title: Containing COVID-19 Among 627,386 Persons in Contact With the Diamond Princess Cruise Ship Passengers Who Disembarked in Taiwan: Big Data Analytics

text: BACKGROUND: Low infection and case-fatality rates have been thus far observed in Taiwan. One of the reasons for this major success is better use of big data analytics in efficient contact tracing and management and surveillance of those who require quarantine and isolation. OBJECTIVE: We present here a unique application of big data analytics among Taiwanese people who had contact with more than 3000 passengers that disembarked at Keelung harbor in Taiwan for a 1-day tour on January 31, 2020, 5 days before the outbreak of coronavirus disease (COVID-19) on the Diamond Princess cruise ship on February 5, 2020, after an index case was identified on January 20, 2020. METHODS: The smart contact tracing–based mobile sensor data, cross-validated by other big sensor surveillance data, were analyzed by the mobile geopositioning method and rapid analysis to identify 627,386 potential contact-persons. Information on self-monitoring and self-quarantine was provided via SMS, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests were offered for symptomatic contacts. National Health Insurance claims big data were linked, to follow-up on the outcome related to COVID-19 among those who were hospitalized due to pneumonia and advised to undergo screening for SARS-CoV-2. RESULTS: As of February 29, a total of 67 contacts who were tested by reverse transcription–polymerase chain reaction were all negative and no confirmed COVID-19 cases were found. Less cases of respiratory syndrome and pneumonia were found after the follow-up of the contact population compared with the general population until March 10, 2020. CONCLUSIONS: Big data analytics with smart contact tracing, automated alert messaging for self-restriction, and follow-up of the outcome related to COVID-19 using health insurance data could curtail the resources required for conventional epidemiological contact tracing.


title: Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2016)

text: This article lists the changes to virus taxonomy approved and ratified by the International Committee on Taxonomy of Viruses (ICTV) in April 2016. Changes to virus taxonomy (the Universal Scheme of Virus Classification of the International Committee on Taxonomy of Viruses [ICTV]) now take place annually and are the result of a multi-stage process. In accordance with the ICTV Statutes (http://www.ictvonline.org/statutes.asp), proposals submitted to the ICTV Executive Committee (EC) undergo a review process that involves input from the ICTV Study Groups (SGs) and Subcommittees (SCs), other interested virologists, and the EC. After final approval by the EC, proposals are then presented for ratification to the full ICTV membership by publication on an ICTV web site (http://www.ictvonline.org/) followed by an electronic vote. The latest set of proposals approved by the EC was made available on the ICTV website by January 2016 (https://talk.ictvonline.org/files/proposals/). A list of these proposals was then emailed on 28 March 2016 to the 148 members of ICTV, namely the EC Members, Life Members, ICTV Subcommittee Members (including the SG chairs) and ICTV National Representatives. Members were then requested to vote on whether to ratify the taxonomic proposals (voting closed on 29 April 2016).


title: Suppression of Adult Lesser Mealworm (Coleoptera: Tenebrionidae) Using Soil Incorporation of Poultry Manure

text: The effectiveness of manure incorporation in reducing the numbers of adult lesser mealworms emerging from caged-layer poultry manure applied to agricultural fields was examined in summer 2002 and 2004. Incorporation treatments included control (no incorporation), disk (7-cm depth), harrow (15-cm depth), chisel plow (30-cm depth), and moldboard plow (33-cm depth) on silt loam soils in New York state. An estimated 55,192 and 183,500 live adult lesser mealworms were applied to the field in 2002 and 2004, respectively. Mortality due to the action of the manure spreader was 32.4% in 2002 and 6.5% in 2004. No significant differences were observed between treatments in 2002. However, moldboard plowing significantly reduced beetle emergence compared with no tillage in 2004. Peak beetle flight was observed 10 and 17 d after manure application in 2002 and 2004, respectively.


title: Coronavirus Transcription: A Perspective

text: At the VIth International Symposium on Corona and Related Viruses held in Québec, Canada in 1994 we presented a new model for coronavirus transcription to explain how subgenome-length minus strands, which are used as templates for the synthesis of subgenomic mRNAs, might arise by a process involving discontinuous RNA synthesis. The old model explaining subgenomic mRNA synthesis, which was called leader-primed transcription, was based on erroneous evidence that only genome-length negative strands were present in replicative intermediates. To explain the discovery of subgenome-length minus strands, a related model, called the replicon model, was proposed: The subgenomic mRNAs would be produced initially by leader-primed transcription and then replicated into minus-strand templates that would in turn be transcribed into subgenomic mRNAs. We review the experimental evidence that led us to formulate a third model proposing that the discontinuous event in coronavirus RNA synthesis occurs during minus strand synthesis. With our model the genome is copied both continuously to produce minus-strand templates for genome RNA synthesis and discontinuously to produce minus-strand templates for subgenomic mRNA synthesis, and the subgenomic mRNAs do not function as templates for minus strand synthesis, only the genome does.


title: Large vessel stroke and COVID-19: Case report and literature review

text: The clinical signs of coronavirus disease-19 (COVID-19) can be heterogenous because of the diversity of potential organ involvement. We describe a 58-year-old woman who developed new-onset dysarthria and hemiplegia and was found to be COVID-19-positive. This is among the first cases of COVID-19 presenting solely with focal neurologic deficits.


Acute generalized exanthematous pustulosis induced by empiric hydroxychloroquine for presumed COVID‐19


title: A rapid risk analysis tool to prioritise response to infectious disease outbreaks

text: Epidemics are influenced by both disease and societal factors and can grow exponentially over short time periods. Epidemic risk analysis can help in rapidly predicting potentially serious outcomes and flagging the need for rapid response. We developed a multifactorial risk analysis tool ‘EpiRisk’ to provide rapid insight into the potential severity of emerging epidemics by combining disease-related parameters and country-related risk parameters. An initial set of 18 disease and country-related risk parameters was reduced to 14 following qualitative discussions and the removal of highly correlated parameters by a correlation and clustering analysis. Of the remaining parameters, three risk levels were assigned ranging from low (1) moderate (2) and high (3). The total risk score for an outbreak of a given disease in a particular country is calculated by summing these 14 risk scores, and this sum is subsequently classified into one of four risk categories: low risk (<21), moderate risk (21–29), high risk (30–37) and extreme risk (>37). Total risk scores were calculated for nine retrospective outbreaks demonstrating an association with the actual impact of those outbreaks. We also evaluated to what extent the risk scores correlate with the number of cases and deaths in 61 additional outbreaks between 2002 and 2018, demonstrating positive associations with outbreak severity as measured by the number of deaths. Using EpiRisk, timely intervention can be implemented by predicting the risk of emerging outbreaks in real time, which may help government and public health professionals prevent catastrophic epidemic outcomes.


title: Language model-based automatic prefix abbreviation expansion method for biomedical big data analysis

text: In biomedical domain, abbreviations are appearing more and more frequently in various data sets, which has caused significant obstacles to biomedical big data analysis. The dictionary-based approach has been adopted to process abbreviations, but it cannot handle ad hoc abbreviations, and it is impossible to cover all abbreviations. To overcome these drawbacks, this paper proposes an automatic abbreviation expansion method called LMAAE (Language Model-based Automatic Abbreviation Expansion). In this method, the abbreviation is firstly divided into blocks; then, expansion candidates are generated by restoring each block; and finally, the expansion candidates are filtered and clustered to acquire the final expansion result according to the language model and clustering method. Through restrict the abbreviation to prefix abbreviation, the search space of expansion is reduced sharply. And then, the search space is continuous reduced by restrained the effective and the length of the partition. In order to validate the effective of the method, two types of experiments are designed. For standard abbreviations, the expansion results include most of the expansion in dictionary. Therefore, it has a high precision. For ad hoc abbreviations, the precisions of schema matching, knowledge fusion are increased by using this method to handle the abbreviations. Although the recall for standard abbreviation needs to be improved, but this does not affect the good complement effect for the dictionary method.


Community‐acquired respiratory viruses


title: One Health proof of concept: Bringing a transdisciplinary approach to surveillance for zoonotic viruses at the human-wild animal interface

text: Abstract As the world continues to react and respond inefficiently to emerging infectious diseases, such as Middle Eastern Respiratory Syndrome and the Ebola and Zika viruses, a growing transdisciplinary community has called for a more proactive and holistic approach to prevention and preparedness – One Health. Such an approach presents important opportunities to reduce the impact of disease emergence events and also to mitigate future emergence through improved cross-sectoral coordination. In an attempt to provide proof of concept of the utility of the One Health approach, the US Agency for International Development’s PREDICT project consortium designed and implemented a targeted, risk-based surveillance strategy based not on humans as sentinels of disease but on detecting viruses early, at their source, where intervention strategies can be implemented before there is opportunity for spillover and spread in people or food animals. Here, we share One Health approaches used by consortium members to illustrate the potential for successful One Health outcomes that can be achieved through collaborative, transdisciplinary partnerships. PREDICT’s collaboration with partners around the world on strengthening local capacity to detect hundreds of viruses in wild animals, coupled with a series of cutting-edge virological and analytical activities, have significantly improved our baseline knowledge on the zoonotic pool of viruses and the risk of exposure to people. Further testament to the success of the project’s One Health approach and the work of its team of dedicated One Health professionals are the resulting 90 peer-reviewed, scientific publications in under 5 years that improve our understanding of zoonoses and the factors influencing their emergence. The findings are assisting in global health improvements, including surveillance science, diagnostic technologies, understanding of viral evolution, and ecological driver identification. Through its One Health leadership and multi-disciplinary partnerships, PREDICT has forged new networks of professionals from the human, animal, and environmental health sectors to promote global health, improving our understanding of viral disease spillover from wildlife and implementing strategies for preventing and controlling emerging disease threats.


Final 2013 Reports of Nationally Notifiable Infectious Diseases


title: Tissue specific expression of hepatitis B virus surface antigen in transgenic plant cells and tissue culture

text: The tobacco plants (Nicotiana tabacum L.) carrying the HBsAg gene controlled by (Aocs)(3)AmasPmas, the hybrid promoter that includes regulatory elements of the agrobacterial octopine and mannopine synthase genes, as well as plants controlled by the same promoter and adh1, maize alcohol dehydrogenase gene intron were obtained. The presence of the adh1 gene intron did not significantly change the level of expression of the HBsAg gene in plants. The analysis of expression of hepatitis B virus surface antigen (HBs-antigen) in transformed plants expressing the HBsAg under the control of different promoters was made. The level of HBs-antigen in plants carrying the HBsAg gene controlled by (Aocs)(3)AmasPmas, the hybrid agrobacterium-derived promoter, was the highest in roots and made up to 0.01% of total amount of soluble protein. The level of HBs-antigen in plants carrying the HBsAg gene controlled by the dual 35S RNA cauliflower mosaic virus promoter was the same in all organs of the plant and made up to 0.06% of the total amount of soluble protein. Hairy root and callus cultures of plants carrying the HBsAg gene and expressing the HBs-antigen were obtained.


title: Quarantine Through History

text: This article reviews in a historical perspective and by means of documented examples the scientific principles relevant to the concept and effectiveness of quarantine, the logistic, economic, and political barriers to its correct implementation through time, and the health impact of local and large-scale quarantine. Quarantine is overall one of the oldest and most disseminated and, despite its limits, most effective health measures elaborated by mankind. The evidence-based history of medicine and evidence-based modern epidemiology indicate that the implementation of correct quarantine procedures is today still feasible and useful provided that a proactive collaboration is operative among those concerned and that the measures are tailored according to geographical, social, and health conditions.


title: Bovine Respiratory Disease Vaccination Against Viral Pathogens: Modified-Live Versus Inactivated Antigen Vaccines, Intranasal Versus Parenteral, What Is the Evidence?

text: Vaccination of cattle against viral respiratory pathogens to minimize losses associated with bovine respiratory disease (BRD) is a common practice among producers and veterinarians. Three different calf populations in which BRD is most prevalent (recently weaned beef calves, preweaning beef calves, and young dairy calves) are the principal focus of morbidity and mortality prevention through vaccination; however, the evidence of vaccination efficacy is inconsistent in the literature. This review addresses the evidence of efficacy of vaccination in the prevention or reduction of naturally occurring and experimentally induced BRD in each calf group.


title: Guillain‐Barré syndrome after SARS‐CoV‐2 infection

text: Since the first reports in December 2019 in Wuhan, China, the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) rapidly developed into a pandemic associated with substantial morbidity and mortality. Guillain‐Barré syndrome (GBS) is an acute immune‐mediated polyradiculoneuropathy that may be triggered by various bacterial and viral infections. Reports on possible neurological manifestations of SARS‐CoV‐2 are still scarce. Hereby, we report a case of GBS after an infection with SARS‐CoV‐2.


title: Human TSLP and TLR3 ligands promote differentiation of Th17 cells with a central memory phenotype under Th2‐polarizing conditions

text: Background Human thymic stromal lymphopoietin (TSLP) is expressed in the human asthmatic lung and activates dendritic cells (DCs) to strongly induce proallergic T‐helper type 2 (Th2) cell responses, suggesting that TSLP plays a critical role in the pathophysiology of human asthma. Th2 cells are predominantly involved in mild asthma, whereas a mixture of Th1 and Th2 cells with neutrophilic inflammation, probably induced by Th17, affects more severe asthmatic disease. Exacerbation of asthmatic inflammation is often triggered by airway‐targeting RNA viral infection; virus‐derived double‐stranded RNA, Toll‐like receptor (TLR)3 ligand, activates bronchial epithelial cells to produce pro‐inflammatory mediators, including TSLP. Objective Because TSLPR‐expressing DCs express TLR3, we examined how the relationship between TSLP and TLR3 ligand stimulation influences DC activation. Methods CD11c(+)DCs purified from adult peripheral blood were cultured in TLR ligands containing media with or without TSLP and then co‐cultured with allogeneic naïve CD4(+)T cells. Results CD11c(+) DCs responded to a combination of TSLP and TLR3 ligand, poly(I : C), to up‐regulate expression of the functional TSLP receptor and TLR3. Although TSLP alone did not induce IL‐23 production by DCs, poly(I : C) alone primed DCs for the production of IL‐23, and a combination of TSLP and poly(I : C) primed DCs for further production of IL‐23. The addition of poly(I : C) did not inhibit TSLP‐activated DCs to prime naïve CD4(+) T cells to differentiate into inflammatory Th2 cells. Furthermore, DCs activated by a combination of TSLP and poly(I : C) primed more naïve CD4(+) T cells to differentiate into Th17‐cytokine–producing cells with a central memory T cell phenotype compared with DCs activated by poly(I : C) alone. Conclusions These results suggest that through DC activation, human TSLP and TLR3 ligands promote differentiation of Th17 cells with the central memory T cell phenotype under Th2‐polarizing conditions.


title: Antimicrobial resistant and extended-spectrum ß-lactamase (ESBL) producing Escherichia coli isolated from fecal samples of African dromedary camels

text: Abstract This study was conducted to determine the distribution of antimicrobial resistance among Escherichia coli isolated from feces of healthy dromedary camels in Kenya. A total of 162 fecal samples were cultivated for E. coli. Samples were also subcultivated to detect E. coli with extended-spectrum ß-lactamases (ESBLs). Antimicrobial susceptibility testing (AST) was performed by disk diffusion using a panel of 16 antimicrobials. In addition, isolates were screened for the presence of the plasmid-mediated colistin resistance genes mcr-1 to mcr-5. Samples from 20 (12.4%) of the camels contained antimicrobial resistant (AMR) E. coli, and 85% of the AMR isolates were multidrug resistant (MDR). The highest frequency of resistance was observed to tetracycline (11.7%), followed by ampicillin and streptomycin (both 10.5%), and sulfamethoxazole/trimethoprim (9.9%). Two (1.2%) of the isolates showed intermediate resistance to cefazolin and streptomycin, respectively. All the isolates were susceptible to amoxycillin/clavulanic acid, ciprofloxacin, fosfomycin, aztreonam and kanamycin, and 86.4% of the isolates were susceptible to all 16 antimicrobials used in this study. The prevalence of fecal carriage of ESBL producing E. coli was 0.6%. PCR and amplicon sequencing showed that the ESBL producer belonged to E. coli phylogenetic group A, sequence type (ST) 48, and harbored bla CTX-M-15. None of the isolates contained mcr genes. The results indicate that dromedary camels in Kenya may be reservoirs of AMR E. coli, including ESBL producers, that could potentially be transmitted to humans by direct contact or via the food chain.


title: In Situ Simulation Enables Operating Room Agility in the COVID-19 Pandemic

text: Supplemental Digital Content is available in the text


title: COVID‐19, Ethics of Care, and Feminist Crisis Management

text: The COVID‐19 pandemic threatens both lives and livelihoods. To reduce the spread of the virus, governments have introduced crisis management interventions that include border closures, quarantines, strict social distancing, marshaling of essential workers and enforced homeworking. COVID‐19 measures are necessary to save the lives of some of the most vulnerable people within society, and yet in parallel they create a range of negative everyday effects for already marginalized people. Likely unintended consequences of the management of the COVID‐19 crisis include elevated risk for workers in low‐paid, precarious, and care‐based employment, over‐representation of minority ethnic groups in case numbers and fatalities, and gendered barriers to work. Drawing upon feminist ethics of care, I theorize a radical alternative to the normative assumptions of rationalist crisis management. Rationalist approaches to crisis management are typified by utilitarian logics, masculine and militaristic language, and the belief that crises follow linear processes of signal detection, preparation/prevention, containment, recovery, and learning. By privileging the quantifiable ‐ resources and measurable outcomes ‐ such approaches tend to omit considerations of pre‐existing structural disadvantage. This paper contributes a new theorization of crisis management that is grounded in feminist ethics to provide a care‐based concern for all crisis affected people.


title: Impact of polymorphisms in the DC-SIGNR neck domain on the interaction with pathogens

text: Abstract The lectins DC-SIGN and DC-SIGNR augment infection by human immunodeficiency virus (HIV), Ebolavirus (EBOV) and other pathogens. The neck domain of these proteins drives multimerization, which is believed to be required for efficient recognition of multivalent ligands. The neck domain of DC-SIGN consists of seven sequence repeats with rare variations. In contrast, the DC-SIGNR neck domain is polymorphic and, in addition to the wild type (wt) allele with seven repeat units, allelic forms with five and six sequence repeats are frequently found. A potential association of the DC-SIGNR genotype and risk of HIV-1 infection is currently under debate. Therefore, we investigated if DC-SIGNR alleles with five and six repeat units exhibit defects in pathogen capture. Here, we show that wt DC-SIGNR and patient derived alleles with five and six repeats bind viral glycoproteins, augment viral infection and tetramerize with comparable efficiency. Moreover, coexpression of wt DC-SIGNR and alleles with five repeats did not decrease the interaction with pathogens compared to expression of each allele alone, suggesting that potential formation of hetero-oligomers does not appreciably reduce pathogen binding, at least under conditions of high expression. Thus, our results do not provide evidence for diminished pathogen capture by DC-SIGNR alleles with five and six repeat units. Albeit, we cannot exclude that subtle, but in vivo relevant differences remained undetected, our analysis suggests that indirect mechanisms could account for the association of polymorphisms in the DC-SIGNR neck region with reduced risk of HIV-1 infection.


title: From δ-aminolevulinic acid to chlorophylls and every step in between: in memory of Constantin (Tino) A. Rebeiz, 1936–2019

text: Constantin A. (Tino) Rebeiz, a pioneer in the field of chlorophyll biosynthesis, and a longtime member of the University of Illinois community of plant biologists, passed away on July 25, 2019. He came to the USA at a time that was difficult for members of minority groups to be in academia. However, his passion for the complexity of the biochemical origin of chlorophylls drove a career in basic sciences which extended into applied areas of environmentally friendly pesticides and treatment for skin cancer. He was a philanthropist; in retirement, he founded the Rebeiz Foundation for Basic Research which recognized excellence and lifetime achievements of selected top scientists in the general area of photosynthesis research. His life history, scientific breakthroughs, and community service hold important lessons for the field.


Human coronavirus OC43 outbreak in wild chimpanzees, Côte d´Ivoire, 2016


Volume contents, author and subject index


title: Can We Reduce Mortality of COVID-19 if We do Better in Glucose Control?

text: The SARS-CoV-2 has infected more than 3 million people and caused more than 240,000 death globally. Among the COVID-19 patients, the prevalence of people with other chronic diseases, such as diabetes, high blood pressure, and coronary heart disease is much higher than others. More strikingly, the survival rate of diabetic patients is also much lower than in non-diabetic patients. In addition to the general damage of high glucose to cells and tissues, a recent discovery that high glucose activates interferon regulatory factor 15 promotes influenza virus -induced cytokine storm. This discovery may shed light on the high incidence of diabetes in COVID-19. Several diabetes prevention strategies together with recent significant data-driven diabetes prediction approaches, which may help COVID-19 treatments, have been proposed.


title: Autophagy as an emerging dimension to adaptive and innate immunity

text: Abstract Autophagy is an evolutionary conserved cellular process during which cytoplasmic material is engulfed in double membrane vacuoles that then fuse with lysosomes, ultimately degrading their cargo. Emerging evidence, however, now suggests that autophagy can form part of our innate and adaptive immune defense programs. Recent studies have identified pattern recognition molecules as mediators of this process and shown that intracellular pathogens can interact with and even manipulate autophagy. Recent translational evidence has also implicated autophagy in the pathogenesis of several immune-mediated diseases, including Crohn disease. In this review, we present autophagy in the context of its role as an immune system component and effector and speculate on imminent and future research directions in this field.


title: Human Coronaviruses 229E and NL63: Close Yet Still So Far

text: HCoV-NL63 and HCoV-229E are two of the four human coronaviruses that circulate worldwide. These two viruses are unique in their relationship towards each other. Phylogenetically, the viruses are more closely related to each other than to any other human coronavirus, yet they only share 65% sequence identity. Moreover, the viruses use different receptors to enter their target cell. HCoV-NL63 is associated with croup in children, whereas all signs suggest that the virus probably causes the common cold in healthy adults. HCoV-229E is a proven common cold virus in healthy adults, so it is probable that both viruses induce comparable symptoms in adults, even though their mode of infection differs. Here, we present an overview of the current knowledge on both human coronaviruses, focusing on similarities and differences.


title: Hepatic failure in a child with anti‐epileptic hypersensitivity syndrome

text: Abstract: An 11‐year‐old boy developed severe hypersensitivity reaction to phenobarbitone resulted in fulminant hepatic failure. During the course of illness, he developed clinical features compatible with severe acute respiratory syndrome (SARS) that may have complicated the recovery of his underlying hypersensitivity reaction, which was subsequently controlled with intravenous immune globulin and corticosteroids.


title: Urology in the time of corona

text: The world is currently in the grip of the COVID-19 pandemic. Rapid changes in medical priorities are being enforced across all health-care systems. Urologists have had to reduce or halt their clinical activity and assist on COVID-19 wards. The repercussions on urological patient outcomes for delayed treatments and diagnosis remain to be defined.


title: Artificial Intelligence‐Based Clinical Decision Support for COVID‐19–Where Art Thou?

text: The COVID‐19 crisis has brought about new clinical questions, new workflows, and accelerated distributed healthcare needs. Although artificial intelligence (AI)‐based clinical decision support seemed to have matured, the application of AI‐based tools for COVID‐19 has been limited to date. In this perspective piece, the opportunities and requirements for AI‐based clinical decision support systems are identified and challenges that impact “AI readiness” for rapidly emergent healthcare challenges are highlighted.


title: Controversies of renin–angiotensin system inhibition during the COVID-19 pandemic

text: The current COVID-19 pandemic is associated with unprecedented morbidity and mortality. Early reports suggested an association between disease severity and hypertension but did not account for sources of confounding. However, the responsible virus — SARS-CoV-2 — gains entry to host cells via angiotensin-converting enzyme 2 (ACE2), highlighting the need to understand the relationship between the virus and the renin–angiotensin system (RAS) and how this might be affected by RAS inhibitors.


title: Smallpox Still Haunts Scientists: Results of a Questionnaire-Based Inquiry on the Views of Health Care and Life Science Experts and Students on Preserving the Remaining Variola Virus Stocks

text: The World Health Organization (WHO) declared eradication of the dreadful disease “smallpox” in 1980. Though the disease has died down, the causative virus “variola” has not, as it has been well preserved in two high security laboratories—one in USA and another in Russia. The debate on whether the remaining stocks of the smallpox virus should be destroyed or not is ongoing, and the World Health Assembly (WHA) in 2011 has decided to postpone the review on this debate to the 67th WHA in 2014. A short questionnaire-based inquiry was organized during a one-day stem cell meeting to explore the views of various health care and life science specialists especially students on this aspect. Among the 200 participants of the meeting, only 66 had answered the questionnaire. 60.6% of participants who responded to the questionnaire were for preserving the virus for future reference, while 36.4% of the participants were for destroying the virus considering the magnitude with which it killed millions. However, 3% of the respondents were not able to decide on any verdict. Therefore, this inquiry expresses the view that “what we cannot create, we do not have the right to destroy.”


title: SARS Transmission Pattern in Singapore Reassessed by Viral Sequence Variation Analysis

text: BACKGROUND: Epidemiological investigations of infectious disease are mainly dependent on indirect contact information and only occasionally assisted by characterization of pathogen sequence variation from clinical isolates. Direct sequence analysis of the pathogen, particularly at a population level, is generally thought to be too cumbersome, technically difficult, and expensive. We present here a novel application of mass spectrometry (MS)–based technology in characterizing viral sequence variations that overcomes these problems, and we apply it retrospectively to the severe acute respiratory syndrome (SARS) outbreak in Singapore. METHODS AND FINDINGS: The success rate of the MS-based analysis for detecting SARS coronavirus (SARS-CoV) sequence variations was determined to be 95% with 75 copies of viral RNA per reaction, which is sufficient to directly analyze both clinical and cultured samples. Analysis of 13 SARS-CoV isolates from the different stages of the Singapore outbreak identified nine sequence variations that could define the molecular relationship between them and pointed to a new, previously unidentified, primary route of introduction of SARS-CoV into the Singapore population. Our direct determination of viral sequence variation from a clinical sample also clarified an unresolved epidemiological link regarding the acquisition of SARS in a German patient. We were also able to detect heterogeneous viral sequences in primary lung tissues, suggesting a possible coevolution of quasispecies of virus within a single host. CONCLUSION: This study has further demonstrated the importance of improving clinical and epidemiological studies of pathogen transmission through the use of genetic analysis and has revealed the MS-based analysis to be a sensitive and accurate method for characterizing SARS-CoV genetic variations in clinical samples. We suggest that this approach should be used routinely during outbreaks of a wide variety of agents, in order to allow the most effective control.


title: Construction and characterisation of a complete reverse genetics system of dengue virus type 3

text: Dengue virulence and fitness are important factors that determine disease outcome. However, dengue virus (DENV) molecular biology and pathogenesis are not completely elucidated. New insights on those mechanisms have been facilitated by the development of reverse genetic systems in the past decades. Unfortunately, instability of flavivirus genomes cloned in Escherichia coli has been a major problem in these systems. Here, we describe the development of a complete reverse genetics system, based on the construction of an infectious clone and replicon for a low passage DENV-3 genotype III of a clinical isolate. Both constructs were assembled into a newly designed yeast- E. coli shuttle vector by homologous recombination technique and propagated in yeast to prevent any possible genome instability in E. coli . RNA transcripts derived from the infectious clone are infectious upon transfection into BHK-21 cells even after repeated passages of the plasmid in yeast. Transcript-derived DENV-3 exhibited growth kinetics, focus formation size comparable to original DENV-3 in mosquito C6/36 cell culture. In vitro characterisation of DENV-3 replicon confirmed its identity and ability to replicate transiently in BHK-21 cells. The reverse genetics system reported here is a valuable tool that will facilitate further molecular studies in DENV replication, virus attenuation and pathogenesis.


title: Acute lower respiratory tract infections by human metapneumovirus in children in Southwest China: A 2‐year study

text: Human metapneumovirus (hMPV) has been reported to cause both upper and lower respiratory tract diseases in susceptible populations, particularly in children and the elderly. In this study, we describe a hospital‐based epidemiological study of hMPV in patients presenting to a children's hospital and show the demographic and clinical characteristics associated with hMPV infection in China, retrospectively. Specimens were collected over a 2‐year period from children hospitalized with acute lower respiratory tract infections (ALRTI) and analyzed for the presence of hMPV using real‐time RT‐PCR assays. The presence of hMPV was detected in 227 (25.9%) of the 878 children studied and may circulate year‐round in the area, peaking during the winter–spring season. Younger children (aged less than 6 months) had the highest positive rate. Infections by hMPV showed similar epidemiology and clinical manifestations as for respiratory syncytial virus (RSV) and were found in high co‐infections with RSV. Subgroup A2 hMPV was the most predominant genotype identified during the study period. This study indicates that hMPV is one of the major respiratory pathogens found in children in southwest China and vaccine development should be under consideration. Pediatr. Pulmonol. 2010; 45:824–831. © 2010 Wiley‐Liss, Inc.


title: Severe acute respiratory syndrome (SARS) in intensive care units (ICUs): limiting the risk to healthcare workers

text: Abstract The global epidemic of severe acute respiratory syndrome (SARS) during the first half of 2003 resulted in over 8000 cases with more than 800 deaths. Many of those who eventually died, did so in the critical (intensive) care units of various hospitals around the world, and many secondary cases of SARS arose in healthcare workers looking after such patients in these units. Research on SARS coronavirus (SARS CoV) demonstrated that this virus belongs to the same family of viruses, the Coronaviridae that causes the common cold, with some important differences. Properties of this virus have been discovered which can be used to develop important infection control policies within hospitals to limit the number of secondary cases. These properties include environmental survival, transmissibility, viral load in various organs and fluids and periods of symptomatic illness during which infectivity is greatest. Various barrier methods were used throughout the epidemic to protect healthcare workers from SARS, with varying degrees of success. Treatment of SARS patients has mainly involved steroid therapy, with or without ribavirin, but there is no consensus on the best treatment protocol, as yet. This review focuses on the implications of SARS for healthcare workers and patients on critical care units.


title: Post weaning diarrhea in pigs: risk factors and non-colistin-based control strategies

text: Post-weaning diarrhea (PWD) is one of the most serious threats for the swine industry worldwide. It is commonly associated with the proliferation of enterotoxigenic Escherichia coli in the pig intestine. Colistin, a cationic antibiotic, is widely used in swine for the oral treatment of intestinal infections caused by E. coli, and particularly of PWD. However, despite the effectiveness of this antibiotic in the treatment of PWD, several studies have reported high rates of colistin resistant E. coli in swine. Furthermore, this antibiotic is considered of very high importance in humans, being used for the treatment of infections due to multidrug-resistant (MDR) Gram-negative bacteria (GNB). Moreover, the recent discovery of the mcr-1 gene encoding for colistin resistance in Enterobacteriaceae on a conjugative stable plasmid has raised great concern about the possible loss of colistin effectiveness for the treatment of MDR-GNB in humans. Consequently, it has been proposed that the use of colistin in animal production should be considered as a last resort treatment only. Thus, to overcome the economic losses, which would result from the restriction of use of colistin, especially for prophylactic purposes in PWD control, we believe that an understanding of the factors contributing to the development of this disease and the putting in place of practical alternative strategies for the control of PWD in swine is crucial. Such alternatives should improve animal gut health and reduce economic losses in pigs without promoting bacterial resistance. The present review begins with an overview of risk factors of PWD and an update of colistin use in PWD control worldwide in terms of quantities and microbiological outcomes. Subsequently, alternative strategies to the use of colistin for the control of this disease are described and discussed. Finally, a practical approach for the control of PWD in its various phases is proposed.


title: Occupational health responses to COVID‐19: What lessons can we learn from SARS?

text: On 31 December 2019, the World Health Organization (WHO) received reports of pneumonia cases of unknown etiology in the city of Wuhan in Hubei Province, China. The agent responsible was subsequently identified as a coronavirus—SARS‐CoV‐2. The WHO declared this disease as a Public Health Emergency of International Concern at the end of January 2020. This event evoked a sense of déjà vu, as it has many similarities to the outbreak of severe acute respiratory syndrome (SARS) of 2002‐2003. Both illnesses were caused by a zoonotic novel coronavirus, both originated during winter in China and both spread rapidly all over the world. However, the case‐fatality rate of SARS (9.6%) is higher than that of COVID‐19 (<4%). Another zoonotic novel coronavirus, MERS‐CoV, was responsible for the Middle East respiratory syndrome, which had a case‐fatality rate of 34%. Our experiences in coping with the previous coronavirus outbreaks have better equipped us to face the challenges posed by COVID‐19, especially in the health care setting. Among the insights gained from the past outbreaks were: outbreaks caused by viruses are hazardous to healthcare workers; the impact of the disease extends beyond the infection; general principles of prevention and control are effective in containing the disease; the disease poses both a public health as well as an occupational health threat; and emerging infectious diseases pose a continuing threat to the world. Given the perspectives gained and lessons learnt from these past events, we should be better prepared to face the current COVID‐19 outbreak.


title: How the COVID-19 pandemic changed the Plastic Surgery activity in a regional referral center in Northen Italy

text: The Covid 19 epidemic has modified the way that plastic surgeons can treat their patients. At our hospital all elective surgery was canceled and only the more severe cases were admitted. The outpatient department activity has been reduced also. We present the number and diagnoses of patients, treated as in- and out-patients, during seven weeks from the onset of the epidemic, comparing our activity from the lockdown of elective surgery with the numbers and diagnoses observed during the same weeks of last year. Finally we underline the importance of using telemedicine and web-based tools to transmit images of lesions that need the surgeon's evaluation, and can be used by the patient to keep in touch with a doctor during the distressing time of delay of the expected procedure.


title: SOFIA(®)RSV: prospective laboratory evaluation and implementation of a rapid diagnostic test in a pediatric emergency ward

text: BACKGROUND: Respiratory syncytial virus (RSV) is responsible for severe respiratory infections and higher costs in medical care. The two aims of this work were to assess the performances of SOFIA(®)RSV tests in “real-life-laboratory” conditions (study 1) and implemented at point-of-care testing in a pediatric emergency department (ED, study 2), during two consecutive winter seasons. METHODS: In study 1, fresh nasopharyngeal swabs from patients of all ages were sampled in 1.5 ml of Universal virological Transport Medium (UTM) and prospectively tested using SOFIA(®)RSV tests. In study 2, conducted in a pediatric ED, nasopharyngeal swabs were placed in 3 ml of UTM. All SOFIA(®)RSV tests were confirmed by molecular testing, considered as reference method. The epidemiological and clinical features of tested patients, as well as the care of these patients after obtaining quick results were evaluated. RESULTS: The sensitivities of SOFIA(®)RSV in infants (aged under 24 months) performed in the laboratory and in the pediatric ED were respectively 95% (95% CI: 86.8–98.1) and 74.8% (95% CI: 68.0–80.9) compared to PCR. In study 1, the sensitivity among children (from 2 to 15 years old) and adults (above 15 years old) dropped to 45% (95% CI: 23.1–68.5) and 59% (95% CI: 32.9–81.6), respectively. In study 2, there were some differences in bed-management of SOFIA(®)RSV positive compared to SOFIA(®)RSV negative infants. CONCLUSIONS: SOFIA(®)RSV tests performed in the laboratory and in the pediatric ED show high and satisfactory sensitivities among young children under 24 months, which supports its robustness and reliability. However, the impact of these tests on patient care at point-of-care cannot be clearly assessed when considering the limits of the study 2 design. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-017-2557-8) contains supplementary material, which is available to authorized users.


title: Advances in mass spectrometry for the identification of pathogens

text: Mass spectrometry (MS) has become an important technique to identify microbial biomarkers. The rapid and accurate MS identification of microorganisms without any extensive pretreatment of samples is now possible. This review summarizes MS methods that are currently utilized in microbial analyses. Affinity methods are effective to clean, enrich, and investigate microorganisms from complex matrices. Functionalized magnetic nanoparticles might concentrate traces of target microorganisms from sample solutions. Therefore, nanoparticle‐based techniques have a favorable detection limit. MS coupled with various chromatographic techniques, such as liquid chromatography and capillary electrophoresis, reduces the complexity of microbial biomarkers and yields reliable results. The direct analysis of whole pathogenic microbial cells with matrix‐assisted laser desorption/ionization MS without sample separation reveals specific biomarkers for taxonomy, and has the advantages of simplicity, rapidity, and high‐throughput measurements. The MS detection of polymerase chain reaction (PCR)‐amplified microbial nucleic acids provides an alternative to biomarker analysis. This review will conclude with some current applications of MS in the identification of pathogens. © 2010 Wiley Periodicals, Inc., Mass Spec Rev 30:1203–1224, 2011


title: Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population

text: Convalescent plasma is currently one of the leading treatments for COVID-19, but there is a paucity of data identifying therapeutic efficacy. A comprehensive analysis of the antibody responses in potential plasma donors and an understanding of the clinical and demographic factors that drive variant antibody responses is needed. Among 126 potential convalescent plasma donors, the humoral immune response was evaluated by a SARS-CoV-2 virus neutralization assay using Vero-E6-TMPRSS2 cells, commercial IgG and IgA ELISA to Spike (S) protein S1 domain (Euroimmun), IgA, IgG and IgM indirect ELISAs to the full-length S or S-receptor binding domain (S-RBD), and an IgG avidity assay. Multiple linear regression and predictive models were utilized to assess the correlations between antibody responses with demographic and clinical characteristics. IgG titers were greater than either IgM or IgA for S1, full length S, and S-RBD in the overall population. Of the 126 plasma samples, 101 (80%) had detectable neutralizing titers. Using neutralization titer as the reference, the sensitivity of the IgG ELISAs ranged between 95-98%, but specificity was only 20-32%. Male sex, older age, and hospitalization with COVID-19 were all consistently associated with increased antibody responses across the serological assays. Neutralizing antibody titers were reduced over time in contrast to overall antibody responses. There was substantial heterogeneity in the antibody response among potential convalescent plasma donors, but sex, age and hospitalization emerged as factors that can be used to identify individuals with a high likelihood of having strong antiviral antibody levels.


title: Impact of community respiratory viral infections in urban children with asthma

text: Abstract Background Upper respiratory tract viral infections cause asthma exacerbations in children. However, the impact of natural colds on children with asthma in the community, particularly in the high-risk urban environment, is less well defined. Objective We hypothesized that children with high-symptom upper respiratory viral infections have reduced airway function and greater respiratory tract inflammation than children with virus-positive low-symptom illnesses or virus-negative upper respiratory tract symptoms. Methods We studied 53 children with asthma from Detroit, Michigan, during scheduled surveillance periods and self-reported respiratory illnesses for 1 year. Symptom score, spirometry, fraction of exhaled nitric oxide (FeNO), and nasal aspirate biomarkers, and viral nucleic acid and rhinovirus (RV) copy number were assessed. Results Of 658 aspirates collected, 22.9% of surveillance samples and 33.7% of respiratory illnesses were virus-positive. Compared with the virus-negative asymptomatic condition, children with severe colds (symptom score ≥5) showed reduced forced expiratory flow at 25% to 75% of the pulmonary volume (FEF25%-75%), higher nasal messenger RNA expression of C-X-C motif chemokine ligand (CXCL)-10 and melanoma differentiation-associated protein 5, and higher protein abundance of CXCL8, CXCL10 and C-C motif chemokine ligands (CCL)-2, CCL4, CCL20, and CCL24. Children with mild (symptom score, 1-4) and asymptomatic infections showed normal airway function and fewer biomarker elevations. Virus-negative cold-like illnesses demonstrated increased FeNO, minimal biomarker elevation, and normal airflow. The RV copy number was associated with nasal chemokine levels but not symptom score. Conclusion Urban children with asthma with high-symptom respiratory viral infections have reduced FEF25%-75% and more elevations of nasal biomarkers than children with mild or symptomatic infections, or virus-negative illnesses.


title: Efficacy of three face masks in preventing inhalation of airborne contaminants in dental practice

text: ABSTRACT Background Up-to-date studies are needed on the protection provided by face masks used by dentists. We assessed the relative filtering efficacy of two currently used surgical face masks (one a molded mask, the other a tie-on mask) and a certified personal particulate respirator, all made by a single manufacturer. Methods The authors sprayed bicarbonate particulate against a porcelain surface (representing the patient's mouth) and collected it via a mannequin head (representing the dentist's head) placed 40 centimeters away and a tube with two airflow rates (0.5 cubic meters per hour and 9 m3/hour). They calculated the dry residue weight. They performed three separate runs for each mask and three runs with no mask at the two airflow rates with and without aerosol. Results With no mask (control), the authors recorded significant weight gains at both airflow rates with and without vaporization. With vaporization, the three masks were associated with different dry residue weights (P < .03 with the Kruskal-Wallis test at both flow rates), the respirator providing the lowest amount. The respirator provided an efficiency of 94 to 96 percent, compared with 90 to 92 percent and 85 to 86 percent for the molded and tie-on surgical masks, respectively. Conclusions These data provide independent evidence that a certified personal respirator can be more effective than high-quality surgical masks in dental settings. Clinical Implications Dentists should be aware that a certified particulate respirator can provide them with superior filtering protection.


title: Glycomics and glycoproteomics of viruses: Mass spectrometry applications and insights toward structure–function relationships

text: The advancement of viral glycomics has paralleled that of the mass spectrometry glycomics toolbox. In some regard the glycoproteins studied have provided the impetus for this advancement. Viral proteins are often highly glycosylated, especially those targeted by the host immune system. Glycosylation tends to be dynamic over time as viruses propagate in host populations leading to increased number of and/or “movement” of glycosylation sites in response to the immune system and other pressures. This relationship can lead to highly glycosylated, difficult to analyze glycoproteins that challenge the capabilities of modern mass spectrometry. In this review, we briefly discuss five general areas where glycosylation is important in the viral niche and how mass spectrometry has been used to reveal key information regarding structure–function relationships between viral glycoproteins and host cells. We describe the recent past and current glycomics toolbox used in these analyses and give examples of how the requirement to analyze these complex glycoproteins has provided the incentive for some advances seen in glycomics mass spectrometry. A general overview of viral glycomics, special cases, mass spectrometry methods and work‐flows, informatics and complementary chemical techniques currently used are discussed. © 2020 The Authors. Mass Spectrometry Reviews published by John Wiley & Sons Ltd. Mass Spec Rev


title: Inhibidores de la enzima convertidora de angiotensina y antagonistas del receptor de angiotensina II: ¿Aumentan el riesgo de padecer COVID-19?

text: Abstract A new coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was discovered in December 2019 in Wuhan, China; the virus escalated rapidly and on March 11, 2020, the World Health Organization declared it a pandemic.Emerging data suggests that older patients with COVID-19 associated with other comorbid conditions such as diabetes, hypertension, heart and lung diseases are particularly more susceptible, compared to general populations, and have higher mortality. It is not yet clear whether this increased association of high blood pressure with COVID-19 and the increased risk of mortality are directly related to high blood pressure or other associated comorbidities, or to antihypertensive treatment.Although the underlying pathogenic mechanism linking hypertension and severity of COVID-19 infection remains to be elucidated, it has been hypothesized that excessive activation of the renin-angiotensin system (RAS) could contribute to the progression of COVID-19 related lung injury.Concern about whether angiotensin II receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors may have deleterious effects on morbidity and mortality in patients with COVID-19 is based on speculation that these drugs would increase the regulation of angiotensin II converting enzyme (ACE2), a receptor for SARS-CoV-2, which would increase viral load and lung damage.Recent studies are consistent with the recommendations of scientific societies that propose avoiding the suspension or change of antihypertensive medication, as there is no evidence that shows that these can be taken as risk factors for severity or mortality from COVID-19.


title: TERAVOLT: Thoracic Cancers International COVID-19 Collaboration

text: Abstract Prior publications on small subsets of cancer patients infected with SARS CoV-2 have shown an increased risk of mortality compared to the general population. Furthermore, patients with thoracic malignancies are thought to be at particularly high risk given their older age, smoking habits, and pre-existing cardio-pulmonary comorbidities. For this reason, physicians around the world have formed TERAVOLT, a global consortium dedicated to understanding the impact of COVID-19 on patients with thoracic malignancies.


title: The Contribution of International Agencies to the Control of Communicable Diseases

text: Although inequality is often measured through three critical indicators—education, income and life expectancy—health-related differences are also essential elements for explaining levels of equality or inequality in modern societies. Investment and investigation in health also involve inequalities at the global level, and this includes insufficient North-South transfer of funds, technology and expertise in the health field, including the specific area of communicable diseases. Globally, epidemics and outbreaks in any geographic region can represent international public health emergencies, and this type of threat requires a global response. Therefore, given the need to strengthen the global capacity for dealing with threats of infectious diseases, a framework is needed for collaboration on alerting the world to epidemics and responding to public health emergencies. This is necessary to guarantee a high level of security against the dissemination of communicable diseases in an ever more globalized world. In response to these needs, international health agencies have put a number of strategies into practice in order to contribute to the control of communicable diseases in poor countries. The principle strategies include: 1) implementation of mechanisms for international epidemiologic surveillance; 2) use of international law to support the control of communicable diseases; 3) international cooperation on health matters; 4) strategies to strengthen primary care services and health systems in general; 5) promotion of the transfer of resources for research and development from the North to the South.


title: Structural comparison of five new halogenated dihydroquinoline-4(1H)-ones

text: Compounds with dihydroquinoline-4(1H)-one nuclei have been reported in the literature for being important in the development of medicines due to their broad spectrum of activities. In this way, the structural knowledge of this class becomes relevant for obtaining new materials with desired biological properties. This study presents the structural elucidation of five halogenated dihydroquinolines, as well as the discussion about the effect on the molecular conformation of the type and position of halogen atom on aromatic rings. Compounds I and IV differ in halogen substitution on 2-phenyl ring, while compounds III and V differ in halogen substitution on the benzylidene ring. Moreover, compound II has a para-substituted 2-phenyl ring in their molecular structure. The crystal packing of all five molecules is mainly ruled by C–H⋯O and C–H···halogen interactions that form dimers and chains. The shift in position and the kind of the halogen in ring C shows a starring role in the conformation of the studied compounds, and the packaging of these compounds is more susceptible to variations when the halogen position changes.


title: Evolutionary history, potential intermediate animal host, and cross‐species analyses of SARS‐CoV‐2

text: To investigate the evolutionary history of the recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in China, a total of 70 genomes of virus strains from China and elsewhere with sampling dates between 24 December 2019 and 3 February 2020 were analyzed. To explore the potential intermediate animal host of the SARS‐CoV‐2 virus, we reanalyzed virome data sets from pangolins and representative SARS‐related coronaviruses isolates from bats, with particular attention paid to the spike glycoprotein gene. We performed phylogenetic, split network, transmission network, likelihood‐mapping, and comparative analyses of the genomes. Based on Bayesian time‐scaled phylogenetic analysis using the tip‐dating method, we estimated the time to the most recent common ancestor and evolutionary rate of SARS‐CoV‐2, which ranged from 22 to 24 November 2019 and 1.19 to 1.31 × 10(−3) substitutions per site per year, respectively. Our results also revealed that the BetaCoV/bat/Yunnan/RaTG13/2013 virus was more similar to the SARS‐CoV‐2 virus than the coronavirus obtained from the two pangolin samples (SRR10168377 and SRR10168378). We also identified a unique peptide (PRRA) insertion in the human SARS‐CoV‐2 virus, which may be involved in the proteolytic cleavage of the spike protein by cellular proteases, and thus could impact host range and transmissibility. Interestingly, the coronavirus carried by pangolins did not have the RRAR motif. Therefore, we concluded that the human SARS‐CoV‐2 virus, which is responsible for the recent outbreak of COVID‐19, did not come directly from pangolins.


title: Social and administrative issues related to the COVID-19 pandemic in Pakistan: better late than never

text: The study critically reviewed Pakistan’s provincial updates of coronavirus disease 2019 (COVID-19) and discussed the current challenges faced by the government in a given context. The coronavirus-associated death tolls have been increasing rapidly in a country. The provincial status of confirmed cases of coronavirus is higher in Punjab, followed by the Sindh, Khyber Pakhtunkhwa (KPK), and Balochistan. The case fatality ratio shows that KPK has a higher ratio, i.e., 5.11%, followed by the Punjab, i.e., 1.82%; Sindh, i.e., 1.80%; Balochistan, i.e., 1.28%; Gilgit-Baltistan, i.e., 0.71%; and Federal territory, i.e., 0.66%. The country has a less testing capacity to identify more suspected coronavirus patients. The study calculated that if we increase five times our testing capacity from the current date, the total registered cases will be reached to 137,370 and death tolls will increase up to 3090. It is highly needed to increase testing capacity across Pakistan in order to minimize the outbreak of coronavirus. The provincial government should follow the Federal Government instructions to contain coronavirus by increasing testing capacities, tracing suspected patients, smart lockdowns, emergency relief to the poor, and vigilant monitoring system.


Antiviral activity of cystatin C against HIV


title: Bat Coronaviruses in China

text: During the past two decades, three zoonotic coronaviruses have been identified as the cause of large-scale disease outbreaks–Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Swine Acute Diarrhea Syndrome (SADS). SARS and MERS emerged in 2003 and 2012, respectively, and caused a worldwide pandemic that claimed thousands of human lives, while SADS struck the swine industry in 2017. They have common characteristics, such as they are all highly pathogenic to humans or livestock, their agents originated from bats, and two of them originated in China. Thus, it is highly likely that future SARS- or MERS-like coronavirus outbreaks will originate from bats, and there is an increased probability that this will occur in China. Therefore, the investigation of bat coronaviruses becomes an urgent issue for the detection of early warning signs, which in turn minimizes the impact of such future outbreaks in China. The purpose of the review is to summarize the current knowledge on viral diversity, reservoir hosts, and the geographical distributions of bat coronaviruses in China, and eventually we aim to predict virus hotspots and their cross-species transmission potential.


title: Monitoring antibody response following SARS-CoV-2 infection: Diagnostic efficiency of four automated immunoassays

text: INTRODUCTION: SARS-CoV-2 seroconversion is important for epidemiological studies as well as contact tracing. MATERIAL AND METHODS: The antibody response against SARS-CoV-2 was examined in 111 patients with a positive qRT-PCR. Seroconversion was assessed using the Elecsys from Roche, the Liaison S1/S2 IgG from Diasorin, the IgG and IgA from Euroimmun as well as the VIDAS IgG and IgM. Specificity was estimated based on the measurement of SARS-CoV-2 antibodies in 96 residual samples collected during a non-pandemic period. RESULTS: The highest overall sensitivity for detecting seroconversion was obtained using the Elecsys (81.1%), the Euroimmun with a combined detection of IgG/IgA (86.5%) and the VIDAS with a simultaneous measurement of IgG/IgM (78.4%).The Elecsys and the VIDAS IgG/IgM demonstrated a specificity as well as a positive predictive value of 100%. CONCLUSIONS: The Elecsys and the VIDAS methods with a combination of IgG/IgM measurement demonstrated a high sensitivity with no false positive results.


title: Infection with SARS-CoV-2 causes abnormal laboratory results of multiple organs in patients

text: Aim: To evaluate the clinical value of abnormal laboratory results of multiple organs in patients with coronavirus disease 2019 (COVID-2019) and to help clinicians perform correct treatment. Results: Elevated neutrophil-to-LYM ratio (NLR), D-dimer(D-D), interleukin (IL)-6, IL-10, IL-2, interferon-Y, and age were significantly associated with the severity of illness. However, significant and sustained decreases were observed in the LYM subset (p<0.05). D-D, T cell counts, and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of mild cases. Second, D-D increased from 0.5 to 8, and the risk ratio increased from 2.75 to 55, eventually leading to disseminated intravascular coagulation. Moreover, the acute renal function damage occurred earlier than abnormal heart and liver functions (p<0.05). Conclusions: The degrees of lymphopenia and proinflammatory cytokine storm were higher in severe COVID-19 patients than in mild cases. The degree was associated with the disease severity. Advanced age, NLR, D-D, and cytokine levels may serve as useful prognostic factors for the early identification of severe COVID-19 cases. Methods: Peripheral blood samples were collected from 93 confirmed COVID-19 patients. The samples were examined for lymphocyte (LYM) subsets by flow cytometry and cytokine profiles by specific immunoassays. The receiver operating characteristic curve was applied to determine the best diagnostic thresholds for laboratory results, and principal component analysis was used to screen the major risk factors. The prognostic values were assessed using the Kaplan–Meier curve and univariate and multivariate COX regression models.


title: The chemokine receptor CXCR2 and coronavirus-induced neurologic disease

text: Abstract Inoculation with the neurotropic JHM strain of mouse hepatitis virus (MHV) into the central nervous system (CNS) of susceptible strains of mice results in an acute encephalomyelitis in which virus preferentially replicates within glial cells while excluding neurons. Control of viral replication during acute disease is mediated by infiltrating virus-specific T cells via cytokine secretion and cytolytic activity, however sterile immunity is not achieved and virus persists resulting in chronic neuroinflammation associated with demyelination. CXCR2 is a chemokine receptor that upon binding to specific ligands promotes host defense through recruitment of myeloid cells to the CNS as well as protecting oligodendroglia from cytokine-mediated death in response to MHV infection. These findings highlight growing evidence of the diverse and important role of CXCR2 in regulating neuroinflammatory diseases.


title: Endemic zoonoses in the tropics: a public health problem hiding in plain sight

text: Zoonotic diseases are a significant burden on animal and human health, particularly in developing countries. Despite recognition of this fact, endemic zoonoses often remain undiagnosed in people, instead being mistaken for febrile diseases such as malaria. Here, as part of Veterinary Record's ongoing series of articles on One Health, a multidisciplinary team of researchers from Scotland, Tanzania and New Zealand argues that a One Health approach is needed to effectively combat these diseases


title: Prevalence of canine enteric coronavirus in a cross-sectional survey of dogs presenting at veterinary practices

text: Abstract In order to determine the prevalence of canine enteric coronavirus (CECoV) in the general dog population, faecal samples were obtained in a cross-sectional study of 249 dogs presenting for any reason at veterinary practices randomly selected from across the UK. Demographic and clinical data was obtained for each of the samples, including signalment, number of dogs in the household, reason for visiting the practice, and any recent history of diarrhoea. The samples were tested by RT-PCR for the presence of both type I and type II CECoV. Seven samples were positive (three from dogs in the same household), a prevalence of 2.8% (95% confidence intervals 1.1–5.7). Phylogenetic analysis of partial M gene sequences revealed that all seven positive samples grouped with type I CECoV, the first report of this virus in the UK. None of the positive dogs presented for gastrointestinal disease. Interestingly five of the positive dogs from three separate households were aged over 6 years, suggesting that older dogs may play an important role in the persistence of CECoV in such populations.


title: Recurrent wheezing 36 months after bronchiolitis is associated with rhinovirus infections and blood eosinophilia

text: AIM: Links between respiratory syncytial virus bronchiolitis and asthma are well known, but few studies have dealt with wheezing following bronchiolitis induced by other viruses. We assessed the risk factors for recurrent wheezing in infants hospitalised for acute viral bronchiolitis. METHODS: We followed 313 infants for three years after they were hospitalised for bronchiolitis, caused by 14 different viruses, to identify risk factors for recurrent wheezing. Parents provided feedback on wheezing episodes during telephone interviews 12 (n = 266), 24 (n = 242) and 36 (n = 230) months after hospitalisation. RESULTS: The frequency of wheezing episodes diminished during the follow‐up period: 137 children (51.7%) at 12 months, 117 (48.3%) at 24 months and 93 (40.4%) at 36 months. The risk of wheeze after three years was OR = 7.2 (95% CI 3.9–13.3) if they had episodes of wheezing during the first year after bronchiolitis, 16.8 (8.7–32.7) if they had episodes of wheezing during the second year and 55.0 (22.7–133.2) if they wheezed during both years. Blood eosinophils >400 cells/μL (OR 7.7; CI 1.4–41.8) and rhinovirus infections (3.1; 1.0–9.4) were the major risk factors for recurrent wheezing. CONCLUSION: Recurrent wheezing 36 months after infant bronchiolitis was associated with rhinoviruses and blood eosinophilia.


title: Development of a SYBR green-based real-time RT-PCR assay for rapid detection of the emerging swine acute diarrhea syndrome coronavirus

text: Abstract Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel coronavirus which was associated with severe diarrhea disease in pigs. SADS-CoV was first detected and identified as the causative agent of a devastating swine disease outbreak in southern China in 2017. Routine monitoring and early detection of the source of infection is therefore integral to the prevention and control of SADS-CoV infection. In this study, a SYBR green-based real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) technique was established for rapid detection and monitoring of this emerging virus. Specific primers were designed based on the conserved region within the M gene of the viral genome. The lowest detection limit of the RT-qPCR assay was 10 copies/μL. This assay was specific and had no cross-reaction with other 11 swine viruses. The positive rate of 84 clinical samples for the SYBR green-based RT-qPCR and the conventional RT-PCR was 73.81% (62/84) and 53.57% (45/84), respectively. These results demonstrated that the SYBR green-based RT-qPCR technique was an effectively diagnostic method with higher sensitivity than probe-based RT-qPCR and gel-based RT-PCR for detection and epidemiological investigations of SADS-CoV.


The need for privacy with public digital contact tracing during the COVID-19 pandemic


title: Analysis of trends in emergency department attendances, hospital admissions and medical staffing in a Hong Kong university hospital: 5-year study

text: BACKGROUND: The workload of emergency departments (ED) continually changes in response to presentations, overcrowding and availability of expertise and investigations. AIMS: To investigate changes in ED presentations and care processes, and the relationship of patient demand and ED staff resources to waiting times and processing times. METHODS: Retrospective analysis of prospectively collected administrative data from January 1999 to April 2005 in an emergency department in a university teaching hospital in Hong Kong. All patients attending the emergency department during the study period were included. Monthly attendance data were retrieved and analysed to determine both qualitative and quantitative changes in the patterns of presentation to the ED using prospectively gathered data. RESULTS: Total ED attendances decreased by 25% during the study with little seasonal variation. The admission rate and the use of ambulances increased steadily and significantly. Medical patients are increasing proportionately, but trauma patients are decreased in number. CONCLUSION: There have been major changes in the patterns of ED attendances and ED waiting times over the study period in this teaching hospital ED. Decreasing overall ED numbers are offset by an increasingly elderly population and a more complex case mix. Reducing clinical staff numbers appears to reduce the ED’s capacity to provide timely assessments and care and to function as hospital gatekeepers. Restoring staff numbers to previous levels may improve the quality and timeliness of ED services. It is necessary to refine measures of ED complexity and workload to determine appropriate staffing levels in the future.


title: Effect of co-axially hybridized gene targets on hybridization efficiency of microarrayed DNA probes

text: Abstract The effect of relative size of two co-axially hybridized gene targets on the hybridization efficiency was studied for two DNA probe configurations and various probe concentrations. Each of two sets of microarrayed probes contained a pair of DNA probes and a pair of their complementary samples labeled with two distinct fluorescent dyes. The sequence of each probe is especially designed so that two targets are simultaneously complementary to two adjacent sections of the probe. The molecular steric effect on the hybridization efficiency is investigated by comparing the dye signals between configurations of one-target and two-target hybridization scenarios. The results show that a low probe concentration gives better hybridization efficiency and the first-hybridization conducted by a shorter-size DNA target improves the hybridization efficiency of the second target coupling onto the same probe.


title: Manejo terapéutico de la fiebre hemorrágica de Crimea-Congo

text: Crimean-Congo haemorrhagic fever has been reported in more than 30 countries in Africa, Asia, the Middle East and Eastern Europe, with an increasing incidence in recent years, especially in Europe. Because no specific treatments have demonstrated efficacy, supportive treatment is essential, as well as the provision of a centre with the appropriate means to guarantee the safety of its healthcare professionals. Laboratory monitoring of thrombocytopenia, severe coagulopathy or liver failure is of critical importance. Patients with Crimean-Congo haemorrhagic fever should be admitted to High Level Isolation Units where appropriate biocontainment procedures can prevent nosocomial transmission through infected fluids or accidents with contaminated material. In case of high-risk exposures, early administration of ribavirin should be considered.


title: The RNA binding of protein A from Wuhan nodavirus is mediated by mitochondrial membrane lipids

text: Abstract RNA replication of positive-strand (+)RNA viruses requires the lipids present in intracellular membranes, the sites of which viral replicases associate with. However, the direct effects of membrane lipids on viral replicases are still poorly understood. Wuhan nodavirus (WhNV) protein A, which associates with mitochondrial membranes, is the sole replicase required for RNA replication. Here, we report that WhNV protein A binds to RNA1 in a cooperative manner. Moreover, mitochondrial membrane lipids (MMLs) stimulated the RNA binding activity and cooperativity of protein A, and such stimulations exhibited strong selectivity for distinct phospholipids. Interestingly, MMLs stimulated the RNA-binding cooperativity only at higher protein A concentrations. Further investigation showed that MMLs stimulate the RNA binding of protein A by promoting its self-interaction. Finally, manipulating MML metabolism affected the protein A-induced RNA1 recruitment in cells. Together, our findings reveal the direct effects of membrane lipids on the RNA binding activity of a nodaviral replicase.


title: Transmissible Gastroenteritis Virus of Pigs and Porcine Epidemic Diarrhea Virus

text: Abstract TGEV and PEDV are porcine coronaviruses with typical coronavirus virion structures and replication cycles. Both viruses cause diarrhea in pigs with similar clinical symptoms. Disease severity is inversely related to the age of animals. While TGEV infections are currently under control, recent emergence of virulent PEDV strains results in significant mortality. No effective treatments are available once animals are infected. Detection of viral antigen and/or genomic RNA is required for diagnosis. Prevention measures include enhanced biosecurity and vaccination with the latter being the most effective approach. Commercial vaccines for both viruses are available and numerous experimental vaccines are in development.


title: From Helpless to Hero: Promoting Values-Based Behavior and Positive Family Interaction in the Midst of COVID-19

text: Parents managing their home environments during government-ordered stay-at-home periods are likely to need new skills for occupying their children’s time with activities that promote health and emotional well-being. Moreover, parents and children know they need help managing these circumstances. Perhaps for the first time, behavior analysts hold the reinforcers for increasing parental involvement in effective child-rearing practices. In fact, behavior analysts can help parents enlist their children in managing the household by framing their behavior in terms of hidden superpowers. In the current article, we argue that behavior analysts have a range of tools to offer that are grounded in evidence-based principles, strategies, and kernels—or essential units of behavioral influence. When combined into scheduled daily practices and invoked by children taught to see their use of the tools as nothing short of heroic, these practices function as “vaccinations” that inoculate families against toxic and unsafe behaviors.


title: Enantioselective syntheses of carbocyclic nuleosides 5′-homocarbovir, epi-4′-homocarbovir and their cyclopropylamine analogs using facially selective Pd-mediated allylations

text: Carbocyclic nucleosides (−)-5′-homocarbovir and (+)-epi-4′-homocarbovir were prepared from an acylnitroso-derived hetero Diels–Alder cycloadduct. A kinetic enzymatic resolution generated an enantiopure aminocyclopentenol and Pd(0)-mediated decarboxylative allylations of allyl 2,2,2-trifluoroethyl malonates were used to install the 4′-hydroxyethyl groups. Late stage derivatization gave access to the cyclopropylamine congenors, (−)-5′-homoabacavir and (+)-epi-4′-homoabacavir. All carbonucleoside target molecules were evaluated for antiviral activity.


title: Host susceptibility to MERS-CoV infection, a retrospective cohort study of the 2015 Korean MERS outbreak

text: Abstract To evaluate host susceptibility factors to Middle East respiratory syndrome coronavirus (MERS-CoV) infection, we conducted a retrospective cohort study from the single largest exposure event of the 2015 Korean MERS outbreak. A total of 175 patients were closely exposed to a super-spreader, 26 of which were infected (14.9%). In a multivariate analysis, history of autologous stem cell transplantation (HR, 31.151; 95% CI, 5.447–178.145; P < 0.001) and tachypnea at ED (HR, 4.392; 95% CI, 1.402–13.761; P = 0.011) were significantly associated with MERS-CoV infection.


title: Multidisciplinary guidance for safe tracheostomy care during the COVID‐19 pandemic: the NHS National Patient Safety Improvement Programme (NatPatSIP)

text: The COVID‐19 pandemic is causing a significant increase in the number of patients requiring relatively prolonged invasive mechanical ventilation and an associated surge in patients who need a tracheostomy to facilitate weaning from respiratory support. In parallel, there has been a global increase in guidance from professional bodies representing staff who care for patients with tracheostomies at different points in their acute hospital journey, rehabilitation, and recovery. Of concern are the risks to healthcare staff of infection arising from tracheostomy insertion and subsequent management. Hospitals are also facing extraordinary demands on critical care services such that many patients who require a tracheostomy will be managed outside established intensive care or head and neck units, cared for by staff with little tracheostomy experience. These concerns led NHS England and NHS Improvement to expedite the National Patient Safety Improvement Programme’s ‘Safe Tracheostomy Care’ workstream as part of the NHS COVID‐19 response. Supporting this workstream, UK stakeholder organisations involved in tracheostomy care were invited to develop consensus guidance based on the available literature and existing multidisciplinary guidelines. Topics with direct relevance for frontline staff were identified. The consensus guidance includes: infectivity of patients with respect to tracheostomy indications and timing; aerosol‐generating procedures and risks to staff; insertion procedures; and management following tracheostomy. These consensus recommendations are based on expert opinion and informed by the best available evidence and published guidance where possible.


title: Comparative In Vivo Analysis of the Nsp15 Endoribonuclease of Murine, Porcine and Severe Acute Respiratory Syndrome Coronaviruses

text: The purpose of this study was to compare the biochemical and biological properties of nonstructural protein (nsp) 15 among mouse hepatitis virus (MHV), severe acute respiratory syndrome coronavirus (SARS-CoV) and transmissible gastroenteritis virus (TGEV) in virus-infected and ectopically expressed cells. In virus-infected cells, MHV nsp15 distributed unevenly throughout the cytoplasm but predominantly in the perinuclear region. When expressed as N-terminal enhanced green fluorescence protein (EGFP) fusion, it predominantly formed speckles in the cytoplasm. In contrast, SARS-CoV and TGEV EGFP-nsp15s distributed smoothly in the whole cell and did not form speckles. Deletion mapping experiments identified two domains responsible for the speckle formation in MHV EGFP-nsp15: Domain I (aa101–150) and Domain III (aa301–374). Interestingly, Domain II (aa151–250) had an inhibitory effect on Domain III- but not Domain I-mediated speckle formation. Expression of a small (35aa) sequence in Domain III alone was sufficient to form speckles for all 3 viral nsp15s. However, addition of surrounding sequences in Domain III abolished the speckle formation for TGEV nsp15 but not for MHV and SARS-CoV nsp15s. Further domain swapping experiments uncovered additional speckle-inducing and -suppressive elements in nsp15s of SARS-CoV and TGEV. Homotypic interaction involving Domain III of MHV nsp15 was further demonstrated biochemically. Moreover, the biological functions of the expressed nsp15s were assessed in MHV-infected cells. It was found that the effects of EGFP-nsp15s on MHV replication were both virus species- and nsp15 domain-dependent. Collectively these results thus underscore the differential biochemical and biological functions among the nsp15s of MHV, TGEV and SARS-CoV in host cells.


title: APOBEC3-mediated restriction of RNA virus replication

text: APOBEC3 family members are cytidine deaminases with roles in intrinsic responses to infection by retroviruses and retrotransposons, and in the control of other DNA viruses, such as herpesviruses, parvoviruses and hepatitis B virus. Although effects of APOBEC3 members on viral DNA have been demonstrated, it is not known whether they edit RNA genomes through cytidine deamination. Here, we investigated APOBEC3-mediated restriction of Coronaviridae. In experiments in vitro, three human APOBEC3 proteins (A3C, A3F and A3H) inhibited HCoV-NL63 infection and limited production of progeny virus, but did not cause hypermutation of the coronaviral genome. APOBEC3-mediated restriction was partially dependent on enzyme activity, and was reduced by the use of enzymatically inactive APOBEC3. Moreover, APOBEC3 proteins bound to the coronaviral nucleoprotein, and this interaction also affected viral replication. Although the precise molecular mechanism of deaminase-dependent inhibition of coronavirus replication remains elusive, our results further our understanding of APOBEC-mediated restriction of RNA virus infections.


title: Medical Management of Hemorrhagic Bowel Syndrome in a Beef Bull

text: A two and a half-year old Simmental bull was presented to Iowa State University's Food Animal and Camelid Hospital for anorexia and lethargy of several days. Clostridium perfringens type A was identified via fecal culture and toxin genotyping. Hemorrhagic bowel syndrome (HBS) was diagnosed based on microbiological results along with abdominal ultrasonography, complete blood count, and serum biochemistry. Aggressive multi-modal therapy was employed including intravenously administered fluid therapy, potassium penicillin, lidocaine, flunixin, and pantoprazole among other supportive care. The bull was discharged after 15 days of hospitalization and recovered uneventfully to full function by the next breeding season. Currently all case reports with regard to HBS in beef cattle describe mortality. While the dairy cattle literature demonstrates that HBS has a high mortality rate, and suggests that surgical intervention has a higher prognosis when compared to medical therapy in dairy cattle. Our case would provide support to aggressive medical treatment for HBS in beef cattle.


title: Reacciones adversas a fármacos utilizados en el tratamiento específico de la infección por SARS-CoV-2

text: RESUMEN Actualmente no hay ningún fármaco aprobado para el tratamiento de la COVID-19. Se emplean fármacos de manera empírica según experiencia y disponibilidad, pero no existen estudios controlados que demuestren su eficacia y seguridad. En este contexto, es importante que los médicos dispongan de información de los posibles efectos adversos tanto inmunológicos como no inmunológicos de estos medicamentos. En esta revisión se repasa el fundamento para su uso en la infección por SARS-Cov-2, así como las reacciones adversas más frecuentes; no se trata de una revisión sistemática sino narrativa. Se han incluido aquellos fármacos que se utilizan con el fin de abordar adecuadamente las dos fases clínicas que parece tener la enfermedad en su manifestación más grave: una primera fase con predominio de infección viral y una segunda fase con predominio de una respuesta inflamatoria. También se han repasado los casos de reacciones a dichos fármacos recogidas en el Programa de Farmacovigilancia del hospital antes del inicio de la pandemia.


title: Prolonged presence of effector‐memory CD8 T cells in the central nervous system after dengue virus encephalitis

text: Dengue virus infection in the central nervous system (CNS) of immunized mice results in a strong influx of CD8 T cells into the brain. Whereas the kinetics of the splenic antiviral response are conventional, i.e. expansion followed by a rapid drop in the frequency of specific CD8 T cells, dengue virus‐specific CD8 T cells are retained in the CNS at a high frequency. These CD8 T cells display a partially activated phenotype (CD69(high), Ly‐6A/E(high), CD62L(low)), characteristic for effector‐memory T cells. CD43 expression, visualized by staining with the 1B11 mAb, decreased in time, suggesting that these persisting CD8 T cells differentiated into memory cells. These data add to the growing evidence implicating the CNS as a non‐lymphoid tissue capable of supporting prolonged T cell survival/maintenance.


title: Obesity as a risk factor for greater severity of COVID-19 in patients with metabolic associated fatty liver disease

text: Abstract Background & Aims. Coronavirus disease 2019 (COVID-19) has been declared a pandemic in 2020. Patients with metabolic associated fatty liver disease (MAFLD) are often obese and have additional metabolic risk factors which may aggravate the severity of respiratory diseases and of COVID-19. This study aims to investigate the association between MAFLD and COVID-19 severity. Methods 214 patients with laboratory-confirmed COVID-19 aged between 18 and 75 years from three hospitals in Wenzhou, China were consecutively enrolled. Sixty-six patients with MAFLD were included in the final analysis. COVID-19 was diagnosed as a positive result by high-throughput sequencing or real-time reverse transcriptase-polymerase chain reaction assay of oropharyngeal swab specimens. COVID-19 severity was assessed during hospitalization and classified as severe and non-severe based on the current management guideline. All patients were screened for fatty liver by computed tomography and subsequently diagnosed as MAFLD according to a recent set of consensus diagnostic criteria. Obesity was defined as BMI >25 kg/m2. Results The presence of obesity in MAFLD patients was associated with a ~ 6-fold increased risk of severe COVID-19 illness (unadjusted-OR 5.77, 95% CI 1.19–27.91, p = .029). Notably, this association with obesity and COVID-19 severity remained significant (adjusted-OR 6.32, 95% CI 1.16–34.54, p = .033) even after adjusting for age, sex, smoking, diabetes, hypertension, and dyslipidaemia. Conclusions Our data demonstrate that the risk of obesity to COVID-19 severity is greater in those with, than those without MAFLD.


Travel medicine, a speciality on the move


title: Implementation of a Novel Remote Physician SBRT Coverage Process during the Coronavirus Pandemic

text: Abstract Introduction During the COVID-19 pandemic, alternative methods of care are needed to reduce the relative risk of transmission in departments. Also needed is the ability to provide vital radiation oncological care if radiation oncologists (RO) are reallocated to other departments. We implemented a novel remote RO SBRT coverage practice, requiring it to be reliable, of high audio and visual quality, timely, and the same level of specialty care as our current in-person treatment coverage practice. Methods All observed failure modes were recorded during implementation over the first 15 sequential fractions. The time from CBCT to treatment was calculated before and after implementation to determine timeliness of remote coverage. Image quality metrics were calculated between the imaging console screen and the RO’s shared screen. Comfort levels with audio/visual communication as well as overall comfort in comparison to in-person RO coverage was evaluated using Likert scale surveys after treatment. Results Remote RO SBRT coverage was successfully implemented in 14/15 fractions with 3 observed process failures that were all corrected before treatment. Average times of pre-treatment coverage before and after implementation were 8.74 and 8.51min, respectively. The cross correlation between the imaging console screen and RO’s shared screen was r=0.96 and lag was 0.05s. The average value for all survey questions was above 4.5, approaching in-person RO coverage comfort levels. Conclusions Our novel method of remote RO SBRT coverage permits reduced personnel and patient interactions surrounding RT procedures. This may help to reduce transmission of COVID-19 in our department and provides a means for SBRT coverage if ROs are reallocated to other areas of the hospital for COVID-19 support.


title: A Re-analysis in Exploring the Association between Temperature and COVID-19 Transmissibility: An Ecological Study with 154 Chinese Cities

text: In this national ecological study across 154 Chinese cities, the ambient temperature was found having nonlinear negative association with the COVID-19’s transmissibility.


Proteomics and Severe Acute Respiratory Syndrome (SARS): Emerging Technology Meets Emerging Pathogen


title: Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection

text: Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 10(4) PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERS(MA)6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 10(6) PFU UV-inactivated MERS(MA)6.1.2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection.


title: Molecular Characterization of HE, M, and E Genes of Winter Dysentery Bovine Coronavirus Circulated in Korea During 2002–2003

text: The different bovine coronavirus (BCoV) strains or isolates exhibited various degrees of substitutions, resulting in altered antigenicity and pathogenicity of the virus. In the previous our study, we demonstrated that the spike glycoprotein gene of Korean winter dysentery (WD) BCoV had a genetic property of both enteric (EBCV) and respiratory BCoV (RBCV) and were significantly distinct from the ancestral enteric strains. In the present study, therefore, we analyzed the other structure genes, the hemagglutinin/esterase (HE) protein, the transmembrane (M) protein and the small membrane (E) protein to characterize 10 WD BCoV circulated in Korea during 2002–2003 and compared the nucleotide and deduced amino acid sequences with the other known BCoV. Phylogenetic analysis indicated that the HE gene among BCoV could be divided into three groups. The first group included only RBCV, while the second group contained calf diarrhea BCoV, RBCV, WD and EBCV, respectively. The third group possessed only all Korean WD strains which were more homologous to each other and were sharply distinct from the other known BCoV, suggesting Korean WD strains had evolutionary distinct pathway. In contrast, the relative conservation of the M and E proteins of BCoV including Korean WD strains and the other coronaviruses suggested that structural constraints on these proteins are rigid, resulting in more limited evolution of these proteins. In addition, BCoV and human coronavirus HCV-OC43 contained four potential O-glycosylation sites in the M gene. However, the M gene sequence of both BCoV and HCV-OC43 might not contain a signal peptide, suggesting the M protein might be unlikely to be exposed to the O-glycosylation machinery in vivo.


title: Localized mid‐face miliaria as a consequence of filtering face piece respirator use during the COVID‐19 pandemic

text: As a novel coronavirus pathogen, COVID-19 and the current associated pandemic has rapidly transformed daily life since its first detection in December 2019 in Wuhan, China. Not only are strict social distancing measures now the status quo, but within the occupational setting of healthcare provision, healthcare workers (HCWs) have had to quickly adapt to an entirely different way of working. Part of this new routine encompasses the now habitual donning of personal protective equipment (PPE), not least the filtering face piece respirator (FFP), particularly for aerosol generating procedures (AGPs). In this regard, front-line workers face the largest risk not only from COVID-19 exposure, but also from the consequences of wearing PPE for extended periods.


title: Comparison of broad-spectrum antiviral activities of the synthetic rocaglate CR-31-B (−) and the eIF4A-inhibitor Silvestrol

text: Rocaglates, a class of natural compounds isolated from plants of the genus Aglaia, are potent inhibitors of translation initiation. They are proposed to form stacking interactions with polypurine sequences in the 5′-untranslated region (UTR) of selected mRNAs, thereby clamping the RNA substrate onto eIF4A and causing inhibition of the translation initiation complex. Since virus replication relies on the host translation machinery, it is not surprising that the rocaglate Silvestrol has broad-spectrum antiviral activity. Unfortunately, synthesis of Silvestrol is sophisticated and time-consuming, thus hampering the prospects for further antiviral drug development. Here, we present the less complex structured synthetic rocaglate CR-31-B (−) as a novel compound with potent broad-spectrum antiviral activity in primary cells and in an ex vivo bronchial epithelial cell system. CR-31-B (−) inhibited the replication of corona-, Zika-, Lassa-, Crimean Congo hemorrhagic fever viruses and, to a lesser extent, hepatitis E virus (HEV) at non-cytotoxic low nanomolar concentrations. Since HEV has a polypurine-free 5′-UTR that folds into a stable hairpin structure, we hypothesized that RNA clamping by Silvestrol and its derivatives may also occur in a polypurine-independent but structure-dependent manner. Interestingly, the HEV 5′-UTR conferred sensitivity towards Silvestrol but not to CR-31-B (−). However, if an exposed polypurine stretch was introduced into the HEV 5′-UTR, CR-31-B (−) became an active inhibitor comparable to Silvestrol. Moreover, thermodynamic destabilization of the HEV 5′-UTR led to reduced translational inhibition by Silvestrol, suggesting differences between rocaglates in their mode of action, most probably by engaging Silvestrol's additional dioxane moiety.


title: Pulmonary Pathology of Early Phase COVID‐19 Pneumonia in a Patient with a Benign Lung Lesion

text: AIMS: An ongoing outbreak of 2019 novel coronavirus (SARS‐CoV‐2) diseases (COVID‐19) has been spreading in multiple countries. One of the reasons for the rapid spread is that the virus can be transmitted from infected individuals without symptoms. Revealing the pathological features of early phase COVID‐19 pneumonia is important to the understanding of its pathogenesis. The aim of this study was to explore pulmonary pathology of early phase COVID‐19 pneumonia in a patient with a benign lung lesion. METHODS AND RESULTS: We analyzed the pathological changes of lung tissue from a 55‐year‐old female patient with early phase SARS‐CoV‐2 infection. In this case, right lower lobectomy was performed for a benign pulmonary nodule. Detailed clinical, laboratory and radiological data were also described. This case was confirmed to have preoperative SARS‐CoV‐2 infection by real‐time RT‐PCR and RNA in situ hybridization on surgically removed lung tissues. Histologically, COVID‐19 pneumonia was characterized by exudative inflammation. The closer to the visceral pleura, the more severe the exudation of monocytes and lymphocytes. Perivascular inflammatory infiltration, intraalveolar multinucleated giant cells, pneumocyte hyperplasia and intracytoplasmic viral‐like inclusion bodies were seen. However, fibrinous exudate and hyaline membrane formation, which were typical pulmonary features of SARS pneumonia, were not evident in this case. Immunohistochemical staining results showed that an abnormal accumulation of CD4+ helper T lymphocytes and CD163+ M2 macrophages in the lung tissue. CONCLUSION: The results highlighted the pulmonary pathological changes of early phase SARS‐CoV‐2 infection and suggested a role of immune dysfunction in the pathogenesis of COVID‐19 pneumonia.