Using Social Media to Disseminate Ophthalmic Information During the #COVID19 Pandemic


CS15.3 More and more coronaviruses after the SARS epidemic: human coronavirus HKU1 and other coronaviruses


title: Making Waves: Wastewater surveillance of SARS-CoV-2 for population-based health management

text: Worldwide, clinical data remain the gold standard for disease surveillance and tracking. However, such data are limited due to factors such as reporting bias and inability to track asymptomatic disease carriers. Disease agents are excreted in the urine and feces of infected individuals regardless of disease symptom severity. Wastewater surveillance – that is, monitoring disease via human effluent – represents a valuable complement to clinical approaches. Because wastewater is relatively inexpensive and easy to collect and can be monitored at different levels of population aggregation as needed, wastewater surveillance can offer a real-time, cost-effective view of a community's health that is independent of biases associated with case-reporting. For SARS-CoV-2 and other disease-causing agents we envision an aggregate wastewater-monitoring system at the level of a wastewater treatment plant and exploratory or confirmatory monitoring of the sewerage system at the neighborhood scale to identify or confirm clusters of infection or assess impact of control measures where transmission has been established. Implementation will require constructing a framework with collaborating government agencies, public or private utilities, and civil society organizations for appropriate use of data collected from wastewater, identification of an appropriate scale of sample collection and aggregation to balance privacy concerns and risk of stigmatization with public health preservation, and consideration of the social implications of wastewater surveillance.


title: Silencing the alarms: Innate immune antagonism by rotavirus NSP1 and VP3

text: Abstract The innate immune response involves a broad array of pathogen sensors that stimulate the production of interferons (IFNs) to induce an antiviral state. Rotavirus, a significant cause of childhood gastroenteritis and a member of the Reoviridae family of segmented, double-stranded RNA viruses, encodes at least two direct antagonists of host innate immunity: NSP1 and VP3. NSP1, a putative E3 ubiquitin ligase, mediates the degradation of cellular factors involved in both IFN induction and downstream signaling. VP3, the viral capping enzyme, utilizes a 2H-phosphodiesterase domain to prevent activation of the cellular oligoadenylate synthase (OAS)/RNase L pathway. Computational, molecular, and biochemical studies have provided key insights into the structural and mechanistic basis of innate immune antagonism by NSP1 and VP3 of group A rotaviruses (RVA). Future studies with non-RVA isolates will be essential to understand how other rotavirus species evade host innate immune responses.


title: Fc receptors and their influence on efficacy of therapeutic antibodies for treatment of viral diseases

text: The lack of vaccines against several important viral diseases necessitates the development of therapeutics to save lives and control epidemics. In recent years, therapeutic antibodies have received considerable attention due to their good safety profiles and clinical success when used against viruses such as respiratory syncytial virus, Ebola virus and Hendra virus. The binding affinity of these antibodies can directly impact their therapeutic efficacy. However, we and others have also demonstrated that the subtype of Fc-gamma receptors (FcγRs) engaged influences the stoichiometric requirement for virus neutralization. Hence, the development of therapeutic antibodies against infectious diseases should consider the FcγRs engaged and Fc-effector functions involved. This review highlights the current state of knowledge about FcγRs and FcγR effector functions involved in virus neutralization, with emphasis on factors that can affect FcγR engagement. A better understanding of Fc-FcγR interactions during virus neutralization will allow development of therapeutic antibodies that are efficacious and can be administered with minimal side effects.


title: Should Autism Spectrum Conditions Be Characterised in a More Positive Way in Our Modern World?

text: In a special issue that focuses on complex presentations related to Autism, we ask the question in this editorial whether an Autism Spectrum Condition without complexity is a disorder, or whether it represents human diversity? Much research into Autism Spectrum Conditions (ASCs) over the years has focused on comparisons between neuro-typical people and people with Autism Spectrum Conditions. These comparisons have tended to draw attention to ‘deficits’ in cognitive abilities and descriptions of behaviours that are characterised as unwanted. Not surprisingly, this is reflected in the classification systems from the World Health Organisation and the American Psychiatric Association. Public opinion about ASC may be influenced by presentations in the media of those with ASC who also have intellectual disability. Given that diagnostic systems are intended to help us better understand conditions in order to seek improved outcomes, we propose a more constructive approach to descriptions that uses more positive language, and balances descriptions of deficits with research finding of strengths and differences. We propose that this will be more helpful to individuals on the Autism Spectrum, both in terms of individual self-view, but also in terms of how society views Autism Spectrum Conditions more positively. Commentary has also been made on guidance that has been adjusted for people with ASC in relation to the current COVID-19 pandemic.


title: Capturing patient‐reported outcomes during the COVID‐19 pandemic: Development of the COVID‐19 Global Rheumatology Alliance Patient Experience Survey

text: The coronavirus disease 2019 (COVID‐19) Global Rheumatology Alliance (C19‐GRA) was formed in March 2020 as a grassroots organization to coordinate the response of the international rheumatology community to the pandemic [1]. The C19‐GRA launched an international, secure, de‐identified physician registry of patients with rheumatic diseases infected with the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) to provide insights into the management and treatment of COVID‐19 in this population.


title: The central role of chloride in the metabolic acid–base changes in canine parvoviral enteritis

text: Abstract The acid–base disturbances in canine parvoviral (CPV) enteritis are not well described. In addition, the mechanisms causing these perturbations have not been fully elucidated. The purpose of the present study was to assess acid–base changes in puppies suffering from CPV enteritis, using a modified strong ion model (SIM). The hypothesis of the study was that severe acid–base disturbances would be present and that the SIM would provide insights into pathological mechanisms, which have not been fully appreciated by the Henderson–Hasselbalch model. The study analysed retrospective data, obtained from 42 puppies with confirmed CPV enteritis and 10 healthy control dogs. The CPV-enteritis group had been allocated a clinical score, to allow classification of the data according to clinical severity. The effects of changes in free water, chloride, l-lactate, albumin and phosphate were calculated, using a modification of the base excess algorithm. When the data were summated for each patient, and correlated to each individual component, the most important contributor to the metabolic acid–base changes, according to the SIM, was chloride (P <0.001). Severely-affected animals tended to demonstrate hypochloraemic alkalosis, whereas mildly-affected puppies had a hyperchloraemic acidosis (P =0.007). In conclusion, the acid–base disturbances in CPV enteritis are multifactorial and complex, with the SIM providing information in terms of the origin of these changes.


title: An updated estimation of the risk of transmission of the novel coronavirus (2019-nCov)

text: The basic reproduction number of an infectious agent is the average number of infections one case can generate over the course of the infectious period, in a naïve, uninfected population. It is well-known that the estimation of this number may vary due to several methodological issues, including different assumptions and choice of parameters, utilized models, used datasets and estimation period. With the spreading of the novel coronavirus (2019-nCoV) infection, the reproduction number has been found to vary, reflecting the dynamics of transmission of the coronavirus outbreak as well as the case reporting rate. Due to significant variations in the control strategies, which have been changing over time, and thanks to the introduction of detection technologies that have been rapidly improved, enabling to shorten the time from infection/symptoms onset to diagnosis, leading to faster confirmation of the new coronavirus cases, our previous estimations on the transmission risk of the 2019-nCoV need to be revised. By using time-dependent contact and diagnose rates, we refit our previously proposed dynamics transmission model to the data available until January 29th(,) 2020 and re-estimated the effective daily reproduction ratio that better quantifies the evolution of the interventions. We estimated when the effective daily reproduction ratio has fallen below 1 and when the epidemics will peak. Our updated findings suggest that the best measure is persistent and strict self-isolation. The epidemics will continue to grow, and can peak soon with the peak time depending highly on the public health interventions practically implemented.


Abstract Type-I IFNs (IFN-I) provide a key mediator of innate antiviral response during virus proliferation. Porcine epidemic diarrhea virus (PEDV), which causes diarrhea in swine of all ages, is a worldwide-distributed alphacoronavirus with economic importance. Here, we screened PEDV RNA modification enzymes involved in regulating antiviral response. Whereas the PEDV nsp13 barely regulates type I IFN, inflammatory cytokines (IL-6, TNF-a) and MHCII, nsp16 and nsp14 (to a lesser extent) down-regulate these antiviral effectors. Importantly, we found nsp16 KDKE tetrad appears to play a key role in interferon inhibition by mutating the D129 catalytic residue. Mechanistically, nsp16 down-regulates the activities of RIG-I and MDA5 mediated IFN-β and ISRE. In turn, the mRNA levels of IFIT family members (IFIT1, IFIT2, IFIT3) was inhibited in cells overexpressing nsp16. In addition, nsp10 enhanced the inhibitory effect of nsp16 on IFN-β. Altogether these results indicate PEDV nsp16 negatively regulates innate immunity to promote viral proliferation. Findings from this study provides novel perspective to advance the understanding in the pathogenesis of PEDV.


title: Channel catfish, Ictalurus punctatus, cysteine proteinases: Cloning, characterisation and expression of cathepsin H and L

text: Abstract The antigen recognition by the host immune system is a complex biochemical process that requires a battery of enzymes. Cathepsins are one of the enzyme superfamilies involved in antigen degradation. We observed the up-regulation of catfish cathepsin H and L transcripts during the early stage of Edwardsiella ictaluri infection in preliminary studies, and speculated that cathepsin H and L may play roles in infection. We identified, sequenced and characterized the complete channel catfish cathepsin H and L cDNAs, which comprised 1415 and 1639 nucleotides, respectively. The open reading frames of cathepsin H appeared to encode a protein of 326-amino acid residues, which that of cathepsin L encoded a protein of 336 amino acids. The degree of conservation of the channel catfish cathepsin H and L amino acid sequences in comparison to other species ranged from 61% to 77%, and 67% to 85%, respectively. The catalytic triad and substrate binding sites are conserved in cathepsin H and L amino acid sequences. The cathepsin L transcript was expressed in all tissues examined, while the cathepsin H was expressed in restricted tissues. These results provide important information for further exploring the roles of channel catfish cathepsins in antigen processing.


title: Broad-Spectrum Drugs Against Viral Agents

text: Development of antivirals has focused primarily on vaccines and on treatments for specific viral agents. Although effective, these approaches may be limited in situations where the etiologic agent is unknown or when the target virus has undergone mutation, recombination or reassortment. Augmentation of the innate immune response may be an effective alternative for disease amelioration. Nonspecific, broad-spectrum immune responses can be induced by double-stranded (ds)RNAs such as poly (ICLC), or oligonucleotides (ODNs) containing unmethylated deocycytidyl-deoxyguanosinyl (CpG) motifs. These may offer protection against various bacterial and viral pathogens regardless of their genetic makeup, zoonotic origin or drug resistance.


title: Phylogenetic Analysis of Turkey Astroviruses Reveals Evidence of Recombination

text: Sequence data was obtained from the capsid (ORF-2) and the polymerase (ORF-lb) genes of 23 turkey astrovirus (TAstV) isolates collected from commercial turkey flocks around the United States between 2003 and 2004. A high level of genetic variation was observed among the isolates, particularly in the capsid gene, where nucleotide sequence identity among them was as low as 69%. Isolates collected on the same farm, on the same day, but from different houses could have as little as 72% identity between their capsid gene sequences when compared. Phylogenetic analysis of the capsid gene revealed no clear assortment by geographic region or isolation date. The polymerase gene was more conserved with between 86 and 99% nucleotide identity and did assort in a geographic manner. Based on differing topologies of the capsid and polymerase gene phylogenetic trees, TAstV appears to undergo recombination.


title: ACE2 receptor expression in testes: implications in coronavirus disease 2019 pathogenesis

text: Expression of angiotensin-converting enzyme 2, receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is high in the testes, therefore SARS-CoV-2 infection and its association with male reproductive health should be investigated in male coronavirus disease 2019 patients.


title: Introductions to the Community: Early-Career Researchers in the Time of COVID-19

text: Abstract COVID-19 has unfortunately halted lab work, conferences, and in-person networking, which is especially detrimental to researchers just starting their labs. Through social media and our reviewer networks, we met some early-career stem cell investigators impacted by the closures. Here, they introduce themselves and their research to our readers.


title: The immediate effects of the severe acute respiratory syndrome (SARS) epidemic on childbirth in Taiwan

text: BACKGROUND: When an emerging infectious disease like severe acute respiratory syndrome (SARS) strikes suddenly, many wonder the public's overwhelming fears of SARS may deterred patients from seeking routine care from hospitals and/or interrupt patient's continuity of care. In this study, we sought to estimate the influence of pregnant women's fears of severe acute respiratory syndrome (SARS) on their choice of provider, mode of childbirth, and length of stay (LOS) for the delivery during and after the SARS epidemic in Taiwan. METHODS: The National Health Insurance data from January 01, 2002 to December 31, 2003 were used. A population-based descriptive analysis was conducted to assess the changes in volume, market share, cesarean rate, and average LOS for each of the 4 provider levels, before, during and after the SARS epidemic. RESULTS: Compared to the pre-SARS period, medical centers and regional hospitals dropped 5.2% and 4.1% in market share for childbirth services during the peak SARS period, while district hospitals and clinics increased 2.1% and 7.1%, respectively. For changes in cesarean rates, only a significantly larger increase was observed in medical centers (2.2%) during the peak SARS period. In terms of LOS, significant reductions in average LOS were observed in all hospital levels except for clinics. Average LOS was shortened by 0.21 days in medical centers (5.6%), 0.21 days in regional hospitals (5.8%), and 0.13 days in district hospitals (3.8%). CONCLUSION: The large amount of patients shifting from the maternity wards of more advanced hospitals to those of less advanced hospitals, coupled with the substantial reduction in their length of maternity stay due to their fears of SARS could also lead to serious concerns for quality of care, especially regarding a patient's accessibility to quality providers and continuity of care.


title: Principles of appropriate antibiotic use for treatment of uncomplicated acute bronchitis: Background

text: Abstract The following principles of appropriate antibiotic use for adults with acute bronchitis apply to immunocompetent adults without complicating comorbid conditions, such as chronic lung or heart disease. 1. The evaluation of adults with an acute cough illness or a presumptive diagnosis of uncomplicated acute bronchitis should focus on ruling out serious illness, particularly pneumonia. In healthy, nonelderly adults, pneumonia is uncommon in the absence of vital sign abnormalities or asymmetrical lung sounds, and chest radiography is usually not indicated. In patients with cough lasting 3 weeks or longer, chest radiography may be warranted in the absence of other known causes. 2. Routine antibiotic treatment of uncomplicated acute bronchitis is not recommended, regardless of duration of cough. If pertussis infection is suspected (an unusual circumstance), a diagnostic test should be performed and antimicrobial therapy initiated. 3. Patient satisfaction with care for acute bronchitis depends most on physician–patient communication rather than on antibiotic treatment. [Gonzales R, Bartlett JG, Besser RE, Cooper RJ, Hickner JM, Hoffman JR, Sande MA. Principles of appropriate antibiotic use for treatment of uncomplicated acute bronchitis: background. Ann Emerg Med. June 2001;37:720-727.]


title: The Basics and the Advancements in Diagnosis of Bacterial Lower Respiratory Tract Infections

text: Lower respiratory tract infections (LRTIs) are the leading infectious cause of death and the sixth-leading cause of death overall worldwide. Streptococcus pneumoniae, with more than 90 serotypes, remains the most common identified cause of community-acquired acute bacterial pneumonia. Antibiotics treat LRTIs with a bacterial etiology. With the potential for antibiotic-resistant bacteria, defining the etiology of the LRTI is imperative for appropriate patient treatment. C-reactive protein and procalcitonin are point-of-care tests that may differentiate bacterial versus viral etiologies of LRTIs. Major advancements are currently advancing the ability to make rapid diagnoses and identification of the bacterial etiology of LRTIs, which will continue to support antimicrobial stewardship, and is the focus of this review.


title: Differentiation of canine coronavirus and porcine transmissible gastroenteritis virus by neutralization with canine, porcine and feline sera

text: Abstract Monospecific antisera were prepared in rabbits against canine coronavirus (CCV) and transmissible gastroenteritis virus of pigs (TGEV), and in 24 pigs and 3 cats against TGEV alone. Neutralizing antibody titres were higher for the immunizing than the heterologous virus, although cross-neutralization usually was detected. This confirmed that CCV and TGEV are distinct, but antigenically related coronaviruses. In sera from 41 dogs, CCV-neutralizing titres were on average 2.7 fold higher than TGEV-neutralizing titres, suggesting that CCV was the causal agent. Sera from 29 cats in colonies with feline infectious peritonitis (FIP) and known to contain TGEV-neutralizing antibody, were found to have titres 12.3 fold higher against CCV. The FIP virus (FIPV) is probably more closely related to CCV than TGEV as judged by antigens involved in virus neutralization. Antisera to two isolates of bovine coronavirus, three isolates of haemagglutinating encephalomyelitis virus, seven strains of avian infectious bronchitis virus and the 229E strain of human coronavirus all failed to neutralize CCV and TGEV. Thus CCV, TGEV and probably FIPV fall into a group of antigenically related agents, separable from other members of the family Coronaviridae, by both virus neutralization and immunofluorescence tests.


Intelligent technologies help operating mobile cabin hospitals effectively cope with COVID-19


title: Case reports study of the first five patients COVID-19 treated with remdesivir in France

text: Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as responsible for the COVID-19 outbreak worldwide. Data on treatment are scare and parallels are made between SARS-CoV-2 and other coronavirus. Remdesivir is a broad spectrum antiviral with efficient in vitro activity against SARS-CoV-2 and controversial evidence of clinical improvement in severe COVID-19 patients. We aimed to describe the clinical outcome and virological monitoring of the first five COVID-19 patients admitted in ICU for severe pneumonia related to SARS-CoV-2 and treated with remdesivir in the University hospital of Bichat, Paris, France. SARS-CoV-2 RT-qPCR in blood plasma, lower and upper respiratory tract were monitored. Among the five treated patients, two needed mechanical ventilation and one high flow cannula oxygen. A significant decrease in SARS-CoV-2 viral load from upper respiratory tract was observed in most cases but two died with active SARS-CoV-2 replication in the lower respiratory tract. Plasma samples were positive for SARS-CoV-2 in only one patient. Remdesivir was interrupted for side effects among four patients, including 2 ALT elevations (3 to 5 N) and 2 renal failures requiring renal replacement. This case series of five COVID-19 patients requiring ICU for a respiratory distress and treated with remdesivir, highlights the complexity of remdesivir use in such critically ill patients.


title: Expression and role of HEPIS in breast cancer

text: Human embryo lung cellular protein interacting with severe acute respiratory syndrome-coronavirus nonstructural protein-10 (HEPIS) is expressed at varying levels in multiple organs and breast cancer cell lines. However, its expression and function in breast cancer cells has yet to be studied. Therefore, RNA in situ hybridization was used to detect the expression of HEPIS in breast cancer and cancer-adjacent normal breast tissue. HEPIS was expressed at lower levels in breast cancer compared with that in adjacent normal tissue. Subcellular localization of HEPIS was mainly found in the cytoplasm of HeLa cells. Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine cell proliferation assays were used to investigate the role of HEPIS in cancer cell proliferation. Ectopic expression of HEPIS in MCF-7 cells was found to significantly inhibit cell proliferation. In contrast, knockdown of HEPIS by RNA interference exhibited the opposite effect. Furthermore, a dual-luciferase reporter assay was performed and HEPIS overexpression specifically inhibited the activity of the NF-κB reporter gene. Results of the gene chip assay revealed that 2,231 genes were differentially expressed in HEPIS-overexpressing cells. Results of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that these genes were enriched in the ‘mitogen-activated protein kinase signaling pathway’, ‘JAK-STAT signaling pathway’ and ‘focal adhesion’. Reverse transcription-quantitative PCR was used to confirm the expression levels of the differentially expressed genes interleukin 2 receptor subunit α (IL2RA), interferon α and β receptor subunit 2 (IFNAR2) and IFα8 (IFNA8). In conclusion, the results of the present study indicated that HEPIS may function as a potential repressor of breast cancer.


title: A persistently infecting coronavirus in hibernating Myotis lucifugus, the North American little brown bat

text: Bats are important reservoir hosts for emerging viruses, including coronaviruses that cause diseases in people. Although there have been several studies on the pathogenesis of coronaviruses in humans and surrogate animals, there is little information on the interactions of these viruses with their natural bat hosts. We detected a coronavirus in the intestines of 53/174 hibernating little brown bats (Myotis lucifugus), as well as in the lungs of some of these individuals. Interestingly, the presence of the virus was not accompanied by overt inflammation. Viral RNA amplified from little brown bats in this study appeared to be from two distinct clades. The sequences in clade 1 were very similar to the archived sequence derived from little brown bats and the sequences from clade 2 were more closely related to the archived sequence from big brown bats. This suggests that two closely related coronaviruses may circulate in little brown bats. Sequence variation among coronavirus detected from individual bats suggested that infection occurred prior to hibernation, and that the virus persisted for up to 4 months of hibernation in the laboratory. Based on the sequence of its genome, the coronavirus was placed in the Alphacoronavirus genus, along with some human coronaviruses, bat viruses and the porcine epidemic diarrhoea virus. The detection and identification of an apparently persistent coronavirus in a local bat species creates opportunities to understand the dynamics of coronavirus circulation in bat populations.


title: Vietnam's war on flu

text: Having suffered heavily from avian influenza in 2004, Vietnam might now be brewing the next human flu pandemic. Yet, as Peter Aldhous discovers, local researchers don't have the resources to investigate the risk properly.


title: Assessing impacts of SARS and Avian Flu on international tourism demand to Asia

text: The purpose of this paper is to investigate the impacts of infectious diseases including Avian Flu and severe acute respiratory syndrome (hereafter SARS) on international tourist arrivals in Asian countries using both single datasets and panel data procedures. An autoregressive moving average model together with an exogenous variables (ARMAX) model are used to estimate the effects of these diseases in each SARS- and Avian Flu-infected country, while a dynamic panel model is adopted to estimate the overall impact on the region of these two diseases. The empirical results from both approaches are consistent and indicate that the numbers of affected cases have a significant impact on SARS-affected countries but not on Avian Flu-affected countries. However, since the potential damage arising from the Avian Flu and subsequent pandemic influenza is much greater than that resulting from the SARS, the need to take the necessary precautions in the event of an outbreak of Avian Flu and pandemic influenza warrants further attention and action. Therefore, the empirical findings of this study could add to the knowledge regarding the relationship between tourism and crisis management, especially in so far as the management of transmissible diseases is concerned.


title: Alpha-ketoamides as broad-spectrum inhibitors of coronavirus and enterovirus replication

text: The main protease of coronaviruses and the 3C protease of enteroviruses share a similar active-site architecture and a unique requirement for glutamine in the P1 position of the substrate. Because of their unique specificity and essential role in viral polyprotein processing, these proteases are suitable targets for the development of antiviral drugs. In order to obtain near-equipotent, broad-spectrum antivirals against alphacoronaviruses, betacoronaviruses, and enteroviruses, we pursued structure-based design of peptidomimetic α-ketoamides as inhibitors of main and 3C proteases. Six crystal structures of protease:inhibitor complexes were determined as part of this study. Compounds synthesized were tested against the recombinant proteases as well as in viral replicons and virus-infected cell cultures; most of them were not cell-toxic. Optimization of the P2 substituent of the α-ketoamides proved crucial for achieving near-equipotency against the three virus genera. The best near-equipotent inhibitors, 11u (P2 = cyclopentylmethyl) and 11r (P2 = cyclohexylmethyl), display low-micromolar EC50 values against enteroviruses, alphacoronaviruses, and betacoronaviruses in cell cultures. In Huh7 cells, 11r exhibits three-digit picomolar activity against Middle East Respiratory Syndrome coronavirus.


title: The pandemic influenza threat: a review from the primary care perspective

text: Summary Aims This paper aims to summarise the growing literature concerning an imminent future influenza pandemic, from the primary care perspective. Methods Sources of literature were scanned and relevant material short-listed for further study from: (1) WHO and CDC websites; (2) PUBMED; and (3) papers mentioned in references of full-text papers. Results Outbreaks of avian influenza in Asia and elsewhere indicate that the world may be moving towards a pandemic influenza outbreak. The WHO Global Influenza Preparedness Plan 2005 unifies the world with the vision of tackling the next pandemic influenza outbreak as a global effort that includes healthcare provider and patient alike. Conclusions We need to update ourselves and keep our staff and patients informed to make infection control measures part of our daily activities. In areas where there are contacts with animal reservoirs of influenza A, patients need to be reminded that they need to protect themselves from being infected.


title: The nucleotide sequence and a first generation gene transfer vector of species B human adenovirus serotype 3

text: Abstract Human adenovirus (Ad) serotype 3 causes respiratory infections. It is considered highly virulent, accounting for about 13% of all Ad isolates. We report here the complete Ad3 DNA sequence of 35,343 base pairs (GenBank accession DQ086466). Ad3 shares 96.43% nucleotide identity with Ad7, another virulent subspecies B1 serotype, and 82.56 and 62.75% identity with the less virulent species B2 Ad11 and species C Ad5, respectively. The genomic organization of Ad3 is similar to the other human Ads comprising five early transcription units, E1A, E1B, E2, E3, and E4, two delayed early units IX and IVa2, and the major late unit, in total 39 putative and 7 hypothetical open reading frames. A recombinant E1-deleted Ad3 was generated on a bacterial artificial chromosome. This prototypic virus efficiently transduced CD46-positive rodent and human cells. Our results will help in clarifying the biology and pathology of adenoviruses and enhance therapeutic applications of viral vectors in clinical settings.


title: Stability analysis of a novel epidemics model with vaccination and nonlinear infectious rate

text: Abstract In this paper, by considering pathogen evolution and human interventions behaviors with vaccines or drugs, we build up a novel SEIRW model with the vaccination to the newborn children. The stability of the SEIRW model with time-varying perturbation to predict the evolution tendency of the disease is analyzed. Furthermore, we introduce a time-varying delay into the susceptible and infective stages in the model and give some global exponential stability criteria for the time-varying delay system. Finally, numerical simulations are presented to verify the results.


Man with productive cough


title: Human Kinase/Phosphatase-Wide RNAi Screening Identified Checkpoint Kinase 2 as a Cellular Factor Facilitating Japanese Encephalitis Virus Infection

text: Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, causes acute encephalitis in humans with high mortality. Not much is known about the interactions between viral and cellular factors that regulate JEV infection. By using a kinase/phosphatase-wide RNAi screening approach, we identified a cell cycle-regulating molecule, checkpoint kinase 2 (CHK2), that plays a role in regulating JEV replication. JEV infection induced G1 arrest and activated CHK2. Inactivation of CHK2 and its upstream ataxia-telangiectasia mutated kinase in JEV-infected cells by using inhibitors reduced virus replication. Likewise, JEV replication was significantly decreased by knockdown of CHK2 expression with shRNA-producing lentiviral transduction. We identified CHK2 as a cellular factor participating in JEV replication, for a new strategy in addressing JEV infection.


title: Hybrid control of delay induced hopf bifurcation of dynamical small-world network

text: In this paper, we focus on the Hopf bifurcation control of a small-world network model with time-delay. With emphasis on the relationship between the Hopf bifurcation and the time-delay, we investigate the effect of time-delay by choosing it as the bifurcation parameter. By using tools from control and bifurcation theory, it is proved that there exists a critical value of time-delay for the stability of the model. When the time-delay passes through the critical value, the model loses its stability and a Hopf bifurcation occurs. To enhance the stability of the model, we propose an improved hybrid control strategy in which state feedback and parameter perturbation are used. Through linear stability analysis, we show that by adjusting the control parameter properly, the onset of Hopf bifurcation of the controlled model can be delayed or eliminated without changing the equilibrium point of the model. Finally, numerical simulations are given to verify the theoretical analysis.


title: Severe acute respiratory syndrome coronavirus spike protein counteracts BST2‐mediated restriction of virus‐like particle release

text: BST2/tetherin, an interferon‐inducible antiviral factor, can block the cellular release of various enveloped viruses. We previously reported that human coronavirus 229E (HCoV‐229E) infection can alleviate the BST2 tethering of HIV‐1 virions by downregulating cell surface BST2, suggesting that coronaviruses are capable of encoding anti‐BST2 factors. Here we report our new finding that severe acute respiratory syndrome coronavirus (SARS‐CoV) spike (S) glycoprotein, similar to Vpu, is capable of antagonizing the BST2 tethering of SARS‐CoV, HCoV‐229E, and HIV‐1 virus‐like particles via BST2 downregulation. However, unlike Vpu (which downmodulates BST2 by means of proteasomal and lysosomal degradation pathways), BST2 downregulation is apparently mediated by SARS‐CoV S through the lysosomal degradation pathway only. We found that SARS‐CoV S colocalized with both BST2 and reduced cell surface BST2, suggesting an association between SARS‐CoV S and BST2 that targets the lysosomal degradation pathway. According to one recent report, SARS‐CoV ORF7a antagonizes BST2 by interfering with BST2 glycosylation(1). Our data provide support for the proposal that SARS‐CoV and other enveloped viruses are capable of evolving supplementary anti‐BST2 factors in a manner that requires virus replication. Further experiments are required to determine whether the BST2‐mediated restriction of authentic SARS‐CoV virions is alleviated by the SARS‐CoV spike protein.


title: Complete genome sequence of a novel S-insertion variant of porcine epidemic diarrhea virus from South Korea

text: Porcine epidemic diarrhea virus (PEDV) is an emerging and re-emerging viral pathogen of pigs that is causing significant economic concerns in the global pork industry. The virulent G2b PEDV subgroup, which was responsible for the 2013–2014 pandemics on the American and Asian continents, hit Jeju Island in 2014, which had been PEDV-free since 2004. This study presents molecular characterization of a novel PEDV variant with a 5-amino acid (aa) insertion (DTHPE) in the spike (S) gene (an S-insertion) that was identified in diarrheic piglets from Jeju Island. The genome of the PEDV strain KOR/KNU-1601/2016 was sequenced and analyzed to characterize the S-insertion variant circulating on Jeju Island. The full-length genome sequence of KNU-1601 is 28,053 nucleotides (nt) in length, which is 24 nt and 15 nt longer than the genome sequences of G1 classical and G2 epidemic field strains, respectively. KNU-1601 shares 99.5–99.6% nucleotide sequence identity at the genome level and 98.0–98.6% amino acid sequence identity at the S gene level with other global G2b PEDV strains. Genetic and phylogenetic analyses indicated that the KNU-1601 variant is most closely related to the G2b field isolates but appears to undergo continuous evolution in the field. These data advance our understanding of the genetic diversity and evolutionary characteristics of the PEDV field strains circulating in South Korea. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-017-3441-y) contains supplementary material, which is available to authorized users.


title: TAP expression reduces IL‐10 expressing tumor infiltrating lymphocytes and restores immunosurveillance against melanoma

text: Many immune therapeutic strategies are under development for melanoma to treat metastatic disease and prevent disease reoccurrence. However, human melanoma cells are often deficient in antigen processing and this appears to play a role in their expansion and escape from immunosurveillance. For example, expression of the transporters associated with antigen processing (TAP1 and TAP2) is down‐regulated in the mouse melanoma cell line B16F10. This results in a lack of tumor‐associated antigen processing, low surface expression of MHC Class I molecules and low immunogenicity. We observe that restoration of TAP1 expression by transfection resurrects the processing and presentation of viral antigens, and the melanoma‐associated antigen, TRP‐2. Immunization with irradiated B16F10/rTAP1 transfected cells generates CTLs that are capable of killing B16F10/rTAP1 transfected targets and B16F10 targets deficient in TAP1. Furthermore, B16F10/rTAP1 transfectants grow at a significantly slower rate in mice than B16F10 cells. In an experimental model that closely recapitulates the clinical situation, treatment of B16F10 tumors in mice with a vaccinia virus vector expressing TAP1 also significantly decreases tumor growth in vivo. Furthermore, tumors treated with vaccinia TAP1 had significantly reduced numbers of immunosuppressive, CD3(+)/IL‐10 positive, tumor infiltrating lymphocytes. Therefore, TAP1 expression restores both antigen presentation and immunogenicity in B16F10 melanoma cells and concomitantly reduces immunosuppressive IL‐10 production at the local tumor site, thereby increasing immunosurveillance mechanisms against tumors. © 2007 Wiley‐Liss, Inc.


title: Effects of a SARS prevention programme in Taiwan on nursing staff's anxiety, depression and sleep quality: A longitudinal survey

text: Abstract The aim of this research is to determine the levels of anxiety, depression, and sleep quality a severe acute respiratory syndrome (SARS) nursing staff experienced before and after a SARS prevention program. The 116 subjects were recruited from nursing staff in the largest obligatory SARS designated treatment hospital in Taiwan. Using general estimating equations (GEE) statistical analysis to control possible for affecting factors, we found that the nursing staff's anxiety and depression along with sleep quality started to improve 2 weeks after the initiation of SARS prevention controls. From this research, we determined that nursing staff members were anxious, depressed, and they could not sleep well at the SARS outbreak. However, the systematic SARS prevention program improved these factors. When faced with these types of diseases, related international medical organizations should establish a comprehensive program to help medical professionals cope better.


title: Serum proteomics analysis and comparisons using iTRAQ in the progression of hepatitis B

text: The aim of this study was to analyze the changes in serum protein levels in the progression of hepatitis B using isobaric tags for relative and absolute quantitation (iTRAQ) analysis, in addition to comparing the serum protein levels of patients with chronic hepatitis B (CHB), patients with hepatitis B virus-induced acute-on-chronic liver failure (HBV-induced ACLF) and normal individuals. Protein analysis was performed on 15 serum samples using iTRAQ. The study population included healthy controls (n=5), patients with CHB (n=5) and patients with HBV-induced ACLF (n=5). Western blotting was used to verify the results in an additional nine serum samples from healthy controls, patients with CHB and patients with HBV-induced ACLF (n=3, respectively). Using iTRAQ analysis, 16 different serum proteins with ≥1.5-fold differences in expression levels were identified in the patients with CHB and ACLF compared with the healthy controls. Five of those proteins, C-reactive protein precursor, hemoglobin β chain variant Hb S-Wake, apolipoprotein J precursor, platelet factor 4 precursor and vitronectin, which demonstrated the greatest differences in their expression levels and the most significant correlation with liver diseases, were subsequently verified using western blotting. The western blotting results were consistent with the results from the iTRAQ. Two of the five proteins are not classified by biological process, and the biological functions of all the proteins in HBV-induced ACLF remain unclear. This preliminary study demonstrated that a correlation between the expression of various serum proteins and the different pathogenetic conditions induced by HBV may exist. The analysis of a larger number of samples is required to identify potential protein biomarkers that may be involved in the pathogenesis and progression of hepatitis B.


title: Fitness Barriers Limit Reversion of a Proofreading-Deficient Coronavirus

text: The 3′-to-5′ exoribonuclease in coronavirus (CoV) nonstructural protein 14 (nsp14-ExoN) mediates RNA proofreading during genome replication. ExoN catalytic residues are arranged in three motifs: I (DE), II (E), and III (D). Alanine replacement of the motif I residues (AA-E-D; four nucleotide substitutions) in murine hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV yields viable mutants with impaired replication and fitness, increased mutation rates, and attenuated virulence in vivo. Despite these impairments, MHV- and SARS-CoV ExoN motif I AA mutants (ExoN-AA) have not reverted at motif I in diverse in vitro and in vivo environments, suggesting that profound fitness barriers prevent motif I reversion. To test this hypothesis, we engineered MHV-ExoN-AA with 1, 2, or 3 nucleotide mutations along genetic pathways to AA-to-DE reversion. We show that engineered intermediate revertants were viable but had no increased replication or competitive fitness compared to that of MHV-ExoN-AA. In contrast, a low-passage-number (passage 10 [P10]) MHV-ExoN-AA showed increased replication and competitive fitness without reversion of ExoN-AA. Finally, engineered reversion of ExoN-AA to ExoN-DE in the presence of ExoN-AA passage-adaptive mutations resulted in significant fitness loss. These results demonstrate that while reversion is possible, at least one alternative adaptive pathway is more rapidly advantageous than intermediate revertants and may alter the genetic background to render reversion detrimental to fitness. Our results provide an evolutionary rationale for lack of ExoN-AA reversion, illuminate potential multiprotein replicase interactions and coevolution, and support future studies aimed at stabilizing attenuated CoV ExoN-AA mutants. IMPORTANCE Coronaviruses encode an exoribonuclease (ExoN) that is important for viral replication, fitness, and virulence, yet coronaviruses with a defective ExoN (ExoN-AA) have not reverted under diverse experimental conditions. In this study, we identify multiple impediments to MHV-ExoN-AA reversion. We show that ExoN-AA reversion is possible but evolutionarily unfavorable. Instead, compensatory mutations outside ExoN-AA motif I are more accessible and beneficial than partial reversion. We also show that coevolution between replicase proteins over long-term passage partially compensates for ExoN-AA motif I but renders the virus inhospitable to a reverted ExoN. Our results reveal the evolutionary basis for the genetic stability of ExoN-inactivating mutations, illuminate complex functional and evolutionary relationships between coronavirus replicase proteins, and identify potential mechanisms for stabilization of ExoN-AA coronavirus mutants.


title: Managing ICU surge during the COVID-19 crisis: rapid guidelines

text: Given the rapidly changing nature of COVID-19, clinicians and policy makers require urgent review and summary of the literature, and synthesis of evidence-based guidelines to inform practice. The WHO advocates for rapid reviews in these circumstances. The purpose of this rapid guideline is to provide recommendations on the organizational management of intensive care units caring for patients with COVID-19 including: planning a crisis surge response; crisis surge response strategies; triage, supporting families, and staff. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06092-5) contains supplementary material, which is available to authorized users.


title: An attempt to support by the Japanese society of travel and health for increasing travel clinics

text: Abstract In recent years, both the number of Japanese travelers to foreign countries and foreign travelers who visit Japan have increased remarkably, and the risk of travelers suffering various infectious diseases is also increasing. In many western countries travel clinics commonly perform medical consultations, vaccinations, and issue prescriptions. However, travel clinics are not yet popular in Japan. In 2011, Japanese society of travel and health (JSTH) began a support project for travel clinic with a goal of increasing their number throughout the country. The project included the release of a manual for education, training, equipment, details of medical treatment, sources of information for travel clinic opening on the JSTH website (http://jstah.umin.jp/20TravelClinicSupport/manual_20120726.pdf), and mediation of short-term visitation to experienced travel clinics registered in the JSTH to facilitate learning above information and aftercare services. JSTH accepted requests for visitation to travel clinics from 39 medical institutions between 2011 and 2018. By 2018, 26 (66.7%) of the 39 medical institutions had opened travel clinics within two years and the 25 travel clinics had registered in the JSTH and one was a campus-limited clinic, while most of the remaining institutions are still in preparation stages. The number of travel clinics registered in the JSTH has increased from 45 in 2011 to 108 in 2018. Twenty-five travel clinics registered in the JSTH between 2011 and 2018 were eventually receiving support from JSTH. Our data indicates travel clinics in Japan have gradually increased and establishment areas are expanding after the beginning of support project for travel clinics by JSTH.


title: Involvement of VCP/UFD1/Nucleolin in the viral entry of Enterovirus A species

text: Abstract Valosin-containing protein (VCP) plays roles in various cellular activities. Recently, Enterovirus A71 (EVA71) infection was found to hijack the VCP protein. However, the mechanism by which VCP participates in the EVA71 life cycle remains unclear. Using chemical inhibitor, RNA interference and dominant negative mutant, we confirmed that the VCP and its ATPase activity were critical for EVA71 infection. To identify the factors downstream of VCP in enterovirus infection, 31 known VCP-cofactors were screened in the siRNA knockdown experiments. The results showed that UFD1 (ubiquitin recognition factor in ER associated degradation 1), but not NPL4 (NPL4 homolog, ubiquitin recognition factor), played critical roles in infections by EVA71. UFD1 knockdown suppressed the activity of EVA71 pseudovirus (causing single round infection) while it did not affect the viral replication in replicon RNA transfection assays. In addition, knockdown of VCP and UFD1 reduced viral infections by multiple human Enterovirus A serotypes. Mechanistically, we found that knockdown of UFD1 significantly decreased the binding and the subsequent entry of EVA71 to host cells through modulating the levels of nucleolin protein, a coreceptor of EVA71. Together, these data reveal novel roles of VCP and its cofactor UFD1 in the virus entry by EVA71.


title: The impact of COVID-19 on emerging stock markets

text: The goal of this study is to investigate the impact of COVID-19 on emerging stock markets over the period March 10 – April 30, 2020. Findings reveal that the negative impact of pandemic on emerging stock markets has gradually fallen and begun to taper off by mid-April. In terms of regional classification, the impact of the outbreak is the highest in Asian emerging markets whereas it is the lowest in the European emerging markets. We also find that response time and the size of stimulus package by the governments matter in offsetting the effects of the pandemic.


docid: tzzlblke

title: COVID-19 y enfermedad inflamatoria intestinal: preguntas surgidas de la atención y seguimiento de los pacientes durante la fase inicial de la pandemia (febrero-abril 2020)

text: RESUMEN El COVID-19 es un síndrome respiratorio agudo grave producido por el coronavirus SARS-CoV-2 que se describió en China a finales de 2019. Actualmente hay más de tres millones de casos diagnosticados, constituyendo una situación de pandemia que ha ocasionado una crisis a nivel mundial. El efecto devastador de esta infección se debe a su alta contagiosidad y, aunque predominan las formas leves, los casos graves y la mortalidad en valores absolutos son muy elevados. La información sobre las características de la infección en la enfermedad inflamatoria intestinal tiene especial interés, y esto es debido a que estos pacientes tienen una mayor frecuentación de centros sanitarios, lo que puede incrementar el riesgo de contagio. Además, los tratamientos que se administran para el control de la actividad inflamatoria podrían modificar la evolución del COVID-19. El Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU), en colaboración con el Grupo Enfermero de Trabajo en EII (GETEII), ha elaborado este documento que tiene como objetivo responder de forma práctica algunas dudas frecuentes en el tratamiento de estos pacientes. ABSTRACT COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was described in China in late 2019. There are currently more than three million diagnosed cases, constituting a pandemic which has caused a worldwide crisis. The devastating effects of this infection are due to its highly contagious nature and although mild forms predominate, in absolute values, the rates for severe forms and mortality are very high. The information on the characteristics of the infection in inflammatory bowel disease is of special interest, as these patients have higher attendance at health centres, which may increase their risk of infection. Furthermore, the treatments used to control the inflammatory activity may modify the disease course of COVID-19. The Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) and the Spanish Nurses Working Group on Inflammatory Bowel Disease (GETEII) have prepared this document as a practical response to some common questions about the treatment of these patients.


title: Maximizing the Calm Before the Storm: Tiered Surgical Response Plan for Novel Coronavirus (COVID-19)

text: Abstract The novel coronavirus (COVID-19) was first diagnosed in Wuhan, China in December 2019 and has now spread throughout the world, being verified by the World Health Organization as a Pandemic on March 11th. This had led to the calling of a national emergency on March 13th in the United States. Many hospitals, healthcare networks, and specifically Departments of Surgery are asking the same questions of how to cope and plan for surge capacity, personnel attrition, novel infrastructure utilization, and resource exhaustion. Herein, we present a tiered plan for surgical department planning based on incident command levels. This includes Acute Care Surgeon deployment (given their critical care training and vertically integrated position in the hospital), recommended infrastructure and transfer utilization, triage principles, and faculty, resident and advanced care practitioner deployment.


Airborne Severe Acute Respiratory Syndrome Coronavirus and Its Implications


title: Personal protective equipment for ENT activity during COVID-19 pandemic

text: BACKGROUND: In the COVID-19 era physicians have to face with need to perform office procedures maintaining the maximum safety for both the patient and the Doctor himself. The purpose of this paper was to suggest some equipment useful to perform outpatient visits in an ENT setting. METHODS: A simple modification of the standard headlight used during an ENT visit provides the operator a better face protection without any impairment in vision and comfort. In addition, in order to perform a safer ENT examination, a droplet protective barrier has been adapted to the patient's chair. RESULTS: Both the devices have been texted with success during a period of 2 months in our ENT clinic. No cases of contamination have been registered among physicians. CONCLUSION: A simple modification to a device used in the routine ENT activity implemented its protective efficacy with low costs. On the other hand, a more structured tool permitted to obtain a more protected environment during patient examination. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00405-020-06177-3) contains supplementary material, which is available to authorized users.


title: A novel pancoronavirus RT-PCR assay: frequent detection of human coronavirus NL63 in children hospitalized with respiratory tract infections in Belgium

text: BACKGROUND: Four human coronaviruses are currently known to infect the respiratory tract: human coronaviruses OC43 (HCoV-OC43) and 229E (HCoV-229E), SARS associated coronavirus (SARS-CoV) and the recently identified human coronavirus NL63 (HCoV-NL63). In this study we explored the incidence of HCoV-NL63 infection in children diagnosed with respiratory tract infections in Belgium. METHODS: Samples from children hospitalized with respiratory diseases during the winter seasons of 2003 and 2004 were evaluated for the presence of HCoV-NL63 using a optimized pancoronavirus RT-PCR assay. RESULTS: Seven HCoV-NL63 positive samples were identified, six were collected during January/February 2003 and one at the end of February 2004. CONCLUSIONS: Our results support the notation that HCoV-NL63 can cause serious respiratory symptoms in children. Sequence analysis of the S gene showed that our isolates could be classified into two subtypes corresponding to the two prototype HCoV-NL63 sequences isolated in The Netherlands in 1988 and 2003, indicating that these two subtypes may currently be cocirculating.


title: Chapter six Mechanism of Function of Viral Channel Proteins and Implications for Drug Development

text: Abstract Viral channel-forming proteins comprise a class of viral proteins which, similar to their host companions, are made to alter electrochemical or substrate gradients across lipid membranes. These proteins are active during all stages of the cellular life cycle of viruses. An increasing number of proteins are identified as channel proteins, but the precise role in the viral life cycle is yet unknown for the majority of them. This review presents an overview about these proteins with an emphasis on those with available structural information. A concept is introduced which aligns the transmembrane domains of viral channel proteins with those of host channels and toxins to give insights into the mechanism of function of the viral proteins from potential sequence identities. A summary of to date investigations on drugs targeting these proteins is given and discussed in respect of their mode of action in vivo.


title: Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD

text: Daily oscillations of pulmonary function depend on the rhythmic activity of the circadian timing system. Environmental tobacco/cigarette smoke (CS) disrupts circadian clock leading to enhanced inflammatory responses. Infection with influenza A virus (IAV) increases hospitalization rates and death in susceptible individuals, including patients with Chronic Obstructive Pulmonary Disease (COPD). We hypothesized that molecular clock disruption is enhanced by IAV infection, altering cellular and lung function, leading to severity in airway disease phenotypes. C57BL/6J mice exposed to chronic CS, BMAL1 knockout (KO) mice and wild-type littermates were infected with IAV. Following infection, we measured diurnal rhythms of clock gene expression in the lung, locomotor activity, pulmonary function, inflammatory, pro-fibrotic and emphysematous responses. Chronic CS exposure combined with IAV infection altered the timing of clock gene expression and reduced locomotor activity in parallel with increased lung inflammation, disrupted rhythms of pulmonary function, and emphysema. BMAL1 KO mice infected with IAV showed pronounced detriments in behavior and survival, and increased lung inflammatory and pro-fibrotic responses. This suggests that remodeling of lung clock function following IAV infection alters clock-dependent gene expression and normal rhythms of lung function, enhanced emphysematous and injurious responses. This may have implications for the pathobiology of respiratory virus-induced airway disease severity and exacerbations.


title: Evaluation of novel antigen-based rapid detection test for the diagnosis of SARS-CoV-2 in respiratory samples

text: OBJECTIVES: In the context of the Covid-19 pandemic, the development and validation of rapid and easy-to-perform diagnostic methods are of high priority. We evaluated a novel rapid antigen detection test (RDT) for SARS-CoV-2 in respiratory samples. METHODS: The fluorescence immunochromatographic SARS-CoV-2 antigen test (Bioeasy Biotechnology Co., Shenzhen, China) was evaluated using universal transport medium with nasopharyngeal (NP) and oropharyngeal (OP) swabs from suspected Covid-19 cases. Diagnostic accuracy was determined in comparison to SARS-CoV-2 real time (RT)-PCR. RESULTS: A total of 127 samples were included; 82 were RT-PCR positive. Median patients’ age was 38 years, 53.5% were male, and 93.7% were from the first week after symptom onset. Overall sensitivity and specificity were 93.9% (CI95% 86.5–97.4) and 100% (CI95% 92.1–100), respectively, with a diagnostic accuracy of 96.1% and Kappa coefficient of 0.9. Sensitivity was significantly higher in samples with high viral loads. CONCLUSIONS: The evaluated RDT showed a high sensitivity and specificity in samples mainly obtained during the first week of symptoms and with high viral loads, despite the use of a non-validated sample material. The assay has the potential to become an important tool for early diagnosis of SARS-CoV-2, particularly in situations with limited access to molecular methods.


title: A probable role for IFN-γ in the development of a lung immunopathology in SARS

text: Abstract Recent work carried out in our laboratory showed the existence of a cytokine storm in SARS patients, dominated by Th1-type mediators. We thus hypothesized that IFN-γ may play a major role in the pathology by triggering immune-mediated alveolar damage. As we assessed or re-assessed some effects of IFN-γ on a number of human lung epithelial and fibroblast cell lines, chosen for their wide use in the literature, we found that alveolar epithelial cells were more sensitive to IFN-γ, in terms of proliferation inhibition and enhancement of Fas-mediated apoptosis. While similar effects were obtained on fibroblasts, concentrations of IFN-γ 4–8-fold greater were required. In addition, both epithelial and fibroblastic cell lines were able to secrete large quantities of T cell-targeting chemokines, similar to the ones detected in SARS patients. Based on the clinical data collected previously, the available literature and our in vitro experimentation, we propose that IFN-γ may be responsible for acute lung injury in the late phase of the SARS pathology.


docid: dwkfnokc

title: Association of Digestive Symptoms and Hospitalization in Patients with SARS-CoV-2 Infection

text: Background: High rates of concurrent gastrointestinal manifestations have been noted in patients with COVID- 19, however the association between these digestive manifestations and need for hospitalization has not been established. Methods: Following expedited approval from our Institutional Review Board, we analyzed retrospectively collected data from consecutive patients with confirmed COVID-19 based on a positive polymerase chain reaction testing at our institution from March 03, 2020 to April 7, 2020. Baseline demographic, clinical, laboratory and patient-reported symptom data were collected at presentation in the emergency room. Multivariable logistic regression analyses were performed to evaluate the association between hospitalization and presence of gastrointestinal symptoms. Results: During this study period, we identified 207 consecutive patients with confirmed COVID-19. 34.5% noted concurrent gastrointestinal symptoms; of which 90% of gastrointestinal symptoms were mild. In a multivariate regression model controlled for demographics and disease severity, an increased risk for hospitalization was noted in patients with any gastrointestinal symptom (adjusted OR 4.84 95% CI: 1.68-13.94]. Diarrhea was associated with a seven-fold higher likelihood for hospitalization (adjusted OR=7.58, 95% CI: 2.49-20.02, P <0.001) and nausea or vomiting had a four times higher odds (adjusted OR 4.39, 95% CI: 1.61-11.4, P = 0.005). Conclusion: We demonstrate that a significant portion of COVID19 patients have concurrent mild gastrointestinal symptoms and that the presence of these digestive symptoms is associated with a need for hospitalization. With the current focus on streamlining triaging efforts, first responders and frontline providers should consider assessing for digestive symptoms in their initial clinical evaluation and decision-making.


In Memoriam: Joshua Lederberg (1925–2008)


title: Human norovirus hyper-mutation revealed by ultra-deep sequencing

text: Abstract Human noroviruses (NoVs) are a major cause of gastroenteritis worldwide. It is thought that, similar to other RNA viruses, high mutation rates allow NoVs to evolve fast and to undergo rapid immune escape at the population level. However, the rate and spectrum of spontaneous mutations of human NoVs have not been quantified previously. Here, we analyzed the intra-patient diversity of the NoV capsid by carrying out RT-PCR and ultra-deep sequencing with 100,000-fold coverage of 16 stool samples from symptomatic patients. This revealed the presence of low-frequency sequences carrying large numbers of U-to-C or A-to-G base transitions, suggesting a role for hyper-mutation in NoV diversity. To more directly test for hyper-mutation, we performed transfection assays in which the production of mutations was restricted to a single cell infection cycle. This confirmed the presence of sequences with multiple U-to-C/A-to-G transitions, and suggested that hyper-mutation contributed a large fraction of the total NoV spontaneous mutation rate. The type of changes produced and their sequence context are compatible with ADAR-mediated editing of the viral RNA.


title: Middle East respiratory syndrome coronavirus (MERS-CoV): Prevention in travelers

text: Summary Middle East respiratory syndrome coronavirus (MERS-CoV), a novel coronavirus that causes a severe lower respiratory tract infection in humans, emerged in the Middle East in 2012. Since then, MERS-CoV has caused an ongoing epidemic in the Arabian Peninsula with sporadic cases imported in Europe, North Africa, Southeast Asia, and the United States of America. As of 28th May 2014, 636 laboratory-confirmed cases of infection with MERS-CoV have been reported to World Health Organization including 14 cases imported by travelers. The epicenter of the current MERS-CoV epidemic is located in Saudi Arabia, where millions of pilgrims travel for two mass gatherings annually. In this review we summarize MERS-CoV cases in relation to travel with focus on the epidemiology and prevention in travelers. It is important to increase awareness of travelers about the risks and appropriate preventive measures and for health professionals to be on alert if a patient with severe respiratory symptoms reports a recent history of travel to the region affected with MERS-CoV. Measures should be taken by local health authorities of the affected countries in order to improve hospital hygiene. Finally, it is crucial to investigate the reasons for travelers' poor compliance with rules and recommendations issued by Saudi officials and to take appropriate measures in order to improve them.


title: Vaccines Produced by Conventional Means to Control Major Infectious Diseases of Man and Animals

text: Publisher Summary This chapter reviews the development of some of vaccines and their use in controlling such major diseases as diphtheria, rinderpest, Newcastle disease, smallpox, pertussis, yellow fever, rabies, etc. Park–Williams Number 8 (PW8) strain is used to make diphtherial toxoid for vaccines. As a source of toxin, it is rendered nontoxic by incubation with formalin under alkaline conditions. The product's retention of antigenicity, enabling it to induce antitoxin antibodies, makes it an excellent pediatric vaccine. Vaccine against Rinderpest Virus was developed by Koch in 1897 by administering bile from infected cattle. Animals that survived were permanently immune. Formalin- and chloroform-inactivated vaccines were developed using tissues from the infected animals. For the control of Newcastle disease, a number of attenuated live-virus vaccines have been developed which are widely used to control the disease. The Bl strain, the LaSota strain, and the F strain are used to immunize birds of all ages by different routes, including by addition to drinking water and by spraying. Protection against rabies correlates with SN antibody, which can be assessed by a number of tests. Pasteur's classical vaccine, developed from infected spinal cord tissue dried at room temperature for 3–14 days, was given in a series of 21–28 inoculations beginning with material dried the longest and progressing through material dried for only 3 days.


title: Conservation of personal protective equipment for head and neck cancer surgery during COVID‐19 pandemic

text: BACKGROUND: COVID‐19 pandemic has led to a global shortage of personal protective equipment (PPE). This study aims to stratify face shield needs when performing head and neck cancer surgery. METHODS: Fifteen patients underwent surgery between March 1, 2020 and April 9, 2020. Operative diagnosis and procedure; droplet count and distribution on face shields were documented. RESULTS: Forty‐five surgical procedures were performed for neck nodal metastatic carcinoma of unknown origin (n = 3); carcinoma of tonsil (n = 2), tongue (n = 2), nasopharynx (n = 3), maxilla (n = 1), and laryngopharynx (n = 4). Droplet contamination was 57.8%, 59.5%, 8.0%, and 0% for operating, first and second assistant surgeons, and scrub nurse respectively. Droplet count was highest and most widespread during osteotomies. No droplet splash was noted for transoral robotic surgery. CONCLUSION: Face shield is not a mandatory adjunctive PPE for all head and neck surgical procedures and health care providers. Judicious use helps to conserve resources during such difficult times.


title: The impact of the SARS‐CoV‐2 outbreak on the safety and availability of blood transfusions in Italy

text: Coronaviruses are enveloped single-stranded RNA viruses belonging to the family of Coronaviridae. While initial research focused on their ability to cause enzootic infections, infections which have emerged in the past two decades demonstrate their ability to cross the species barrier and infect humans [1,2]. The ensuing epidemics have included Severe Acute Respiratory Syndrome (SARS) in 2002 and the more recent Middle East Respiratory Syndrome (MERS) in 2012, and have resulted in severe disease burden, mortality and economic disruption [3]. A novel flu-like coronavirus, emerging towards the end of 2019 and subsequently named SARS-CoV-2, has been associated with an epidemic initially focused in Wuhan, China.


title: Viral pathophysiology of multiple sclerosis: A role for Epstein-Barr virus infection?

text: Abstract Multiple sclerosis (MS) is the most common inflammatory demyelinating and degenerative disease of the CNS. The cause of MS is unknown but environmental risk factors are implicated in MS. Several viruses have been proposed as a trigger for MS, and lately Epstein-Barr virus (EBV) has become the leading candidate. An infectious aetiology fits with a number of epidemiological observations in addition to the immunopathological features of the disease. In this review we will summarize the emerging evidence, which demonstrates a strong association between EBV infection and MS. The conundrum remains as to whether EBV is directly involved in the pathophysiology of MS, or alternatively if the immunopathology of MS somehow affects the regulation of EBV infection.


title: COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses

text: The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China and spread around the world. Genomic analysis revealed that SARS-CoV-2 is phylogenetically related to severe acute respiratory syndrome-like (SARS-like) bat viruses, therefore bats could be the possible primary reservoir. The intermediate source of origin and transfer to humans is not known, however, the rapid human to human transfer has been confirmed widely. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. However, few broad-spectrum antiviral drugs have been evaluated against COVID-19 in clinical trials, resulted in clinical recovery. In the current review, we summarize and comparatively analyze the emergence and pathogenicity of COVID-19 infection and previous human coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). We also discuss the approaches for developing effective vaccines and therapeutic combinations to cope with this viral outbreak.


Imported COVID-19 Cases Pose New Challenges for China


title: Change of the diagnostic distribution in applicants to dermatology after COVID ‐19 pandemic: What it whispers to us?

text: We aim to evaluate the change in the diagnostic spectrum in dermatology outpatient applications compared to before COVID‐19. All patients were enrolled from the Department of Dermatology between February 12 and May 8, 2020, the duration of 4 weeks before COVID‐19 and eight weeks after were analyzed in 3 parts consisting of 4 weeks. Data obtained from the database such as age, gender, diagnoses were anonymized. Repeated applications with the same diagnosis in ten days after the first presentation were ignored. Compared to the pre‐outbreak, there was a 3.5‐fold decrease in dermatology applications in the first month after COVID‐19 and an 8.8‐fold in the second month. We found a significant increase in the frequency of diagnoses such as generalized pruritus, pityriasis rosea, alopecia areata, bacterial skin/mucosa diseases, and zona zoster after COVID‐19. The frequency declined in diseases such as verruca vulgaris, hyperpigmentation, skin tag, melanocytic nevus, seborrheic keratosis/solar lentigo. It has been found that the frequencies of most diseases, including acne (⁓25% of patients), did not change. We think that many factors, such as affecting the quality of life, risk perception, increased stress burden may cause a change in the diagnostic distribution of the dermatology applications. This article is protected by copyright. All rights reserved.


title: Potent Inhibition of Zika Virus Replication by Aurintricarboxylic Acid

text: Zika virus (ZIKV) is one of the recently emerging vector-borne viruses in humans and is responsible for severe congenital abnormalities such as microcephaly in the Western Hemisphere. Currently, only a few vaccine candidates and therapeutic drugs are being developed for the treatment of ZIKV infections, and as of yet none are commercially available. The polyanionic aromatic compound aurintricarboxylic acid (ATA) has been shown to have a broad-spectrum antimicrobial and antiviral activity. In this study, we evaluated ATA as a potential antiviral drug against ZIKV replication. The antiviral activity of ATA against ZIKV replication in vitro showed median inhibitory concentrations (IC(50)) of 13.87 ± 1.09 μM and 33.33 ± 1.13 μM in Vero and A549 cells, respectively; without showing any cytotoxic effect in both cell lines (median cytotoxic concentration (CC(50)) > 1,000 μM). Moreover, ATA protected both cell types from ZIKV-induced cytopathic effect (CPE) and apoptosis in a time- and concentration-dependent manner. In addition, pre-treatment of Vero cells with ATA for up to 72 h also resulted in effective suppression of ZIKV replication with similar IC(50). Importantly, the inhibitory effect of ATA on ZIKV infection was effective against strains of the African and Asian/American lineages, indicating that this inhibitory effect was not strain dependent. Overall, these results demonstrate that ATA has potent inhibitory activity against ZIKV replication and may be considered as a potential anti-ZIKV therapy for future clinical evaluation.


title: Detection of economically important viruses in boar semen by quantitative RealTime PCR™ technology

text: Abstract The objective of this study was to develop quantitative real-time polymerase chain reaction (ReTi-PCR) tests for the detection of five economically important viruses in swine semen namely, pseudorabies virus (PRV), classical swine fever virus (CSFV), foot-and-mouth disease virus (FMDV), swine vesicular disease virus (SVDV), and porcine reproductive and respiratory syndrome virus (PRRSV). Each ReTi-PCR test was validated for specificity, analytical sensitivity (detection limits), and experimental infection studies were performed to compare the conventional virus isolation methods with the newly developed ReTi-PCR tests. All five developed ReTi-PCR tests are very rapid compared to virus isolation, highly specific, and even more sensitive (lower detection limits) than conventional virus isolation methods for the detection of mentioned viruses in semen. In semen of experimentally infected boars, viruses were detected much earlier after infection and more frequently by ReTi-PCR tests than by virus isolations. The high throughput of these rapid ReTi-PCR tests makes it possible to screen large number of semen samples for the presence of viruses prior to insemination. This is a substantial advantage, in particular for boar semen the quality of which deteriorates quickly after storage. In general, the newly developed ReTi-PCR tests are valuable tools for the early, reliable and rapid detection of five economically important viruses, namely PRV, CSFV, FMDV, SVDV, and PRRSV in boar semen. These ReTi-PCR tests will improve the control of viral diseases transmitted via semen.


title: Respiratory droplets get suspended longer and spread wider in temperate environments compared to tropics and implications for SARS-CoV-2 transmission

text: The new pandemic of SARS-CoV-2 has shown stark differences in number of affected patients between countries in the tropics and those with temperate environments. Though there have been many theories on reasons for these differences, we hypothesise that this could be due to differences in the fate of respiratory droplets in the two environments. A simple understanding of the mechanics of droplet size, dispersion and displacement could help infection control and public health measures to minimize spread and mitigate the risk of people getting infected especially in hotspots like hospital environments or other closed spaces. This paper discusses the possibility of differences in number of infections and spread between different countries based on the spread of droplets.


Uneventful course in IBD patients during SARS-CoV-2 outbreak in northern Italy


title: Influenza and Parainfluenza Associated Pediatric ICU Morbidity

text: OBJECTIVES: To investigate if morbidity in young children admitted to a pediatric intensive care unit (PICU with a laboratory proven diagnosis of influenza and parainfluenza infection) had increased. METHODS: Retrospective study from January 2003 through December 2009 was carried out. Every child in the PICU with a laboratory-confirmed influenza or parainfluenza infection was included. RESULTS: 18 influenza (influenza A = 13 and influenza B = 5) and 17 parainfluenza admissions were identified over the 7-year period. Parainfluenza type 3 (n = 9) was the commonest subtype of parainfluenza infection. The median age of children admitted with influenza was higher than parainfluenza (4.5 vs 1.7 years, p = 0.044). Admissions associated with proven influenza and parainfluenza infections accounted for 2% of PICU annual admissions. There was only one death in 2003. 51% of these patients required ventilatory support, 45% received systemic corticosteroids, and 91% received initial broad spectrum antibiotic coverage. Bacterial co-infections were identified in 25% of these patients. The incidence of influenza admissions had not increased significantly in 2009 (H1N1 pandemic) when compared with 2003 (SARS epidemic) (p = 0.3). There were only two PICU cases of pandemic H1N1 in 2009 and both survived. The annual incidence of severe PICU cases of influenza and parainfluenza were 0.94 and 0.88 per 100,000 children per annum, respectively. CONCLUSIONS: Pandemic H1N1, influenza and parainfluenza viruses may be associated with significant childhood morbidity and PICU admissions.


title: An OpenData portal to share COVID-19 drug repurposing data in real time

text: The National Center for Advancing Translational Sciences (NCATS) has developed an online open science data portal for its COVID-19 drug repurposing campaign – named OpenData – with the goal of making data across a range of SARS-CoV-2 related assays available in real-time. The assays developed cover a wide spectrum of the SARS-CoV-2 life cycle, including both viral and human (host) targets. In total, over 10,000 compounds are being tested in full concentration-response ranges from across multiple annotated small molecule libraries, including approved drug, repurposing candidates and experimental therapeutics designed to modulate a wide range of cellular targets. The goal is to support research scientists, clinical investigators and public health officials through open data sharing and analysis tools to expedite the development of SARS-CoV-2 interventions, and to prioritize promising compounds and repurposed drugs for further development in treating COVID-19.


title: Psychiatric adverse events with hydrochloroquine during COVID-19 Pandemic

text: • Hydrochloroquine, well known in rheumatology, dermatology and tropical medicine is now considered in the treatment and prophylaxy for the SARS-CoVid19. • Mental and neurological manifestations should be assessed following the use of hydrochloroquine particularly following prophylactic use. • For acute malaria studies, hydroxychloroquine was associated with high prevalence of mental neurological manifestations amongst anti-malaria drugs. • Recommendations of using hydrochloroquine in COVID are variable and sometimes contradictory depending on agencies and countries.


title: Cross‐species transmission of the newly identified coronavirus 2019‐nCoV

text: The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019‐nCoV by the World Health Organization, as determined by sequencing the viral RNA genome. Many initial patients were exposed to wildlife animals at the Huanan seafood wholesale market, where poultry, snake, bats, and other farm animals were also sold. To investigate possible virus reservoir, we have carried out comprehensive sequence analysis and comparison in conjunction with relative synonymous codon usage (RSCU) bias among different animal species based on the 2019‐nCoV sequence. Results obtained from our analyses suggest that the 2019‐nCoV may appear to be a recombinant virus between the bat coronavirus and an origin‐unknown coronavirus. The recombination may occurred within the viral spike glycoprotein, which recognizes a cell surface receptor. Additionally, our findings suggest that 2019‐nCoV has most similar genetic information with bat coronovirus and most similar codon usage bias with snake. Taken together, our results suggest that homologous recombination may occur and contribute to the 2019‐nCoV cross‐species transmission.


title: Comparison of commercial systems for extraction of nucleic acids from DNA/RNA respiratory pathogens

text: Abstract This study compared six automated nucleic acid extraction systems and one manual kit for their ability to recover nucleic acids from human nasal wash specimens spiked with five respiratory pathogens, representing Gram-positive bacteria (Streptococcus pyogenes), Gram-negative bacteria (Legionella pneumophila), DNA viruses (adenovirus), segmented RNA viruses (human influenza virus A), and non-segmented RNA viruses (respiratory syncytial virus). The robots and kit evaluated represent major commercially available methods that are capable of simultaneous extraction of DNA and RNA from respiratory specimens, and included platforms based on magnetic-bead technology (KingFisher mL, Biorobot EZ1, easyMAG, KingFisher Flex, and MagNA Pure Compact) or glass fiber filter technology (Biorobot MDX and the manual kit Allprep). All methods yielded extracts free of cross-contamination and RT-PCR inhibition. All automated systems recovered L. pneumophila and adenovirus DNA equivalently. However, the MagNA Pure protocol demonstrated more than 4-fold higher DNA recovery from the S. pyogenes than other methods. The KingFisher mL and easyMAG protocols provided 1- to 3-log wider linearity and extracted 3- to 4-fold more RNA from the human influenza virus and respiratory syncytial virus. These findings suggest that systems differed in nucleic acid recovery, reproducibility, and linearity in a pathogen specific manner.


Globalization of Chikungunya: 10 years to invade the world


title: From guidance to practice: Promoting risk communication and community engagement for prevention and control of coronavirus disease (COVID‐19) outbreak in China

text: Integrating risk communication and community engagement into the national public health emergency response is crucial. Considering the difficulties and challenges faced by China in the prevention and control of coronavirus disease (COVID‐19) and based on interim guidelines from the World Health Organization, this article makes several recommendations addressing the outbreak in China. These include improvements in the internal governmental risk communication systems, enhancing the coordination between internal and partner governmental emergency management, and promoting public communication in response to societal concerns. Regarding these recommendations, we emphasize community engagement in joint prevention and control, confronting uncertainty and countering rumors effectively, and strengthening international cooperation and evidence‐based decision making for prevention and control measures.


title: A novel low virulent respiratory infectious bronchitis virus originating from the recombination of QX, TW and 4/91 genotype strains in China

text: Abstract In China, variants of infectious bronchitis virus (IBV) evolve continually and diverse recombinant strains have been reported. Here, an IBV strain, designated as ck/CH/LJX/2017/07 (referred as JX17) was isolated from chicken vaccinated with H120 and 4/91 in Jiangxi, China, in 2017. Sequence analysis reveals of the S1 gene of JX17 the highest nucleotide identity of 98.15% with that of GI-7 genotype TW2575/98 strain. Furthermore, whole genome analysis among JX17 and other 18 IBV strains demonstrates that JX17 has the highest nucleotide identity of 95.94% with GI-19 genotype YX10 strain. Among all genes of JX17 except the S1 gene, the N gene and 3’ UTR have the highest identity to GI-13 genotype 4/91 strain and the rest genes are the most identical to GI-19 genotype YX10 strain. Analyzed by the RDP and SimPlot, the recombination of JX17 strain was shown to occur in regions which include 5’-terminal S1 gene (20,344 to 22,447 nt), most N gene and 3’ UTR (26,163 to 27,648 nt). The pathogenicity study shows that JX17 is a natural low virulent IBV variant which caused respiratory symptoms but no death. Taken together, these results indicate that IBV strains continue to evolve through genetic recombination and three prevalent genotypes in China including QX, TW and 4/91 have started to recombine.


title: Progression of CXR features on a COVID-19 survivor

text: COVID-19 causes consolidations or ground glass opacities that are predominantly peripheral, basal, and bilateral on chest x-ray (CXR). There are no published case reports that present over ten serial CXRs on the same patient. We present a case report of a 68-year-old patient with confirmed COVID-19 and a prolonged course of admission, receiving nasal and humidified oxygen, non-invasive and then mechanical ventilation. She self-extubated, but remained stable on nasal oxygen only and was transferred for rehabilitation. We present 12 of her serial CXRs over six weeks, showing progression from subtle changes to overt widespread pneumonitis to slow resolution. She is also an example of a rare case of COVID-19 pneumonitis causing persistent hypoxia for over six weeks.


title: Localization of major neutralizing epitopes on the S1 polypeptide of the murine coronavirus peplomer glycoprotein

text: Abstract A recombinant baculovirus system has been used to express the amino terminal half of the murine coronavirus (JHMV) peplomer glycoprotein in insect cells. The expressed polypeptide is glycosylated and is recognized by a set of monoclonal antibodies (mAbs) specific for JHMV S protein. Three of these mAbs have a very high neutralizing activity for JHMV but not for other MHV strains. These results indicate that JHMV-specific, major neutralizing epitopes reside in the amino terminal S1 subunit of the peplomer glycoprotein.


title: Influenza Virus Infections

text: Abstract Influenza, commonly known as flu, is a contagious, febrile viral disease. Common symptoms are chills, fever, sore throat, coughing, sneezing, muscle pains, headache, myalgia, etc. Influenza viruses (IVs) belonging to orthomyxovirus group are of three types (types A, B, and C). IVs are enveloped, segmented, negative-stranded RNA viruses containing eight distinct RNA segments (types A and B) and seven RNA segments (type C). Only type A viruses exhibit different subtypes. Currently, 18 hemagglutination (HA) subtypes (H1 to H18) and 11 neuraminidase (NA) subtypes (N1 to N11) are known in humans and other warm-blooded animals. Flu outbreaks occur as annual epidemics in fall and winter and infrequently, as worldwide pandemics. Annual epidemics are caused by antigenic drift due to mutations in HA and NA antigens, whereas pandemics are caused by antigenic shift due to genetic reassortment among different subtype viruses. The first pandemic of the twenty-first century, declared by the World Health Organization (WHO) in 2009, was caused by an H1N1 virus, derived from quadruple reassortment among swine, avian, and human IVs. Currently, two types of antiinfluenza drugs, based on either blocking the M2 proton channel (amantadine and rimantadine) or inhibiting NA (oseltamivir or Tamiflu by Roche and zanamivir or Relanza by GlaxoSmithKline) are available. The virus is commonly spread by aerosol droplets and by fingertips. Therefore, washing hands and avoiding contact with infected persons are the first lines of defense. Indoor living and closeness of people in an enclosed environment in winter facilitate virus transmission leading to epidemics. Annual vaccination is the best preventative measure. Currently, two types of vaccines (subunit vaccine by injection and live attenuated vaccine by nasal spray) are available and recommended by WHO and Centers for Disease Control.


title: Production of a monoclonal antibody against SARS-CoV spike protein with single intrasplenic immunization of plasmid DNA

text: Abstract Severe acute respiratory syndrome (SARS) is a highly infectious disease caused by a novel coronavirus (SARS-CoV). Specific monoclonal antibodies (mAbs) against the SARS-CoV are vital for early diagnosis and pathological studies of SARS. Direct intrasplenic inoculation of plasmid DNA encoding antigen is an effective and fast approach to generate specific mAb when the protein antigen is difficult to prepare or dangerous in use. In this study, we selected one fragment of SARS-CoV spike protein (S1-3) as antigenic determinant by immunoinformatics. Single intrasplenic immunization of plasmid DNA encoding S1-3 induced anti-spike protein antibodies. We established one hybridoma cell line secreting specific mAb and evaluated this mAb with murine leukemia virus pseudotyped with SARS-CoV spike protein (MLV/SARS-CoV). The mAb could recognize the spike protein on the MLV/SARS-CoV-infected Vero E6 cells albeit with no neutralizing effect on the infectivity of the pseudotype virus. Our results show that a single-shot intrasplenic DNA immunization is efficient for the production of specific mAb against SARS spike protein, and a linear epitope of the spike protein is recognized in this study.


Lack of Mimivirus Detection in Patients with Respiratory Disease, China


title: High-resolution Chest CT Features and Clinical Characteristics of Patients Infected with COVID-19 in Jiangsu, China

text: Abstract Background A pneumonia associated with the coronavirus disease 2019 (COVID-19) recently emerged in China. It was recognized as a global health hazard. Methods 234 inpatients with COVID-19 were included. Detailed clinical data, chest HRCT basic performances and certain signs were recorded, and ground-glass opacity (GGO), consolidation, fibrosis and air trapping were quantified. Both clinical types and CT stages were evaluated. Results Most patients (approximately 90%) were classified as common type and with epidemiologic history. Fever and cough were main symptoms. Chest CT showed abnormal attenuation in bilateral multiple lung lobes, distributed in the lower and/or periphery of the lungs (94.98%), with multiple shapes. GGO and vascular enhancement sign were most frequent seen, followed by interlobular septal thickening and air bronchus sign as well as consolidation, fibrosis and air trapping. There were significant differences in most of CT signs between different stage groups. The SpO2 and OI were decreased in stage IV, and the CT score of consolidation, fibrosis and air trapping was significantly lower in stage I (P <0.05). A weak relevance was between the fibrosis score and the value of PaO2 and SpO2 (P <0.05). Conclusions Clinical performances of patients with COVID-19, mostly with epidemiologic history and typical symptoms, were critical valuable in the diagnosis of the COVID-19. While chest HRCT provided the distribution, shape, attenuation and extent of lung lesions, as well as some typical CT signs of COVID-19 pneumonia.


title: Performances of different diagnostic tests for feline infectious peritonitis in challenging clinical cases

text: Objectives: Feline infectious peritonitis (FIP) can be difficult to diagnose. Histopathology is considered the gold standard test but immunohistochemistry (IHC) is mandatory to confirm/exclude the disease. This study aimed to assess the performances of tests carried out in vivo or at postmortem examination in challenging cases in which FIP was confirmed or excluded based on IHC or on adequate follow‐up. Methods: Twelve cases (four without FIP, eight with FIP) were retrospectively studied. Clinical findings, serum protein electrophoresis (SPE), analysis of the effusions (AE), antifeline coronavirus serology, serum concentration of α1‐acid glycoprotein (AGP) and histopathology were classified as consistent, doubtful or non‐consistent with FIP. Sensitivity, specificity and concordance (κ) with the final diagnosis were calculated. Results: Concordance was absent for serology (κ=−0·08) and AE (κ=−0·52), poor for histopathology (κ=0·09), fair for SPE (κ=0·25) and perfect for AGP (κ=1·00). Sensitivity was high for AGP (100%) and low for AE (50%), SPE (37·5%) and histopathology (37·5%). Specificity was high for AGP or histopathology (100%) and low for SPE (50%) and AE (0%). Clinical Significance: IHC must always be performed to confirm FIP. If this is not possible, when histopathology is controversial, elevated AGP concentrations may support the diagnosis of FIP.


title: Spatial–temporal transmission of influenza and its health risks in an urbanized area

text: Cities and urban areas play an important role in fostering influenza transmission, often leading to epidemics and even pandemics. Although there is growing literature on influenza transmission at national and international scales, little attention has been paid to a city scale. This article aims to understand the spatial–temporal transmission of influenza and identify its health risks in the urbanized area of Buffalo, New York. An individual-based spatially explicit model is established to replicate an urban contact network, and simulate influenza epidemics. The resulting epidemic curves and infection intensity maps are used to analyze the transmission dynamics, possible contributing factors, and high-risk places and times. The results indicate that the city-wide transmission of influenza can be described by five stages: local growth, expansion, fast city-wide growth, slow city-wide growth, and fade-out. The places and times associated with higher risk are closely related to spatial heterogeneity in the population, and travel behaviors of individuals. Interestingly, these high-risk places and times are insensitive to where infection sources are introduced. This research suggests that high-risk places can be pre-identified as control targets using census and land use data. In addition, a better understanding on the city-wide travel of individuals is critical for designing proper timelines for influenza control. These suggestions will be valuable for local health agencies as they prepare to combat new waves of H1N1 influenza.


docid: xemarhlv

title: Apoptosis induced by a cytopathic hepatitis A virus is dependent on caspase activation following ribosomal RNA degradation but occurs in the absence of 2′–5′ oligoadenylate synthetase

text: Abstract We have presented previously evidence that the cytopathogenic 18f strain of hepatitis A virus (HAV) induced degradation of ribosomal RNA (rRNA) in infected cells [Arch. Virol. 148 (2003) 1275–1300]. In contrast, the non-cytopathogenic parent virus HM175 clone 1 had no effect on rRNA integrity. We present here data showing that rRNA degradation is followed by apoptosis accompanied by characteristic DNA laddering in the cytoplasm of 18f infected cells. The DNA laddering coincided with the detection of caspase 3 and PARP-1 cleavage and was dependent upon activation of the caspase pathway, since treatment with Z-VAD-FMK, a pan-caspase inhibitor, inhibited both events. RNase L mRNA was present in both virus-infected and uninfected cells. Messenger RNA for the interferon inducible enzyme 2′–5′ oligoadenylate synthetase (2′–5′ OAS), which polymerizes ATP into 2′–5′ oligo adenylate (2–5A, the activator of RNase L) in the presence of double-stranded RNA, was not detected following virus infection. 2′–5′ OAS mRNA was induced by treatment of the cells with interferon-β (IFN-β). IFN-β mRNA was marginally induced following infection. However, phosphorylated STAT 1, a key regulator of interferon-stimulated gene transcription was not detected in virus infected cells. STAT 1 phosphorylation in response to IFN treatment was lower in virus-infected cells, compared to uninfected cells treated with interferon, suggesting that 18f virus infection interferes with interferon signaling. The results suggest that 18f infection causes the induction of a 2–5A independent RNase L like activity.


title: Which Melbourne metropolitan areas are vulnerable to COVID-19 based on age, disability and access to health services? Using spatial analysis to identify service gaps and inform delivery

text: Abstract Ageing adults (65+) with disability are especially vulnerable to COVID-19 and upon contracting, are a cohort most likely to require palliative care. Therefore, it is very important that health services - particularly health services providing palliative care - are proximately available. Treating the Melbourne metropolitan area as a case-study, a spatial analysis was conducted to clarify priority areas with a significantly high percentage and number of ageing adults (65+) with disability, and high barriers to accessing primary health services. After, travel times from priority areas to (i) palliative medicine, and (ii) hospital services were calculated. The geographic dispersion of areas with people vulnerable to COVID-19 with poor access to palliative care and health services are clarified. Unique methods of health service delivery are required to ensure that vulnerable populations in under-serviced metropolitan areas receive prompt and adequate care. The spatial methodology employed can be implemented in different contexts to support evidence-based COVID-19 and pandemic palliative care service decisions.