title: Clinical and Th1/Th2 immune response features of hospitalized children with human rhinovirus infection

text: This study aimed to assess the clinical characteristics and T‐helper 1 (Th1)/Th2 profile of human rhinovirus (HRV) infection in children with bronchiolitis and pneumonia, compared with the respiratory syncytial virus (RSV). In September 2013 to August 2014, 335 nasopharyngeal aspirates from children below 14 with bronchiolitis and pneumonia were screened for HRV and 13 other respiratory viruses by PCR or reverse transcription PCR. Interferon (IFN)‐γ, interleukin (IL)‐2, IL‐4, IL‐6, IL‐10, and tumor necrosis factor (TNF)‐α were detected by multiplex enzyme‐linked immunosorbent assay. HRVs were found in 66 cases (19.7%), including 35 bronchiolitis and 31 pneumonia cases. Compared with the RSV alone group, children with pneumonia had more frequent wheezing episodes in HRV (P (a) = .001) and HRV + non‐RSV (P (b) = .002) groups, and fever in the HRV (P (f) = .004) and HRV + RSV (P (g) = .005) groups. Among patients with bronchiolitis, cases with HRV alone were more likely to present in winter than those with RSV alone (P (i) = .010) and HRV + non‐RSV (P (j) = .014), and less numerous in summer compared with HRV + non‐RSV (P (h) = .005). Children with HRV alone were more susceptible to have a history of eczema than RSV alone among bronchiolitis (P (c) < .001) and pneumonia (P (e) = .033) cases. HRV bronchiolitis cases had increased IL‐4/IFN‐γ and decreased TNF‐α/IL‐10 ratios, compared with HRV pneumonia counterparts. HRV is a major non‐RSV pathogen causing hospitalization in children with bronchiolitis and pneumonia and induces an imbalanced Th1/Th2 response in bronchiolitis. Compared with RSV infection, HRV bronchiolitis and pneumonia differ significantly regarding wheezing episodes, susceptibility to eczema, fever occurrence, and seasonal prevalence.


COVID‐19 and Clinical Pharmacy Worldwide ‐ A Wake Up Call and a Call to Action


Optimising medication management during the COVID‐19 pandemic


title: From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses

text: Abstract This article introduces a series of invited papers in Antiviral Research marking the 10th anniversary of the outbreak of severe acute respiratory syndrome (SARS), caused by a novel coronavirus that emerged in southern China in late 2002. Until that time, coronaviruses had not been recognized as agents causing severe disease in humans, hence, the emergence of the SARS-CoV came as a complete surprise. Research during the past ten years has revealed the existence of a diverse pool of coronaviruses circulating among various bat species and other animals, suggesting that further introductions of highly pathogenic coronaviruses into the human population are not merely probable, but inevitable. The recent emergence of another coronavirus causing severe disease, Middle East respiratory syndrome (MERS), in humans, has made it clear that coronaviruses pose a major threat to human health, and that more research is urgently needed to elucidate their replication mechanisms, identify potential drug targets, and develop effective countermeasures. In this series, experts in many different aspects of coronavirus replication and disease will provide authoritative, up-to-date reviews of the following topics: – clinical management and infection control of SARS; – reservoir hosts of coronaviruses; – receptor recognition and cross-species transmission of SARS-CoV; – SARS-CoV evasion of innate immune responses; – structures and functions of individual coronaviral proteins; – anti-coronavirus drug discovery and development; and – the public health legacy of the SARS outbreak. Each article will be identified in the last line of its abstract as belonging to the series “From SARS to MERS: 10years of research on highly pathogenic human coronaviruses.”


title: Coordinate induction of IFN-α and -γ by SARS-CoV also in the absence of virus replication

text: Abstract Background: Severe acute respiratory syndrome (SARS) is an emerging infection caused by a novel coronavirus known as SARS-CoV, characterized by an over-exuberant immune response with lung lymphomononuclear cells infiltration and proliferation that may account for tissue damage more than the direct effect of viral replication. This study is aimed at investigating the capability of SARS-CoV to activate IFN-α and -γ expression in lymphomonocytes (PBMC) from healthy donors, evaluating whether viral replication is necessary for this activation. Results: SARS-CoV virus is able to induce both IFN-α and -γ mRNA accumulation and protein release in a dose-dependent manner, MOI 10 being the most effective. The time course curve indicated that IFN-α mRNA induction peaked at 24 h.p.i,. whereas IFN-γ mRNA was still increasing at 48 h.p.i. Released IFN (both types) reached a plateau after 24–48 h.p.i. and remained rather stable over a 5-day period. A transient peak of negative strand viral RNA was detected after 1–2 days of infection, but neither infectious virus progeny yield nor newly produced viral genomic RNA could be evidenced in infected cultures, even after prolonged observation time (up to 13 days). Cocultivation of PBMC with fixed SARS-CoV-infected Vero cells was even more efficient than exposure to live virus in eliciting IFN-α and -γ induction. A combination of IFN-α and -γ strongly inhibited SARS-CoV replication in Vero cells, while the single cytokines were much less effective. Conclusions: This study provides evidence that SARS-CoV is able to induce in normal PBMC a coordinate induction of IFN-α and -γ gene expression. Virus replication is not necessary for IFN induction since efficient IFN expression could be obtained also by the cocultivation of normal PBMC with fixed SARS-CoV-infected cells. Concomitant activation of IFN-α and -γ gene expression by SARS-CoV in vivo may be relevant for the pathogenesis of the disease, both for the possible involvement in immunomediated damage of the tissues and for the strong inhibition of SARS-CoV replication as a result of combined cytokine action.


title: Evidence that Processing of the Severe Fever with Thrombocytopenia Syndrome Virus Gn/Gc Polyprotein Is Critical for Viral Infectivity and Requires an Internal Gc Signal Peptide

text: The severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging, highly pathogenic bunyavirus against which neither antivirals nor vaccines are available. The SFTSV glycoproteins, Gn and Gc, facilitate viral entry into host cells. Gn and Gc are generated from a precursor protein, Gn/Gc, but it is currently unknown how the precursor is converted into the single proteins and whether this process is required for viral infectivity. Employing a rhabdoviral pseudotyping system, we demonstrate that a predicted signal sequence at the N-terminus of Gc is required for Gn/Gc processing and viral infectivity while potential proprotein convertase cleavage sites in Gc are dispensable. Moreover, we show that expression of Gn or Gc alone is not sufficient for host cell entry while particles bearing both proteins are infectious, and we provide evidence that Gn facilitates Golgi transport and virion incorporation of Gc. Collectively, these results suggest that signal peptidase liberates mature Gc from the Gn/Gc precursor and that this process is essential for viral infectivity and thus constitutes a potential target for antiviral intervention.


title: 9-O-Acetylation of Sialomucins: A Novel Marker of Murine CD4 T Cells that Is Regulated during Maturation and Activation

text: Terminal sialic acids on cell surface glycoconjugates can carry 9-O-acetyl esters. For technical reasons, it has previously been difficult to determine their precise distribution on different cell types. Using a recombinant soluble form of the Influenza C virus hemagglutinin-esterase as a probe for 9-O-acetylated sialic acids, we demonstrate here their preferential expression on the CD4 T cell lineage in normal B10.A mouse lymphoid organs. Of total thymocytes, 8–10% carry 9-O-acetylation; the great majority of these are the more mature PNA(−), HSA(−), and TCR(hi) medullary cells. While low levels of 9-O-acetylation are seen on some CD4/CD8 double positive (DP) and CD8 single positive (SP) cells, high levels are present primarily on 80– 85% of CD4 SP cells. Correlation with CD4 and CD8 levels suggests that 9-O-acetylation appears as an early differentiation marker as cells mature from the DP to the CD4 SP phenotype. This high degree of 9-O-acetylation is also present on 90–95% of peripheral spleen and lymph node CD4 T cells. In contrast, only a small minority of CD8 T cells and B cells show such levels of 9-O-acetylation. Among mature peripheral CD4 T lymphocytes, the highly O-acetylated cells are Mel 14(hi), CD44(lo), and CD45R(exon B)(hi), features typical of naive cells. Digestions with trypsin and O-sialoglycoprotease (OSGPase) and ELISA studies of lipid extracts indicate that the 9-O-acetylated sialic acids on peripheral CD4 T cells are predominantly on O-linked mucintype glycoproteins and to a lesser degree, on sialylated glycolipids (gangliosides). In contrast, sialic acids on mucin type molecules of CD8 T cells are not O-acetylated; instead these molecules mask the recognition of O-acetylated gangliosides that seem to be present at similar levels as on CD4 cells. The 9-O-acetylated gangliosides on mouse T cells are not bound by CD60 antibodies, which recognize O-acetylated gangliosides in human T cells. Tethering 9-O-acetylated mucins with the Influenza C probe with or without secondary cross-linking did not cause activation of CD4 T cells. However, activation by other stimuli including TCR ligation is associated with a substantial decrease in surface 9-O-acetylation, primarily in the mucin glycoprotein component. Thus, 9-O-acetylation of sialic acids on cell surface mucins is a novel marker on CD4 T cells that appears on maturation and is modulated downwards upon activation.


Please cite this paper as: Zuccotti et al. (2011) Epidemiological and clinical features of respiratory viral infections in hospitalized children during the circulation of influenza virus A(H1N1) 2009. Influenza and Other Respiratory Viruses 5(6), e528–e534. Background Seasonal influenza viruses and respiratory syncytial virus (RSV) are primary causes of acute respiratory tract infections (ARTIs) in children. New respiratory viruses including human metapneumovirus (hMPV), human bocavirus (hBoV), and influenza 2009 A(H1N1) virus have a strong impact on the pediatric population. Objectives To evaluate epidemiological and clinical features of ARTIs in hospitalized children. Methods From December 1, 2008, to December 31, 2009, all children under age fifteen (n = 575) hospitalized for ARTIs were investigated for influenza A (subtype H1N1, H3N2, and 2009 H1N1) and B, RSV A and B, hMPV, and hBoV by PCR. Results Fifty‐one percent of samples were positive for these respiratory viruses. The frequencies of virus detection were RSV 34·1%, hBoV 6·8%, hMPV 5%, seasonal influenza A 5%, and seasonal influenza B 0%. From April 2009, 11·6% of collected samples were influenza 2009 A(H1N1) positive. Respiratory syncytial virus activity peaked in January, hBoV in February, and hMPV in April. Seasonal influenza A was detected only between January and April 2009, while influenza 2009 A(H1N1) peaked in November. Respiratory syncytial virus and hMPV were mainly associated with lower respiratory tract infections (LRTIs) and with necessity of O(2) administration. The 2009 pandemic influenza was more frequently detected in elder children (P < 0·001) and was associated with higher, longer‐lasting fevers compared with other viral infections (P < 0·05). Conclusions All considered viruses were involved in LRTIs. The primary clinical relevance of RSV and a similar involvement of both seasonal influenza and emerging viruses investigated were observed on the pediatric population.


title: The difference in the incubation period of 2019 novel coronavirus (SARS-CoV-2) infection between travelers to Hubei and non-travelers: The need of a longer quarantine period

text: Data collected from the individual cases reported by the media were used to estimate the distribution of the incubation period of travelers to Hubei and non-travelers. Upon the finding of longer and more volatile incubation period in travelers, the duration of quarantine should be extended to three weeks.


title: Remote reporting in the COVID-19 era: from pilot study to practice

text: Abstract Aim To assess the benefits and challenges of remote reporting using an intra-departmental teleradiology system. Materials And Methods A pilot of an in-hospital Trust radiologist reporting on in-hospital Trust patients via a remote login was undertaken. Reporting output, training impact, and quality improvement were measured. Results Reporting output increased by 140%. Trainee satisfaction was high in a qualitative survey, particularly for out-of-hours support and teaching. Clinicians found the service to be similar to the same service provided by a locally based radiologist. Conclusion In the COVID-19 era, remote working has developed rapidly. This study shows that radiology departments can provide remote reporting that is equal in standard to reporting from within the hospital, and in addition, that there are advantages to output and training.


title: The Susceptible-Unidentified infected-Confirmed (SUC) epidemic model for estimating unidentified infected population for COVID-19

text: In this article, we propose the Susceptible-Unidentified infected-Confirmed (SUC) epidemic model for estimating the unidentified infected population for coronavirus disease 2019 (COVID-19) in China. The unidentified infected population means the infected but not identified people. They are not yet hospitalized and still can spread the disease to the susceptible. To estimate the unidentified infected population, we find the optimal model parameters which best fit the confirmed case data in the least-squares sense. Here, we use the time series data of the confirmed cases in China reported by World Health Organization. In addition, we perform the practical identifiability analysis of the proposed model using the Monte Carlo simulation. The proposed model is simple but potentially useful in estimating the unidentified infected population to monitor the effectiveness of interventions and to prepare the quantity of protective masks or COVID-19 diagnostic kit to supply, hospital beds, medical staffs, and so on. Therefore, to control the spread of the infectious disease, it is essential to estimate the number of the unidentified infected population. The proposed SUC model can be used as a basic building block mathematical equation for estimating unidentified infected population.


COVID‐19 Abortion Bans and Their Implications for Public Health


title: Infections in Patients with Cystic Fibrosis Diagnostic Microbiology Update

text: Survival has improved in patients with cystic fibrosis (CF), in part because of aggressive antimicrobial management. Two multidrug-resistant environmental bacteria, the Burkholderia cepacia group and nontuberculous mycobacteria, have emerged. Improving genomic and proteomic technologies are allowing better identification of bacteria and fungi found in the CF lung and detection of viral agents that may be associated with pulmonary exacerbations. Anaerobic bacteria and Streptococcus angionsus group organisms may play a role in chronic CF lung infections. The diversity of organisms declines perhaps as a result of aggressive antimicrobial therapy, and an apex predator, Pseudomonas aeruginosa, may emerge in many patients with CF.


Health risks among travelers to Brazil: Implications for the 2014 FIFA World Cup and 2016 Olympic Games


title: Neutralization of Animal Viruses

text: Publisher Summary Various aspects of the interaction of bacterial viruses and antibody were studied by Andrewes and Elford in England. Similar studies, as well as studies on animal viruses, were carried out in Australia by Burnet and his colleagues. One result of their extensive studies, which were summarized in great detail, was the conclusion that, with respect to their interaction with antibody, bacterial and animal viruses were basically different. Specifically, the difference resided in the stability of the union of virus and antibody, whereas bacterial viruses formed stable complexes, animal viruses formed complexes that tended to dissociate readily. The introduction of animal cell cultures as host systems greatly aided in the study of animal viruses, with respect to fewer and more readily controlled variables, and by the use of the plaque assay in enhanced quantitative reliability. In 1956, Dulbecco et al. described the interaction of two animal viruses with their respective antibodies. The results of these studies led these investigators to conclude, among other things, that animal viruses, at least the two they studied, reacted with antibodies to form complexes that did not dissociate spontaneously. This interpretation was challenged by Fazekas de St. Groth and Reid. As more animal virus-antibody systems were studied by many investigators, there seemed to be a greater accord for irreversible, rather than reversible, interaction. For this reason, in this chapter it is assumed that there are no differences between bacterial viruses, as one category, and animal viruses, as a separate category, concerning their interaction with antibodies. Rather, differences, when they exist, are considered to be related to the viruses per se. Although this chapter is intended to survey the neutralization of animal viruses, occasional reference is made to the studies on bacterial viruses when these studies are pertinent and illuminating to the topic at hand.


title: Creation and preliminary characterization of a Tp53 knockout rat

text: The tumor suppressor TP53 plays a crucial role in cancer biology, and the TP53 gene is the most mutated gene in human cancer. Trp53 knockout mouse models have been widely used in cancer etiology studies and in search for a cure of cancer with some limitations that other model organisms might help overcome. Via pronuclear microinjection of zinc finger nucleases (ZFNs), we created a Tp53 knockout rat that contains an 11-bp deletion in exon 3, resulting in a frameshift and premature terminations in the open reading frame. In cohorts of 25 homozygous (Tp53(Δ11/Δ11)), 37 heterozygous (Tp53(Δ11/+)) and 30 wild-type rats, the Tp53(Δ11/Δ11) rats lived an average of 126 days before death or removal from study because of clinical signs of abnormality or formation of tumors. Half of Tp53(Δ11/+) were removed from study by 1 year of age because of tumor formation. Both Tp53(Δ11/+) and Tp53(Δ11/Δ11) rats developed a wide spectrum of tumors, most commonly sarcomas. Interestingly, there was a strikingly high incidence of brain lesions, especially in Tp53(Δ11/Δ11) animals. We believe that this mutant rat line will be useful in studying cancer types rarely observed in mice and in carcinogenicity assays for drug development.


title: Palliating a Pandemic: “All Patients Must Be Cared For”

text: Abstract In the event of an overwhelming influenza pandemic, many health care systems will implement a triage system that would potentially deny critical care treatment to some seriously ill patients. Although all triage systems have guaranteed palliative care for those who are denied critical care, no jurisdiction has yet developed a plan to accommodate the anticipated “surge” in demand for palliative care. The authors present a mathematical and ethical justification for a palliative care surge plan and outline some of the key elements that should be included in such a plan.


title: The mystery of the COVID toes – turning evidence-based medicine on its head

text: The recent and rapid emergence of COVID-19 infection has led to a flood of publications describing all aspects of the disease and its presentation. The appearance of chilblain-like lesions, in children and young adults has particularly caught the attention of healthcare professionals with an interest in the foot. With such a novel infection, demand for information is high at a time when evidence is scarce. Consequently, there has been a renaissance in the publication of case studies. This type of research, previously relegated from many mainstream journals, as a low level source of evidence, has permitted the rapid reporting, publication and dissemination of much needed clinical data which can be used as a foundation to inform further research and investigations about a new global infection.


title: The Silver Lining in Gain-of-Function Experiments with Pathogens of Pandemic Potential

text: Half a decade after the contentious “gain-of-function” (GOF) debate of 2012 that followed experimentation showing that highly pathogenic avian influenza virus could become mammalian transmissible, it is possible to reflect on the arguments for and against this type of research. In this essay we argue that GOF-type experiments have already produced important information not available from any other source while also providing information on pathogenesis and the requirements for optimizing strains for vaccine production. We analyze the moral arguments against GOF and find them less compelling for a variety of reasons ranging from the uncertainty of risk-benefit analysis to the reduced likelihood of accidents given the enhanced biosafety and biosecurity protocols currently in place. In our view the most important consequence of the GOF debate is that it brought renewed attention to biosafety protocols and ushered innovation in answering the relevant biological questions with greater safety. We conclude that GOF experiments should go forward provided that necessary biosafety and biosecurity conditions are in place.


title: Diagnostic Molecular Microbiology A 2013 Snapshot

text: Molecular testing has a large and increasing role in the diagnosis of infectious diseases. It has evolved significantly since the first probe tests were FDA approved in the early 1990s. This article highlights the uses of molecular techniques in diagnostic microbiology, including “older,” as well as innovative, probe techniques, qualitative and quantitative RT-PCR, highly multiplexed PCR panels, some of which use sealed microfluidic test cartridges, MALDI TOF, and nuclear magnetic resonance. Tests are grouped together by technique and target. Tests with similar roles for similar analytes are compared with respect to benefits, drawbacks, and possible problems.


title: A survey of visitors on Swedish livestock farms with reference to the spread of animal diseases

text: BACKGROUND: In addition to livestock movements, other between-farm contacts such as visitors may contribute to the spread of contagious animal diseases. Knowledge about such contacts is essential for contingency planning. Preventive measures, risk-based surveillance and contact tracing may be facilitated if the frequency and type of between-farm contacts can be assessed for different types of farms. The aim of this study was to investigate the frequency and types of visitors on farms with cloven-hoofed animals in Sweden and to analyse whether there were differences in the number of visitors attributable to region, season, and type of herd. Data were collected from Swedish farmers through contact-logs covering two-week periods during four different seasons. RESULTS: In total, 482 (32%) farmers filled in the contact log for at least one period and the data represent 18,416 days. The average number of professional and non-professional visitors per day was 0.3 and 0.8, respectively. Whereas the number of professional visitors seemed to increase with increasing herd size, this relation was not seen for non-professional visits. The mean numbers of visitors per day were highest in the summer and in the farm category ‘small mixed farm’. Reports of the visitors’ degree of contact with the animals showed that veterinarians, AI-technicians, animal transporters and neighbours were often in direct contact with the animals or entered the stables and 8.8% of the repairmen were also in direct contact with animals, which was unexpected. In a multivariable analysis, species, herd size and season were significantly associated with the number of professional visitors as well as the number of visitors in direct contact with the animals. CONCLUSION: In conclusion there was a large variation between farms in the number and type of contacts. The number of visitors that may be more likely to spread diseases between farms was associated with animal species and herd size.


title: Expression of the Severe Acute Respiratory Syndrome Coronavirus 3a Protein and the Assembly of Coronavirus-Like Particles in the Baculovirus Expression System

text: The Bac-to-Bac Baculovirus expression system was used to generate a recombinant baculovirus capable of expressing the severe acute respiratory syndrome (SARS)-coronavirus (CoV) 3a protein. Using the same expression system, two structural proteins, membrane (M) and envelope (E), were co-expressed to form SARS-CoV virus-like particles (VLPs) within an insect cell. Expression of viral proteins was confirmed by Western blot analysis and the formation of VLPs was studied by transmission electron microscopy.


title: Clinical and Transmission Dynamics Characteristics of 406 Children with Coronavirus Disease 2019 in China: A Review

text: Abstract Objective Chinese pediatricians are working on the front line to fight COVID-19. They have published a great amount of first-hand clinical data. Collecting their data and forming a large sample for analysis is more conducive to the recognition, prevention and treatment of coronavirus disease 2019 in children. The epidemic prevention and control experience of Chinese pediatricians should be shared with the world. Methods By searching Chinese and English literature, the data of 406 children with COVID-19 in China were analyzed. Results It was found that the clustered incidence of children's families is a dynamic transmission feature; the incidence is low; asymptomatic infections and mild cases account for 44.8%, with only 7 cases of critical illness; laboratory examination of lymphocyte counts is not reduced, as it is for adults; chest CT findings are less severe than those for adults. These presentations are the clinical features of COVID-19 in children. Only 55 of the 406 cases were tested by anal swab for virus nucleic acid, 45 of which were positive, accounting for 81.8% of stool samples. Conclusion There are more children than adults with asymptomatic infections, milder conditions, faster recovery, and a better prognosis. Some concealed morbidity characteristics also bring difficulties to the early identification, prevention and control of COVID-19. COVID-19 screening is needed in the pediatric fever clinic, and respiratory and digestive tract nucleic acid tests should be performed. Efforts should be made to prevent children from becoming a hidden source of transmission in kindergartens, schools or families. Furthermore, China's experience in treating COVID-19 in children has led to faster recovery of sick children.


title: FIP: a novel approach to vaccination Proceedings from the 2nd International FCoV/FIP Symposium, Glasgow, 4–7 August 2002

text: Abstract Feline infectious peritonitis (FIP) is a fatal disease of cats. Early attempts at vaccination have been unsuccessful, some even serving to exacerbate the disease through antibody-dependent enhancement. Replication-incompetent feline foamy virus (FFV) transducing vectors are being developed as potential vaccine agents, into which immunogenic fragments of feline coronavirus (FCoV) proteins will be inserted. To use a recombinant viral vector to express FCoV proteins, the agent chosen should be apathogenic and replication incompetent within the host following gene delivery. Spumaviruses confer several advantages over the more traditionally explored retroviral vectors. Stable helper cell line clones have been established by transfection of CRFK cells with FFV tas and assessed using β-galactosidase assays, PCR, immunofluorescence and western blotting. The generation of infectious virions using these cell lines has been investigated using tas-deleted FFV vectors containing the enhanced green fluorescent protein (eGFP) cassette.


Challenging the dogma


title: Applying proteomic technology to clinical virology

text: Developing antiviral drugs, vaccines and diagnostic markers is still the most ambitious challenge in clinical virology. In the past few decades, data from high-throughput technologies have allowed for the rapid development of new antiviral therapeutic strategies, thus making a profound impact on translational research. Most of the current preclinical studies in virology are aimed at evaluating the dynamic composition and localization of the protein platforms involved in various host–virus interactions. Among the different possible approaches, mass spectrometry-based proteomics is increasingly being used to define the protein composition in subcellular compartments, quantify differential protein expression among samples, characterize protein complexes, and analyse protein post-translational modifications. Here, we review the current knowledge of the most useful proteomic approaches in the study of viral persistence and pathogenicity, with a particular focus on recent advances in hepatitis C research.


title: Influenza Virus Glycoprotein-reactive Human Monoclonal Antibodies

text: Influenza continues to be a significant public health challenge. Two glycoproteins on the surface of influenza virus, hemagglutinin and neuraminidase, play a prominent role in the process of influenza virus infection and release. Monoclonal antibodies targeting glycoproteins can effectively prevent the spread of the virus. In this review, we summarized currently reported human mAbs targeting glycoproteins of influenza A and B viruses.


title: Traffic COPs: rules of detection

text: EMBO J (2013) 32:11, 926–937 doi:10.1038/emboj.2013.41; published online 03122013 Dev Cell (2012) 23: 1255–62 doi:10.1016/j.devcel.2012.10.017; published online 12112012 How specific cargo recognition by coat proteins is achieved and how this recognition event may regulate vesicle formation are still under investigation. In two recent papers by the Owen and Goldberg labs, the binding mode of dilysine motifs to the coatomer of the COPI coat has been analysed. Collectively, their findings suggest that the dilysine motif containing cargo proteins may stabilize coat complexes on membranes and enhance the chance for coat polymerization and vesicle budding.


title: An overview of development in gene therapeutics in China

text: After setbacks related to serious adverse events 20 years ago, gene therapy is now coming back to the central stage worldwide. In the past few years, gene therapy has shown astonishing efficacy against genetic diseases and cancers. In history, China carried out the world’s second gene therapy clinical trial in 1991 for hemophilia B and approved the world’s first gene therapy product—Gendicine—in 2003. In recent years, numerous efforts have been made on gene editing. Here, we reviewed the past of gene therapy in China and highlighted recent advances. We also discussed the regulations and future perspectives of gene therapy in China.


Edaravone: a potential treatment for the COVID-19-induced inflammatory syndrome?


title: Is hand hygiene frequency associated with the onset of outbreaks in pediatric long-term care?

text: BACKGROUND: Studies in adult long-term care facilities (LTCFs) have shown a correlation between hand hygiene (HH) and viral outbreak reduction, but no such studies have been conducted in pediatric LTCFs where the epidemiology of viral pathogens is different. METHODS: We compared electronically monitored facility-wide HH frequency in the weeks immediately prior to outbreaks of acute respiratory or gastrointestinal infections versus control weeks in a 137-bed pediatric LTCF from October 2012-August 2015. Control weeks were the 8-14 day (control 1) and 15-21 day (control 2) periods prior to the onset of each outbreak. RESULTS: There was no difference in HH frequency in the weeks leading up to the outbreaks versus control weeks (odds ratio [OR], 1.0; 95% confidence interval CI, 1.00-1.001 using control 1 and OR, 1.0; 95% CI, 1.00-1.001 using control 2). CONCLUSIONS: Our findings differed from those in adult LTFCs, possibly because of the greater contact between residents and staff in the pediatric setting, increased susceptibility to viral pathogens because of immunologic immaturity, or differences in the types of pathogens prevalent in each setting. Although HH may be important for limiting the number of residents infected during outbreaks, we found no association between HH frequency and subsequent outbreak onset.


title: Effects of (L)-Cystine and (L)-Theanine Supplementation on the Common Cold: A Randomized, Double-Blind, and Placebo-Controlled Trial

text: The common cold is one of the most frequent illnesses caused by viral infection. Recently, we have reported that oral administration of cystine and theanine (CT) to mice enhanced the humoral immune response associated with antibody production. Based on this mouse study, we investigated the effects of CT supplementation on the common cold in humans as a pilot study. A total of 176 healthy male volunteers were randomized to receive either placebo or CT (490 mg) tablets twice daily for 35 days. The incidence outcome was assessed using the definition in our laboratory based on questionnaires regarding cold symptoms. The incidence of subjects with colds during the trial was significantly lower in the CT group than in the placebo group, although the duration of the colds was not significantly different between the groups. These results suggest that CT supplementation may be useful for the prevention of the common cold.


title: COVID-19 and the other pandemic: populations made vulnerable by systemic inequity

text: Greater than the coronavirus disease 2019 (COVID-19) crisis, systemic inequity in social determinants of health is the pandemic that has long fostered vulnerability to disease and poor health outcomes in the USA. Our response has major implications for the health of our nations.


title: Development of Broad-Spectrum Halomethyl Ketone Inhibitors Against Coronavirus Main Protease 3CL(pro)

text: Coronaviruses comprise a large group of RNA viruses with diverse host specificity. The emergence of highly pathogenic strains like the SARS coronavirus (SARS-CoV), and the discovery of two new coronaviruses, NL-63 and HKU1, corroborates the high rate of mutation and recombination that have enabled them to cross species barriers and infect novel hosts. For that reason, the development of broad-spectrum antivirals that are effective against several members of this family is highly desirable. This goal can be accomplished by designing inhibitors against a target, such as the main protease 3CL(pro) (M(pro)), which is highly conserved among all coronaviruses. Here 3CL(pro) derived from the SARS-CoV was used as the primary target to identify a new class of inhibitors containing a halomethyl ketone warhead. The compounds are highly potent against SARS 3CL(pro) with K(i)'s as low as 300 nM. The crystal structure of the complex of one of the compounds with 3CL(pro) indicates that this inhibitor forms a thioether linkage between the halomethyl carbon of the warhead and the catalytic Cys 145. Furthermore, Structure Activity Relationship (SAR) studies of these compounds have led to the identification of a pharmacophore that accurately defines the essential molecular features required for the high affinity.


title: First detection and genomic characteristics of bovine torovirus in dairy calves in China

text: Bovine torovirus (BToV) is a diarrhea-causing pathogen. In this study, 92 diarrheic fecal samples from five farms in four provinces in China were collected and tested for BToV using a RT-PCR assay, and 21.73% samples were found to be BToV positive. Moreover, two complete BToV genome sequences (MN073058 and MN073059) were obtained from the clinical samples, which were 28,297 and 28,301 nucleotides in length, respectively. Sequence analysis showed that the two isolates shared 10 identical amino acid mutations in the S protein compared to the complete S sequences of BToV available in the GenBank database. In addition, seven consecutive amino acid mutations were found from aa 1,486 to 1,492 in the S protein of isolate MN073058. Moreover, the two isolates shared one identical amino acid mutation in the receptor binding sites of the HE protein. To the best of our knowledge, this is the first report on the epidemic and genomic characterization of BToV in China, which is helpful for further understanding the genetic evolution of BToV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04657-9) contains supplementary material, which is available to authorized users.


title: COVID‐19 pandemic: Practical considerations on the organization of an allergy clinic – an EAACI/ARIA Position Paper

text: BACKGROUND: The Coronavirus disease 2019 (COVID‐19) has evolved as a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS‐CoV‐)2. Allergists and other health care providers (HCPs) in the field of allergies and associated airway diseases are in the front line, taking care of patients potentially infected with SARS‐CoV‐2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics. METHOD: The scientific information on COVID‐19 was analyzed by a literature search in Medline, Pubmed, national and international guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library and the Internet. RESULTS: Based on diagnostic and treatment standards developed by EAACI, on international information regarding COVID‐19, on guidelines of the World Health Organization (WHO) and other international organizations as well as on previous experience, a panel of experts including clinicians, psychologists, IT experts and basic scientists along with EAACI and the “Allergic Rhinitis and its Impact on Asthma (ARIA)” inititiative have developed recommendations for the optimal management of allergy clinics during the current COVID‐19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies. CONCLUSIONS: This international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients whilst ensuring necessary safety in the current COVID‐19 pandemic.


title: Full-length sequence of a Canadian porcine reproductive and respiratory syndrome virus (PRRSV) isolate

text: Presently, one of the most economically important pathogens affecting swine is the porcine reproductive and respiratory syndrome virus (PRRSV). This virus is prevalent in herds throughout the world and continues to pose a significant threat as newer and more virulent disease phenotypes emerge. In this report we describe the full-length nucleotide sequence of a Canadian PRRSV isolate, designated PA8. A consecutive sequence of 15,411 nucleotides was obtained from a set of overlapping cDNA clones. In order to determine the extent of genetic variation among isolates recovered from swine in Canada and the US, as well as to understand the molecular mechanisms governing the evolution of PRRSV, the full-length sequence of PA8 was compared with that of two US isolates, VR2332 and 16244B. The genomic sequence of PA8 shared 98.2% and 99.2% identity with 16244B and VR2332, respectively. The untranslated regions (UTR) at the 5′ and 3′ ends of the genome were very well conserved. Notable exceptions include an eight nucleotide difference at the 5′ end of the 5′ UTR of VR2332 relative to PA8 and 16244B and a two nucleotide difference in the 3′ UTR of PA8 relative to VR2332 and 16244B. In contrast to PA8 and VR2332, 16244B possessed two nucleotide differences within the RNA pseudoknot structure of the ribosomal frameshift region between open reading frame (ORF)1a and ORF1b. Amino acid differences were distributed throughout the genome, however they appeared to be most extensive in Nsp1β and ORF5 of the nonstructural and structural coding regions, respectively, suggesting that the evolutionary pressure to conserve these viral genes is somewhat lower.


title: New understanding of the damage of SARS-CoV-2 infection outside the respiratory system

text: Abstract Since early December 2019, a number of pneumonia cases associated with unknown coronavirus infection were identified in Wuhan, China, and many additional cases were identified in other regions of China and in other countries within 3 months. Currently, more than 80,000 cases have been diagnosed in China, including more than 3,000 deaths. The epidemic is spreading to the rest of the world, posing a grave challenge to prevention and control. On February 12, 2020, the International Committee on Taxonomy of Viruses and the World Health Organization officially named the novel coronavirus and associated pneumonia as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19), respectively. According to the recent research on SARS-CoV-2, the virus mainly infects the respiratory system but may cause damage to other systems. In this paper, we will systematically review the pathogenic features, transmission routes, and infection mechanisms of SARS-CoV-2, as well as any adverse effects on the digestive system, urogenital system, central nervous system, and circulatory system, in order to provide a theoretical and clinical basis for the diagnosis, classification, treatment, and prognosis assessment of SARS-CoV-2 infection.


Lupus erkennen und gezielt behandeln


title: Health care team training and simulation-based education in obstetrics during the COVID-19 pandemic

text: ABSTRACT Health care team training and simulation-based education are important for preparing obstetrical services to meet the challenges of the COVID-19 pandemic. Priorities for training are identified in two key areas. First, the impact of infection prevention and control protocols on processes of care (e.g., appropriate and correct use of personal protective equipment, patient transport, preparation for emergency cesarean delivery with the potential for emergency intubation, management of simultaneous obstetric emergencies, delivery in alternate locations in the hospital, potential for increased decision-to-delivery intervals, and communication with patients). And second, the effects of COVID-19 pathophysiology on obstetrical patients (e.g., testing and diagnosis, best use of modified obstetric early warning systems, approach to maternal respiratory compromise, collaboration with critical care teams, and potential need for cardiopulmonary resuscitation). However, such training is more challenging during the COVID-19 pandemic because of the requirements for social distancing. This article outlines strategies (spatial, temporal, video-recording, video-conferencing, and virtual) to effectively engage in health care team training and simulation-based education while maintaining social distancing during the COVID-19 pandemic.


title: Biometrics firms help in the response to Coronavirus

text: The global Coronavirus health scare has prompted a number of biometric tech firms to take action to help combat its spread.


title: Origin, Evolution, and Virulence of Porcine Deltacoronaviruses in the United States

text: A novel porcine deltacoronavirus (PdCV) was first discovered in Ohio and Indiana in February 2014, rapidly spread to other states in the United States and Canada, and caused significant economic loss in the swine industry. The origin and virulence of this novel porcine coronavirus are not known. Here, we characterized U.S. PdCV isolates and determined their virulence in gnotobiotic and conventional piglets. Genome analyses revealed that U.S. PdCV isolates possess unique genetic characteristics and share a close relationship with Hong Kong and South Korean PdCV strains and coronaviruses (CoVs) of Asian leopard cats and Chinese ferret-badgers. The PdCV-positive intestinal content (Ohio CVM1) and the cell culture-adapted PdCV Michigan (MI) strain were orally inoculated into gnotobiotic and/or conventional piglets. Within 1 to 3 days postinfection, profuse watery diarrhea, vomiting, and dehydration were observed. Clinical signs were associated with epithelial necrosis in the gastric pits and small intestine, the latter resulting in severe villous atrophy. Mild interstitial pneumonia was identified in the lungs of PdCV-infected piglets. High levels of viral RNA (8 to 11 log RNA copies/g) were detected in intestinal tissues/luminal contents and feces of infected piglets, whereas moderate RNA levels (2 to 5 log RNA copies/g) were detected in blood, lung, liver, and kidney, indicating multisystemic dissemination of the virus. Polyclonal immune serum against PdCV but not immune serum against porcine epidemic diarrhea virus (PEDV) reacted with PdCV-infected small-intestinal epithelial cells, indicating that PdCV is antigenically distinct from PEDV. Collectively, we demonstrate for the first time that PdCV caused severe gastrointestinal diseases in swine.


title: Crime, Justice & the COVID-19 Pandemic: Toward a National Research Agenda

text: The novel corona virus COVID-19 has become a worldwide public health pandemic that has induced anomic conditions impacting daily routines. COVID-19 response measures specifically alter regular schedules and both restrict and expand opportunities for various types of crime while presenting unprecedented challenges for the criminal justice system. For criminologists and criminal justice scientists, the virus also presents natural experiment conditions allowing for real-world theory tests and observation of the relative effectiveness of practice and policy options under weighty conditions. Toward synthesizing scientific discourse and forthcoming empirical work, we suggest the benefits of a COVID-19 crime and justice research program and offer some anchoring concepts. Contagion, containment measures (social distancing, facemasks, shelter-in-place, economic shutdown, virtual work and schooling, banned group gatherings), and social ordinance compliance (voluntary or enforced) posture a conceptual framework from which to align research on crime, justice, and victimization during the virus. After observing crime trends and justice system challenges, we suggest how the pandemic presents opportunities for review of various criminal justice, especially incarceration, policies. System change is a recurring theme across this special issue of the American Journal of Criminal Justice that features twenty additional contributions from a wide range of authoritative crime and justice scholars. These articles on traditional crime during the virus, virus specific hate crime and domestic violence, and the challenges posed by COVID-19 to law enforcement, the courts, and corrections will hopefully provide initial commentary toward deeper inquiry.


title: Erhöhtes Risiko für tiefe Beinvenenthrombosen bei Intensivpatienten mit CoViD-19-Infektion? – Erste Daten

text: BACKGROUND: The incidence of deep vein thrombosis (DVT) in CoViD-19 patients in intensive care units (ICU) has so far been investigated in only a few studies. Prospective comparative studies with non-CoViD-19 ICU patients are completely lacking. OBJECTIVE: Evaluation of the incidence of DVT in ICU patients with CoViD-19 compared to non-CoViD-19 ICU patients who were treated in the University Hospital Augsburg during the same period. In addition, the aim was to investigate what type of anticoagulation was present in CoViD-19 patients at the time the DVT occurred and to what extent DVT is associated with increased mortality in this patient population. MATERIAL AND METHODS: In this prospective single center study, which was conducted between 18 April 2020 and 30 April 2020, 20 SARS-CoV2 positive patients were compared with 20 non-CoVid-19 patients in the ICU with respect to the occurrence of DVT. For this purpose, demographic data, laboratory parameters, and clinical outcomes were recorded and evaluated. RESULTS: The rate of DVT in the investigated patient collective was markedly higher in patients with SARS-CoV2 (CoViD-19 patients 20% vs. non-CoViD-19 patients 5%). Both DVT and elevated D‑dimer levels were associated with increased mortality in the present study. CONCLUSION: We recommend the determination of D‑dimer levels and, in the case of elevated levels, the broad indication for compression sonography of the deep leg veins on admission of patients with suspected or confirmed SARS-CoV2. In this way DVT in the setting of CoViD-19 can be recognized early and therapeutic anticoagulation can be started. All inpatient CoViD-19 patients should receive thrombosis prophylaxis with low molecular weight heparin. Further studies on point of care methods (TEG®, ROTEM®) for the detection of hypercoagulability in SARS-CoV2 are necessary.


Clinical Findings, Treatment and Prognosis in Patients with Severe Acute Respiratory Syndrome (SARS)


Hydroxychloroquine for COVID‐19: Myths vs Facts


title: Talking about colds and flu: The lay diagnosis of two common illnesses among older British people

text: This paper reports on a study of the ways in which 54 older people in South Wales (UK) talk about the symptoms and causes of cold and influenza (flu). The study was designed to understand why older people might reject or accept the offer of seasonal flu vaccine, and in the course of the interviews respondents were also asked to express their views about the nature and causes of the two key illnesses. The latter are among the most common infections in human beings. In terms of the biomedical paradigm the common cold is caused by numerous respiratory viruses, whilst flu is caused by the influenza virus. Medical diagnosis is usually made on clinical grounds without laboratory confirmation. Symptoms of flu include sudden onset of fever and cough, and colds are characterized by sneezing, sore throat, and runny nose, but in practice the symptoms often overlap. In this study we examine the degree by which the views of lay people with respect to both diagnosis and epidemiology diverge with that which is evident in biomedical discourse. Our results indicate that whilst most of the identified symptoms are common to lay and professional people, the former integrate symptoms into a markedly different observational frame from the latter. And as far as causation is concerned it is clear that lay people emphasize the role of ‘resistance’ and ‘immunity’ at least as much as ‘infection’ in accounting for the onset of colds and flu. The data are analyzed using novel methods that focus on the co-occurrence of concepts and are displayed as semantic networks. As well as reporting on its findings the authors draw out some implications of the study for social scientific and policy discussions concerning lay diagnosis, lay expertise and the concept of an expert patient.


title: Population-Level Mortality Rates from Novel Coronavirus (COVID-19) in South Korea

text: Background: South Korea was among the first countries to report a case of the novel coronavirus (COVID-19) outside of China. As of 22 March, 2020, South Korea reported 8897 confirmed cases of and 104 deaths from COVID-19. Methods: We collected the number of laboratory-confirmed cases and deaths in South Korea from the World Health Organization (as of 21 March, 2020) and case distribution and fatality rates by age from the Korean Center for Disease Control and Prevention (as of 22 March, 2020). We estimated population-level mortality rates by fitting a negative binomial regression model with the number of deaths as the outcome and population by age as an offset. We then calculated the age-standardized death rate (ASDR) based on the current COVID-19 figures and for alternative scenarios of increased prevalence. Findings: The COVID-19 population-level mortality rate (per 100,000 person-years) increased with age: from 0.1 deaths among 30-39 year olds to 9.5 deaths among ≥80 year olds. The ASDR (per 100,000 person-years) was 0.8 deaths. The ASDR would increase to 52.0 deaths at a 1% prevalence (becoming the third leading cause of death) and 155.9 deaths at 3% prevalence (becoming the leading cause of death). Interpretation: Currently, the population-level mortality burden of COVID-19 in South Korea, as measured by the ASDR, was relatively low compared to other causes of death partly due to the low prevalence of COVID-19. If the prevalence increases from another outbreak, the mortality burden could increase substantially and surpass other leading causes.


Covid‐19: biotechnologists make their contribution


title: A manual reduction of hernia under analgesia/sedation (Taxis) in the acute inguinal hernia: a useful technique in COVID-19 times to reduce the need for emergency surgery—a literature review

text: BACKGROUND: Acute IH is a common surgical presentation. Despite new guidelines being published recently, a number of important questions remained unanswered including the role of taxis, as initial non-operative management. This is particularly relevant now due to the possibility of a lack of immediate surgical care as a result of COVID-19. The aim of this review is to assess the role of taxis in the management of emergency inguinal hernias. METHODS: A review of the literature was undertaken. Available literature published until March 2019 was obtained and reviewed. 32,021 papers were identified, only 9 were of sufficient value to be used. RESULTS: There was a large discrepancy in the terminology of incarcerated/strangulated used. Taxis can be safely attempted early after the onset of symptoms and is effective in about 70% of patients. The possibility of reduction en-mass should be kept in mind. Definitive surgery to repair the hernia can be delayed by weeks until such time as surgery can be safely arranged. CONCLUSIONS: The use of taxis in emergency inguinal hernia is a useful first line of treatment in areas or situations where surgical care is not immediately available, including the COVID-19 pandemic. Emergency surgery remains the mainstay of management in the strangulated hernia setting.


The legal void and COVID‐19 governance


title: High Diversity of Genogroup I Picobirnaviruses in Mammals

text: In a molecular epidemiology study using 791 fecal samples collected from different terrestrial and marine mammals in Hong Kong, genogroup I picobirnaviruses (PBVs) were positive by RT-PCR targeting the partial RdRp gene in specimens from five cattle, six monkeys, 17 horses, nine pigs, one rabbit, one dog, and 12 California sea lions, with 11, 9, 23, 17, 1, 1, and 15 sequence types in the positive specimens from the corresponding animals, respectively. Phylogenetic analysis showed that the PBV sequences from each kind of animal were widely distributed in the whole tree with high diversity, sharing 47.4–89.0% nucleotide identities with other genogroup I PBV strains based on the partial RdRp gene. Nine complete segment 1 (viral loads 1.7 × 10(4) to 5.9 × 10(6)/ml) and 15 segment 2 (viral loads 4.1 × 10(3) to 1.3 × 10(6)/ml) of otarine PBVs from fecal samples serially collected from California sea lions were sequenced. In the two phylogenetic trees constructed using ORF2 and ORF3 of segment 1, the nine segment 1 sequences were clustered into four distinct clades (C1–C4). In the tree constructed using RdRp gene of segment 2, the 15 segment 2 sequences were clustered into nine distinct clades (R1–R9). In four sea lions, PBVs were detected in two different years, with the same segment 1 clade (C3) present in two consecutive years from one sea lion and different clades present in different years from three sea lions. A high diversity of PBVs was observed in a variety of terrestrial and marine mammals. Multiple sequence types with significant differences, representing multiple strains of PBV, were present in the majority of PBV-positive samples from different kinds of animals.


title: 1.16 Cryo-Electron Microscopy and Tomography of Virus Particles

text: Abstract Human infectious disease is classified into five etiologies: bacterial, viral, parasitic, fungal, and prion. Viral infections are unique in that they recruit human cellular machinery to replicate themselves and spread infection. The number of viruses causing human disease is vast, and viruses can be broadly categorized by their structures. Many viruses, such as influenza, appear to be amorphous particles, whereas others, such as herpes simplex virus, rhinovirus, dengue virus, and adenovirus, have roughly symmetric structural components. Icosahedral viruses have been a target of electron microscopists for years, and they were some of the first objects to be reconstructed three-dimensionally from electron micrographs. The ease with which highly purified and conformationally uniform virus samples can be produced makes them an ideal target structural studies. Apart from their biological significance, these virus samples have played a pivotal role in the development of new methodologies in the field of molecular biology as well as in cryo-electron microscopy and cryo-electron tomography.


Oncologie et COVID-19


title: “Not Wars, Water pumps” – From emotive to rational language in managing the Covid‐19 pandemic

text: At the date of writing this editorial, there is now agreement amongst experts that the first wave of the United Kingdom’s (UK) COVID‐19 pandemic is in decline (1). The number of deaths reported each day is now around 1% of the cumulative total and falling. In general, the approach to predicting pandemic policy has been through a comparison of inter‐country performance in managing this crisis. While all countries are paying a high price in economic slowdown and lives lost, the health consequences in terms of cases and deaths have varied considerably. Countries with lower relative mortality and infection numbers have shown a more structured logical approach to pandemic management.


title: Knowledge model for emergency response based on contingency planning system of China

text: Abstract China is severely exposed to natural hazards. Currently, there are more than 5.5 million contingency plans for handling various incidents. Similar to those produced in other counties, the paper-based plans in China are limited in that emergency responders cannot easily extract helpful information for them. In this paper, a knowledge-based system will be proposed for providing different stakeholders with helpful information in the emergency response. The conceptual model is the core for the whole system, which can link plans in the physical world and the ontology in the cyber world.


title: Receptor-bound porcine epidemic diarrhea virus spike protein cleaved by trypsin induces membrane fusion

text: Porcine epidemic diarrhea virus (PEDV) infection in Vero cells is facilitated by trypsin through an undefined mechanism. The present study describes the mode of action of trypsin in enhancing PEDV infection in Vero cells during different stage of the virus life cycle. During the viral entry stage, trypsin increased the penetration of Vero-cell-attached PEDV by approximately twofold. However, trypsin treatment of viruses before receptor binding did not enhance infectivity, indicating that receptor binding is essentially required for trypsin-mediated entry upon PEDV infection. Trypsin treatment during the budding stage of virus infection induces an obvious cytopathic effect in infected cells. Furthermore, we also show that the PEDV spike (S) glycoprotein is cleaved by trypsin in virions that are bound to the receptor, but not in free virions. These findings indicate that trypsin affects only cell-attached PEDV and increases infectivity and syncytium formation in PEDV-infected Vero cells by cleavage of the PEDV S protein. These findings strongly suggest that the PEDV S protein may undergo a conformational change after receptor binding and cleavage by exogenous trypsin, which induces membrane fusion.


title: Distinguishing Between Reservoir Exposure and Human-to-Human Transmission for Emerging Pathogens Using Case Onset Data

text: Pathogens such as MERS-CoV, influenza A/H5N1 and influenza A/H7N9 are currently generating sporadic clusters of spillover human cases from animal reservoirs. The lack of a clear human epidemic suggests that the basic reproductive number R0 is below or very close to one for all three infections. However, robust cluster-based estimates for low R0 values are still desirable so as to help prioritise scarce resources between different emerging infections and to detect significant changes between clusters and over time. We developed an inferential transmission model capable of distinguishing the signal of human-to-human transmission from the background noise of direct spillover transmission (e.g. from markets or farms). By simulation, we showed that our approach could obtain unbiased estimates of R0, even when the temporal trend in spillover exposure was not fully known, so long as the serial interval of the infection and the timing of a sudden drop in spillover exposure were known (e.g. day of market closure). Applying our method to data from the three largest outbreaks of influenza A/H7N9 outbreak in China in 2013, we found evidence that human-to-human transmission accounted for 13% (95% credible interval 1%–32%) of cases overall. We estimated R0 for the three clusters to be: 0.19 in Shanghai (0.01-0.49), 0.29 in Jiangsu (0.03-0.73); and 0.03 in Zhejiang (0.00-0.22). If a reliable temporal trend for the spillover hazard could be estimated, for example by implementing widespread routine sampling in sentinel markets, it should be possible to estimate sub-critical values of R0 even more accurately. Should a similar strain emerge with R0>1, these methods could give a real-time indication that sustained transmission is occurring with well-characterised uncertainty.


Brain natriuretic peptide to predict successful liberation from mechanical ventilation in critically ill patients: the results need to be interpreted with more caution


title: Travel-related health problems of Hong Kong residents: Assessing the need for travel medicine services

text: Summary Background Although there has been a marked increase in travel among Hong Kong residents, travel-related health risks have not been well characterized nor has their use of travel medicine services. Objectives To assess the travel health care needs of Chinese residents in Hong Kong by examining travel health problems of returning Hong Kong residents and by understanding their use of travel health services before or after travel. Methods Review of available data followed by a cross-sectional telephone survey of 280 travellers and 15 service providers. A structured pre-tested questionnaire was used for data collection. Household members, who were ethnic Chinese, aged 15–64 years, able to communicate in Cantonese, and who had travelled at least once during the preceding 12 months were invited to participate. Results There was a scarcity of travel medicine services in Hong Kong. The most common destinations for travellers were countries in the Asia-Pacific region, especially mainland China (33%). Twenty percent of the respondents developed health problems during or shortly after travel. Although only 9% of respondents had received pre-travel health advice, 61% used some form of precautions. Twelve percent had lost at least a day due to travel-related health problems. The service providers agreed that there are demands for travel health services. However, half of the service providers had not been trained in travel or tropical medicine. Conclusions This study indicates the need for specialized travel medicine services in Hong Kong to improve the health of travellers.


title: Highly pathogenic coronaviruses: thrusting vaccine development in the spotlight

text: Coronaviruses (CoVs) are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has caused major public health crises. There have been more than 4,400,000 reported cases of COVID-2019 and more than 300,000 reported deaths to date (16/05/2020). SARS-CoV, MERS-CoV and SARS-CoV-2 have attracted widespread global attention due to their high infectivity and pathogenicity. To date, there is no specific treatment proven effective against these viral infectious diseases. Vaccination is considered one of the most effective strategies to prevent viral infections. Therefore, the development of effective vaccines against highly pathogenic coronaviruses is essential. In this review, we will briefly describe coronavirus vaccine design targets, summarize recent advances in the development of coronavirus vaccines, and highlight current adjuvants for improving the efficacy of coronavirus vaccines.


title: Incidence of COVID-19 in a cohort of adult and paediatric patients with rheumatic diseases treated with targeted biologic and synthetic disease-modifying anti-rheumatic drugs

text: OBJECTIVES: To investigate the incidence of COVID-19 in a cohort of adult and paediatric patients with rheumatic diseases receiving targeted biologic and synthetic disease modifying anti-rheumatic drugs (tDMARDs) and to explore the possible effect of these treatments in the clinical expression of COVID-19. METHODS: A cross-sectional study comprising of a telephone survey and electronic health records review was performed including all adult and paediatric patients with rheumatic diseases treated with tDMARDs in a large rheumatology tertiary centre in Barcelona, Spain. Demographics, disease activity, COVID-19 related symptoms and contact history data were obtained from the start of the 2020 pandemic. Cumulative incidence of confirmed cases (SARS-CoV-2 positive PCR test) was compared to the population estimates for the same city districts from a governmental COVID-19 health database. Suspected cases were defined following WHO criteria and compared to those without compatible symptoms. RESULTS: 959 patients with rheumatic diseases treated with tDMARDs were included. We identified 11 confirmed SARS-CoV-2 positive cases in the adult cohort and no confirmed positive cases in the paediatric cohort. COVID-19 incidence rates of the rheumatic patient cohort were very similar to that of the general population [(0.48% (95% CI 0.09 to 8.65%)] and [0.58% (95% CI 5.62 to 5.99%)], respectively. We found significant differences in tDMARDs proportions between the suspected and non-suspected cases (p=0.002). CONCLUSION: Adult and paediatric patients with rheumatic diseases on tDMARDs do not seem to present a higher risk of COVID-19 or a more severe disease outcome when compared to general population.


title: The sequence of human ACE2 is suboptimal for binding the S spike protein of SARS coronavirus 2

text: The rapid and escalating spread of SARS coronavirus 2 (SARS-CoV-2) poses an immediate public health emergency. The viral spike protein S binds ACE2 on host cells to initiate molecular events that release the viral genome intracellularly. Soluble ACE2 inhibits entry of both SARS and SARS-2 coronaviruses by acting as a decoy for S binding sites, and is a candidate for therapeutic, prophylactic and diagnostic development. Using deep mutagenesis, variants of ACE2 are identified with increased binding to the receptor binding domain of S. Mutations are found across the interface, in the N90-glycosylation motif, and at buried sites where they are predicted to enhance local folding and presentation of the interaction epitope. When single substitutions are combined, large increases in binding can be achieved. The mutational landscape offers a blueprint for engineering high affinity proteins and peptides that block receptor binding sites on S to meet this unprecedented challenge.


COVID-19 and ethnicity: challenges in rheumatology


title: Global Health Security: The Lessons from the West African Ebola Virus Disease Epidemic and MERS Outbreak in the Republic of Korea

text: The Ebola virus disease outbreak in West Africa and the Middle East Respiratory Syndrome outbreak in the Republic of Korea have given huge impacts in different aspects. Health security is no more a new coinage. Global health security became more realistic in its practical application. In the perspective of global health, it will be helpful to peruse lessons learned from the Ebola outbreak in West Africa and MERS outbreak in Korea.


title: This really is nothing like flu

text: Those downplaying the coronavirus ignore our lack of immunity and vaccines


title: Coronavirus non-structural protein 16: Evasion, attenuation, and possible treatments

text: The recent emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV), nearly a decade after the Severe Acute Respiratory Syndrome (SARS) CoV, highlights the importance of understanding and developing therapeutic treatment for current and emergent CoVs. This manuscript explores the role of NSP16, a 2′O-methyl-transferase (2′O-MTase), in CoV infection and the host immune response. The review highlights conserved motifs, required interaction partners, as well as the attenuation of NSP16 mutants, and restoration of these mutants in specific immune knockouts. Importantly, the work also identifies a number of approaches to exploit this understanding for therapeutic treatment and the data clearly illustrate the importance of NSP16 2′O-MTase activity for CoV infection and pathogenesis.


title: Pulmonary penetration of piperacillin and tazobactam in critically ill patients

text: Pulmonary infections in critically ill patients are common and associated with high morbidity and mortality. Piperacillin-tazobactam is a frequently used therapy in critically ill patients with pulmonary infection. Antibiotic concentrations in the lung reflect target site antibiotic concentrations in patients with pneumonia. The aim of this study was to assess the plasma and intra-pulmonary pharmacokinetics (PK) of piperacillin-tazobactam in critically ill patients administered standard piperacillin-tazobactam regimens. A population PK model was developed to describe plasma and intra-pulmonary piperacillin and tazobactam concentrations. The probability of piperacillin exposures reaching pharmacodynamic endpoints and the impact of pulmonary permeability on piperacillin and tazobactam pulmonary penetration was explored. The median piperacillin and tazobactam pulmonary penetration ratio was 49.3% and 121.2%, respectively. Pulmonary piperacillin and tazobactam concentration were unpredictable and negatively correlated to pulmonary permeability. Current piperacillin-tazobactam regimens may be insufficient to treat pneumonia caused by piperacillin-tazobactam susceptible organisms in some critically ill patients.


title: Porcine reproductive and respiratory syndrome virus induces apoptosis through a mitochondria-mediated pathway

text: Abstract As with a number of other viruses, Porcine reproductive and respiratory syndrome virus (PRRSV) has been shown to induce apoptosis, although the mechanism(s) involved remain unknown. In this study we have characterized the apoptotic pathways activated by PRRSV infection. PRRSV-infected cells showed evidence of apoptosis including phosphatidylserine exposure, chromatin condensation, DNA fragmentation, caspase activation (including caspase-8, 9, 3), and PARP cleavage. DNA fragmentation was dependent on caspase activation but blocking apoptosis by a caspase inhibitor did not affect PRRSV replication. Upregulation of Bax expression by PRRSV infection was followed by disruption of the mitochondria transmembrane potential, resulting in cytochrome c redistridution to the cytoplasm and subsequent caspase-9 activation. A crosstalk between the extrinsic and intrinsic pathways was demonstrated by dependency of caspase-9 activation on active caspase-8 and by Bid cleavage. Furthermore, in this study we provide evidence of the possible involvement of reactive oxygen species (ROS)-mediated oxidative stress in apoptosis induced by PRRSV. Our data indicated that cell death caused by PRRSV infection involves necrosis as well as apoptosis. In summary, these findings demonstrate mechanisms by which PRRSV induces apoptosis and will contribute to an enhanced understanding of PRRSV pathogenesis.


title: Love of Neighbor During a Pandemic: Navigating the Competing Goods of Religious Gatherings and Physical Health

text: In light of the present pandemic, many religious communities have been asked to suspend their services and meetings. From the perspective of these communities, this comes at considerable cost to the spiritual good that these religious services bring about. Empirical evidence also indicates that the suspension of these services will have costs concerning physical and mental health as well. However, in the case of a pandemic, because it is an infectious disease that is the concern, love of neighbor arguably does entail the suspension of services for the sake of the preservation of life for others. Religious communities and individuals can, and have, found ways to partially offset the losses from not being able to meet. These have included increased personal and family prayer and devotion, video-streaming of services, and online prayer and discussion meetings. While none of these fully compensates for the loss of in-person meetings, the sacrifice entailed may itself be seen as a means to greater love of God and love of neighbor.


title: Pulmonary complications after T-cell-depleted allogeneic stem cell transplantation: low incidence and strong association with acute graft-versus-host disease

text: Lung injury limits the success of allogeneic stem cell transplantation (SCT). The overall incidence varies from 30 to 50% and non-infectious causes occur in one-third to one-half of these. We reviewed pulmonary complications in 369 consecutive patients who received a partially T-cell-depleted myeloablative allogeneic hematopoietic SCT at our institution between 1993 and 2003. All patients were treated uniformly with cyclophosphamide followed by total body irradiation. Control subjects were matched on sex, underlying diagnosis, age, type of transplantation and cytomegalovirus (CMV)-serostatus. Sixty-one patients (16.5%) developed pulmonary complications. Twenty-one patients (5.7%) developed infectious pneumonia. Forty patients developed non-infectious complications which were further subclassified as bronchiolitis obliterans (3.5%), bronchiolitis obliterans-organizing pneumonia (0.5%), diffuse alveolar hemorrhage (0.8%), idiopathic pneumonia syndrome (5.5%) or mixed etiology (0.5%). Acute graft-versus-host disease (GVHD) ⩾grade II was significantly more common in pulmonary patients than in the controls (36/61 versus 22/61 patients, P=0.02). There was no significant difference in the incidence of chronic GVHD (P=0.09). CMV reactivation was significantly more frequent in patients with lung injury (P=0.02). Median survival was 41 weeks for the pulmonary patients and 350 weeks for the controls (P=0.001). Altogether, the incidence of pulmonary complications is low after T-cell-depleted SCT and is associated with acute GVHD and CMV reactivation.


title: Identification and isolation of a novel herpesvirus in a captive mob of eastern grey kangaroos (Macropus giganteus)

text: Abstract A novel herpesvirus was detected in a captive mob of eastern grey kangaroos (Macropus giganteus) during diagnostic workup for individuals with ulcerative cloacitis. Virus was initially detected in tissues using a consensus herpesvirus PCR. No viral inclusions or particles had been evident in routine histologic or transmission electron microscopic sections of cloacal lesions. Virus was isolated from samples and transmission electron microscopy of the resulting isolates confirmed that the virus was morphologically consistent with a herpesvirus. Nucleotide sequencing of the PCR product from tissue samples and from the isolates revealed that the virus was in the subfamily Gammaherpesvirinae and was distinct from other known herpesviruses. The correlation between the lesions and the novel virus remains unknown. Two herpesviruses, both in the subfamily Alphaherpesvirinae, have previously been described in macropods and are known to cause systemic clinical disease. This is the first reported gammaherpesvirus within the order Marsupialia, and may provide valuable information regarding the evolution and phylogeny of this virus family. Based on current herpesvirus nomenclature convention, the authors propose the novel herpesvirus be named Macropodid herpesvirus 3 (MaHV-3).


title: Searching for animal models and potential target species for emerging pathogens: Experience gained from Middle East respiratory syndrome (MERS) coronavirus

text: Emerging and re-emerging pathogens represent a substantial threat to public health, as demonstrated with numerous outbreaks over the past years, including the 2013–2016 outbreak of Ebola virus in western Africa. Coronaviruses are also a threat for humans, as evidenced in 2002/2003 with infection by the severe acute respiratory syndrome coronavirus (SARS-CoV), which caused more than 8000 human infections with 10% fatality rate in 37 countries. Ten years later, a novel human coronavirus (Middle East respiratory syndrome coronavirus, MERS-CoV), associated with severe pneumonia, arose in the Kingdom of Saudi Arabia. Until December 2016, MERS has accounted for more than 1800 cases and 35% fatality rate. Finding an animal model of disease is key to develop vaccines or antivirals against such emerging pathogens and to understand its pathogenesis. Knowledge of the potential role of domestic livestock and other animal species in the transmission of pathogens is of importance to understand the epidemiology of the disease. Little is known about MERS-CoV animal host range. In this paper, experimental data on potential hosts for MERS-CoV is reviewed. Advantages and limitations of different animal models are evaluated in relation to viral pathogenesis and transmission studies. Finally, the relevance of potential new target species is discussed.


title: Harnessing artificial intelligence (AI) to increase wellbeing for all: The case for a new technology diplomacy

text: The field of artificial intelligence (AI) is experiencing a period of intense progress due to the consolidation of several key technological enablers. AI is already deployed widely and has a high impact on work and daily life activities. The continuation of this process will likely contribute to deep economic and social changes. To realise the tremendous benefits of AI while mitigating undesirable effects will require enlightened responses by many stakeholders. Varying national institutional, economic, political, and cultural conditions will influence how AI will affect convenience, efficiency, personalisation, privacy protection, and surveillance of citizens. Many expect that the winners of the AI development race will dominate the coming decades economically and geopolitically, potentially exacerbating tensions between countries. Moreover, nations are under pressure to protect their citizens and their interests—and even their own political stability—in the face of possible malicious or biased uses of AI. On the one hand, these different stressors and emphases in AI development and deployment among nations risk a fragmentation between world regions that threatens technology evolution and collaboration. On the other hand, some level of differentiation will likely enrich the global AI ecosystem in ways that stimulate innovation and introduce competitive checks and balances through the decentralisation of AI development. International cooperation, typically orchestrated by intergovernmental and non-governmental organisations, private sector initiatives, and by academic researchers, has improved common welfare and avoided undesirable outcomes in other technology areas. Because AI will most likely have more fundamental effects on our lives than other recent technologies, stronger forms of cooperation that address broader policy and governance challenges in addition to regulatory and technological issues may be needed. At a time of great challenges among nations, international policy coordination remains a necessary instrument to tackle the ethical, cultural, economic, and political repercussions of AI. We propose to advance the emerging concept of technology diplomacy to facilitate the global alignment of AI policy and governance and create a vibrant AI innovation system. We argue that the prevention of malicious uses of AI and the enhancement of human welfare create strong common interests across jurisdictions that require sustained efforts to develop better, mutually beneficial approaches. We hope that new technology diplomacy will facilitate the dialogues necessary to help all interested parties develop a shared understanding and coordinate efforts to utilise AI for the benefit of humanity, a task whose difficulty should not be underestimated.


title: Prior Infections With Seasonal Influenza A/H1N1 Virus Reduced the Illness Severity and Epidemic Intensity of Pandemic H1N1 Influenza in Healthy Adults

text: Background. A new influenza A/H1N1 (pH1N1) virus emerged in April 2009, proceeded to spread worldwide, and was designated as an influenza pandemic. A/H1N1 viruses had circulated in 1918–1957 and 1977–2009 and were in the annual vaccine during 1977–2009. Methods. Serum antibody to the pH1N1 and seasonal A/H1N1 viruses was measured in 579 healthy adults at enrollment (fall 2009) and after surveillance for illness (spring 2010). Subjects reporting with moderate to severe acute respiratory illness had illness and virus quantitation for 1 week; evaluations for missed illnesses were conducted over holiday periods and at the spring 2010 visit. Results. After excluding 66 subjects who received pH1N1 vaccine, 513 remained. Seventy-seven had reported with moderate to severe illnesses; 31 were infected with pH1N1 virus, and 30 with a rhinovirus. Determining etiology from clinical findings was not possible, but fever and prominent myalgias favored influenza and prominent rhinorrhea favored rhinovirus. Tests of fall and spring antibody indicated pH1N1 infection of 23% had occurred, with the rate decreasing with increasing anti-pH1N1 antibody; a similar pattern was seen for influenza-associated illness. A reducing frequency of pH1N1 infections was also seen with increasing antibody to the recent seasonal A/H1N1 virus (A/Brisbane/59/07). Preexisting antibody to pH1N1 virus, responses to a single vaccine dose, a low infection-to-illness ratio, and a short duration of illness and virus shedding among those with influenza indicated presence of considerable preexisting immunity to pH1N1 in the population. Conclusions. The 2009 A/H1N1 epidemic among healthy adults was relatively mild, most likely because of immunity from prior infections with A/H1N1 viruses.


title: Role for phospholipid acyl chains and cholesterol in pulmonary infections and inflammation

text: Bacterial and viral respiratory tract infections result in millions of deaths worldwide and are currently the leading cause of death from infection. Acute inflammation is an essential element of host defense against infection, but can be damaging to the host when left unchecked. Effective host defense requires multiple lipid mediators, which collectively have proinflammatory and/or proresolving effects on the lung. During pulmonary infections, phospholipid acyl chains and cholesterol can be chemically and enzymatically oxidized, as well as truncated and modified, producing complex mixtures of bioactive lipids. We review recent evidence that phospholipids and cholesterol and their derivatives regulate pulmonary innate and adaptive immunity during infection. We first highlight data that oxidized phospholipids generated in the lung during infection stimulate pattern recognition receptors, such as TLRs and scavenger receptors, thereby amplifying the pulmonary inflammatory response. Next, we discuss evidence that oxidation of endogenous pools of cholesterol during pulmonary infections produces oxysterols that also modify the function of both innate and adaptive immune cells. Last, we conclude with data that n-3 polyunsaturated fatty acids, both in the form of phospholipid acyl chains and through enzymatic processing into endogenous proresolving lipid mediators, aid in the resolution of lung inflammation through distinct mechanisms. Unraveling the complex mechanisms of induction and function of distinct classes of bioactive lipids, both native and modified, may hold promise for developing new therapeutic strategies for improving pulmonary outcomes in response to infection.


title: Evaluation of a combined MxA and CRP point-of-care immunoassay to identify viral and/or bacterial immune response in patients with acute febrile respiratory infection

text: BACKGROUND: Challenges in the clinical differentiation of viral and/or bacterial respiratory infection lead to the misappropriation of antibiotics and increased healthcare costs. A tool to facilitate rapid and accurate point-of-care (POC) differentiation is needed. METHODS AND FINDINGS: A prospective, single center, blinded, observational clinical trial was conducted at Beth Israel Deaconess Medical Center from December 2012 to August 2013 to determine the accuracy of a POC immunoassay to identify a clinically significant immune response to viral and/or bacterial infection. Sixty patients with acute febrile respiratory infection (19 pharyngitis and 41 lower respiratory tract infection [LRTI]) were enrolled. Participants provided fingerstick blood for immunoassay testing (myxovirus A [MxA] and c-reactive protein [CRP]) and four oropharyngeal samples for viral PCR and routine bacterial cell culture. A venous blood sample was collected. An ELISA was used to measure CRP and MxA. Paired serological testing was used to confirm atypical bacteria. A urine sample was provided for Streptococcus and Legionella antigen testing. Patients with suspected LRTI had sputum and blood cultures, chest X-ray, and WBC count measured. Viral infection was confirmed if oropharyngeal PCR was positive for viral pathogens. Bacterial infection was confirmed in positive throat or sputum cultures. Elevated immunoglobulin M antibodies or twofold increase in IgG antibodies between acute and convalescent phase indicated atypical bacteria. Positive Streptococcus or Legionella urine antigen assays also confirmed bacterial infection. The immunoassay correctly categorized subjects as 92% (22/24) negative, 80% (16/20) with bacterial infection, and 70% (7/10) with viral infection. CONCLUSIONS: The interplay between an MxA value and a semi-quantitative CRP value can aid in the differentiation of infectious etiology. In isolation, neither MxA nor CRP alone is sensitive or specific. However, the pattern of results in a rapid immunoassay provides a sensitive and specific method to differentiate acute febrile respiratory infections. This diagnostic information may help reduce antibiotic misuse and resistance and lower healthcare costs.


title: COVID-19 Financial Resources for Physicians

text: Abstract The appropriate focus in dealing with the COVID-19 pandemic in the United States has been addressing access and delivery of care to the population impacted by the outbreak. All sectors of the U.S economy have been significantly impacted including physicians. Physician groups of all specialties and sizes have experienced the financial impact of the pandemic. Hospitals have received billions of dollars to support and enable them to handle emergencies and cover the cost of the disruption. However, many Vascular Surgeons are under great financial pressure because of postponement of all non-emergency procedures. The Federal Government has announced a myriad of programs in the form of grants and loans to reimburse physicians for some expenses and loss of revenue. It is more than likely that unless the public health emergency subsides significantly, many practices will suffer dire consequences without additional financial assistance. We attempt to provide a concise listing of such programs and resources available to assist Vascular Surgeons who are small businesses in accessing these opportunities.


title: Influenza virus but not MERS coronavirus circulation in Iran, 2013–2016: Comparison between pilgrims and general population

text: Abstract Background The pilgrimage to Mecca and Karbala bring many Muslims to a confined area. Respiratory tract infections are the most common diseases transmitted during mass gatherings in Hajj, Umrah and Karbala. The aim of this study was to determine and compare the prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) and influenza virus infections among Iranian general population and pilgrims with severe acute respiratory infections (SARI) returning from Mecca and Karbala during 2013–2016. Methods During 2013–2016, a total of 42351 throat swabs were examined for presence of influenza viruses and MERS-CoV in Iranian general population and pilgrims returning from Mecca and Karbala with SARI by using one step RT-PCR kit. Results None of the patients had MERS-CoV but influenza viruses were detected in 12.7% with high circulation of influenza A/H1N1 (47.1%). Conclusion This study showed the prevalence of influenza infections among Iranian pilgrims and general population and suggests continuing surveillance, infection control and appropriate vaccination especially nowadays that the risk of influenza pandemic threatens the world, meanwhile accurate screening for MERS-CoV is also recommended.


title: Lessons from Severe Acute Respiratory Syndrome (SARS): Implications for Infection Control

text: Severe acute respiratory syndrome (SARS), the first global epidemic in the 21st century, affected over 8500 people in approximately 30 countries (1–7). With a crude mortality of 9%, its cause was quickly identified as a novel coronavirus that jumped species from animals to man. The SARS coronavirus epidemic, which began in the Fall of 2002, was related to the exotic food industry in southern China, initially involving disproportionate numbers of animal handlers, chefs, and caterers. Subsequently, person-to-person transmission spawned the outbreak. What distinguished this illness clinically was the fact that approximately half of the victims were health care workers (8), infected while caring for recognized or unrecognized patients with SARS. There are many curiosities and uncertainties surrounding the epidemic of SARS with lessons that may be useful to the community of infectious diseases physicians, especially when looking ahead to the next epidemic. Herein we relate our perspectives on useful lessons derived from a review of the SARS epidemic.


title: COVID-19 and autism

text: The current pandemic of Covid-19 has created a paradigm for possibly gaining greater insight in two conditions: 1).. Inflammatory maladies in pregnancy, and. 2).. The biology of IGF-1 in autism. Studies since the beginning of this century have supported the view that IGF-1 deficiency in the neonate defines the basis of autism. As a result, it appears that interleukin-6 in corona virus-based infections causes reduced defenses because of suppressed IGF-1, especially in older patients. This may also portend an increase of autism in the offspring of gravidas currently affected severely by Covid-19.


title: MERS-CoV in a healthcare worker in Jeddah, Saudi Arabia: an index case investigation

text: Summary In September 2015, a confirmed case of Middle East respiratory syndrome (MERS) was diagnosed in a healthcare worker in Jeddah, Saudi Arabia. Given the absence of confirmed MERS cases in Jeddah at the time, an epidemiological index case investigation took place. The investigation identified a probable source of an index case who had been in hospital in Jordan in August 2015 while there was an ongoing MERS outbreak and who then subsequently sought medical care in Jeddah.


title: Procedural precautions and personal protective equipment during head and neck instrumentation in the COVID‐19 era

text: BACKGROUND: Otolaryngologists represent a subset of health care workers uniquely vulnerable to COVID‐19 transmission. Given the segmentation of extant guidelines concerning precautions and protective equipment for SARS‐CoV2, we aimed to provide consolidated recommendations regarding appropriate personal protective equipment (PPE) in head neck surgery during the COVID‐19 era. METHODS: Guidelines published by international and US governing bodies were reviewed in conjunction with published literature concerning COVID‐19 transmission risk, testing, and PPE, to compile situation‐specific recommendations for head and neck providers managing COVID‐19 patients. RESULTS: High‐quality data regarding the aerosolization potential of head and neck instrumentation and appropriate PPE during head and neck surgeries are lacking. However, extrapolation of recommendations by governing bodies suggests strongly that head and neck mucosal instrumentation warrants strict adherence to airborne‐level precautions. CONCLUSION: We present a series of situation‐specific recommendations for PPE use and other procedural precautions for otolaryngology providers to consider in the COVID‐19 era.


title: Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID‐19

text: The new coronavirus, classified as SARS-CoV-2 that emerged in Hubei province in China, causes a new coronavirus disease, which was termed COVID-19 by WHO on February 11, 2020. COVID-19 claimed almost 19000 lives around the world by March 25, 2020.


title: Estimation of effects of contact tracing and mask adoption on COVID-19 transmission in San Francisco: a modeling study

text: The current COVID-19 pandemic has spurred concern about what interventions may be effective at reducing transmission. The city and county of San Francisco imposed a shelter-in-place order in March 2020, followed by use of a contact tracing program and a policy requiring use of cloth face masks. We used statistical estimation and simulation to estimate the effectiveness of these interventions in San Francisco. We estimated that self-isolation and other practices beginning at the time of San Francisco’s shelter-in-place order reduced the effective reproduction number of COVID-19 by 35.4% (95% CI, −20.1%–81.4%). We estimated the effect of contact tracing on the effective reproduction number to be a reduction of approximately 44% times the fraction of cases that are detected, which may be modest if the detection rate is low. We estimated the impact of cloth mask adoption on reproduction number to be approximately 8.6%, and note that the benefit of mask adoption may be substantially greater for essential workers and other vulnerable populations, residents return to circulating outside the home more often. We estimated the effect of those interventions on incidence by simulating counterfactual scenarios in which contact tracing was not adopted, cloth masks were not adopted, and neither contact tracing nor cloth masks was adopted, and found increases in case counts that were modest, but relatively larger than the effects on reproduction numbers. These estimates and model results suggest that testing coverage and timing of testing and contact tracing may be important, and that modest effects on reproduction numbers can nonetheless cause substantial effects on case counts over time.


title: Current situation, genetic relationship and control measures of infectious bronchitis virus variants circulating in African regions

text: Abstract Infectious bronchitis virus (IBV) is a major viral pathogen of commercial poultry, affecting chickens of all ages and causing major economic losses in poultry industry worldwide. Frequent points of mutations and recombination events in the S1 gene region, result in the emergence of new IBVs variants circulating in the form of several serotypes/genotypes that can be partially or poorly neutralized by current vaccines. IBV is well studied worldwide, nevertheless in African countries epidemiological and scientific data are poor and not updated. This review aims to give a current overview of IBV situation, to establish evolutionary relationship between the African variants and to list some of the potential measures to control IBV in Africa. Three S1 gene hypervariable regions were studied and compared to the reference genotypes/serotypes that found emerging in African regions. This comparison was based on phylogenetic trees, nucleotide and amino-acid sequence analysis. It clearly appears that IBV variants reported in Africa, display a low genetic relationship between them and with the majority of the reference strains emerging in neighboring countries, except the case of variants from Libya and Egypt that show a high relatedness. Also the Massachusetts serotypes were the most prevalent co-circulating with both serotypes, Italy02 type in Morocco and Qx-like genotype in South part of the African continent. In order to control the IBV variants in African regions, an efficient vaccination strategy program should be implemented.


title: Using Cerenkov radiation for measuring the refractive index in thick samples by interferometric cathodoluminescence

text: Cathodoluminescence (CL) has evolved into a standard analytical technique in (scanning) transmission electron microscopy. CL utilizes light excited due to the interactions between the electron-beam and the sample. In the present study we focus on Cerenkov radiation. We make use of the fact that the electron transparent specimen acts as a Fabry-P\'erot interferometer for coherently emitted radiation. From the wavelength dependent interference pattern of thickness dependent measurements we calculate the refractive index of the studied material. We describe the limits of this approach and compare it with the determination of the refractive index by using valence electron energy loss spectrometry (VEELS)