title: The hypothetical role of Phosphatidic Acid in subverting ER membranes during SARS‐CoV infection

text: Positive sense (+) RNA viruses exploit membranes from a variety of cellular organelles to support the amplification of their genomes. This association concurs with the formation of vesicles whose main morphological feature is that of being wrapped by a double membrane. In the case of the SARS‐CoV virus, the outer membrane is not discrete for each vesicle, but seems to be continuous and shared between many individual vesicles, a difference with other +RNA viruses whose nature has remained elusive. I present morphological, biochemical and pharmacological arguments defending the striking analogy of this arrangement and that of entangled, nascent Lipid Droplets whose birth has been aborted by an excess of Phosphatidic Acid. Since Phosphatidic Acid can be targeted with therapeutical purposes, considering this working hypothesis may prove important in tackling SARS‐CoV infection. This article is protected by copyright. All rights reserved.


title: Bioavailability of the flavonol quercetin in neonatal calves after oral administration of quercetin aglycone or rutin

text: Abstract Polyphenols, such as flavonoids, are secondary plant metabolites with potentially health-promoting properties. In newborn calves flavonoids may improve health status, but little is known about the systemically availability of flavonoids in calves to exert biological effects. The aim of this study was to investigate the oral bioavailability of the flavonol quercetin, applied either as quercetin aglycone (QA) or as its glucorhamnoside rutin (RU), in newborn dairy calves. Twenty-one male newborn German Holstein calves were fed equal amounts of colostrum and milk replacer according to body weight. On d 2 and 29 of life, 9mg of quercetin equivalents/kg of body weight, either fed as QA or as RU, or no quercetin (control group) were fed together with the morning meal. Blood samples were taken before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24, and 48h after feed intake. Quercetin and quercetin metabolites with an intact flavonol structure (isorhamnetin, tamarixetin, and kaempferol) were analyzed in blood plasma after treatment with glucuronidase or sulfatase by HPLC with fluorescence detection. Maximum individual plasma concentration was depicted from the concentration-time-curve on d 2 and 29, respectively. Additional blood samples were taken to measure basal plasma concentrations of total protein, albumin, urea, and lactate as well as pre- and postprandial plasma concentrations of glucose, nonesterified fatty acids, insulin, and cortisol. Plasma concentrations of quercetin and its metabolites were significantly higher on d 2 than on d 29 of life, and administration of QA resulted in higher plasma concentrations of quercetin and its metabolites than RU. The relative bioavailability of total flavonols (sum of quercetin and its metabolites isorhamnetin, tamarixetin, and kaempferol) from RU was 72.5% on d 2 and 49.6% on d 29 when compared with QA (100%). Calves fed QA reached maximum plasma concentrations of total flavonols much earlier than did RU-fed calves. Plasma metabolites and hormones were barely affected by QA and RU feeding in this experiment. Taken together, orally administrated QA resulted in a greater bioavailability of quercetin than RU on d 2 and 29, respectively, and quercetin bioavailability of quercetin and its metabolites differed markedly between calves aged 2 and 29 d.


title: The Egyptian Rousette Genome Reveals Unexpected Features of Bat Antiviral Immunity

text: Summary Bats harbor many viruses asymptomatically, including several notorious for causing extreme virulence in humans. To identify differences between antiviral mechanisms in humans and bats, we sequenced, assembled, and analyzed the genome of Rousettus aegyptiacus, a natural reservoir of Marburg virus and the only known reservoir for any filovirus. We found an expanded and diversified KLRC/KLRD family of natural killer cell receptors, MHC class I genes, and type I interferons, which dramatically differ from their functional counterparts in other mammals. Such concerted evolution of key components of bat immunity is strongly suggestive of novel modes of antiviral defense. An evaluation of the theoretical function of these genes suggests that an inhibitory immune state may exist in bats. Based on our findings, we hypothesize that tolerance of viral infection, rather than enhanced potency of antiviral defenses, may be a key mechanism by which bats asymptomatically host viruses that are pathogenic in humans.


title: Prevalence of hydroxychloroquine retinopathy using 2018 Royal College of Ophthalmologists diagnostic criteria

text: INTRODUCTION: To measure the prevalence of hydroxychloroquine retinopathy in patients attending a hydroxychloroquine monitoring service using 2018 Royal College of Ophthalmologists diagnostic criteria. METHODS: A service evaluation audit of a hydroxychloroquine retinopathy monitoring service was undertaken. Results of Humphrey 10–2 field tests, spectral-domain optical coherence tomography and fundus autofluorescence were collected with data on dose, weight, duration of treatment, estimated glomerular filtration rate, and concurrent tamoxifen therapy. Visual field tests were assessed as reliable or unreliable, and classified as normal, hydroxychloroquine-like, poor test or related to other pathology. Cases of definite and possible retinopathy were identified using the 2018 RCOphth criteria. RESULTS: There were 1976 attendances over two years of 1597 patients. Seven hundred and twenty-eight patients had taken hydroxychloroquine for less than 5 years and 869 had taken hydroxychloroquine for 5 years or more. Fourteen patients were identified with definite hydroxychloroquine retinopathy (1.6%), and 41 patients with possible retinopathy (4.7%). Sixty-seven per cent of 861 visual fields were performed reliably, with 66.9% classified as normal, 24.9% as poor test, 5.2% hydroxychloroquine-like and 3.0% abnormal due to other pathology. CONCLUSIONS: The 1.6% prevalence of hydroxychloroquine retinopathy is lower than the previously reported prevalence of 7.5% as reported by Melles and Marmor JAMA Ophthalmol 132: 1453–60 (2014). This is because of a difference in the diagnostic criteria. Both definite and possible retinopathy would meet the diagnostic criteria of the Melles and Marmor study; 6.3% in our data, compared with 7.5%, a much smaller difference and likely to be explained by differences in the risk characteristics of the two groups.


title: Poverty and infection in the developing world: Healthcare-related infections and infection control in the tropics

text: Summary In many hospitals serving the poorest communities of Africa and other parts of the developing world, infection control activities are limited by poor infrastructure, overcrowding, inadequate hygiene and water supply, poorly functioning laboratory services and a shortage of trained staff. Hospital transmission of communicable diseases, a high prevalence of human immunodeficiency virus and multidrug-resistant tuberculosis, lack of resources for isolation and disinfection, and widespread antimicrobial resistance create major risks for healthcare-related infections. Few data exist on the prevalence or impact of these infections in such environments. There is a need for interventions to reduce the burden of healthcare-related infections in the tropics and to set up effective surveillance programmes to determine their impact. Both the Global (G8) International Development Summit of 2005 and the United Nations Millennium Development Goals (MDGs) have committed major resources to alleviating poverty and poor health in the developing world over the next decade. Targeting resources specifically to infection control in low-resource settings must be a part of this effort, if the wider aims of the MDGs to improve healthcare are to be achieved.


A Comparison of the Cambodian and the South Korean Health Care System


title: Human metapneumovirus infection in an immunocompetent adult presenting as mononucleosis-like illness

text: Summary A 37-year-old man was presented with incidental findings of neutropenia, atypical lymphocytosis, thrombocytopenia and deranged liver parenchymal enzymes. Four days later, he developed fever, sore throat and cervical lymphadenopathy, compatible with mononucleosis-like illness (MLI). Polymerase chain reaction (PCR) and viral culture of the nasopharyngeal swab showed human metapneumovirus (hMPV). There was a ≥4-fold rise in IgG against hMPV. This is the first case report illustrating the natural clinical course of hMPV-related MLI.


title: Wind tunnel study of odor impact and air ventilation assessments for relocating sewage treatment works to caverns

text: Abstract In recent years, the topicality of environment-related issues has been frequently emphasized in terms of sustainability and the better management of development in harmony with the environment. As for Hong Kong, one of the most densely populated cities, the scarcity of land has always been assumed as a major impediment for its long-term development. Therefore, the Hong Kong government actively explores approaches to enhance usable land resources. One viable approach is rock cavern development. This paper presents a feasibility assessment of relocating a sewage treatment works to a cavern, with emphasis on the evaluation of environmental sustainability. Wind tunnel tests were carried out with efforts to estimate the prospective odor impact, as well as the wind availability at pedestrian level. It is noted that the sewage odor concentration depends greatly on the dispersion distance and the surrounding topography. The results indicate that when the sewage treatment works is relocated to the cavern, the predicted odor concentration will not cause damage to human health as long as the ventilation shaft is properly placed. In addition, the air ventilation assessments were conducted for both before/after the planned building development. It shows that the new building development at the current plant site will not significantly influence the wind availability at pedestrian level in the surrounding areas. This paper highlights the importance of sustainable development in connection with the environment, and shows that rock cavern development can be an attractive alternative for strategic urban planning in Hong Kong.


title: Dataset on dynamics of Coronavirus on Twitter

text: Abstract In this data article, we provide a dataset of 8,982,694 Twitter posts around the coronavirus health global crisis. The data were collected through the Twitter REST API search. We used the rtweet R package to download raw data. The term searched was “Coronavirus” which included the word itself and its hashtag version. We collected the data over 23 days, from January 21 to February 12, 2020. The dataset is multilingual, prevailing English, Spanish, and Portuguese. We include a new variable created from other four variables; it is called “type” of tweets, which is useful for showing the diversity of tweets and the dynamics of users on Twitter. The dataset comprises seven databases which can be analysed separately. On the other hand, they can be crossed to set other researches, among them, trends and relevance of different topics, types of tweets, the embeddedness of users and their profiles, the retweets dynamics, hashtag analysis, as well as to perform social network analysis. This dataset can attract the attention of researchers related to different fields on knowledge, such as data science, social science, network science, health informatics, tourism, infodemiology, and others.


title: Symptomatic and Asymptomatic Respiratory Viral Infections in the First Year of Life: Association With Acute Otitis Media Development

text: Background. Sensitive diagnostic assays have increased the detection of viruses in asymptomatic individuals. The clinical significance of asymptomatic respiratory viral infection in infants is unknown. Methods. High-throughput, quantitative polymerase chain reaction assays were used to detect 13 common respiratory viruses from nasopharyngeal specimens collected during 2028 visits from 362 infants followed from near birth up to 12 months of age. Specimens were collected at monthly interval (months 1–6 and month 9) and during upper respiratory tract infection (URTI) episodes. Subjects were followed closely for acute otitis media (AOM) development. Results. Viruses were detected in 76% of 394 URTI specimens and 27% of asymptomatic monthly specimens. Rhinovirus was detected most often; multiple viruses were detected in 29% of the specimens. Generalized mixed-model analyses associated symptoms with increasing age and female sex; detection of respiratory syncytial virus (RSV), influenza, rhinovirus, metapneumovirus, and adenovirus was highly associated with symptoms. Increasing age was also associated with multiple virus detection. Overall, 403 asymptomatic viral infections in 237 infants were identified. Viral load was significantly higher in URTI specimens than asymptomatic specimens but did not differentiate cases of URTI with and without AOM complication. The rate of AOM complicating URTI was 27%; no AOM occurred following asymptomatic viral infections. AOM development was associated with increasing age and infection with RSV, rhinovirus, enterovirus, adenovirus, and bocavirus. Conclusions. Compared to symptomatic infection, asymptomatic viral infection in infants is associated with young age, male sex, low viral load, specific viruses, and single virus detection. Asymptomatic viral infection did not result in AOM.


title: Mouse LSECtin as a model for a human Ebola virus receptor

text: The biochemical properties of mouse LSECtin, a glycan-binding receptor that is a member of the C-type lectin family found on sinusoidal endothelial cells, have been investigated. The C-type carbohydrate-recognition domain of mouse LSECtin, expressed in bacteria, has been used in solid-phase binding assays, and a tetramerized form has been used to probe a glycan array. In spite of sequence differences near the glycan-binding sites, the mouse receptor closely mimics the properties of the human receptor, showing high affinity binding to glycans bearing terminal GlcNAcβ1-2Man motifs. Site-directed mutagenesis has been used to confirm that residues near the binding site that differ between the human and the mouse proteins do not affect this binding specificity. Mouse and human LSECtin have been shown to bind Ebola virus glycoprotein with equivalent affinities, and the GlcNAcβ1-2Man disaccharide has been demonstrated to be an effective inhibitor of this interaction. These studies provide a basis for using mouse LSECtin, and knockout mice lacking this receptor, to model the biological properties of the human receptor.


Wissenschaft in Zeiten von Corona – alles und nichts geht


title: What are the most appropriate methods of surveillance for monitoring an emerging respiratory infection such as SARS?

text: Effective surveillance is necessary for the successful management of emerging infection. It allows public health protection measures such as contact tracing and isolation to be put in place. This study aimed to find the most appropriate surveillance method for a disease like SARS. Existing surveillance methods were evaluated against a set of new criteria in a qualitative manner. Influenza and tuberculosis (TB) surveillance were used as models. A literature search was undertaken to find relevant evidence. The results show that TB surveillance is more appropriate than influenza surveillance as a model because it is more complete in its reporting. Clinician‐based reporting is better than laboratory‐based because it is more timely. The results suggest a clinician‐based notification system would be the most appropriate form of surveillance for a disease like SARS for public health purposes.


COVID-19: The Italian Viral “Gerocide” of the 21 st Century


title: Childhood Infectious Diseases: Overview

text: Of the annual burden of 10 million deaths among children under 5 years, a large proportion is associated with infectious diseases. These include 36% of the 4 million newborn deaths due to sepsis, pneumonia, diarrhea, and tetanus. Among the postneonatal deaths due to infections, estimates and uncertainty bounds include: 22% of deaths attributed to diarrhea (14–30%), 21% to pneumonia (14–24%), 9% to malaria (6–13%), and 1% to measles (1–9%). Some 42 countries alone account for almost 90% of the global burden of child mortality. There is now sufficient evidence available on evidence-based interventions that can make a difference. It is estimated that almost two-thirds of these deaths are potentially preventable if interventions can be delivered at scale. Newborn infections and related mortality can be reduced by maternal tetanus toxoid vaccination, clean delivery, cord hygiene, exclusive and early breast-feeding, and prompt diagnosis and therapy. Diarrheal deaths can be prevented by adequate attention to breast-feeding, hand-washing and sanitation strategies, rota virus vaccine, adequate treatment including oral rehydration, appropriate dietary therapy, and oral zinc administration. Similarly, the global burden of pneumonia deaths can be reduced by vaccination strategies for measles, Hib, and pneumococcal disease, timely case detection, and treatment with appropriate antibiotics.


title: Prevalence of respiratory viruses among adults, by season, age, respiratory tract region and type of medical unit in Paris, France, from 2011 to 2016

text: BACKGROUND: Multiplex PCR tests have improved our understanding of respiratory viruses’ epidemiology by allowing their wide range detection. We describe here the burden of these viruses in hospital settings over a five-year period. METHODS: All respiratory samples from adult patients (>20 years old) tested by multiplex-PCR at the request of physicians, from May 1 2011 to April 30 2016, were included retrospectively. Viral findings are reported by season, patient age group, respiratory tract region (upper or lower) and type of clinical unit (intensive care unit, pneumology unit, lung transplantation unit and other medical units). RESULTS: In total, 7196 samples (4958 patients) were included; 29.2% tested positive, with viral co-infections detected in 1.6% of samples. Overall, two viral groups accounted for 60.2% of all viruses identified: picornaviruses (rhinovirus or enterovirus, 34.3%) and influenza (26.6%). Influenza viruses constituted the group most frequently identified in winter (34.4%), in the upper respiratory tract (32%) and in patients over the age of 70 years (36.4%). Picornavirus was the second most frequently identified viral group in these populations and in all other groups, including lower respiratory tract infections (41.3%) or patients in intensive care units (37.6%). CONCLUSION: This study, the largest to date in Europe, provides a broad picture of the distribution of viruses over seasons, age groups, types of clinical unit and respiratory tract regions in the hospital setting. It highlights the burden associated with the neglected picornavirus group. These data have important implications for the future development of vaccines and antiviral drugs.


title: Letalidad del COVID-19: ausencia de patrón epidemiológico

text: ABSTRACT Objective: Analyze a set of indicators to understand the variability of the evolution and impact of the COVID-19 epidemic in a set of selected countries. Method: Ecological study of a group of countries with more than 200 reported cases. Demographic variables, health expenditure variables, and variables about characteristics of health services were included as explanatory variables. and incidence, mortality and fatality rates have been analyzed as response variables. In addition, a relative fatality index has been created. Data are from international organizations. Spearman's correlation coefficient was used to estimate the magnitude of the associations. Results: Number of tests and of medical professionals are associated with a higher incidence rate. Mortality and case fatality rate are not associated with demographic, health expenditure, or health services variables. Conclusion: Differences suggest a general underestimation of the magnitude of the epidemic. Improvement of case identification and effectiveness of epidemiological surveillance systems is necessary.


Mechanisms of Demyelination


title: SARS-CoV-2 and the Testis: similarity to other viruses and routes of infection

text: Abstract Since the latest coronavirus outbreak, the number of infected individuals and COVID-19 cases have been increasing exponentially worldwide. Of interest is the evidence that orchitis can develop due coronavirus infection. Therefore, it is not unreasonable to believe that the latest coronavirus, SARS-CoV-2, could be transmitted by semen. Consequently, it is paramount that individuals who could potentially be infected take all possible care to mitigate the likely risk of infection through sexual intercourse.


title: Target selectivity in mRNA silencing

text: Despite the excitement and promise of RNA interference in treating neurodegenerative disease, disease gene mRNA might resist mRNA silencing. Conventional siRNA design does not uniformly distinguish a mutant from a wild-type allele. CAG expansions in trinucleotide repeat diseases are unselective targets for small siRNAs. This review will consider recent discoveries in mechanisms of RNA interference and siRNA modifications that improve siRNA selectivity, delivery and performance.


docid: fhvstenq

title: MHV nucleocapsid synthesis in the presence of cycloheximide and accumulation of negative strand MHV RNA

text: Abstract We have found that genomic RNA synthesis is inhibited by cycloheximide in cells infected with mouse hepatitis virus, strain A59 (MHV-A59), in agreement with previously published results (Sawicki S.G. and Sawicki D.L. (1986) J. Virol. 57, 328–334). In the present study, the fate of the residual genomic RNA synthesized in the presence of cycloheximide was determined. Nearly all of the genomic RNA synthesized in the presence of drug was incorporated into nucleocapsid structures, suggesting that even in the absence of protein synthesis, genomic RNA synthesis and encapsidation are coupled in MHV-infected cells. Sufficient free nucleocapsid N protein was available for this purpose, since the pool of soluble N protein was determined to decay with a half-life of approximately one hour. Negative strand RNA is the template for the synthesis of both genomic and subgenomic positive strand RNA, and would be predicted to accumulate primarily during the early phases of the lytic cycle. In agreement with this prediction, negative strand RNA accumulated during the first 5–6 h of infection, with little additional accumulation occurring over the next 2.5 h. In marked contrast, positive strand RNA increased 5–6-fold over the same 2.5 h period. These results, taken in conjunction with published data, suggest that negative strand RNA is synthesized during the early period of the infectious cycle and is stable in infected cells and also suggest that treatment with cycloheximide at late times does not inhibit positive strand RNA synthesis indirectly by blocking the formation of negative strand templates.


title: A simulation approach to measure critical safety behaviors when evaluating training methods for respirator education in healthcare workers

text: BACKGROUND: The N95 respirator is the most common safety tool used in hospitals to protect healthcare workers (HCW) from inhaling airborne particles. Focusing on HCW behavior related to respirator use is an effective route to improve HCW safety and respiratory health. METHODS: Participants were asked to perform the donning and doffing of an N95 respirator to camera. Then they were randomized to a video alone or a reflective practice intervention. After the intervention they repeated the donning and doffing to camera. A critical safety behavior scoring tool (CSBST) was developed to compare the performance of the participants over time at pre-test, post-test and one month later for follow-up. RESULTS: The reflective practice intervention group was found to have significantly higher scores on the CSBST at post-test and follow-up than the video alone group. In the reflective practice intervention group, the participants perceived they were better at performing the N95 donning and doffing than the experts scored them. CONCLUSIONS: The CSBST is a tool to measure the performance of HCWs on a specific targeted safety behaviors. The addition of a reflective practice intervention may result in a measurable and sustained improvement in the safety behaviors demonstrated when using the N95 respirator.


title: Bovine respiratory syncytial virus ISCOMs—Immunity, protection and safety in young conventional calves

text: Bovine respiratory syncytial virus (BRSV) is a major cause of bronchiolitis and pneumonia in cattle and causes yearly outbreaks with high morbidity in Europe. Commercial vaccines against this virus needs improvement of efficacy, especially in calves with BRSV-specific maternally derived antibodies (MDA). We previously reported that an experimental BRSV-ISCOM vaccine, but not a commercial vaccine, induced strong clinical and virological protection in calves with MDA, immunized at 7–15 weeks of age. The aim of the present study was to characterize the immune responses, as well as to investigate the efficacy and safety in younger animals, representing the target population for vaccination. Four groups of five 3–8 week old calves with variable levels of BRSV-specific MDA were immunized s.c. twice at a 3 weeks interval with (i) BRSV immunostimulating complexes (BRSV-ISCOMs), (ii) BRSV-protein, (iii) adjuvant, or (iv) PBS. All calves were challenged with virulent BRSV by aerosol 2 weeks later and euthanized on day 6 after infection. The cellular and humoral responses were monitored as well as the clinical signs, the viral excretion and the pathology following challenge. Despite presence of MDA at the time of the immunization, only a minimum of clinical signs were observed in the BRSV-ISCOM group after challenge. In contrast, in all control groups, clinical signs of disease were observed in most of the animals (respiratory rates up to 76 min(−1) and rectal temperatures up to 41 °C). The clinical protection was associated to a highly significant reduction of virus replication in the upper and lower respiratory tract of calves, rapid systemic and local antibody responses and T helper cell responses dominated by IFNγ production. Animals that did not shed virus detectable by PCR or cell culture following challenge possessed particularly high levels of pulmonary IgA. The protective immunological responses to BRSV proteins and the ability to overcome the inhibiting effect of MDA were dependent on ISCOM borne antigen presentation.


title: Qualitative and Quantitative Determination of MERS-CoV S1-Specific Antibodies Using ELISA

text: Indirect enzyme-linked immunosorbent assay (ELISA) enables detection and quantification of antigen-specific antibodies in biological samples such as human or animal sera. Most current MERS-CoV serological assays such as neutralization, immunofluorescence, or protein microarray rely on handling of live MERS-CoV in high containment laboratories, highly trained personnel as well as the need for expensive and special equipment and reagents representing a hurdle for most laboratories especially when resources are limited. In this chapter, we describe a validated and optimized indirect ELISA protocol based on recombinant S1 subunit (amino acids 1–725) of MERS-CoV for qualitative and quantitative determination of MERS-CoV-binding antibodies.


title: Viral Infection Triggers Central Nervous System Autoimmunity Via Activation of Dual TCR-Expressing CD8(+) T Cells

text: Multiple sclerosis (MS) is an inflammatory, demyelinating, central nervous system disease mediated by myelin-specific T cells. Environmental triggers that cause a breakdown of myelin-specific T cell tolerance are unknown. We found that CD8(+) myelin basic protein (MBP)-specific T cell tolerance can be broken and autoimmunity induced by infection with a virus that does not express MBP cross-reactive epitopes and does not depend on bystander activation. Instead, the virus activated dual T cell receptor (TCR)-expressing T cells capable of recognizing both MBP and viral antigens. These results demonstrate the importance of dual TCR T cells in autoimmunity and suggest a mechanism by which a ubiquitous viral infection could trigger autoimmunity in a subset of infected individuals, as hypothesized in the etiology of MS.


title: Comparative analysis of the activation of unfolded protein response by spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus HKU1

text: BACKGROUND: Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. Spike (S) protein of SARS-CoV activates the unfolded protein response (UPR). It is not understood whether HCoV-HKU1 S protein has similar activity. In addition, the UPR-activating domain in SARS-CoV S protein remains to be identified. RESULTS: In this study we compared S proteins of SARS-CoV and HCoV-HKU1 for their ability to activate the UPR. Both S proteins were found in the endoplasmic reticulum. Transmembrane serine protease TMPRSS2 catalyzed the cleavage of SARS-CoV S protein, but not the counterpart in HCoV-HKU1. Both S proteins showed a similar pattern of UPR-activating activity. Through PERK kinase they activated the transcription of UPR effector genes such as Grp78, Grp94 and CHOP. N-linked glycosylation was not required for the activation of the UPR by S proteins. S1 subunit of SARS-CoV but not its counterpart in HCoV-HKU1 was capable of activating the UPR. A central region (amino acids 201–400) of SARS-CoV S1 was required for this activity. CONCLUSIONS: SARS-CoV and HCoV-HKU1 S proteins use distinct UPR-activating domains to exert the same modulatory effects on UPR signaling.


title: Reduced Macrophage Infiltration and Demyelination in Mice Lacking the Chemokine Receptor CCR5 Following Infection with a Neurotropic Coronavirus

text: Abstract Studies were performed to investigate the contributions of the CC chemokine receptor CCR5 in host defense and disease development following intracranial infection with mouse hepatitis virus (MHV). T cell recruitment was impaired in MHV-infected CCR5−/− mice at day 7 postinfection (pi), which correlated with increased (P ≤ 0.03) titers within the brain. However, by day 12 pi, T cell infiltration into the CNS of infected CCR5−/− and CCR5+/+ mice was similar and both strains exhibited comparable viral titers, indicating that CCR5 expression is not essential for host defense. Following MHV infection of CCR5+/+ mice, greater than 50% of cells expressing CCR5 antigen were activated macrophage/microglia (determined by F4/80 antigen expression). In addition, infected CCR5−/− mice exhibited reduced (P ≤ 0.02) macrophage (CD45highF4/80+) infiltration, which correlated with a significant reduction (P ≤ 0.001) in the severity of demyelination compared to CCR5+/+ mice. These data indicate that CCR5 contributes to MHV-induced demyelination by allowing macrophages to traffic into the CNS.


title: Impact on health care workers employed in high-risk areas during the Toronto SARS outbreak

text: Abstract Background A number of publications focusing on health care workers (HCWs) during a severe acute respiratory syndrome (SARS) outbreak have suggested that HCWs experienced psychological distress, particularly increased levels of posttraumatic stress symptomatology (PTSS). Factors contributing to increased distress in HCWs working in high-risk areas treating patients with SARS have not been fully elucidated. The goal of this study was to quantify the psychological effects of working in a high-risk unit during the SARS outbreak. Methods HCWs in a Toronto hospital who worked in high-risk areas completed a questionnaire regarding their attitude toward the SARS crisis along with the Impact of Event Scale—Revised, which screens for PTSS. The comparison group consisted of clinical units that had no contact with patients infected with SARS. Results Factors that were identified to cause distress in the 248 respondent HCWs were the following: (a) perception of risk to themselves, (b) impact of the SARS crisis on their work life, (c) depressive affect, and (d) working in a high-risk unit. In addition, HCWs who cared for only one SARS patient in comparison to those caring for multiple SARS patients experienced more PTSS. Conclusions As expected, HCWs who were working in high-risk units experienced greater distress. Contrary to expectations, HCWs who experienced greater contact with SARS patients while working in the high-risk units were less distressed. This suggests that HCW experience in treating patients infected with SARS may be a mediating factor that could be amenable to intervention in future outbreaks.


title: The experiences of health-care providers during the COVID-19 crisis in China: a qualitative study

text: Summary Background In the early stages of the outbreak of coronavirus disease 2019 (COVID-19) in Hubei, China, the local health-care system was overwhelmed. Physicians and nurses who had no infectious disease expertise were recruited to provide care to patients with COVID-19. To our knowledge, no studies on their experiences of combating COVID-19 have been published. We aimed to describe the experiences of these health-care providers in the early stages of the outbreak. Methods We did a qualitative study using an empirical phenomenological approach. Nurses and physicians were recruited from five COVID-19-designated hospitals in Hubei province using purposive and snowball sampling. They participated in semi-structured, in-depth interviews by telephone from Feb 10 to Feb 15, 2020. Interviews were transcribed verbatim and analysed using Haase's adaptation of Colaizzi's phenomenological method. Findings We recruited nine nurses and four physicians. Three theme categories emerged from data analysis. The first was “being fully responsible for patients' wellbeing—‘this is my duty’”. Health-care providers volunteered and tried their best to provide care for patients. Nurses had a crucial role in providing intensive care and assisting with activities of daily living. The second category was “challenges of working on COVID-19 wards”. Health-care providers were challenged by working in a totally new context, exhaustion due to heavy workloads and protective gear, the fear of becoming infected and infecting others, feeling powerless to handle patients' conditions, and managing relationships in this stressful situation. The third category was “resilience amid challenges”. Health-care providers identified many sources of social support and used self-management strategies to cope with the situation. They also achieved transcendence from this unique experience. Interpretation The intensive work drained health-care providers physically and emotionally. Health-care providers showed their resilience and the spirit of professional dedication to overcome difficulties. Comprehensive support should be provided to safeguard the wellbeing of health-care providers. Regular and intensive training for all health-care providers is necessary to promote preparedness and efficacy in crisis management. Funding National Key R&D Program of China, Project of Humanities and Social Sciences of the Ministry of Education in China.


title: Human coronavirus NL63 in hospitalized children with respiratory infection: A 2-year study from Chongqing, China

text: Human coronavirus (HCoV) NL63, a newly discovered coronavirus, has been associated with acute lower respiratory tract infections (ALRTI). We detected HCoV-NL63 via reverse transcriptional PCR (RT-PCR) in eight out of 878 respiratory specimens freshly collected from hospitalized children with ALRTI between April 2006 and March 2008 in Children’s Hospital of Chongqing Medical University. Peak of HCoV-NL63 activity often appeared during the summer and autumn in Chongqing area. All children with HCoV-NL63 infection were <1 year of age. The diagnosis included bronchial pneumonia, bronchitis, interstitial pneumonia and bronchiolitis. All children recovered.


title: Influence of intron and exon splicing enhancers on mammalian cell expression of a truncated spike protein of SARS-CoV and its implication for subunit vaccine development

text: The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is important for vaccine development. A truncated S protein of the TW1 strain, S(TR2) (88 kDa), carrying three S fragments (S74–253, S294–739, and S1129–1255) was investigated to study the influences of intron and exon splicing enhancers to improve S(TR2) protein expression in mammalian cells. Our results showed that S(TR2) protein expression with the use of an 138 base-pair intron addition increased by 1.9-, 2.5-, and 4.1-fold in Vero E6, QBI-293A cells, and CHO/dhFr− cells (dihydrofolate reductase [dhfr] gene deficient CHO cells), respectively. Using the exon splicing enhancers, including a bidirectional splicing enhancer (BSE) or an exon splicing enhancer derived from the EDA alternative exon of the fibronectin gene (EDA ESE), were also found to increase S(TR2) protein expression in CHO/dhFr− cells by 1.7- and 2.6-fold. Nevertheless, combination of the intron and the exon splicing enhancers resulted in suppressing the intron-enhancing e S(TR2) protein expression in in CHO/dhFr− cells. Our studies also demonstrated the S(TR2) protein was mainly as the Endo H-sensitive glycoprotein (115 kDa) expressed in Vero E6, QBI-293A, and CHO/dhFr− cells. However, only a minor form of the Endo H-resistant glycoproteins (∼130 kDa) was detected in CHO/dhFr− cells. Taken together, our results indicated that intron had a better enhancing effect on S(TR2) protein expression than exon splicing enhancers, and the expression of ∼130 kDa S(TR2) glycoprotein was enhanced by the intron addition into the expression vector construct. Results of the present study can provide an optimal strategy to enhance SARS-CoV S protein expression in mammalian cells and may contribute to the development of SARS-CoV subunit vaccine.


title: Chapter Six A Perspective on Cryptosporidium and Giardia, with an Emphasis on Bovines and Recent Epidemiological Findings

text: Abstract Cryptosporidium and Giardia are two common aetiological agents of infectious enteritis in humans and animals worldwide. These parasitic protists are usually transmitted by the faecal–oral route, following the ingestion of infective stages (oocysts or cysts). An essential component of the control of these parasitic infections, from a public health perspective, is an understanding of the sources and routes of transmission in different geographical regions. Bovines are considered potential sources of infection for humans, because species and genotypes of Cryptosporidium and Giardia infecting humans have also been isolated from cattle in molecular parasitological studies. However, species and genotypes of Cryptosporidium and Giardia of bovids, and the extent of zoonotic transmission in different geographical regions in the world, are still relatively poorly understood. The purpose of this article is to (1) provide a brief background on Cryptosporidium and Giardia, (2) review some key aspects of the molecular epidemiology of cryptosporidiosis and giardiasis in animals, with an emphasis on bovines, (3) summarize research of Cryptosporidium and Giardia from cattle and water buffaloes in parts of Australasia and Sri Lanka, considering public health aspects and (4) provide a perspective on future avenues of study. Recent studies reinforce that bovines harbour Cryptosporidium and Giardia that likely pose a human health risk and highlight the need for future investigations of the biology, population genetics and transmission dynamics of Cryptosporidium and Giardia in cattle, water buffaloes and other ruminants in different geographical regions, the fate and transport of infective stages following their release into the environment, as well as for improved strategies for the control and prevention of cryptosporidiosis and giardiasis, guided by molecular epidemiological studies.


title: Construction and characterisation of a recombinant vaccinia virus expressing human papillomavirus proteins for immunotherapy of cervical cancer

text: Abstract The presence and consistent expression of the genes encoding the human papillomavirus (HPV) E6 and E7 proteins in the great majority of cervical tumours presents the opportunity for an immunotherapeutic approach for control of the disease. This report describes the construction and characterisation of a recombinant vaccinia virus designed to express modified forms of the E6 and E7 proteins from HPV16 and HPV18, the viruses most commonly associated with cervical cancer. The recombinant virus (designated TA-HPV) was based on the Wyeth vaccine strain of vaccinia, and was shown to express the desired gene products. Studies in mice indicated that the recombinant virus was less neurovirulent than the parental virus and was capable of inducing an HPV-specific CTL response. This pre-clinical evaluation has provided a basis for the initiation of human trials in cervical cancer patients.


docid: fhvkxpyf

title: Are your IT staff ready for the pandemic-driven insider threat?

text: As this article is being written it's mid-March. The situation likely will have changed significantly by the time you read this, as it does by the day and even the hour. The World Health Organisation (WHO) has declared Covid-19 to be a global pandemic and the UK Government has stepped up its response from the ‘contain’ to the ‘delay’ phase. Public spaces and transport are noticeably quieter and many workplaces are getting emptier as staff members work from home. The Covid-19 pandemic and consequent lockdowns are hitting businesses hard. And as workforces move to remote working, IT departments are under pressure. At the same time, cyber criminals are exploiting the pandemic, with rises in phishing and other forms of attacks. The cyber security workforce, already suffering a skills crisis, may lack the soft skills required to effectively tackle these issues, many of which could be solved if the industry didn't rely so heavily on recruiting graduates and rather looked towards hiring apprentices, argues Phil Chapman of Firebrand Training.


title: Genetic characterization of canine parvovirus type 2c from domestic dogs in Korea

text: Canine parvovirus type 2 (CPV‐2) is an aetiological agent that causes acute haemorrhagic enteritis and fatal myocarditis in dogs. Since CPV‐2 first emerged in the late 1970s, its rapid evolution has resulted in three antigenic variants: CPV‐2a, CPV‐2b and CPV‐2c. Here, we report, for the first time in Korea, two cases of CPV‐2c infection in two dogs with severe diarrhoea. The complete open reading frame (4,269nt) of CPV‐2, encoding both non‐structural (NS) and structural (VP) proteins, was sequenced. Based on the amino acid Gln present at residue 426 of the VP2 gene, these strains were typed as CPV‐2c, and were named Korea CPV‐2c_1 and Korea CPV‐2c_2. These strains shared 99.48% reciprocal nucleotide sequence identity and had the highest nucleotide identity (99.77%–99.34%) with Asian CPV strains isolated in China, Italy (found in a dog imported from Thailand), and Vietnam from 2013 to 2017. Phylogenetic analysis based on the non‐structural (NS1) and capsid (VP2) genes revealed that Korean CPV‐2c strains clustered closely to Asian CPV strains, and separately from strains isolated in Europe, South America and North America. Amino acid changes never reported before were observed in NS1 (Thr70Pro, Cys287Tyr), VP1 (Lys17Arg, Phe33Leu) and VP2 (Gln365His, Ala516Val). Additional observed mutations, including Phe267Tyr, Tyr324Ile and Gln370Arg, have been previously reported in the recent CPV‐2c strains with Asian origins. These results suggest that the Korean CPV‐2c strains were potentially introduced via neighbouring Asian countries.


title: Infecciones en el paciente inmunocomprometido (II). Paciente trasplantado

text: Resumen Los receptores de los diferentes tipos de trasplante presentan un riesgo elevado de infección. En los trasplantados de precursores hematopoyéticos predominan las infecciones nosocomiales. Durante el periodo posprendimiento temprano (30-100 días tras la infusión del trasplante), la incidencia de infección es más elevada en pacientes con enfermedad de injerto contra huésped. En el pulmón pueden aparecer lesiones nodulares por infección fúngica invasora o bien un patón difuso habitualmente secundario a infección vírica o a neumonía por P. jirovecii. Después de los primeros 100 días persiste un moderado riesgo de infección por microorganismos convencionales y oportunistas, como la infección tardía por CMV. Los avances en las técnicas quirúrgicas y el empleo de calcineurínicos han reducido la mortalidad por infecciones en trasplantados de órgano sólido. Durante el primer mes, son frecuentes las infecciones nosocomiales; entre el primer y sexto mes son más frecuentes las infecciones oportunistas dependientes de la inmunidad celular y a partir de sexto mes el riesgo baja y predominan las infecciones comunitarias semejantes a las de los pacientes inmunocompetentes. Abstract Recipients of the different types of transplantation are at high risk of infection. Nosocomial infections predominate in patients who have undergone haematopoietic stem cell transplantation during the early post-engraftment period (30-100 days after the infusion); the incidence of infection is higher in graft-versus-host disease. Nodular lesions can appear in the lungs due to invasive fungal infection. A diffuse pattern is usually secondary to viral infection or P. jirovecii pneumonia. After the first 100 days a moderate risk of infection by conventional and opportunistic infections persists, such as late CMV infection. Advances in surgical techniques and the use of calcineurinics have reduced mortality from infections in recipients of solid organ transplantations. Nosocomial infections are common during the first month; opportunistic infections that are dependent on cellular immunity are more common between the first and the sixth month, from the sixth month the risk lowers and community-based infections similar to those of immunocompetent patients predominate.


title: Awareness of droplet and airborne isolation precautions among dental health professionals during the outbreak of corona virus infection in Riyadh city, Saudi Arabia

text: BACKGROUND: This study aimed to determine knowledge, attitude and practice of airborne and droplet isolation precautions among Dental Health Professionals (DHPs) (dental students, interns, practitioners and auxiliaries) during the outbreak of MERS (Middle East Respiratory Syndrome), corona virus infection in Riyadh city, Saudi Arabia. MATERIAL AND METHODS: A cross-sectional survey was conducted among 406 dental health professionals (DHPs) working in selected dental facilities in Riyadh city, Saudi Arabia during the outbreak of MERS (April-June 2013). A structured, close-ended, self-administered questionnaire explored the knowledge, attitude, and practice towards droplet and isolation precautions. Collected data was subjected to descriptive statistics to express demographic information, mean knowledge score, mean attitude score and practice score of DHPs. Inferential statistics (Mann-Whitney U test and Kruskal Wallis tests, p < 0.05) were used to examine differences between study variables. Spearman’s rho correlation was used to identify the association between the knowledge-attitude, knowledge-practice, and attitude-practice. RESULTS: A response rate of rate of 90.22% (406 out of 452) was obtained. The mean scores of knowledge, attitude and practice were 10.61 ± 1.19, 50.54 ± 7.53 and 8.50 ± 2.14 respectively. Spearman’s correlation test revealed a significant linear positive correlation between knowledge and attitude (r-0.501, P- 0.01), knowledge and practice (r-0.185, P-0.01) and attitude and practice (r-0.351, P- 0.01) of DHPs about airborne isolation precautions. CONCLUSIONS: Dental health professionals considered in the present study showed good knowledge, positive attitude and good practice towards droplet and airborne isolation precautions during outbreak of MERS. Key words:Knowledge, attitude, practice, droplet, airborne, precaution, dental professionals.


title: Challenge and strategies of infection control in psychiatric hospitals during biological disasters—From SARS to COVID-19 in Taiwan

text: Psychiatric hospitals play an important role in supporting patients with mental illness to relieve symptoms and improve functioning in a physically and psychologically safe environment. However, these hospitals are also vulnerable to emerging infectious diseases. In early 2020, a psychiatric hospital and a psychiatric unit were reported to have nosocomial coronavirus disease 2019 (COVID-19) infection. A large number of patients and staff were severely impacted. This type of nosocomial infection threatens patient safety and quality of care. By learning from previous experiences of severe acute respiratory syndrome (SARS) and previous studies, psychiatric hospitals can provide safeguards to prevent nosocomial infection among patients and staff during an epidemic or biological disaster. These strategies include a series of actions such as following national guidelines for infection control, reserving adequate support for disinfection equipment, providing relevant and sufficient pro-service and in-service education and training, establishing regular surveillance of hand hygiene habits, proper communication and health education, and providing opportunities for vaccination if possible. Based on the harm reduction concept, staff division of office breaks and ward classification and shunting are recommended and should be further implemented.


docid: tdsyengw

title: Disaster resiliency of U.S. local governments: Insights to strengthen local response and recovery from the COVID‐19 pandemic

text: This research presents implications of the global pandemic on local government resiliency in the United States. We explore insights from local government officials and managers at the frontlines of response and recovery efforts to the biological natural disaster. Also, findings from the latest nationwide survey of U.S. local governments regarding their preparedness for weather‐related natural disasters informs responses to the current crisis. Results indicate that local governments are innovating and taking strategic actions to fight the virus. This, even though COVID‐19 has exposed social inequities exacerbated as the virus spreads. Survey findings of disaster readiness of local governments to weather‐related disasters shows that small, resource poor governments will not be able to respond well, and social inequities will grow. Policy strategies at all levels of government must recognize and account for these inequities as threat of this virus subsides, to support stronger, more effective readiness for the next biological catastrophe. This article is protected by copyright. All rights reserved.


title: Bocavirus Infection in Hospitalized Children, South Korea

text: This study presents the first evidence of human bocavirus infection in South Korean children. The virus was detected in 27 (8.0%) of 336 tested specimens, including 17 (7.5%) of 225 virus-negative specimens, collected from children with acute lower respiratory tract infection.


docid: kbhuoiyc

title: Case Fatality Rates Based on Population Estimates of Influenza-Like Illness Due to Novel H1N1 Influenza: New York City, May–June 2009

text: BACKGROUND: The public health response to pandemic influenza is contingent on the pandemic strain's severity. In late April 2009, a potentially pandemic novel H1N1 influenza strain (nH1N1) was recognized. New York City (NYC) experienced an intensive initial outbreak that peaked in late May, providing the need and opportunity to rapidly quantify the severity of nH1N1. METHODS AND FINDINGS: Telephone surveys using rapid polling methods of approximately 1,000 households each were conducted May 20–27 and June 15–19, 2009. Respondents were asked about the occurrence of influenza-like illness (ILI, fever with either cough or sore throat) for each household member from May 1–27 (survey 1) or the preceding 30 days (survey 2). For the overlap period, prevalence data were combined by weighting the survey-specific contribution based on a Serfling model using data from the NYC syndromic surveillance system. Total and age-specific prevalence of ILI attributed to nH1N1 were estimated using two approaches to adjust for background ILI: discounting by ILI prevalence in less affected NYC boroughs and by ILI measured in syndromic surveillance data from 2004–2008. Deaths, hospitalizations and intensive care unit (ICU) admissions were determined from enhanced surveillance including nH1N1-specific testing. Combined ILI prevalence for the 50-day period was 15.8% (95% CI:13.2%–19.0%). The two methods of adjustment yielded point estimates of nH1N1-associated ILI of 7.8% and 12.2%. Overall case-fatality (CFR) estimates ranged from 0.054–0.086 per 1000 persons with nH1N1-associated ILI and were highest for persons ≥65 years (0.094–0.147 per 1000) and lowest for those 0–17 (0.008–0.012). Hospitalization rates ranged from 0.84–1.34 and ICU admission rates from 0.21–0.34 per 1000, with little variation in either by age-group. CONCLUSIONS: ILI prevalence can be quickly estimated using rapid telephone surveys, using syndromic surveillance data to determine expected “background” ILI proportion. Risk of severe illness due to nH1N1 was similar to seasonal influenza, enabling NYC to emphasize preventing severe morbidity rather than employing aggressive community mitigation measures.


title: Cytoplasmic Viral RNA Sensors: RIG-I-Like Receptors

text: Abstract The interferon (IFN) response is a powerful system that was evolutionarily acquired by vertebrates including mammals to protect against viral infection. The cytoplasmic RNA helicases, RIG-I-like receptors (RLRs), were discovered in 2004 as viral sensors that trigger the antiviral IFN response by recognizing the nonself signatures of viral RNAs. The mechanisms underlying the recognition of viral RNAs and signal transduction leading to the production of type I IFN have been intensively studied following the discovery of RLRs. Moreover, a dysregulation in the expression of RLR or aberrant RLR signaling has been implicated in the development of a number of autoimmune diseases. We herein provide an overview of recent advances in RLR research and discussed future directions.


title: Nosocomial viral ventilator-associated pneumonia in the intensive care unit: a prospective cohort study

text: OBJECTIVE: To determine the incidence, risk factors, and clinical relevance of viral ventilator-associated pneumonia (VAP) in an adult intensive care unit (ICU). DESIGN: Prospective observational study. SETTING: A 22-bed adult medical ICU in a university hospital. PATIENTS: All consecutive adult patients ventilated more than 48 h in a 9-month period including regular seasonal viral infections. INTERVENTIONS: A tracheobronchial aspirate upon enrollment and at the time of VAP suspicion. MEASUREMENTS AND RESULTS: All respiratory specimens were tested in culture, indirect immunofluorescence assay, and PCR or RT-PCR for virological assessment. Patients were followed until ICU discharge or death. One hundred thirty-nine patients were included. Upon enrollment, a respiratory virus was detected in the tracheobronchial aspirate in 25% of patients (35 of 139). The incidence of VAP, defined according to clinical daily evaluation, was 28% (39 of 139 patients). A bacteria was documented in 74% of cases, whereas no case of a causative viral infection was encountered among VAP patients; however, herpes simplex virus type-1 (HSV 1) infection was detected in respiratory specimens of 31% of VAP (12 of 39). CONCLUSIONS: We found a high incidence of HSV-1 infection in VAP patients; however, nosocomial viral VAP is likely to be rare in ICU, as assessed by the absence of respiratory virus-induced VAP identified in this prospective cohort study.


title: Appropriate measures of influenza immunization program effectiveness

text: Abstract Groll and Thomson's evaluation of the effectiveness of Ontario's Universal Influenza Immunization Campaign used per capita cases of laboratory-confirmed influenza. We argue that these data are susceptible to various biases and should not be used as an outcome measure. Laboratory data are traditionally used to identify the presence of influenza activity rather than to identify levels of influenza activity. A better measure of viral activity is the proportion of influenza tests positive; whereas the weekly proportion of tests positive was relatively consistent, a marked increase over time in the numbers of laboratory-confirmed cases paralleled an increase in the number of tests performed. Regardless, for evaluating universal influenza immunization program effectiveness, other established and available measures employed in previous studies describing the epidemiology of influenza should be used instead of laboratory data.


title: International Biological Reference Preparations for Epidemic Infectious Diseases

text: Recent years have seen unprecedented investment in research and development for countermeasures for high-threat pathogens, including specific and ambitious objectives for development of diagnostics, therapeutics, and vaccines. The inadequate availability of biological reference materials for these pathogens poses a genuine obstacle in pursuit of these objectives, and the lack of a comprehensive and equitable framework for developing reference materials is a weakness. We outline the need for internationally standardized biological materials for high-threat pathogens as a core element of global health security. We also outline the key components of a framework for addressing this deficiency.


docid: qqhgmqrg

title: Molecular Biology and Infection of Hepatitis E Virus

text: Hepatitis E virus (HEV) is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotypes 3 and 4 are zoonotic, whereas those from genotypes 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasi-enveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy, and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus.


title: COVID-19 – What does a paediatrician need to know?

text: COVID-19 is a coronavirus responsible for a global pandemic that started in China in December 2019 and has quickly spread to almost all countries. Approximately 2% of cases are diagnosed in children. There is increasing evidence for transmission by asymptomatic or presymptomatic adults and children. The clinical features do not differ from those of other respiratory viral infections, although rare cases manifest an unusual rash involving the digits. Disease is generally mild in children but deaths have been reported. Risk groups for severe disease in children are yet to be delineated. All treatments remain experimental.


title: Antiviral Activities of Polysaccharides from Natural Sources

text: Abstract The ever increasing resistance of human pathogens to current anti-infective agents is a serious medical problem, leading to the need to develop novel antibiotic prototype molecules. In the case of viruses, the search for antiviral agents involves additional difficulties, particularly due to the nature of the infectious viral agents. Thus, many compounds that may cause the death of viruses are also very likely to injure the host cell that harbours them. Natural products are increasingly appreciated as leads for drug discovery and development. Screening studies have been carried out in order to find antiviral agents from natural sources, and the occurrence of antiviral activity in extracts of plants, marine organisms and fungi is frequent. The evidence indicates that there may be numerous potentially useful antiviral phytochemicals in nature, waiting to be evaluated and exploited. In addition, other plants, not previously utilized medicinally, may also reveal antivirals. Among natural antiviral agents, recent investigations have reconsidered the interest of phyto-polysaccharides, which act as potent inhibitors of different viruses. This chapter will illustrate a variety of antiviral polysaccharides from natural sources since 1990, with the aim of making this matter more accessible to drug development


title: FGL2 is positively correlated with enhanced antitumor responses mediated by T cells in lung adenocarcinoma

text: Lung cancer is the most common malignant tumor, accounting for 25% of cancer-related deaths and 14% of new cancers worldwide. Lung adenocarcinoma is the most common type of pulmonary cancer. Although there have been some improvements in the traditional therapy of lung cancer, the outcome and prognosis of patients remain poor. Lung cancer is the leading cause of cancer-related deaths worldwide, with 1.8 million new cases being diagnosed each year. Precision medicine based on genetic alterations is considered a new strategy of lung cancer treatment that requires highly specific biomarkers for precision diagnosis and treatment. Fibrinogen-like protein 2 (FGL2) plays important roles in both innate and adaptive immunity. However, the diagnostic value of FGL2 in lung cancer is largely unknown. In this study, we systematically investigated the expression profile and potential functions of FGL2 in lung adenocarcinoma. We used the TCGA and Oncomine datasets to compare the FGL2 expression levels between lung adenocarcinoma and adjacent normal tissues. We utilized the GEPIA, PrognoScan and Kaplan-Meier plotter databases to analyze the relationship between FGL2 expression and the survival of lung adenocarcinoma patients. Then, we investigated the potential roles of FGL2 in lung adenocarcinoma with the TIMER database and functional enrichment analyses. We found that FGL2 expression was significantly lower in lung adenocarcinoma tissue compared with adjacent normal tissue. A high expression level of FGL2 was correlated with better prognostic outcomes of lung adenocarcinoma patients, including overall survival and progression-free survival. FGL2 was positively correlated with the infiltration of immune cells, including dendritic cells, CD8(+) T cells, macrophages, B cells, and CD4(+) T cells, in lung adenocarcinoma. Functional enrichment analyses also showed that a high expression level of FGL2 was positively correlated with enhanced T cell activities, especially CD8(+) T cell activation. Thus, we propose that high FGL2 expression, which is positively associated with enhanced antitumor activities mediated by T cells, is a beneficial marker for lung adenocarcinoma treatment outcomes.


title: Correction to Lancet Infect Dis 2019; published online April 20. https://doi.org/10.1016/S1473-3099(20)30160-2

text: [This corrects the article DOI: 10.1016/S1473-3099(20)30160-2.].


title: Baculovirus expression systems for production of recombinant proteins in insect and mammalian cells

text: Baculovirus vector systems are extensively used for the expression of foreign gene products in insect and mammalian cells. New advances increase the possibilities and applications of the baculovirus expression system, which makes it possible to express multiple genes simultaneously within a single infected insect cell and to obtain multimeric proteins functionally similar to their natural analogs. Recombinant viruses with expression cassettes active in mammalian cells are used to deliver and express genes in mammalian cells in vitro and in vivo. Further improvement of the baculovirus expression system and its adaptation to specific target cells can open up a wide variety of applications. The review considers recent achievements in the use of modified baculoviruses to express recombinant proteins in eukaryotic cells, advantages and drawbacks of the baculovirus expression system, and ways to optimize the expression of recombinant proteins in both insect and mammalian cell lines.


title: Laboratory diagnosis of emerging human coronavirus infections – the state of the art

text: The three unprecedented outbreaks of emerging human coronavirus (HCoV) infections at the beginning of the twenty-first century have highlighted the necessity for readily available, accurate and fast diagnostic testing methods. The laboratory diagnostic methods for human coronavirus infections have evolved substantially, with the development of novel assays as well as the availability of updated tests for emerging ones. Newer laboratory methods are fast, highly sensitive and specific, and are gradually replacing the conventional gold standards. This presentation reviews the current laboratory methods available for testing coronaviruses by focusing on the coronavirus disease 2019 (COVID-19) outbreak going on in Wuhan. Viral pneumonias typically do not result in the production of purulent sputum. Thus, a nasopharyngeal swab is usually the collection method used to obtain a specimen for testing. Nasopharyngeal specimens may miss some infections; a deeper specimen may need to be obtained by bronchoscopy. Alternatively, repeated testing can be used because over time, the likelihood of the SARS-CoV-2 being present in the nasopharynx increases. Several integrated, random-access, point-of-care molecular devices are currently under development for fast and accurate diagnosis of SARS-CoV-2 infections. These assays are simple, fast and safe and can be used in the local hospitals and clinics bearing the burden of identifying and treating patients.


title: Post-Discharge Prophylaxis With Rivaroxaban Reduces Fatal and Major Thromboembolic Events in Medically Ill Patients

text: BACKGROUND: Hospitalized acutely ill medical patients are at risk for fatal and major thromboembolic events. Whether use of extended-duration primary thromboprophylaxis can prevent such events is unknown. OBJECTIVES: The purpose of this study was to evaluate whether extended-duration rivaroxaban reduces the risk of venous and arterial fatal and major thromboembolic events without significantly increasing major bleeding in acutely ill medical patients after discharge. METHODS: MARINER (A Study of Rivaroxaban [JNJ-39039039] on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients) studied acutely ill medical patients with additional risk factors for venous thromboembolism (VTE). Medically ill patients with a baseline creatinine clearance ≥50 ml/min were randomized in a double-blind fashion to rivaroxaban 10 mg or placebo daily at hospital discharge for 45 days. Exploratory efficacy analyses were performed with the intent-to-treat population including all data through day 45. Time-to-event curves were calculated using the Kaplan-Meier method. A blinded independent committee adjudicated all clinical events. RESULTS: In total, 4,909 patients were assigned to rivaroxaban and 4,913 patients to placebo. The mean age was 67.8 years, 55.5% were men, mean baseline creatinine clearance was 87.8 ml/min, and mean duration of hospitalization was 6.7 days. The pre-specified composite efficacy endpoint (symptomatic VTE, myocardial infarction, nonhemorrhagic stroke, and cardiovascular death) occurred in 1.28% and 1.77% of patients in the rivaroxaban and placebo groups, respectively (hazard ratio: 0.72; 95% confidence interval: 0.52 to 1.00; p = 0.049), whereas major bleeding occurred in 0.27% and 0.18% of patients in the rivaroxaban and placebo groups, respectively (hazard ratio: 1.44; 95% confidence interval: 0.62 to 3.37; p = 0.398). CONCLUSIONS: Extended-duration rivaroxaban in hospitalized medically ill patients resulted in a 28% reduction in fatal and major thromboembolic events without a significant increase in major bleeding. (A Study of Rivaroxaban [JNJ-39039039] on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients [MARINER]; NCT02111564)


title: Date of origin of the SARS coronavirus strains

text: BACKGROUND: A new respiratory infectious epidemic, severe acute respiratory syndrome (SARS), broke out and spread throughout the world. By now the putative pathogen of SARS has been identified as a new coronavirus, a single positive-strand RNA virus. RNA viruses commonly have a high rate of genetic mutation. It is therefore important to know the mutation rate of the SARS coronavirus as it spreads through the population. Moreover, finding a date for the last common ancestor of SARS coronavirus strains would be useful for understanding the circumstances surrounding the emergence of the SARS pandemic and the rate at which SARS coronavirus diverge. METHODS: We propose a mathematical model to estimate the evolution rate of the SARS coronavirus genome and the time of the last common ancestor of the sequenced SARS strains. Under some common assumptions and justifiable simplifications, a few simple equations incorporating the evolution rate (K) and time of the last common ancestor of the strains (T(0)) can be deduced. We then implemented the least square method to estimate K and T(0 )from the dataset of sequences and corresponding times. Monte Carlo stimulation was employed to discuss the results. RESULTS: Based on 6 strains with accurate dates of host death, we estimated the time of the last common ancestor to be about August or September 2002, and the evolution rate to be about 0.16 base/day, that is, the SARS coronavirus would on average change a base every seven days. We validated our method by dividing the strains into two groups, which coincided with the results from comparative genomics. CONCLUSION: The applied method is simple to implement and avoid the difficulty and subjectivity of choosing the root of phylogenetic tree. Based on 6 strains with accurate date of host death, we estimated a time of the last common ancestor, which is coincident with epidemic investigations, and an evolution rate in the same range as that reported for the HIV-1 virus.


title: Factors determining human-to-human transmissibility of zoonotic pathogens via contact

text: The pandemic potential of zoonotic pathogens lies in their ability to become efficiently transmissible amongst humans. Here, we focus on contact-transmitted pathogens and discuss the factors, at the pathogen, host and environmental levels that promote or hinder their human-to-human transmissibility via the following modes of contact transmission: skin contact, sexual contact, respiratory contact and multiple route contact. Factors common to several modes of transmission were immune evasion, high viral load, low infectious dose, crowding, promiscuity, and co-infections; other factors were specific for a pathogen or mode of contact transmission. The identification of such factors will lead to a better understanding of the requirements for human-to-human spread of pathogens, as well as improving risk assessment of newly emerging pathogens.


docid: uwqsotcy

title: Focus on kidney disease among the coronavirus disease 2019 patients: A comparative perspective between China, Italy and the United States

text: Coronavirus disease 2019 (COVID‐19) has rapidly spread to more than 200 countries and areas. As of May 11, 2020, more than 4 million cases have been confirmed globally and more than 280000 deaths have been recorded. In China, Italy and America, the mortality was 5.5% (4644/84451), 14.0% (30739/219814) and 6.1% (78652/1298287), respectively.(1)


title: An insulated isothermal PCR method on a field-deployable device for rapid and sensitive detection of canine parvovirus type 2 at points of need

text: Abstract Canine parvovirus type 2 (CPV-2), including subtypes 2a, 2b and 2c, causes an acute enteric disease in both domestic and wild animals. Rapid and sensitive diagnosis aids effective disease management at points of need (PON). A commercially available, field-deployable and user-friendly system, designed with insulated isothermal PCR (iiPCR) technology, displays excellent sensitivity and specificity for nucleic acid detection. An iiPCR method was developed for on-site detection of all circulating CPV-2 strains. Limit of detection was determined using plasmid DNA. CPV-2a, 2b and 2c strains, a feline panleukopenia virus (FPV) strain, and nine canine pathogens were tested to evaluate assay specificity. Reaction sensitivity and performance were compared with an in-house real-time PCR using serial dilutions of a CPV-2b strain and 100 canine fecal clinical samples collected from 2010 to 2014, respectively. The 95% limit of detection of the iiPCR method was 13 copies of standard DNA and detection limits for CPV-2b DNA were equivalent for iiPCR and real-time PCR. The iiPCR reaction detected CPV-2a, 2b and 2c and FPV. Non-targeted pathogens were not detected. Test results of real-time PCR and iiPCR from 99 fecal samples agreed with each other, while one real-time PCR-positive sample tested negative by iiPCR. Therefore, excellent agreement (k =0.98) with sensitivity of 98.41% and specificity of 100% in detecting CPV-2 in feces was found between the two methods. In conclusion, the iiPCR system has potential to serve as a useful tool for rapid and accurate PON, molecular detection of CPV-2.


Paniculitis eosinofílica secundaria a infección por COVID-19


title: Development of real‐time fluorescent reverse transcription loop‐mediated isothermal amplification assays for rhinovirus detection

text: Human rhinoviruses (RVs) belong to the genus Enterovirus of the family Picornaviridae, and are classified into RV‐A, ‐B, and ‐C species. Two assays were developed to detect RVs by a real‐time fluorescent reverse transcription loop‐mediated isothermal amplification method: one was designed based on the 5′‐untranslated regions (UTRs) of RV‐A and ‐B, and the other was designed based on the 5′‐UTR of RV‐C. The competence of both assays for the diagnosis of RV infection was tested using isolated viruses and compared with real‐time reverse transcription polymerase chain reaction assays on clinical specimens. Neither assay demonstrated cross‐reactivity with other tested enteroviruses, and they detected 19 out of 21 tested RV‐As and seven out of eight tested RV‐Cs. The specificity of the assays was 100% for the detection of RVs and their sensitivity for RV‐A and RV‐C was 86.3% and 77.3%, respectively, on clinical specimens by the combined use of both assays. Considering that both developed assays were highly specific and detected the majority of recently circulating RVs, they are helpful for the diagnosis of RV infection. Consequently, the results generated by these assays will enhance the surveillance of respiratory illness and the study of the roles of RVs associated with clinical features and disease severity.


title: An optimised method for the production of MERS-CoV spike expressing viral pseudotypes

text: The production and use of pseudotyped viral particles are widely established for many viruses, and applications in the fields of serology and vaccine development are manifold. Viral pseudotypes have proven to be powerful tools to study the effects of viral evolution on serological outcomes, viral tropism and immunogenicity studies. Pseudotyped viruses are chimeric constructs in which the outer (surface) glycoprotein(s) of one virus is combined with the replication-defective viral “core” of another virus. Pseudotypes allow for accurate, sequence-directed, sensitive antibody neutralisation assays and antiviral screening to be conducted within a low biosecurity facility and offer a safe and efficient alternative to wildtype virus use. The protocol outlined here represents a rapid and reliable method for the generation of high-titre pseudotype viral particles with the MERS-CoV spike protein on a lentiviral core, and is adapted from previously published protocols. This protocol is optimised for transfection in a 100 mm Petri dish with 7 ml of supernatant harvested, however it can be readily scaled to different production volumes. This protocol has a number of advantages including: • Use of readily available reagents. • Consistent, high virus titres. • Rapid generation of novel glycoproteins for research into strain variation.


title: Interactions of LSECtin and DC-SIGN/DC-SIGNR with viral ligands: Differential pH dependence, internalization and virion binding

text: Abstract The calcium-dependent lectins DC-SIGN and DC-SIGNR (collectively termed DC-SIGN/R) bind to high-mannose carbohydrates on a variety of viruses. In contrast, the related lectin LSECtin does not recognize mannose-rich glycans and interacts with a more restricted spectrum of viruses. Here, we analyzed whether these lectins differ in their mode of ligand engagement. LSECtin and DC-SIGNR, which we found to be co-expressed by liver, lymph node and bone marrow sinusoidal endothelial cells, bound to soluble Ebola virus glycoprotein (EBOV-GP) with comparable affinities. Similarly, LSECtin, DC-SIGN and the Langerhans cell-specific lectin Langerin readily bound to soluble human immunodeficiency virus type-1 (HIV-1) GP. However, only DC-SIGN captured HIV-1 particles, indicating that binding to soluble GP is not necessarily predictive of binding to virion-associated GP. Capture of EBOV-GP by LSECtin triggered ligand internalization, suggesting that LSECtin like DC-SIGN might function as an antigen uptake receptor. However, the intracellular fate of lectin–ligand complexes might differ. Thus, exposure to low-pH medium, which mimics the acidic luminal environment in endosomes/lysosomes, released ligand bound to DC-SIGN/R but had no effect on LSECtin interactions with ligand. Our results reveal important differences between pathogen capture by DC-SIGN/R and LSECtin and hint towards different biological functions of these lectins.


title: Isolation of a Novel Fusogenic Orthoreovirus from Eucampsipoda africana Bat Flies in South Africa

text: We report on the isolation of a novel fusogenic orthoreovirus from bat flies (Eucampsipoda africana) associated with Egyptian fruit bats (Rousettus aegyptiacus) collected in South Africa. Complete sequences of the ten dsRNA genome segments of the virus, tentatively named Mahlapitsi virus (MAHLV), were determined. Phylogenetic analysis places this virus into a distinct clade with Baboon orthoreovirus, Bush viper reovirus and the bat-associated Broome virus. All genome segments of MAHLV contain a 5' terminal sequence (5'-GGUCA) that is unique to all currently described viruses of the genus. The smallest genome segment is bicistronic encoding for a 14 kDa protein similar to p14 membrane fusion protein of Bush viper reovirus and an 18 kDa protein similar to p16 non-structural protein of Baboon orthoreovirus. This is the first report on isolation of an orthoreovirus from an arthropod host associated with bats, and phylogenetic and sequence data suggests that MAHLV constitutes a new species within the Orthoreovirus genus.


title: Portable chest X-ray in coronavirus disease-19 (COVID-19): A pictorial review

text: Abstract/introduction As the global pandemic of coronavirus disease-19 (COVID-19) progresses, many physicians in a wide variety of specialties continue to play pivotal roles in diagnosis and management. In radiology, much of the literature to date has focused on chest CT manifestations of COVID-19 (Zhou et al. [1]; Chung et al. [2]). However, due to infection control issues related to patient transport to CT suites, the inefficiencies introduced in CT room decontamination, and lack of CT availability in parts of the world, portable chest radiography (CXR) will likely be the most commonly utilized modality for identification and follow up of lung abnormalities. In fact, the American College of Radiology (ACR) notes that CT decontamination required after scanning COVID-19 patients may disrupt radiological service availability and suggests that portable chest radiography may be considered to minimize the risk of cross-infection (American College of Radiology [3]). Furthermore, in cases of high clinical suspicion for COVID-19, a positive CXR may obviate the need for CT. Additionally, CXR utilization for early disease detection may also play a vital role in areas around the world with limited access to reliable real-time reverse transcription polymerase chain reaction (RT-PCR) COVID testing. The purpose of this pictorial review article is to describe the most common manifestations and patterns of lung abnormality on CXR in COVID-19 in order to equip the medical community in its efforts to combat this pandemic.


title: Clinical and diagnostic virology G. Kudesia T. Wreghitt

text: Unknown


title: A cluster of the Corona Virus Disease 2019 caused by incubation period transmission in Wuxi, China

text: Background The infectivity and transmission capacity of COVID-2019 cases during the incubation period are not very clear. The manuscript described a cluster to provide information for research on incubation period infection. Methods We collected the required data from “Public Health Emergency Reporting Management Information System”, epidemiological questionnaires for the cases, and laboratories. Results The cluster involved four generations, each of which was transmitted to the next generation during the incubation period. The time was 2–7 days, 6–7days, 3–8 days and 9 days prior to onset. As of March 11, the fourth-generation cases had no symptoms. Combined with the epidemiological data, we inferred that the source of the cluster was caused by the first-generation, who contacted with more than ten Wuhan people during the annual meeting from January 15 to 16. Two cases in this cluster were tested positive again during isolation and observation after discharge. Conclusions We determined incubation period was infectious, and confirmed that it was contagious 9 days before the onset. The patients who were discharged might need to be observed for a period of time. This study was useful for the practical work, such as in the investigation of close contacts.


title: A stochastic SIR epidemic model with Lévy jump and media coverage

text: A stochastic susceptible–infectious–recovered epidemic model with temporary immunity and media coverage is proposed. The effects of Lévy jumps on the dynamics of the model are considered. A unique global positive solution for the epidemic model is obtained. Sufficient conditions are derived to guarantee that the epidemic disease is extinct and persistent in the mean. The threshold behavior is discussed. Numerical simulations are given to verify our theoretical results.


title: Covid-19 growth rate analysis: application of a low-complexity tool for understanding and comparing epidemic curves

text: INTRODUCTION: The acceleration of new cases is important for the characterization and comparison of epidemic curves. The objective of this study was to quantify the acceleration of daily confirmed cases and death curves using the polynomial interpolation method. METHODS: Covid-19 epidemic curves from Brazil, Germany, the United States, and Russia were obtained. We calculated the instantaneous acceleration of the curve using the first derivative of the representative polynomial. RESULTS: The acceleration for all curves was obtained. CONCLUSIONS: Incorporating acceleration into an analysis of the Covid-19 time series may enable a better understanding of the epidemiological situation.


title: Kidney Infarction in Patients With COVID-19

text: Coronavirus disease 2019 (COVID-19) is a contagious, life-threatening infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent findings indicate an increased risk of acute kidney injury during COVID-19. The pathophysiological mechanisms leading to acute kidney injury in COVID-19 are unclear, but may include direct cytopathic effects of the virus on kidney tubular and endothelial cells, indirect damage caused by virus-induced cytokine release, and kidney hypoperfusion due to a restrictive fluid strategy. In this case-report we propose an additional pathophysiological mechanism. We describe two cases in which patients with COVID-19 developed a decrease in kidney function due to kidney infarction. These patients did not have atrial fibrillation. One of these patients was treated with therapeutic doses of low molecular weight heparin, whereafter no further deterioration of kidney function was observed. Our findings implicate that the differential diagnosis of acute kidney injury in COVID-19 patients should include kidney infarction, which may have important preventive and therapeutic implications.


docid: yuemczly

title: PI3K/Akt/p53 pathway inhibits reovirus infection

text: Abstract Viral infections activate many host signaling pathways, including the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which has recently attracted considerable interest due to its central role in modulating virus replication. This study demonstrated that the sero-type 3 reovirus strain Masked Palm Civet/China/2004 (MPC/04) could transiently activate the PI3K/Akt pathway in A549 cells at earlier time points of infection. The blockage of PI3K/Akt activation increased viral RNA synthesis and yield. The role of the downstream effectors MDM2/p53 of PI3K/Akt in regulating reovirus replication was further analyzed. We found that during reovirus infection, the level of phosphorylated MDM2 (p-MDM2) was increased and the expression of p53 was reduced. In addition, the blockage of PI3K/Akt by Ly294002 or knockdown of Akt by siRNA reduced the level of p-MDM2 and increased the level of p53. Both indicated that the downstream effectors MDM2/p53 of PI3K/Akt were activated. Pre-treatment with Nutlin, which can destroy MDM2 and p53 cross-talk and increase the expression of p53 RNA and protein, dose-dependently enhanced reovirus replication. Additionally, the overexpression of p53 alone also supported reovirus replication, and knockdown of p53 significantly inhibited viral replication. This study demonstrates that PI3K/Akt/p53 activated by mammalian reovirus can serve as a pathway for inhibiting virus replication/infection, yet the precise mechanism of this process remains under further investigation.


docid: fycmvkkq

title: Understand potential legal implications of pandemic's economic impact on athletics

text: The numerous public health measures that were implemented as a result of the COVID‐19 pandemic and the subsequent impact on the nation's economy have created a new world of emergency planning at every educational institution and within every athletics department. Between the money that had to be returned for room and board and/or tuition reimbursements; the decline in or disappearance of digital rights payments, ticket sales, donations, and corporate sponsorships; the cancellation of March Madness, and the loss of many other revenue streams, the economic vise‐grip created by COVID‐19 tightened quickly and dramatically. Within the public sector, a future reduction in legislative appropriations in various states for higher education is likewise being discussed.


title: SARS: Epidemiology, Clinical Presentation, Management, and Infection Control Measures

text: Severe acute respiratory syndrome (SARS) is a recently recognized febrile respiratory illness that first appeared in southern China in November 2002, has since spread to several countries, and has resulted in more than 8000 cases and more than 750 deaths. The disease has been etiologically linked to a novel coronavirus that has been named the SARS-associated coronavirus. It appears to be spread primarily by large droplet transmission. There is no specific therapy, and management consists of supportive care. This article summarizes currently available information regarding the epidemiology, clinical features, etiologic agent, and modes of transmission of the disease, as well as infection control measures appropriate to contain SARS.


title: Modified vaccinia virus Ankara as a vaccine against feline coronavirus: immunogenicity and efficacy

text: Abstract Feline infectious peritonitis virus (FIPV) is a coronavirus that induces a fatal systemic disease mediated by an inappropriate immune response. Most previous vaccination attempts against FIPV were unsuccessful because IgG antibodies against the surface protein enhance the infection. However, two studies have shown that poxvirus vectors (vaccinia WR and canarypox) expressing only the FIPV membrane (M) protein can elicit a partially protective immunity which is supposed to be cell-mediated (Virology 181 (1991) 327; International patent WO 97/20054 (1997)). In our study, we report the construction of another poxvirus, the modified vaccinia virus Ankara (MVA), as an expression vector for the FIPV M protein. In this vector, the M gene has been inserted downstream a strong early/late promoter, whereas the two previously described poxviruses expressed the M protein during their early stage only. The immunogenicity of the recombinant MVA-M was evaluated in the murine model which revealed an effect of the vector on the Th1/Th2 balance. The vaccine was then tested in cats to evaluate its efficacy in an FIPV 79-1146 challenge. Vaccinated kittens developed FIPV-specific antibodies after immunization, however, none of them was protected against FIPV. Our results suggest a crucial role for the type of poxviral promoter that must be used to induce an effective immune response against FIPV.


title: Major cluster of pediatric “ true ” primary chilblains during the COVID‐19 pandemic: a consequence of lifestyle changes due to lockdown

text: BACKGROUND: Over the last months, during the COVID‐19 pandemic, a growing number of chilblain‐like lesions was reported mainly in children, rarely in young adults. The relationship with SARS‐CoV‐2 infection was postulated, often without any laboratory, instrumental or clinical confirmation. The disclosure of information about chilblain‐like lesions as a COVID‐19 manifestation in social media has created concern in children’s families and pediatricians OBJECTIVES: to verify whether the chilblain‐like lesions were caused by SARS‐CoV‐2 infection. METHODS: prospective study on a case series including children who presented with acral lesions at the Pediatric Dermatology Outpatient and Pediatric Emergency Unit of the University of Bologna, from April 1 to April 30, 2020. We reported demographical, laboratory and clinical features, history of close contact with COVID‐19 patients, presence of similar skin lesions in other family members, precipitating and risk factors for chilblain onset. RESULTS: We evaluated 8 patients (5 females, 3 males) aged between 11 and 15 years. We excluded acute or previous SARS‐CoV‐2 infection with RT‐PCR nasopharyngeal swab, serum antibody levels using chemiluminescent immunoassays. Other acute infections causing purpuric lesions at the extremities were negative in all patients. Skin lesion biopsy for histological and immunohistochemical evaluation was made in two cases and was consistent with chilblain. PCR‐assay on skin lesion biopsy for Parvovirus B19, Mycoplasma pneumoniae and SARS‐CoV‐2 was performed in a patient and resulted negative. We identified common precipitating and risk factors: physical (cold and wet extremities, low BMI), cold and wet indoor and outdoor environment, behaviors, habits, lifestyle. We therefore reached a diagnosis of primary chilblains. CONCLUSIONS: During the COVID‐19 pandemic, a “cluster” of primary chilblains developed in predisposed subjects, mainly teenagers, due to to cold exposure in the lockdown period. Laboratory findings support our hypothesis, although it is also possible that an unknown infectious trigger may have contributed to the pathogenesis.


title: Complete Genome of Avian coronavirus Vaccine Strains Ma5 and BR-I

text: Avian coronavirus (AvCoV) is a ubiquitous multiple-serotype pathogen of poultry, and its control is mainly based on the use of vaccines. We report here the previously unknown full genomes of the Ma5 (27,652 nucleotides [nt]) and BR-I (27,618 nt) AvCoV vaccine strains of the GI-1 (Massachusetts) and GI-11 (Brazil) types.


title: Connecting clusters of COVID-19: an epidemiological and serological investigation

text: Summary Background Elucidation of the chain of disease transmission and identification of the source of coronavirus disease 2019 (COVID-19) infections are crucial for effective disease containment. We describe an epidemiological investigation that, with use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays, established links between three clusters of COVID-19. Methods In Singapore, active case-finding and contact tracing were undertaken for all COVID-19 cases. Diagnosis for acute disease was confirmed with RT-PCR testing. When epidemiological information suggested that people might have been nodes of disease transmission but had recovered from illness, SARS-CoV-2 IgG serology testing was used to establish past infection. Findings Three clusters of COVID-19, comprising 28 locally transmitted cases, were identified in Singapore; these clusters were from two churches (Church A and Church B) and a family gathering. The clusters in Church A and Church B were linked by an individual from Church A (A2), who transmitted SARS-CoV-2 infection to the primary case from Church B (F1) at a family gathering they both attended on Jan 25, 2020. All cases were confirmed by RT-PCR testing because they had active disease, except for A2, who at the time of testing had recovered from their illness and tested negative. This individual was eventually diagnosed with past infection by serological testing. ELISA assays showed an optical density of more than 1·4 for SARS-CoV-2 nucleoprotein and receptor binding domain antigens in titres up to 1/400, and viral neutralisation was noted in titres up to 1/320. Interpretation Development and application of a serological assay has helped to establish connections between COVID-19 clusters in Singapore. Serological testing can have a crucial role in identifying convalescent cases or people with milder disease who might have been missed by other surveillance methods. Funding National Research Foundation (Singapore), National Natural Science Foundation (China), and National Medical Research Council (Singapore).


title: Proteomics of Bronchoalveolar Lavage Fluid Reveals a Lung Oxidative Stress Response in Murine Herpesvirus-68 Infection

text: Murine herpesvirus-68 (MHV-68) productively infects mouse lungs, exhibiting a complex pathology characteristic of both acute viral infections and chronic respiratory diseases. We sought to discover proteins differentially expressed in bronchoalveolar lavage (BAL) from mice infected with MHV-68. Mice were infected intranasally with MHV-68. After nine days, as the lytic phase of infection resolved, differential BAL proteins were identified by two-dimensional (2D) electrophoresis and mass spectrometry. Of 23 unique proteins, acute phase proteins, vitamin A transport, and oxidative stress response factors Pdx6 and EC-SOD (Sod3) were enriched. Correspondingly, iNOS2 was induced in lung tissue by seven days post-infection. Oxidative stress was partly a direct result of MHV-68 infection, as reactive oxygen species (ROS) were induced in cultured murine NIH3T3 fibroblasts and human lung A549 cells infected with MHV-68. Finally, mice infected with a recombinant MHV-68 co-expressing inflammatory cytokine murine interleukin 6 (IL6) showed exacerbated oxidative stress and soluble type I collagen characteristic of tissue recovery. Thus, oxidative stress appears to be a salient feature of MHV-68 pathogenesis, in part caused by lytic replication of the virus and IL6. Proteins and small molecules in lung oxidative stress networks therefore may provide new therapeutic targets to ameliorate respiratory virus infections.


title: Lipoteichoic acid from Staphylococcus aureus exacerbates respiratory disease in porcine respiratory coronavirus-infected pigs

text: The objective of this study was to assess if lipoteichoic acid (LTA), produced by Staphylococcus aureus, exacerbates respiratory disease in porcine respiratory coronavirus (PRCV)-infected pigs, as has previously been shown with lipopolysaccharide. Piglets were inoculated with PRCV and 24 h later with S. aureus LTA. Clinical signs, lung virus titres, inflammatory cells and cytokines in bronchoalveolar lavage fluid (BALF) were compared with those of animals in PRCV- and LTA- inoculated control groups. All PRCV-LTA inoculated pigs except one developed severe respiratory disease, whereas clinical signs in the control groups were minimal or absent. Virus titres and grossly visible pulmonary lesions were similar in the PRCV-LTA- and PRCV-inoculated groups and were not detected in the LTA-group. Neutrophil percentages in BALF were higher in the PRCV-LTA than in the PRCV group. There was no significant difference in interferon (IFN)-γ, interleukin (IL)-1, IL-6, IL-12/IL-23 and tumour necrosis factor (TNF)-α concentrations in BALF between the PRCV-LTA and PRCV groups, but levels of IL-6, IL-12/IL-23 and IFN-γ were higher in the PRCV-LTA-inoculated than in the LTA-inoculated controls. The findings suggest that the experimentally-induced respiratory disease was not mediated by cytokine over-production, but rather reflected the concerted action of particular cytokine interactions and/or as yet unidentified mediators. This is the first in vivo study to report the synergistic interaction between a virus and LTA in enhancing the severity of respiratory disease in the pig. Given that Gram-positive bacteria, capable of producing LTA, are commonly found in pig accommodation, the role of this compound in the development of the porcine respiratory disease complex requires further investigation.