV SA 1. Robust transcriptional changes distinguished the two MERS-CoV strains predominantly at the late time points. Combining statistical analysis of infection and cytokine-stimulated Calu-3 transcriptomics, we identified differential innate responses, including up-regulation of extracellular remodeling genes following MERS-CoV Eng 1 infection and differential pro-inflammatory responses. CONCLUSIONS: Through our genomics-based approach, we found topological differences in the kinetics and magnitude of the host response to MERS-CoV SA 1 and MERS-CoV Eng 1, with differential expression of innate immune and pro-inflammatory responsive genes as a result of IFN, TNF and IL-1α signaling. Predicted activation for STAT3 mediating gene expression relevant for epithelial cell-to-cell adherens and junction signaling in MERS-CoV Eng 1 infection suggest that these transcriptional differences may be the result of amino acid differences in viral proteins known to modulate innate immunity during MERS-CoV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1161) contains supplementary material, which is available to authorized users.


title: Evolution, antigenicity and pathogenicity of global porcine epidemic diarrhea virus strains

text: Emerging and re-emerging coronaviruses cause morbidity and mortality in human and animal populations, resulting in serious public and animal health threats and economic losses. The ongoing outbreak of a highly contagious and deadly porcine epidemic diarrhea virus (PEDV) in Asia, the Americas and Europe is one example. Genomic sequence analyses of PEDV variants have revealed important insights into the evolution of PEDV. However, the antigenic variations among different PEDV strains are less explored, although they may contribute to the failure of PEDV vaccines in Asian countries. In addition, the evolution of PEDV results in variants with distinct genetic features and virulence differences; thus PEDV can serve as a model to explore the molecular mechanisms of coronavirus evolution and pathogenesis. In this article, we review the evolution, antigenic relationships and pathologic features of PEDV strains. This information and review of researches will aid in the development of strategies for control and prevention of PED.


title: Situación actual en el desarrollo de una vacuna preventiva frente al VIH

text: El avance de la epidemia de sida ha convertido la obtención de una vacuna eficaz frente al virus de la inmunodeficiencia humana (VIH) como un objetivo científico prioritario. En el momento actual no disponemos de una vacuna preventiva frente a la infección por el VIH y en ningún modelo animal se ha conseguido la protección frente a la infección. En esta revisión se analizan las dificultades existentes en el desarrollo de una vacuna contra el sida, en especial los mecanismos de escape viral a la respuesta inmunitaria y se describen los prototipos de vacunas preventivas y terapéuticas en desarrollo y los resultados obtenidos. Por otra parte se sitúa esta investigación en el contexto sanitario, económico y social de la pandemia de sida y se analizan las polémicas actualmente planteadas en el desarrollo de ensayos clínicos con los diferentes tipos de vacunas. Due to the uncontrolled progression of the aids epidemic the development of an HIV vaccine has become a major objective of scientific research. An effective preventive vaccine against human immunodeficiency virus (HIV) is not available and sterilising immunity has not yet been achieved in animal models. In this review major challenges in developing an aids vaccine, in particular the mechanisms involved in viral escape to the immune response are analysed, and results obtained with the different prototypes of therapeutic and preventive vaccines summarized. Finally, social, economic and health aspects related to research on HIV vaccines and present controversies regarding the development of clinical trials are discussed.


Prevention of renal failure: The Malaysian experience. Renal replacement therapy in Malaysia has shown exponential growth since 1990. The dialysis acceptance rate for 2003 was 80 per million population, prevalence 391 per million population. There are now more than 10,000 patients on dialysis. This growth is proportional to the growth in gross domestic product (GDP). Improvement in nephrology and urology services with widespread availability of ultrasonography and renal pathology has improved care of renal patients. Proper management of renal stone disease, lupus nephritis, and acute renal failure has decreased these as causes of end-stage renal disease (ESRD) in younger age groups. Older patients are being accepted for dialysis, and 51% of new patients on dialysis were diabetic in 2003. The prevalence of diabetes is rising in the country (presently 7%); glycemic control of such patients is suboptimal. Thirty-three percent of adult Malaysians are hypertensive and blood pressure control is poor (6%). There is a national coordinating committee to oversee the control of diabetes and hypertension in the country. Primary care clinics have been provided with kits to detect microalbuminuria, and ACE inhibitors for the treatment of hypertension and diabetic nephropathy. Prevention of renal failure workshops targeted at primary care doctors have been launched, opportunistic screening at health clinics is being carried out, and public education targeting high-risk groups is ongoing. The challenge in Malaysia is to stem the rising tide of diabetic ESRD.


title: Altered pathogenicity in the liver induced by a mouse hepatitis virus type 3 thermosensitive mutant

text: Abstract Intraperitoneal inoculation into sensitive BALB/c mice of D85, a thermosensitive (ts) mutant, provokes acute hepatitis followed by recovery of the mice. The ts mutant was able to replicate in the liver. However, the maximal viral titre was obtained 2 days later than was the case with the wild-type (wt) MHV 3 infection; the viral antigens remained localized within small foci and no invasion of the entire liver was observed. The hepatocytes infected with D85 showed strong steatosis similar to that induced by wt virus, but the other lesions induced by MHV 3 (closing of endothelial cell fenestrae and hepatocytolysis) were not seen. An important feature noticed with the D85 mutant concerned the establishment, in the surviving animals, of persistent infection: this phenomenon was demonstrated by the decrease of viral titre in the liver, viral RNA detection, and the fact that viral antigens gradually decreased until the 3rd month post-infection.


title: Cocirculation of Four Infectious Bronchitis Virus Lineages in Broiler Chickens in the Eastern Region of Saudi Arabia from 2012 to 2014

text: Avian infectious bronchitis virus (IBV) is an evolving and dynamic virus that causes major economic losses for the poultry industry worldwide. Continuous evolution and emergence of new variants of this virus are the major challenges for controlling the disease with routine vaccination. Successful vaccination usually requires the use of a homologous vaccine, which in turn necessitates continuous investigation of the circulating strains. Herein, we performed a reverse transcriptase-polymerase chain reaction- (RT-PCR-) based investigation in broiler chicken flocks of the Eastern Region of Saudi Arabia. IBV was detected in 36.5% of the tested flocks (42 out of 115) from January 2012 to March 2014. Direct sequencing of hypervariable region-3 (HVR-3) of the Spike (S)-1 gene was performed, followed by phylogenetic analysis to determine the circulating IBV genotypes. Four lineages appear to coexist in this region, including the GI-13 or 4/91 IBV (31%), GI-16 or CK/CH/LDL/97I IBV (28.6%), GI-1 or Mass IBV (19%), and GI-23 or Middle East IBV (21.4%). The latter lineage include two subgroups: IS/720/99 IBV (16.7%) and IS/Variant2/98 IBV (4.7%). Some of the detections made in the 4/91 and Mass lineages are expected to belong to the vaccine strains. Lineages without a homologous vaccine in use (CK/CH/LDL/97I and Middle East) represent 50% of the isolates recovered in this study. Based on identity with the vaccine sequences, field observations, and frequent detection, these two lineages appear to be out of coverage of the IBV vaccines used in Saudi Arabia. This is the first time to identify Middle East lineage (IS/720/99 IBV and IS/Variant2/98 IBV) in the Eastern Region of Saudi Arabia.


title: Assay Techniques and Test Development for COVID-19 Diagnosis

text: An ongoing theme of the COVID-19 pandemic is the need for widespread availability of accurate and eﬃcient diagnostic testing for detection of SARS-CoV-2 and antiviral antibodies in infected individuals. This report describes various assay techniques and tests for COVID-19 diagnosis. Most tests for early detection of SARS-CoV-2 RNA rely on the reverse transcription-polymerase chain reaction, but isothermal nucleic acid ampliﬁcation assays, including transcription-mediated ampliﬁcation and CRISPR-based methodologies, are promising alternatives. Identiﬁcation of individuals who have developed antibodies to the SARS-CoV-2 virus requires serological tests, including enzyme-linked immunosorbent assay (ELISA) and lateral ﬂow immunoassay. This report also provides an overview of current development in COVID-19 diagnostic techniques and products to facilitate future improvement and innovation.


title: POLD1: central mediator of DNA replication and repair, and implication in cancer and other pathologies

text: The evolutionarily conserved human polymerase delta (POLD1) gene encodes the large p125 subunit which provides the essential catalytic activities of polymerase δ (Polδ), mediated by 5’–3’ DNA polymerase and 3’–5’ exonuclease moieties. POLD1 associates with three smaller subunits (POLD2, POLD3, POLD4), which together with Replication Factor C and Proliferating Nuclear Cell Antigen constitute the polymerase holoenzyme. Polδ function is essential for replication, with a primary role as the replicase for the lagging strand. Polδ also has an important proofreading ability conferred by the exonuclease activity, which is critical for ensuring replicative fidelity, but also serves to repair DNA lesions arising as a result of exposure to mutagens. Polδ has been shown to be important for multiple forms of DNA repair, including nucleotide excision repair, double strand break repair, base excision repair, and mismatch repair. A growing number of studies in the past decade have linked germline and sporadic mutations in POLD1 and the other subunits of Polδ with human pathologies. Mutations in Polδ in mice and humans lead to genomic instability, mutator phenotype and tumorigenesis. The advent of genome sequencing techniques has identified damaging mutations in the proofreading domain of POLD1 as the underlying cause of some inherited cancers, and suggested that mutations in POLD1 may influence therapeutic management. In addition, mutations in POLD1 have been identified in the developmental disorders of mandibular hypoplasia, deafness, progeroid features and lipodystrophy and atypical Werner syndrome, while changes in expression or activity of POLD1 have been linked to senescence and aging. Intriguingly, some recent evidence suggests POLD1 function may also be altered in diabetes. We provide an overview of critical Polδ activities in the context of these pathologic conditions.


title: Are Cryptocurrencies a Safe Haven for Equity Markets? An International Perspective from the COVID-19 Pandemic

text: Abstract The COVID-19 pandemic provided the first widespread bear market conditions since the inception of cryptocurrencies. We test the widely mooted safe haven properties of Bitcoin, Ethereum and Tether from the perspective of international equity index investors. Bitcoin and Ethereum are not a safe haven for the majority of international equity markets examined, with their inclusion adding to portfolio downside risk. Only investors in the Chinese CSI 300 index realized modest downside risk benefits (contingent on very limited allocations to Bitcoin or Ethereum). As Tether successfully maintained its peg to the US dollar during the COVID-19 turmoil, it acted as a safe haven investment for all of the international indices examined. We caveat the latter findings with a warning that Tether's dollar peg has not always been maintained, with evidence of impaired downside risk hedging properties earlier in our sample.


title: Comparison of Copan ESwab and FLOQSwab for COVID-19 Diagnosis: Working around a Supply Shortage

text: On March 16th 2020, WHO Director-General stated "You cannot fight a fire blindfolded. And we cannot stop this [COVID-19] pandemic if we don't know who is infected. We have a simple message for all countries: test, test, test. Test every suspected case." (https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---16-march-2020) This strategy hinges on the availability of appropriate, validated collection and transport systems to ensure preservation of nucleic acids and compatibility with downstream molecular testing - an acute challenge in the current pandemic. We present direct comparison of COVID-19 specimens collected with FLOQswab Nasopharyngeal Swab preserved in universal transport medium (Copan UTM System, Copan, Italy, catalog No.305C), optimized for viral specimens, and flocked regular nylon tip swab preserved in liquid amies (Eswab Collection system, Copan, Italy, catalog No. 480C), optimized for bacterial specimens.


title: Artificial Intelligence: Promise, Pitfalls, and Perspective

text: In this Medical News article, JAMA Fishbein Fellow Angel N Desai, MD, MPH, speaks with scientist and entrepreneur Gary Marcus, PhD, about the potential of artificial intelligence in health care and the current coronavirus pandemic [ABSTRACT FROM AUTHOR] Copyright of JAMA: Journal of the American Medical Association is the property of American Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )


title: The Discovery of a Putative Allosteric Site in the SARS-CoV-2 Spike Protein Using an Integrated Structural/Dynamic Approach

text: [Image: see text] SARS-CoV-2 has caused the largest pandemic of the twenty-first century (COVID-19), threatening the life and economy of all countries in the world. The identification of novel therapies and vaccines that can mitigate or control this global health threat is among the most important challenges facing biomedical sciences. To construct a long-term strategy to fight both SARS-CoV-2 and other possible future threats from coronaviruses, it is critical to understand the molecular mechanisms underlying the virus action. The viral entry and associated infectivity stems from the formation of the SARS-CoV-2 spike protein complex with angiotensin-converting enzyme 2 (ACE2). The detection of putative allosteric sites on the viral spike protein molecule can be used to elucidate the molecular pathways that can be targeted with allosteric drugs to weaken the spike-ACE2 interaction and, thus, reduce viral infectivity. In this study, we present the results of the application of different computational methods aimed at detecting allosteric sites on the SARS-CoV-2 spike protein. The adopted tools consisted of the protein contact networks (PCNs), SEPAS (Affinity by Flexibility), and perturbation response scanning (PRS) based on elastic network modes. All of these methods were applied to the ACE2 complex with both the SARS-CoV2 and SARS-CoV spike proteins. All of the adopted analyses converged toward a specific region (allosteric modulation region [AMR]), present in both complexes and predicted to act as an allosteric site modulating the binding of the spike protein with ACE2. Preliminary results on hepcidin (a molecule with strong structural and sequence with AMR) indicated an inhibitory effect on the binding affinity of the spike protein toward the ACE2 protein.


title: Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-κB

text: Abstract High levels of interleukin-6 (IL-6) in the acute stage associated with lung lesions were found in SARS patients. To evaluate the mechanisms behind this event, we investigated the roles of SARS-CoV proteins in the regulation of IL-6. Results showed that the viral nucleocapsid (N) protein activated IL-6 expression in a concentration-dependent manner. Promoter analyses suggested that NF-κB binding element was required for IL-6 expression regulated by N protein. Further studies demonstrated that N protein bound directly to NF-κB element on the promoter. We also showed that N protein activated IL-6 expression through NF-κB by facilitating the translocation of NF-κB from cytosol to nucleus. Mutational analyses revealed that two regions of N protein were essential for its function in the activation of IL-6. These results provided new insights into understanding the mechanism involved in the function of SARS-CoV N protein and pathogenesis of the virus.


title: Epidemiological and phylogenic study of human metapneumovirus infections during three consecutive outbreaks in Normandy, France

text: Human metapneumovirus (hMPV) is responsible for respiratory tract disease, particularly in the young and elderly population. An epidemiological and phylogenic study was performed on children admitted to hospital with an acute lower respiratory tract infection (LRI). Data were obtained and analyzed over three consecutive winters, from 2002–2003 to 2004–2005. Each year during the winter period, from November to March, 2,415 nasal swabs were tested by a direct immunofluorescence assay (DFA) for influenza viruses A and B, respiratory syncytial virus, parainfluenza viruses, and adenoviruses. Rhinoviruses, enteroviruses, and coronaviruses OC43 and 229E were detected by RT‐PCR. A RT‐PCR designed for the M gene was performed on negative samples for hMPV detection and phylogenic analyses. For the three consecutive winters, hMPV represented 10%, 22.6%, and 8.8% of virus‐negative samples, respectively. In most cases, clinical symptoms indicated a LRI with a final diagnosis of bronchiolitis. During the winter of 2003–2004, all viral clusters (A1, A2, B1, and B2) that circulated in France shifted progressively from the A group to the B group. This study determined the prevalence of hMPV in Normandy, its clinical impact and permitted the analysis of the molecular evolution during the successive outbreaks. J. Med. Virol. 83:517–524, 2011. © 2011 Wiley‐Liss, Inc.


COVID-19, una nueva oportunidad para la educación sanitaria global


title: Seasonality of Coronavirus 229E, HKU1, NL63 and OC43 from 2014-2020

text: Abstract The possibility of seasonality of Covid-19 is being discussed; here we show clinical microbiology laboratory data illustrating seasonality of coronaviruses 229E, HKU1, NL63 and OC43. The data shown are specific to the four studied coronaviruses, and may or may not generalize to Covid-19.


title: Viral interactions with macroautophagy: A double-edged sword

text: Abstract Autophagy is a conserved eukaryotic mechanism that mediates the removal of long-lived cytoplasmic macromolecules and damaged organelles via a lysosomal degradative pathway. Recently, a multitude of studies have reported that viral infections may have complex interconnections with the autophagic process. These observations strongly imply that autophagy has virus-specific roles relating to viral replication, host innate and adaptive immune responses, virus-induced cell death programs, and viral pathogenesis. Autophagy can supply internal membrane structures necessary for viral replication or may prolong cell survival during viral infections and postpone cell death. It can influence the survival of both infected and bystander cells. This process has also been linked to the recognition of viral signature molecules during innate immunity and has been suggested to help rid the cell of infection. This review discusses interactions between different viruses and the autophagy pathway, and surveys the current state of knowledge and emerging themes within this field.


title: CD13 is dispensable for normal hematopoiesis and myeloid cell functions in the mouse

text: The robust and consistent expression of the CD13 cell surface marker on very early as well as differentiated myeloid hematopoietic cells has prompted numerous investigations seeking to define roles for CD13 in myeloid cells. To address the function of myeloid CD13 directly, we created a CD13 null mouse and assessed the responses of purified primary macrophages or DCs from WT and CD13 null animals in cell assays and inflammatory disease models, where CD13 has been implicated previously. We find that mice lacking CD13 develop normally with normal hematopoietic profiles except for an increase in thymic but not peripheral T cell numbers. Moreover, in in vitro assays, CD13 appears to be largely dispensable for the aspects of phagocytosis, proliferation, and antigen presentation that we tested, although we observed a slight decrease in actin-independent erythrocyte uptake. However, in agreement with our published studies, we show that lack of monocytic CD13 completely ablates anti-CD13-dependent monocyte adhesion to WT endothelial cells. In vivo assessment of four inflammatory disease models showed that lack of CD13 has little effect on disease onset or progression. Nominal alterations in gene expression levels between CD13 WT and null macrophages argue against compensatory mechanisms. Therefore, although CD13 is highly expressed on myeloid cells and is a reliable marker of the myeloid lineage of normal and leukemic cells, it is not a critical regulator of hematopoietic development, hemostasis, or myeloid cell function.


title: On the mechanisms of bananin activity against severe acute respiratory syndrome coronavirus

text: In a previous study, severe acute respiratory syndrome coronavirus (SARS‐CoV) was cultured in the presence of bananin, an effective adamantane‐related molecule with antiviral activity. In the present study, we show that all bananin‐resistant variants exhibit mutations in helicase and membrane protein, although no evidence of bananin interference on their mutual interaction has been found. A structural analysis on protein sequence mutations found in SARS‐CoV bananin‐resistant variants was performed. The S259/L mutation of SARS‐CoV helicase is always found in all the identified bananin‐resistant variants, suggesting a primary role of this mutation site for bananin activity. From a structural analysis of SARS‐CoV predicted helicase structure, S259 is found in a hydrophilic surface pocket, far from the enzyme active sites and outside the helicase dimer interface. The S/L substitution causes a pocket volume reduction that weakens the interaction between bananin and SARS‐CoV mutated helicase, suggesting a possible mechanism for bananin antiviral activity.


title: Synthesis and testing of azaglutamine derivatives as inhibitors of Hepatitis A Virus (HAV) 3C proteinase

text: Abstract Hepatitis A virus (HAV) 3C proteinase is a picornaviral cysteine proteinase that is essential for cleavage of the initially synthesized viral polyprotein precursor to mature fragments and is therefore required for viral replication in vivo. Since the enzyme generally recognizes peptide substrates with l-glutamine at the P1 site, four types of analogues having an azaglutamine residue were chemically synthesized: hydrazo-o-nitrophenylsulfenamides A (e.g. 16); frame-shifted hydrazo-o-nitrophenylsulfenamides B (e.g. 25–28); the azaglutamine sulfonamides C (e.g. 7, 8, 11, 12); and haloacetyl azaglutamine analogues 2 and 3. Testing of these compounds for inhibition of the HAV 3C proteinase employed a C24S mutant in which the non-essential surface cysteine was replaced with serine and which displays identical catalytic parameters to the wild-type enzyme. Sulfenamide 16 (type A) showed no significant inhibition. Sulfenamide 27 (type B) had an IC50 of ca 100μM and gave time-dependent inactivation of the enzyme due to disulfide bond formation with the active site cysteine thiol, as demonstrated by electrospray mass spectrometry. Sulfonamide 8 (type C) was a weak competitive inhibitor with an IC50 of approximately 75μM. The haloacetyl azaglutamine analogues 2 and 3 were time-dependent irreversible inactivators of HAV 3C proteinase with rate constants k obs/[I] of 680M−1 s−1 and 870M−1 s−1, respectively, and were shown to alkylate the active site thiol. ©


18FDG PET/CT scan reveals hypoactive orbitofrontal cortex in anosmia of COVID-19


title: Potential effects of curcumin in the treatment of COVID‐19 infection

text: Coronavirus disease 2019 (COVID‐19) outbreak is an ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) with considerable mortality worldwide. The main clinical manifestation of COVID‐19 is the presence of respiratory symptoms, but some patients develop severe cardiovascular and renal complications. There is an urgency to understand the mechanism by which this virus causes complications so as to develop treatment options. Curcumin, a natural polyphenolic compound, could be a potential treatment option for patients with coronavirus disease. In this study, we review some of the potential effects of curcumin such as inhibiting the entry of virus to the cell, inhibiting encapsulation of the virus and viral protease as well as modulating various cellular signaling pathways. This review provides a basis for further research and development of clinical applications of curcumin for the treatment of newly emerged SARS‐CoV‐2. This article is protected by copyright. All rights reserved.


title: “Your Health Essential for Your Hajj”: Muslim pilgrims' knowledge, attitudes and practices regarding Middle East respiratory syndrome coronavirus (MERS-CoV) during Hajj season

text: Abstract Background Up to date, there have been no studies to evaluate pilgrims' knowledge, attitude and practices regarding MERS-CoV during the annual Hajj pilgrimage in order to see whether there is a need for these aspects to be improved. Methods A cross-sectional survey study was conducted with a convenience sampling. Participants were pilgrims, aged over 18, and able to speak Arabic or English. A self-administered structured questionnaire was distributed during Hajj season in Mecca. Descriptive and multiple linear regression analysis were used in data analysis. Results Two hundred and fifty-seven participants completed the study, 80% of whom were female, and the median (IQR) age was 35 (24.5–43.5) years. Pilgrims had moderately correct knowledge and accurate attitudes about MERS-CoV with median scores of 5 (IQR 4–7) and 6 (IQR: 5–7) respectively. Educational level and employment status were significantly associated with knowledge whereas gender and age were significantly associated with attitude and practices respectively (P < 0.05). The correlation between knowledge, attitude and practices was significant (correlation coefficient: 0.207; P < 0.05). Better knowledge was found to be a predictor for positive practice. Conclusions These findings will provide insight when designing future interventions to promote specific messages to enhance knowledge, change attitude and improve practice regarding MERS-CoV.


title: Prevalence and clinical significance of respiratory viruses and bacteria detected in tuberculosis patients compared to household contact controls in Tanzania: a cohort study

text: Abstract Objectives To describe the prevalence of respiratory pathogens in tuberculosis (TB) patients and in their household contact controls, and to determine the clinical significance of respiratory pathogens in TB patients. Methods We studied 489 smear-positive adult TB patients and 305 household contact controls without TB with nasopharyngeal swab samples within an ongoing prospective cohort study in Dar es Salaam, Tanzania, between 2013 and 2015. We used multiplex real-time PCR to detect 16 respiratory viruses and seven bacterial pathogens from nasopharyngeal swabs. Results The median age of the study participants was 33 years; 61% (484/794) were men, and 21% (168/794) were HIV-positive. TB patients had a higher prevalence of HIV (28.6%; 140/489) than controls (9.2%; 28/305). Overall prevalence of respiratory viral pathogens was 20.4% (160/794; 95%CI 17.7–23.3%) and of bacterial pathogens 38.2% (303/794; 95%CI 34.9–41.6%). TB patients and controls did not differ in the prevalence of respiratory viruses (Odds Ratio [OR] 1.00, 95%CI 0.71–1.44), but respiratory bacteria were less frequently detected in TB patients (OR 0.70, 95%CI 0.53–0.94). TB patients with both respiratory viruses and respiratory bacteria were likely to have more severe disease (adjusted OR [aOR] 1.6, 95%CI 1.1–2.4; p 0.011). TB patients with respiratory viruses tended to have more frequent lung cavitations (aOR 1.6, 95%CI 0.93–2.7; p 0.089). Conclusions Respiratory viruses are common for both TB patients and household controls. TB patients may present with more severe TB disease, particularly when they are co-infected with both bacteria and viruses.


title: Good deeds and cheap marketing—The food industry in the times of COVID‐19

text: The consumption of ultra‐processed foods is one of the main drivers of the global obesity and non‐communicable disease (NCDs) epidemic(1). It is well known that obesity is associated with a low intensity chronic inflammatory state that creates a suboptimal immune response,(2) which negatively affects the prognosis of COVID‐19(3). The epidemic of obesity and COVID‐19 can be viewed as a syndemic as they negatively interact with one another to exacerbate the course of disease, leading to greater complications and severe illness. Together, they create a simultaneous and significant burden on the health system(4). Thus, an in‐depth analysis on the food industry’s role in this pandemic and in our society is necessary.


title: Characterization of neuraminidase inhibitor-resistant influenza virus isolates from immunocompromised patients in the Republic of Korea

text: BACKGROUND: The emergence of influenza viruses resistant to anti-influenza drugs is a threat to global public health. The Korea Centers for Disease Control and Prevention operates the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS) to monitor epidemics of influenza and Severe Acute Respiratory Infection (SARI) to identify mutated influenza viruses affecting drug resistance, pathogenesis, and transmission. METHODS: Oropharyngeal swab samples were collected from KINRESS and SARI during the 2018–2019 season. The specimens confirmed influenza virus using real-time RT-PCR on inoculated MDCK cells. HA and NA sequences of the influenza viruses were analyzed for phylogeny and mutations. Neuraminidase inhibition and hemagglutination inhibition assays were utilized to characterize the isolates. RESULTS: Two A(H1N1)pdm09 isolates harboring an H275Y substitution in the neuraminidase sequence were detected in patients with acute hematologic cancer. They had prolonged respiratory symptoms, with the virus present in the respiratory tract despite oseltamivir and peramivir treatment. Through the neuraminidase inhibition assay, both viruses were found to be resistant to oseltamivir and peramivir, but not to zanamivir. Although hemagglutinin and neuraminidase phylogenetic analyses suggested that the 2 A(H1N1)pdm09 isolates were not identical, their antigenicity was similar to that of the 2018–19 influenza vaccine virus. CONCLUSIONS: Our data indicate the utility of monitoring influenza-infected immunocompromised patients in general hospitals for the early detection of emerging neuraminidase inhibitor-resistant viruses and maintaining continuous laboratory surveillance of patients with influenza-like illness in sentinel clinics to monitor the spread of such new variants. Finally, characterization of the virus can inform the risk assessment for future epidemics and pandemics caused by drug-resistant influenza viruses.


Will Community Health Centers Survive COVID‐19?


title: Immunogenicity assay of the Leishmune(®) vaccine against canine visceral leishmaniasis in Brazil

text: Leishmune(®) is the industrialized version of the FML-saponin vaccine which has been shown to develop 92–95% protection in vaccinated dogs and 76–80% vaccine efficacy against field canine visceral leishmaniasis (CVL) in Brazil. Leishmune(®) has been proven to be safe and tolerable and a transmission-blocking vaccine which renders vaccinated dogs non-infectious to sand fly vectors. In the present investigation, 550 healthy seronegative dogs of endemic and epidemic areas of Brazil were monitored for Leishmune(®)-induced immunogenicity during a 2-year trial. Another group of 588 untreated exposed dogs was also studied in parallel. Both groups were seronegative on day 0. The strong immunogenicity induced by Leishmune(®) vaccine was demonstrated by the 98% of FML-seroconversion, increase in absorbencies, the 82.7% DTH positive reactions and increase in skin test size diameters, the average increase in CD8+ total lymphocytes population in blood (27.1%), expected for QS21 saponin-containing vaccine, the sustained proportions of CD4+ T cells, and the average increased proportions of CD21+ B lymphocytes (42.3%). The Leishmune(®)-induced protection against CVL is demonstrated by the results: 98.8% asymptomatic dogs (at the end of first year) and 99% healthy survivors (at the end of the second year) among vaccinated dogs, compared to the 79.4% asymptomatic and 61% survivor dogs (p < 0.001) monitored in the untreated exposed cohort. In spite of the low vaccine coverage, it was possible to detect a 66.1% (p < 0.005) reduction in Belo Horizonte and an 80.2% (p < 0.005) reduction in Araçatuba of the incidence of CVL among vaccinated dogs, when compared to the global incidence of CVL of each town, respectively. Our preliminary results support the potential use of Leishmune(®) to prevent CVL epidemics.


title: High SARS-CoV-2 Antibody Prevalence among Healthcare Workers Exposed to COVID-19 Patients

text: The seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was examined among 105 healthcare workers (HCWs) exposed to four patients who were laboratory confirmed with coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2 infection. These HCWs were immediately under quarantine for 14 days as soon as they were identified as close contacts. The nasopharyngeal swab samples were collected on the first and 14(th) day of the quarantine, while the serum samples were obtained on the 14(th) day of the quarantine. With the assay of enzyme immunoassay (EIA) and microneutralization assay, 17.14% (18/105) of HCWs were seropositive, while their swab samples were found to be SARS-CoV-2 RNA negative. Risk analysis revealed that wearing face mask could reduce the infection risk (odds ratio [OR], 0.127, 95% confidence interval [CI] 0.017, 0.968), while when exposed to COVID-19 patients, doctors might have higher risk of seroconversion (OR, 346.837, 95% CI 8.924, 13479.434), compared with HCWs exposed to colleagues as well as nurses and general service assistants who exposed to patients. Our study revealed that the serological testing is useful for the identification of asymptomatic or subclinical infection of SARS-CoV-2 among close contacts with COVID-19 patients.


title: DECONTAMINATION INTERVENTIONS FOR THE REUSE OF SURGICAL MASK PERSONAL PROTECTIVE EQUIPMENT: A SYSTEMATIC REVIEW

text: BACKGROUND: The high demand for personal protective equipment during the novel coronavirus outbreak has prompted the need to develop strategies to conserve supply. Little is known regarding decontamination interventions to allow for surgical mask reuse. AIM: Identify and synthesize data from original research evaluating interventions to decontaminate surgical masks for the purpose of reuse. METHODS: We searched MEDLINE, Embase, CENTRAL, Global Health, the WHO COVID-19 database, Google Scholar, DisasterLit, preprint servers, and prominent journals from inception to April 8, 2020 for prospective original research on decontamination interventions for surgical masks. Citation screening was conducted independently in duplicate. Study characteristics, interventions, and outcomes were extracted from included studies by two independent reviewers. Outcomes of interest included impact of decontamination interventions on surgical mask performance and germicidal effects. FINDINGS: Seven studies met eligibility criteria: one evaluated the effects of heat and chemical interventions applied after mask use on mask performance, and six evaluated interventions applied prior to mask use to enhance antimicrobial properties and/or mask performance. Mask performance and germicidal effects were evaluated with heterogenous test conditions. Safety outcomes were infrequently evaluated. Mask performance was best preserved with dry heat decontamination. Good germicidal effects were observed in salt-, N-halamine-, and nanoparticle-coated masks. CONCLUSION: There is limited evidence on the safety or efficacy of surgical mask decontamination. Given the heterogenous methods used in studies to date, we are unable to draw conclusions on the most efficacious and safe intervention for decontaminating surgical masks.


title: Efficacy of H120 and Ma5 avian infectious bronchitis vaccines in early challenge against QX strain

text: Infectious bronchitis (IB) is a highly infectious avian pathogen, which affects the respiratory tract, gut, reproductive system, and kidney of chicks of all ages. Many different serotypes of IB virus (IBV) are recognized which cause different clinical manifestations. According to the antigenic differences, different serotypes of the virus do not cross-protect. Massachusetts serotype induces the best cross-protection against other serotypes. Recently, the IBV QX strain has been detected in Iran. QX strain causes permanent damage to the oviduct if it occurs in the early life cycle and is a significant factor in layer and breeder chicken flocks. In this study, we compare the H120 and Ma5 vaccines’ protection against early challenge with the QX strain in commercial chicks. one-day-old commercial chicks were divided into six groups. Groups 1 and 2 were unvaccinated groups. Groups 3 and 5 were vaccinated with the H120 vaccine (eye drop) and groups 4 and 6 were vaccinated with Ma5 (eye drop) on the 6th day (5 days after vaccination). Groups 2, 3 and 4 challenged (oculonasal) with QX strain (10^(4) EID50). Ciliostasis test, histopathology, and quantitative real-time RT-PCR were done at 11 days-old of age. Results showed that neither H120 nor Ma5 could induce proper cross-protection against QX early challenge, but the viral load and adverse pathological records in vaccinated chicks were less than that in the non-vaccinated groups. It can be concluded that vaccination on the first day of the life of a chick offers not full protection against the IBV QX strain but reduced the viral load and pathological damages in vaccinated chickens. Applying other forms of vaccination and using different genotypes on one-day-old chicks are suggested.


title: The Transformative Potential of Disruptions: A Viewpoint

text: I engage with the impact of disruptions on my work life, and consider the transformative potential that these disruptions offer. I focus on four parts of my life: as a researcher, teacher, administrator and editor. In each, I examine the nature of the disruption and the way I deal with it. I also consider how the present disruption may facilitate a transformation of current practices that lead to a better world at the individual and institutional levels. Rather than lamenting the inconvenience of a crisis, I prefer to celebrate the opportunity to do better.


Impact of COVID-19 on orthopedic surgery: Experience from Saudi Arabia


Offline: COVID-19 and the NHS—“a national scandal”


title: Label-Free Electrochemical Detection of DNA Hybridization: A Method for COVID-19 Diagnosis

text: This paper presents label-free electrochemical transduction as a suitable scheme for COVID-19-specific viral RNA/c-DNA detection, with an aim to facilitate point of care diagnosis. In lieu of this, we discuss the proposed electrochemical biosensing scheme, based on electrodeposited gold nanoparticles as the transducing elements. Specific to this approach, here, the protocols associated with the immobilization of the single-stranded probe nucleotide on to the biosensor, have also been laid out. This paper also discusses the methods of electrochemical analysis, to be used for data acquisition and subsequent calibration, in relation to target analyte detection. Towards facilitating portable diagnosis, development of miniaturized sensors and their integration with readout units have also been discussed.


title: The experience of SARS-related stigma at Amoy Gardens

text: Severe Acute Respiratory Syndrome (SARS) possesses characteristics that render it particularly prone to stigmatization. SARS-related stigma, despite its salience for public health and stigma research, has had little examination. This study combines survey and case study methods to examine subjective stigma among residents of Amoy Gardens (AG), the first officially recognized site of community outbreak of SARS in Hong Kong. A total of 903 residents of AG completed a self-report questionnaire derived from two focus groups conducted toward the end of the 3-month outbreak. Case studies of two residents who lived in Block E, the heart of the SARS epidemic at AG, complement the survey data. Findings show that stigma affected most residents and took various forms of being shunned, insulted, marginalized, and rejected in the domains of work, interpersonal relationships, use of services and schooling. Stigma was also associated with psychosomatic distress. Residents’ strategies for diminishing stigma varied with gender, age, education, occupation, and proximity to perceived risk factors for SARS such as residential location, previous SARS infection and the presence of ex-SARS household members. Residents attributed stigma to government mismanagement, contagiousness of the mysterious SARS virus, and alarmist media reporting. Stigma clearly decreased, but never completely disappeared, after the outbreak. The findings confirm and add to existing knowledge on the varied origins, correlates, and impacts of stigma. They also highlight the synergistic roles of inconsistent health policy responses and risk miscommunication by the media in rapidly amplifying stigma toward an unfamiliar illness. While recognizing the intrinsically stigmatizing nature of public health measures to control SARS, we recommend that a consistent inter-sectoral approach is needed to minimize stigma and to make an effective health response to future outbreaks.


title: Quantitative Computed Tomography of the Coronavirus Disease 2019 (COVID-19) Pneumonia

text: Abstract Objective To quantify coronavirus diseases 2019 (COVID-19) pneumonia and to explore whether quantitative computer tomography (CT) could be used to assess severity on admission. Materials and Methods From January 17 to February 9, 2020, 38 hospitalized patients with COVID-19 pneumonia were consecutively enrolled in our hospitals. All clinical data and the chest CT on admission were retrospectively reviewed and analyzed. Firstly, a quantitative method based on multi-scale convolutional neural networks was used to assess the infected lung segments and this was compared with the semi-quantitative method. Secondly, the quantitative method was tested with laboratory results and the pneumonia severity index (PSI) by correlation analyses. Thirdly, both quantitative and semi-quantitative parameters between patients with different PSI were compared. Results Thirty cases were finally enrolled: 16 (53.33%) of them were male, and the mean age was 48 years old. The interval from onset symptoms to first chest CT scan was 8 days. The proportion of ground glass opacity (GGO), consolidation and the total lesion based on the quantitative method was positively correlated with the semi-quantitative CT score (P < 0.001 for all; rs=0.88, 0.87, 0.90), CRP (P=0.0278, 0.0168, 0.0078; rs=0.40, 0.43, 0.48) and ESR (P=0.0296, 0.0408, 0.0048; rs=0.46, 0.44, 0.58), respectively, and was negatively correlated with the lymphocyte count (P=0.0222, 0.0024, 0.0068; rs=-0.42, -0.53, -0.48). There was a positive correlation trend between the proportion of total infection and the pneumonia severity index (P=0.0994; rs=0.30) and a tendency that patients with severe COVID-19 pneumonia had higher percentage of consolidation and total infection (P=0.0903, 0.0989). Conclusions Quantitative CT may have potential in assessing the severity of COVID-19 pneumonia on admission.


title: Prevalence and severity of corona virus disease 2019 (COVID-19): A systematic review and meta-analysis

text: Abstract Background Since being first reported in Wuhan, China, in December 8, 2019, the outbreak of the novel coronavirus, now known as COVID-19, has spread globally. Some case studies regarding the characteristics and outcome of patients with COVID-19 have been published recently. We conducted a meta-analysis to evaluate the risk factors of COVID-19. Methods Medline, SinoMed, EMBASE, and Cochrane Library were searched for clinical and epidemiological studies on confirmed cases of COVID-19. Results The incidence of fever, cough, fatigue, and dyspnea symptoms were 85.6 % (95CI 81.3–89.9 %), 65.7 % (95CI 60.1–71.4 %), 42.4 % (95CI 32.2–52.6 %) and 21.4 % (95CI 15.3–27.5 %). The prevalence of diabetes was 7.7 % (95CI 6.1–9.3 %), hypertension was 15.6 % (95CI 12.6–18.6 %), cardiovascular disease was 4.7 % (95CI 3.1–6.2 %), and malignancy was 1.2 % (95CI 0.5–1.8 %). The complications, including ARDS risk, ranged from 5.6–13.2 %, with the pooled estimate of ARDS risk at 9.4 %, ACI at 5.8 % (95CI 0.7–10.8 %), AKI at 2.1 % (95CI 0.6–3.7 %), and shock at 4.7 % (95CI 0.9–8.6 %). The risks of severity and mortality ranged from 12.6 to 23.5% and from 2.0 to 4.4 %, with pooled estimates at 18.0 and 3.2 %, respectively. The percentage of critical cases in diabetes and hypertension was 44.5 % (95CI 27.0–61.9 %) and 41.7 % (95CI 26.4–56.9 %), respectively. Conclusion Fever is the most common symptom in patients with COVID-19. The most prevalent comorbidities are hypertension and diabetes which are associated with the severity of COVID-19. ARDS and ACI may be the main obstacles for patients to treatment recovery. The case severe rate and mortality is lower than that of SARS and MERS.


title: Isolation of the Binding Protein of Periplocoside E from BBMVs in Midgut of the Oriental Amyworm Mythimna separata Walker (Lepidoptera: Noctuidae) through Affinity Chromatography

text: Periplocosides, which are insecticidal compounds isolated from the root bark of Periploca sepium Bunge, can affect the digestive system of insects. However, the mechanism though which periplocosides induces a series of symptoms remains unknown. In this study, affinity chromatography was conducted by coupling periplocoside E-semi-succinic acid ester with epoxy amino hexyl (EAH) sepharose 4B. Sodium dodecyl sulfonate-polyacrylamide gelelectrophoresis (SDS-PAGE) was performed to analyze the fraction eluted by periplocoside E. Eight binding proteins (luciferin 4-monooxygenase, aminopeptidase N, aminopeptidase N3, nicotinamide adenine dinucleotide health (NADH) dehydrogenase subunit 5, phosphatidylinositol 3-phosphate 3-phosphatase myotubularin, actin, uncharacterized family 31 glucosidase KIAA1161, and 2OG-Fe(2) oxygenase superfamily protein) were obtained and identified through liquid chromatography/quadrupole-time of flight-mass spectrometry (LC/Q-TOF-MS) analysis of the midgut epithelium cells of Mythimna separata larvae. Aminopeptidase N and N3 are potential putative targets of periplocosides. This study establishes the foundation for further research on the mechanism of action and target localization of periplocosides in agricultural pests.


title: The potential of drug repositioning as a short-term strategy for the control and treatment of COVID-19 (SARS-CoV-2): a systematic review

text: The novel human coronavirus (SARS-CoV-2), the causative agent of COVID-19, has quickly become a threat to the public health and economy worldwide. Despite the severity of some cases, there are no current pathogen-specific antivirals available to treat the disease. Therefore, many studies have focused on the evaluation of the anti-SARS-CoV-2 activity of clinically available drugs. Here, we conducted a systematic review to describe the drug repositioning strategy against SARS-CoV-2 and to discuss the clinical impact of this approach in the current pandemic context. The systematic review was performed on March 23, 2020, using PubMed/MEDLINE, Scopus, Cochrane Library, and Biblioteca Virtual de Saúde (BVS). The data were summarized in tables and critically analyzed. After the database search, 12 relevant studies were identified as eligible for the review. Among the drugs reported in these studies, 57 showed some evidence of antiviral activity. Antivirals, especially antiretrovirals, are the main class of therapeutic agents evaluated against COVID-19. Moreover, studies have reported the anti-SARS-CoV-2 activity of antitumor (16%; 9/57), antimalarial (7%, 4/57), and antibacterial (5%; 3/57) agents. Additionally, seven pharmacological agents (chloroquine, tetrandrine, umifenovir (arbidol), carrimycin, damageprevir, lopinavir/ritonavir) are in phase IV of clinical trials. Due to the evidence of the anti-SARS-CoV-2 activity of various clinically available agents, drug repositioning stands out as a promising strategy for a short-term response in the fight against the novel coronavirus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04693-5) contains supplementary material, which is available to authorized users.


title: When COVID-19 will decline in India? Prediction by combination of recovery and case load rate

text: BACKGROUND: The World Health Organization (WHO) declared COVID-19 as a pandemic on March 11, 2020. There is sudden need of statistical modeling due to onset of COVID-19 pandemic across the world. But health planning and policy requirements need the estimates of disease problem from clinical data. OBJECTIVE: The present study aimed to predict the declination of COVID-19 using recovery rate and case load rate on basis of available data form India. METHODS: The reported COVID-19 cases in the country were obtained from website (https://datahub.io/core/covid-19#resource-covid-19_zip/). The confirmed cases, recovered cases and deaths were used for estimating recovery rate, case load rate and death rate till date June 04, 2020. RESULTS: A total of 216919 confirmed cases were reported nationwide in India on June 04, 2020. It is found that the recovery rate increased to 47.99% and case load rate decreased to 49.21%. Death rate is found to be very low 2.80%. Accordingly, coincidence of the difference of cases load rate and recovery rate (delta) will reveal a declination in expected COVID-19 cases. CONCLUSION: The epidemic in the country was mainly caused by the movement of people from various foreign countries to India. Lockdown as restricting the migration of population and decision taken by the government to quarantine the population may greatly reduce the risk of continued spread of the epidemic in India. This study predicts that when the case load rate gets lesser than recovery rate, there after COVID-19 patients would be started to decline.


title: Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling

text: Bats are reservoirs for many RNA viruses that are highly pathogenic in humans yet relatively apathogenic in the natural host. It has been suggested that differences in innate immunity are responsible. The antiviral OAS-RNase L pathway is well characterized in humans, but there is little known about its activation and antiviral activity in bats. During infection, OASs, upon sensing double-stranded RNA (dsRNA), produce 2′-5′ oligoadenylates (2-5A), leading to activation of RNase L which degrades viral and host RNA, limiting viral replication. Humans encode three active OASs (OAS1 to -3). Analysis of the Egyptian Rousette bat genome combined with mRNA sequencing from bat RoNi/7 cells revealed three homologous OAS proteins. Interferon alpha treatment or viral infection induced all three OAS mRNAs, but RNase L mRNA is constitutively expressed. Sindbis virus (SINV) or vaccinia virus (VACVΔE3L) infection of wild-type (WT) or OAS1-KO (knockout), OAS2-KO, or MAVS-KO RoNi/7 cells, but not RNase L-KO or OAS3-KO cells, induces robust RNase L activation. SINV replication is 100- to 200-fold higher in the absence of RNase L or OAS3 than in WT cells. However, MAVS-KO had no detectable effect on RNA degradation or replication. Thus, in RoNi/7 bat cells, as in human cells, activation of RNase L during infection and its antiviral activity are dependent primarily on OAS3 while MAVS signaling is not required for the activation of RNase L and restriction of infection. Our findings indicate that OAS proteins serve as pattern recognition receptors (PRRs) to recognize viral dsRNA and that this pathway is a primary response to virus rather than a secondary effect of interferon signaling.


title: Nicht jeder Video-Anbieter ist erlaubt!: Telesprechstunde

text: Beschleunigt durch die COVID-19-Pandemie steigt bei Ärzten und Patienten die Begeisterung für Videosprechstunden oder Videokonferenzen. Alte Datenschutzbedenken scheinen weithin ausradiert worden zu sein. Um das Sicherheitsniveau zu heben, wurden nun technische Regeln für die Videotelefonie-Systeme aufgestellt.


Cardiovascular Disease and Surgery Amid COVID-19 Pandemic


Postmortem diagnosis in sudden cardiac death victims: macroscopic, microscopic and molecular findings


title: Clinical and Molecular Epidemiological Features of Coronavirus HKU1–Associated Community-Acquired Pneumonia

text: BackgroundRecently, we described the discovery of a novel group 2 coronavirus, coronavirus HKU1 (CoV-HKU1), from a patient with pneumonia. However, the clinical and molecular epidemiological features of CoV-HKU1–associated pneumonia are unknown MethodsProspectively collected (during a 12-month period) nasopharyngeal aspirates (NPAs) from patients with community-acquired pneumonia from 4 hospitals were subjected to reverse-transcription polymerase chain reaction, for detection of CoV-HKU1. The epidemiological, clinical, and laboratory characteristics of patients with CoV-HKU1–associated pneumonia were analyzed. The pol spike (S), and nucleocapsid (N) genes were also sequenced ResultsNPAs from 10 (2.4%) of 418 patients with community-acquired pneumonia were found to be positive for CoV-HKU1. All 10 cases occurred in spring and winter. Nine of these patients were adults, and 4 had underlying diseases of the respiratory tract. In the 6 patients from whom serum samples were available, all had a 4-fold change in immunoglobulin (Ig) G titer and/or presence of IgM against CoV-HKU1. The 2 patients who died had significantly lower hemoglobin levels, monocyte counts, albumin levels, and oxygen saturation levels on admission and had more-extensive involvement visible on chest radiographs. Sequence analysis of the pol S, and N genes revealed 2 genotypes of CoV-HKU1 ConclusionsCoV-HKU1 accounts for 2.4% of community-acquired pneumonia, with 2 genotypes in the study population. Without performance of diagnostic tests, the illness was clinically indistinguishable from other community-acquired pneumonia illnesses


title: Characterization of a 105-kDa Polypeptide Encoded in Gene 1 of the Human Coronavirus HCV 229E

text: Abstract Gene 1 of the human coronavirus HCV 229E encompasses approximately 20.7 kb and contains two overlapping open reading frames, ORF 1a and ORF 1b. The downstream ORF 1b is expressed by a mechanism involving (−1) ribosomal frameshifting. Translation of mRNA 1, which is thought to be equivalent to the viral genomic RNA, results in the synthesis of two large polyproteins, pp1a and pp1ab. These polyproteins contain motifs characteristic of papain-like and 3C-like proteinases, RNA-dependent RNA polymerases, helicases, and metal-binding proteins. In this study, we have produced pp1ab-specific monoclonal antibodies and have used them to detect an intracellular, 105-kDa viral polypeptide that contains the putative RNA polymerase domain. Furthermore, usingtranscleavage assays with bacterially expressed HCV 229E 3C-like proteinase, we have demonstrated that the 105-kDa polypeptide is released from pp1ab by cleavage at the dipeptide bonds Gln-4068/Ser-4069 and Gln-4995/Ala-4996. These data contribute to the characterization of coronavirus 3C-like proteinase-mediated processing of pp1ab and provide the first identification of an HCV 229E ORF 1ab-encoded polypeptide in virus-infected cells.


title: Antiviral Treatments

text: Most viral respiratory tract infections are caused by classic respiratory viruses, including influenza, respiratory syncytial virus, human metapneumovirus, parainfluenza, rhinovirus, and adenovirus, whereas other viruses, such as herpes simplex, cytomegalovirus, and measles virus, can opportunistically affect the respiratory tract. The M2 inhibitors, amantadine and rimantadine, were historically effective for the prevention and treatment of influenza A but all circulating strains are currently resistant to these drugs. Neuraminidase inhibitors are the sole approved class of antivirals to treat influenza. Ribavirin, especially when combined with intravenous antibody, reduces morbidity and mortality among immunosuppressed patients.


title: Characteristics of registered studies for Coronavirus disease 2019 (COVID-19): A systematic review

text: Abstract Background The World Health Organization characterized the Coronavirus disease 2019 (COVID-19) as a pandemic on March 11th. Many clinical trials on COVID-19 have been registered, and we aim to review the study characteristics and provide guidance for future trials to avoid duplicated effort. Methods Studies on COVID-19 registered before March 3rd, 2020 on eight registry platforms worldwide were searched and the data of design, participants, interventions, and outcomes were extracted and analyzed. Results Three hundred and ninety-three studies were identified and 380 (96.7%) were from mainland China, while 3 in Japan, 3 in France, 2 in the US, and 3 were international collaborative studies. Two hundred and sixty-six (67.7%) aimed at therapeutic effect, others were for prevention, diagnosis, prognosis, etc. Two hundred and two studies (51.4%) were randomized controlled trials. Two third of therapeutic studies tested Western medicines including antiviral drugs (17.7%), stem cell and cord blood therapy (10.2%), chloroquine and derivatives (8.3%), 16 (6.0%) on Chinese medicines, and 73 (27.4%) on integrated therapy of Western and Chinese medicines. Thirty-one studies among 266 therapeutic studies (11.7%) used mortality as primary outcome, while the most designed secondary outcomes were symptoms and signs (47.0%). Half of the studies (45.5%) had not started recruiting till March 3rd. Conclusions Inappropriate outcome setting, delayed recruitment and insufficient numbers of new cases in China implied many studies may fail to complete. Strategies and protocols of the studies with robust and rapid data sharing are warranted for emergency public health events, helping the timely evidence-based decision-making.