title: Challenges of global surveillance during an influenza pandemic

text: Summary Surveillance is an essential foundation for monitoring and evaluating any disease process, and is especially critical when new disease agents appear. The H1N1 influenza pandemic of 2009 tested the capacities of countries to detect, assess, notify and report events as required by the 2005 International Health Regulations (IHR). As detailed in the IHR, the World Health Organization drew on official reports from Member States as well as unofficial sources (e.g. media alerts) to quickly report and disseminate information about the appearance of the novel influenza virus. The pre-existing Global Influenza Surveillance Network for virological surveillance also provided crucial information for rapid development of a vaccine and for detection of changes in the virus. However, the pandemic also highlighted a number of shortcomings in global epidemiological surveillance for respiratory disease. These included the lack of standards for reporting illness, risk factor and mortality data, and a mechanism for systematic reporting of epidemiological data. Such measures would have facilitated direct comparison of data between countries and improved timely understanding of the characteristics and impact of the pandemic. This paper describes the surveillance strategies in place before the pandemic and the methods that were used at global level to monitor the pandemic. Enhancements of global surveillance are proposed to improve preparedness and response for similar events in the future.


A Low-cost Solution for Retrofitment of HEPA Filter in Healthcare Facilities Providing Care to COVID-19 Patients


title: Proteasome Inhibitors as a Possible Therapy for SARS-CoV-2

text: The COVID-19 global pandemic is caused by SARS-CoV-2, and represents an urgent medical and social issue. Unfortunately, there is still not a single proven effective drug available, and therefore, current therapeutic guidelines recommend supportive care including oxygen administration and treatment with antibiotics. Recently, patients have been also treated with off-label therapies which comprise antiretrovirals, anti-inflammatory compounds, antiparasitic agents and plasma from convalescent patients, all with controversial results. The ubiquitin–proteasome system (UPS) is important for the maintenance of cellular homeostasis, and plays a pivotal role in viral replication processes. In this review, we discuss several aspects of the UPS and the effects of its inhibition with particular regard to the life cycle of the coronaviruses (CoVs). In fact, proteasome inhibition by various chemical compounds, such as MG132, epoxomycin and bortezomib, may reduce the virus entry into the eucariotic cell, the synthesis of RNA, and the subsequent protein expression necessary for CoVs. Importantly, since UPS inhibitors reduce the cytokine storm associated with various inflammatory conditions, it is reasonable to assume that they might be repurposed for SARS-CoV-2, thus providing an additional tool to counteract both virus replication as well as its most deleterious consequences triggered by abnormal immunological response.


Aspartate aminotransferase: a prognostic marker rather than a specific liver injury marker in COVID-19


title: Impedimetric cell-based biosensor for real-time monitoring of cytopathic effects induced by dengue viruses

text: Abstract We describe an impedimetric cell-based biosensor constructed from poly-l-lysine (PLL)-modified screen-printed carbon electrode for real-time monitoring of dengue virus (DENV) infection of surface-immobilized baby hamster kidney (BHK-21) fibroblast cells. Cytopathic effects (CPE) induced by DENV-2 New Guinea C strain (including degenerative morphological changes, detachment, membrane degradation and death of host cells), were reflected by drastic decrease in impedance signal response detected as early as ~30 hours post-infection (hpi). In contrast, distinct CPE by conventional microscopy was evident only at ~72hpi at the corresponding multiplicity of infection (MOI) of 10. A parameter that describes the kinetics of cytopathogenesis, CIT50, which refers to the time taken for 50% reduction in impedance signal response, revealed an inverse linear relationship with virus titer and MOI. CIT50 values were also delayed by 31.5h for each order of magnitude decrease in MOI. Therefore, based on the analysis of CIT50, the virus titer of a given sample can be determined from the measured impedance signal response. Furthermore, consistent impedance results were also obtained with clinical isolates of the four DENV serotypes verified by RT-PCR and cycle sequencing. This impedimetric cell-based biosensor represents a label-free and continuous approach for the dynamic measurement of cellular responses toward DENV infection, and for detecting the presence of infectious viral particles.


title: Quercetin, Inflammation and Immunity

text: In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity.


title: SEROEPIDEMIOLOGIC SURVEY OF CORONAVIRUS (STRAIN OC 43) RELATED INFECTIONS IN A CHILDREN'S POPULATION

text: Kaye, H. S. (CDC, Atlanta, Ga. 30333), H. B. Marsh and W. R. Dowdle. Sero-epidemiologic survey of coronavirus (strain OC 43) related infections in a children's population. Amer J Epid 94: 43–49, 1971.—Acute and convalescent serum pairs and control sera collected from subjects living in a children's home over a 7-year period (1960–1967) were examined by hemagglutination-inhibition (HI) test with coronavirus strain OC 43. Ninety-three serologic conversions were observed; 44 were associated with reported illnesses and 49 with no reported illnesses. In three distinct outbreaks during the winter and spring quarter of 1960–1961, 1964–1965, and 1966–1967, 67 conversions occurred. Seroconversions to strain OC 43 were associated with as much as 19% of the respiratory diseases in a single season. Over the 7-year period coronavirus strain OC 43 accounted for 3% of the total 1328 respiratory illnesses. Evidence of preexisting antibody was apparent in one-third of the children showing seroconversions. The HI test was more sensitive for serodiagnosis than the complement-fixaticn test. The major presenting complaints of the children with respiratory disease associated with coronavirus strain OC 43 were sore throat, cough and coryza; the predominating symptoms were pharyngitis, coryza, fever and cervical adenitis.


title: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection

text: Enhancing the response to interferon could offer an immunological advantage to the host. In support of this concept, we used a modified form of the transcription factor STAT1 to achieve hyper-responsiveness to interferon without toxicity and markedly improve antiviral function in transgenic mice and transduced human cells. We found that the improvement depended on expression of a PARP9-DTX3L complex with distinct domains for interaction with STAT1 and for activity as an E3 ubiquitin ligase that acted on host histone H2BJ to promote interferon-stimulated gene expression and on viral 3C proteases to degrade these proteases via the immunoproteasome. Thus, PARP9-DTX3L acted on host and pathogen to achieve a double layer of immunity within a safe reserve in the interferon signaling pathway. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ni.3279) contains supplementary material, which is available to authorized users.


title: Determination of Ferret Enteric Coronavirus Genome in Laboratory Ferrets

text: Ferret enteric coronavirus (FRECV) RNA was detected in laboratory ferrets. Analysis of the complete genome sequence of 2 strains, FRCoV4370 and FRCoV063, revealed that FRECV shared 49.9%–68.9% nucleotide sequence identity with known coronaviruses. These results suggest that FRECV might be classified as a new species in the genus Alphacoronavirus.


title: Structure-activity relationships of cryptopleurine analogs with E-ring modifications as anti-hepatitis C virus agents

text: Abstract The tylophorine analog rac-cryptopleurine exhibited potent anti-hepatitis C virus (HCV) activity through allosteric regulation of ATPase activity of heat shock cognate protein 70 (Hsc70). We evaluated the impact of modifications on the E-ring of rac-cryptopleurine to the inhibitory activity against HCV replication and regulation of ATPase activity of Hsc70. Cryptopleurine analog YXM-110 with a 13α-hydroxyl group maintained activity against HCV and promoted ATP/ADP turnover of Hsc70; however, compounds with hydroxyl groups at other positions or with other orientations (YXM-109, YXM-139, and YXM-140) did not exhibit similar activities. Size modification or heteroatom incorporation of the E-ring led to loss of anti-HCV activity. Promotion of the chaperone activity of Hsc70 with carboxyl terminus Hsc70 interacting protein (CHIP) further enhanced the anti-HCV activity of rac-cryptopleurine and XYM-110. This structure-activity relationship (SAR) study refined structural design and optimization for developing rac-crytopleurine analogs as potent anti-HCV agents targeted against the host factor involved in HCV replication.


title: Heterogeneity of the L2 gene of field isolates of bluetongue virus serotype 17 from the San Joaquin Valley of California

text: Abstract Genome segment 2 (L2) from six field isolates of bluetongue virus (BTV) serotype 17 was sequenced by cycling sequencing after the amplification of the viral cDNA by the polymerase chain reaction. The viruses were isolated from sheep, cattle and a goat in the San Joaquin Valley of California during the years 1981 and 1990. These viruses exhibit divergent patterns of neutralization with BTV 17-specific monoclonal antibodies. The six L2 genes of the BTV 17 field isolates all encode a protein of 955 amino acids. Similarity of the nucleotide sequences of the L2 genes with respect to the prototype strain ranges between 93.8% and 95.1%, whereas the similarity between the field isolates ranges from 96.8% to 99.1%. Although very closely related, the L2 gene of each virus is distinct. Furthermore, mutations in the L2 gene of field isolates of BTV do not consistently follow a linear pattern of accumulation over time. Some amino acid changes in the VP2 protein of field strains were conserved over time, whereas others were not correlated with the year of isolation and some substitutions were unique to individual viruses. The predicted VP2s constitute a group of non-identical, but closely related proteins. Phylogenetic analyses suggest that the viral variants which co-circulate in the San Joaquin Valley could evolve by different evolutionary pathways.


title: What can we do for part‐time nursing students during the COVID‐19 pandemic?

text: In our Bachelor of Nursing programme (part-time), students are registered nurses working within various clinical and primary care settings. In light of the COVID-19 pandemic, all face-to-face teaching has been suspended since early February and our epidemiology course has moved entirely to online teaching. We needed to address the following challenges: The course is offered to final year students who are simultaneously working on front line. It was thought imperative, therefore, that students graduate on-time and that the the online learning activities be flexible.


title: Brief Summary of Potential SARS-CoV-2 Prophylactic and Treatment Drugs in the Emergency Department

text: As of March 30(th), 2020 there were 161,807 total cases and 2,953 total deaths of SARS-CoV-2 in the United States, with the number of cases expected to rise. Other than supportive care, there are no SARS-CoV-2 specific treatments available for patients discharged from the emergency department (ED) or those admitted to the hospital. In addition, there are no vaccines available to protect our at-risk healthcare workers. The National Institutes of Health is conducting a Phase 1 clinical trial to evaluate for a potential vaccine and the recipients have started to receive the investigational vaccine.2 We present a brief overview of the potential prophylactic and treatment agents under investigation, some which could be initiated in the ED if proven effective.


title: Evolving status of the 2019 novel coronavirus infection: Proposal of conventional serologic assays for disease diagnosis and infection monitoring

text: The novel coronavirus (nCoV-2019) outbreak in Wuhan, China has spread rapidly nationwide, with some cases occurring in other parts of the world. Although most patients present with mild febrile illness with patchy pulmonary inflammation, a significant portion develop severe acute respiratory distress syndrome (ARDS), with a current case fatality of 2.3-3%. Diagnosis is based on clinical history and laboratory and chest radiographic findings, but confirmation currently relies on nucleic acid-based assays. The latter are playing an important role in facilitating patient isolation, treatment and assessment of infectious activities. However, due to their limited capacity to handle an epidemic of the current scale and insufficient supply of assay kits, only a portion of suspected cases can be tested, leading to incompleteness and inaccuracy in updating new cases, as well as delayed diagnosis. Furthermore, there has not been enough time to assess specificity and sensitivity. Conventional serological assays, such as enzyme-linked immunoassay (ELISA) for specific IgM and IgG antibodies, should offer a high-throughput alternative, which allows for uniform tests for all suspected patients, and can facilitate more complete identification of infected cases and avoidance of unnecessary cross infection among unselected patients. This article is protected by copyright. All rights reserved.


title: Synthesis, characterization and biological activity of a niobium-substituted-heteropolytungstate on hepatitis B virus

text: Abstract To synthesise and characterize the polyoxometalate Cs2K4Na[SiW9Nb3O40]·H2O 1 for its anti-hepatitis B virus (HBV) properties by using the HepG2.2.15 cell. The methylthiazol tetrazolium assay was used to evaluate the growth inhibitory effect of Compound 1 on HepG2.2.15 cell. By using ELISA and real-time PCR, respectively, the presence of extracellular hepatitis B surface antigen (HBsAg), e antigen (HBeAg), and HBV DNA were measured. The levels of intracellular HBV DNA and mRNA were determined by using Southern blot or reverse-transcription-PCR, respectively. Intracellular distribution of antigen were measured by Western blot. A 1995μmol/L concentration of the commercially-available hepatitis B drug, adefovir dipivoxil (ADV), was required to achieve 50% cytotoxicity against cultured cells (CC50) by day nine; in contrast, only 1747μmol/L of Compound 1 was required for the same result. Treatment of HepG2.2.15 cells with Compound 1 effectively suppress the secretion of HBV antigens and HBV DNA in a dose-dependent and time-dependent manner. IC50 values were determined to be 80μmol/L for HBsAg, 75μmol/L for HBeAg and 3.72μmol/L for supernatant HBV DNA at day nine post-exposure, as opposed to 266, 296, 30.09μmol/L, respectively, for ADV. Intracellular HBV DNA, mRNA and antigen were also found to be decreased by Compound 1. The same dose of ADV yielded a significantly less robust inhibitory effect. Compound 1 can clear HBV from hepatic cells and may represent a therapeutic agent to treat HBV infection.


title: Severe Acute Respiratory Syndrome Beyond Amoy Gardens: Completing the Incomplete Legacy

text: The temporal and spatial distributions of the 2003 severe acute respiratory syndrome (SARS) outbreak in Amoy Gardens of Hong Kong was reexamined using all confirmed cases. The outbreak actually extended to nearby residential complexes. Airborne spread was the most likely explanation, and the SARS coronavirus could have spread over a distance of 200 m.


title: Thrombocytopenia is independently associated with poor outcome in patients hospitalized for COVID‐19

text: Thrombocytopenia (defined by platelet count <150 x 10(9)/L) has been observed in up to 36% of patients with the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus responsible for Coronavirus disease 2019 (COVID‐19; Guan et al, 2020). In this setting, thrombocytopenia is usually mild, caused by platelet activation and consumption (Thachil, 2020; Pavord et al, 2020). In a recent paper published in the British Journal of Haematology, Jiang et al. conducted a meta‐analysis of 31 studies involving 7613 participants and found a significant association between thrombocytopenia and severe COVID‐19 hospitalized patients or poor outcome in this setting (Jiang et al, 2020). However, other clinical, biological and radiological factors strongly impact COVID‐19 outcome. Whether thrombocytopenia is independently associated to poor outcome in this population is unknown. This study was aimed at addressing this question.


title: SARS-CoV-2 Infection Leads to Neurological Dysfunction

text: A number of neurological disease complications have been seen following infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While most person with COVID-19 respiratory disease demonstrate headache, nausea and vomiting, up to 40% present also experience dizziness, confusion, cerebrovascular disease, muscle pain, ataxia and seizures. Loss of taste and smell, defects in visual acuity and pain occur in parallel. Such central nervous system (CNS) signs and symptoms linked to laboratory-confirmed SARS-CoV-2 infection is often life threatening. Health care providers currently evaluating patients with neurologic symptoms need consider COVID-19 in any differential diagnosis. These considerations will facilitate prompt testing, isolation and prevention of viral transmission speeding best clinical outcomes. [Figure: see text]


title: Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites

text: The outbreak of coronavirus disease (COVID-19) in China caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. It is currently no specific viral protein targeted therapeutics yet. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein is yet to be clear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although overall structure is similar with other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the β-sheet core. Complemented by in vitro binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.


title: Triaging Total Hip Arthroplasty During the COVID-19 Pandemic

text: PURPOSE OF REVIEW: The purpose of this review was to evaluate the available literature to determine what may be considered urgent indications for total hip arthroplasty, in the unprecedented setting of the worldwide COVID-19 pandemic. RECENT FINDINGS: SARS-CoV-2 is a novel coronavirus currently presenting in the form of a global pandemic, referred to as COVID-19. In this setting, multiple states have issued executive orders prohibiting “elective” surgery, including arthroplasty, in order to preserve healthcare resources. However, during this unprecedented reduction in elective surgery, there is likely to be some controversy as to what constitutes a purely “elective” procedure, versus an “urgent” procedure, particularly regarding hip arthroplasty. We reviewed the available literature for articles discussing the most commonly encountered indications for primary, conversion, and revision hip arthroplasty. Based upon the indications discussed in these articles, we further stratified these indications into “elective” versus “urgent” categories. SUMMARY: In patients presenting with hip arthroplasty indications, the decision to proceed urgently with surgery should be based upon (a) the potential harm incurred by the patient if the surgery was delayed and (b) the potential risk incurred by the patient in the context of COVID-19 if surgery was performed. The authors present a decision-making algorithm for determining surgical urgency in three patients who underwent surgery in this context. Urgent total hip arthroplasty in the setting of the COVID-19 pandemic is a complex decision-making process, involving clinical and epidemiological factors. These decisions are best made in coordination with a multidisciplinary committee of one’s peers. Region-specific issues such as hospital resources and availability of PPE may also inform the decision-making process.


title: Natural antiviral compound silvestrol modulates human monocyte‐derived macrophages and dendritic cells

text: Outbreaks of infections with viruses like Sars‐CoV‐2, Ebola virus and Zika virus lead to major global health and economic problems because of limited treatment options. Therefore, new antiviral drug candidates are urgently needed. The promising new antiviral drug candidate silvestrol effectively inhibited replication of Corona‐, Ebola‐, Zika‐, Picorna‐, Hepatis E and Chikungunya viruses. Besides a direct impact on pathogens, modulation of the host immune system provides an additional facet to antiviral drug development because suitable immune modulation can boost innate defence mechanisms against the pathogens. In the present study, silvestrol down‐regulated several pro‐ and anti‐inflammatory cytokines (IL‐6, IL‐8, IL‐10, CCL2, CCL18) and increased TNF‐α during differentiation and activation of M1‐macrophages, suggesting that the effects of silvestrol might cancel each other out. However, silvestrol amplified the anti‐inflammatory potential of M2‐macrophages by increasing expression of anti‐inflammatory surface markers CD206, TREM2 and reducing release of pro‐inflammatory IL‐8 and CCL2. The differentiation of dendritic cells in the presence of silvestrol is characterized by down‐regulation of several surface markers and cytokines indicating that differentiation is impaired by silvestrol. In conclusion, silvestrol influences the inflammatory status of immune cells depending on the cell type and activation status.


title: Changing worlds of revenue management

text: Vinod sets out how the airline industries' cashflow has been effected by COVID-19 pandemic, setting out new rules for APTCo rule categories Whereas Oance discusses how airlines presently optimize fare structure based upon expertise and market awareness of its pricing professionals Whereas in the future, a new world of new distribution capability (NDC)-enabled airlines, the pricing function is likely to see a tremendous science evolution, enlarging its scope beyond its historical focus on ticket pricing Artificial intelligence will help Pricing to enrich the offer creation with willingness to pay forecasting models, true dynamic pricing of bundles or even continuous pricing models, building adaptive models of customer segmentation and optimizing the prices, and their respective rules for each offer made Narwal and Nayak investigate customers' evaluation of the offered price suggestion for a consumer durable sold under Pay-What-You-Want pricing (PWYW) Findings demonstrated that the external reference price (ERP) has greater impact on price assessments and perceived price fairness than internal reference price (IRP) The inclusion of two mediators, i e , price instability and interpurchase time interval has accounted for the fundamental attributes of PWYW price settings and consumer durable product shopping Cab aggregators are making rapid waves across India and the world Ola and Uber have seized the opportunity with both the hands through startup and stand up India campaign to tap the potential of the Indian market Anirvinna and Deshmukh critically evaluate the pricing strategy employed by and Ola and Uber in India, from an economic perspective The lot-sizing problem with a defective processing system is one of the most widely known inventory control models that can be regarded as the generalized form of the economic production quantity (EPQ) Nobil and colleagues paper proposes a model for lot-sizing problem within a defective processing system Optimal queuing system design includes deciding about some variables such as location, capacity, price, and delivery time In order to develop an optimized system, it is essential to solve the optimization problem for all the decision variables simultaneously Teimoury and colleagues consider a make-to-order system and conclude that by knowing customers and effective factors on their utility, profit can increase This research focuses on entertainment subscription platforms (e g , movies, books, and music) and the personalizing of services through recommender systems Recommender systems offer individual users a personalized assortment (i e , a subset of possible alternatives) based on each user's previous search and selection history, as well as stated or revealed preferences Mushtaque and Pazour develop a random utility model extending previous studies in the problem dilemma Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations


Index to volume 42, July–December 2003


title: A missing link between SARS‐CoV‐2 and the eye?: ACE2 expression on the ocular surface

text: We applaud Lange et al.1 for their extensive efforts to analyse entry factors for severe acute respiratory syndrome coronavirus (SARS-CoV-2) into conjunctival epithelial cells covering the ocular surface, which is an important albeit controversially discussed issue1,2 . This article is protected by copyright. All rights reserved.


Covid-19: Selected NHS patients will be treated with remdesivir


title: Human complement receptor type 1 (CR1) protein levels and genetic variants in chronic Chagas Disease

text: Complement is an essential element in both innate and acquired immunity contributing to the immunopathogenesis of many disorders, including Chagas Disease (CD). Human complement receptor 1 (CR1) plays a role in the clearance of complement opsonized molecules and may facilitate the entry of pathogens into host cells. Distinct CR1 exon 29 variants have been found associated with CR1 expression levels, increased susceptibility and pathophysiology of several diseases. In this study, CR1 plasma levels were assessed by ELISA and CR1 variants in exon 29 by sequencing in a Brazilian cohort of 232 chronic CD patients and 104 healthy controls. CR1 levels were significantly decreased in CD patients compared to controls (p < 0.0001). The CR1 rs1704660G, rs17047661G and rs6691117G variants were significantly associated with CD and in high linkage disequilibrium. The CR1*AGAGTG haplotype was associated with T. cruzi infection (p = 0.035, OR 3.99, CI 1.1-14.15) whereas CR1*AGGGTG was related to the risk of chagasic cardiomyopathy (p = 0.028, OR 12.15, CI 1.13-113). This is the first study that provides insights on the role of CR1 in development and clinical presentation of chronic CD.


title: Elevated transmission of upper respiratory illness among new recruits in military barracks in Thailand

text: BACKGROUND: New recruits within military barracks present conditions favorable for the spread of respiratory pathogens. However, respiratory pathogen transmission in such confined settings in the tropics has not been well studied. METHODS: Recruits in four successive Royal Thai Army basic training classes living in military barracks were monitored for the symptoms of influenza-like illness (ILI) or upper respiratory illness (URI). Classes 1 and 2 were also monitored after basic training. Nasal/throat swabs from acute illnesses were collected and tested by influenza RT-PCR (all four classes). In addition, class 1 had multiplex PCR performed along with the analysis of bed locations within the barracks. RESULTS: Influenza-like illness/upper respiratory illness rates ranged from 4·7 to 6·9 per 100 recruit-weeks in the four classes and generally decreased during the course of basic training (P < 0·05 in three of four classes). Rates during basic training were 1·7 (95% CI: 1·29, 2·29) and 2·5 (95% CI: 1·5, 4·1) times higher than after basic training (classes 1 and 2, respectively). In class 1, coronavirus, parainfluenza virus, and rhinovirus were the most commonly identified respiratory pathogens; only one influenza PCR-positive infection was detected in all four classes. Bed locations of URI/ILI cases in class 1 tended to be in closer proximity to each other. CONCLUSION: Basic training recruits in military barracks in the tropics had high rates of acute respiratory illnesses with illness patterns consistent with external seeding followed by substantial internal transmission. Our findings may contribute to control measures in similar confined settings both within and outside the military.


title: Transboundary spread of pig diseases: the role of international trade and travel

text: As globalization increases the interconnectedness between nations, economies, and industries, the introduction of diseases will continue to remain a prominent threat to the livestock sector and the trade of animals and animal products, as well as the livelihoods of farmers, food security and public health. The global pig sector, with its size and dichotomy between production type and biosecurity level, is particularly vulnerable to the transmission of transboundary animal diseases such as African and classical swine fever, foot and mouth disease, or porcine reproductive and respiratory syndrome. All of the above pose a constant threat to swine health, mainly as a result of both formal and informal international trade. Inspired in the risk assessment methodology, this paper classifies and provides an overview of the different pig disease introduction and exposure pathways, illustrated with abundant examples. Introduction pathways are classified as formal international trade (by product), informal international trade (by product), and spread through fomites. Formal trade of pigs and pork products is regulated by legislation and measures protecting animal populations from exotic diseases. Much more difficult to control is the transboundary swine disease transmission originating through informal trade, which entails illegal smuggling, but also the informal cross-border transfer of animals and products for personal use or within informal market chains. Meat products are most commonly mentioned, although fomites have also played a role in some cases, with live pigs, being more difficult to smuggle playing a role less frequently. The main exposure pathways are also described with the oral route playing a prominent role. Risk assessments can aid in the identification of pathways of pathogen introduction and exposure. However, quantitative information on informal disease introduction pathways remains very scarce and often incomplete, making it difficult to estimate the actual magnitudes of risks. Nevertheless, this knowledge is deemed essential to set up risk based awareness, prevention and surveillance programs that correspond to reality.


title: IL-12 deficiency transiently improves viral clearance during the late phase of respiratory tract infection with influenza A virus in mice

text: Abstract T helper 1-driven immune responses have been implicated in protective immunity against viral infections. Interleukin (IL)-12 is a heterodimeric proinflammatory cytokine formed by a p35 and a p40 subunit that can induce differentiation of naïve T cells towards a T helper 1-response. To determine the role of IL-12 in respiratory tract infection with influenza, p35 gene deficient (p35−/−) and normal wild type mice were intranasally infected with influenza A virus. IL-12 p35−/− mice displayed a transiently enhanced rather than an impaired viral clearance, as indicated by a 10-fold reduction in viral loads on day 8 after infection. Although interferon-γ levels were significantly lower in the lungs of IL-12 p35−/− mice, their cellular immune responses were not altered, as reflected by similar T cell CD69 expression and influenza-specific T cell recruitment. Our data indicate that endogenous IL-12 impairs viral clearance during the late phase of influenza A virus infection in mice.


title: Design, synthesis, antitubercular and antiviral properties of new spirocyclic indole derivatives

text: ABSTRACT: A series of indole-based spirothiazolidinones have been designed, synthesized and evaluated, in vitro, for their antitubercular, antiviral, antibacterial, and antifungal activities. The structures of the new compounds were established by IR, (1)H NMR, (13)C NMR (proton decoupled, APT, and DEPT), electrospray ionization mass spectrometry, and microanalysis. Compounds bearing a phenyl substituent at position 8 of the spiro ring, exhibited significant antitubercular activity against Mycobacterium tuberculosis H37Rv ATCC 27294 at concentrations of 3.9 and 7.8 µM. Still, some of the tested compounds displayed activity on mycobacteria with MIC values of 16 and 31 µM. Four of the indole-spirothiazolidinone derivatives were found to be moderately active against Punta Toro virus, yellow fever virus or Sindbis virus in Vero cells. The antiviral EC(50) values were in the range of 1.9–12 µM and the selectivity index (ratio of cytotoxic to antivirally effective concentration) was above 10 in some cases. The most potent effect was seen with the compound that is methylated at positions 2 and 8 of the spirothiazolidinone system. GRAPHIC ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00706-019-02457-9) contains supplementary material, which is available to authorized users.


title: MicroR‐9‐5p suppresses EV71 replication through targeting NFκB of the RIG‐I‐mediated innate immune response

text: Accumulating evidence demonstrates that there is a causative link between hsa‐microRNA‐9‐5p (miR‐9) and pathophysiological processes. Enterovirus 71 (EV71) has been found to contribute to numerous severe clinical symptoms which result in death. The exact mechanism by which EV71 influences miR‐9 expression is unknown, and the relationship between miR‐9 and EV71 is still unclear. Here, miR‐9 expression was found to be impaired upon EV71 infection in several cell lines and in an EV71 infection mouse model. Additionally, we confirmed that EV71 infection induces robust expression of pro‐inflammatory cytokines (TNF‐α, IL‐6, and IL‐1) and interferons (IFN‐α and IFN‐β). Overexpression of miR‐9 attenuated EV71 proliferation and reduced protein and gene expressions of virion protein 1 (VP1) of EV71. Furthermore, we observed that the inflammation caused by EV71 infection was restored to a moderate level via miR‐9 overexpression. Nuclear factor kappa B (NFκB) in the retinoic acid‐induced gene 1 (RIG‐I) signaling pathway, but not interferon regulating factor 3 (IRF3), was significantly decreased and inactivated by ectopic miR‐9 expression. Moreover, in mouse infection experiments, administration of miR‐9 agomirs caused a significant decrease in VP1 levels and pro‐inflammatory cytokine production after viral inoculation. Taken together, the present data demonstrate that miR‐9 exerts an anti‐EV71 effect in cells and a mouse model via mediating NFκB activity of the RIG‐I signal pathway, thereby suggesting a new candidate for antiviral drug development.


title: VIRUSES OF THE LUNG

text: Respiratory viruses include rhinoviruses and enteroviruses (Picornaviridae), influenza viruses (Orthomyxoviridae), parainfluenza, metapneumoviruses and respiratory syncytial viruses (Paramyxoviridae), coronaviruses (Coronaviridae), and several adenoviruses. With the exception of adenoviruses, all possess an RNA genome. They are usually transmitted by direct hand to surface to hand contact and/or aerosol inhalation, and replicate in both upper and lower airways. Cellular and humoral immunity are both activated in response to respiratory viral infections as well as neural pathways, which contribute to distant inflammatory effects. Respiratory viruses are responsible for a wide variety of clinical syndromes including the common cold, acute otitis media, laryngitis, sinusitis, pneumonia, bronchiolitis, influenza, and exacerbations of asthma and chronic obstructive pulmonary disease. Diagnosis of respiratory viral infections is primarily clinical and is further supported by laboratory techniques such as antigen detection, culture, serology and more recently nucleic acid detection. Preventive strategies are based on avoidance of risk factors and vaccination when indicated. Treatment modalities include over-the-counter and non-specific remedies along with a small number of specific antiviral medications such as the influenza neuraminidase inhibitors.


title: European Union training programme for tuberculosis laboratory experts: design, contribution and future direction

text: BACKGROUND: Tuberculosis (TB) control programmes rely heavily on laboratories to support both clinical care and public health. Qualified personnel with adequate technical and managerial skills comprise an integral component of any quality assured laboratory. Training a new generation of TB laboratory specialists was identified as a critical priority in the European Union /European Economic Area (EU/EEA). A tailored training programme for TB reference laboratory professionals was developed and implemented within the European Reference Laboratory Network for Tuberculosis to increase the pool of technical experts available to step into leadership roles in the TB laboratory community. Three cohorts of selected laboratory specialists participated in a series of trainings from 2009 to 2016. METHODS: We conducted an evaluation of the training programme using a structured questionnaire administered via the EUSurvey website, with the aim of documenting the benefits and contribution as well as suggesting improvements and future direction of the programme. All graduated participants and all current ERLTB-Net members were invited to participate in the online survey and descriptive quantitative analysis was performed. RESULTS: The evaluation found significant benefits for both the participants and the participants’ institutions, with improvements being reported in laboratory practices and management including implementation of new diagnostic techniques and career progression for participants. The training programme differed from other international and European initiatives in a number of important ways; the curriculum is unique in the scope and range of topics covered; the programme targets senior level professionals and future directors; cohorts were limited to 8–10 participants; and the programme involved a number of workshops (5–7) taking place over a two-year period. Relationships and collaborations established between individuals and institutions were valued as an important success of the initiative. Suggestions on how the impact of the programme could be enhanced included equipping participants to perform laboratory assessments in low-resource settings outside the EU, thus bolstering global TB control. CONCLUSION: Based on the findings presented the training programme has proved to be successful in developing leadership, expertise, partnerships and networks to support TB laboratories and has contributed significant benefits to strengthening European National Reference laboratories in the fight against TB.


title: Let’s talk about sex in the context of COVID-19

text: In recent months, the coronavirus disease 2019 (COVID-19) pandemic has sent many countries into crisis. Studies have shown that this virus causes worse outcomes and a higher mortality in men than in women. It has been recognized that sex can affect the immune response to a pathogenic agent, as well as the susceptibility for some respiratory diseases. These different responses in males and females may be related to the actions of sex hormones. Angiotensin-converting enzyme 2 (ACE2) acts as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. The expression of ACE2 is influenced by sex hormones; therefore, we discuss in this article that this could be one of the reasons why COVID-19 is more prevalent in men than in women.


What’s Important: COVID-19—Helpers, Not Heroes


Anesthesiology, the Tragedy of the Commons, and Coronavirus Disease 2019


title: Chinese immigrant parents’ vaccination decision making for children: a qualitative analysis

text: BACKGROUND: While immunization coverage rates for childhood routine vaccines in Hong Kong are almost 100%, the uptake rates of optional vaccines remain suboptimal. Understanding parental decision-making for children’s vaccination is important, particularly among minority groups who are most vulnerable and underserved. This study explored how a subsample of new immigrant mothers from mainland China, a rapidly-growing subpopulation in Hong Kong, made decisions on various childhood and adolescent vaccines for their offspring, and identified key influences affecting their decision making. METHODS: Semi-structured in-depth interviews were conducted with 23 Chinese new immigrant mothers recruited by purposive sampling. All interviews were audio-taped, transcribed and analyzed using a Grounded Theory approach. RESULTS: Participants’ conversation revealed five underlying themes which influenced parents’ vaccination decision-making: (1) Institutional factors, (2) Insufficient vaccination knowledge and advice, (3) Affective impacts on motivation, (4) Vaccination barriers, and (5) Social influences. The role of social norms appeared overwhelmingly salient influencing parents’ vaccination decision making. Institutional factors shaped parent’s perceptions of vaccination necessity. Fear of vaccine-targeted diseases was a key motivating factor for parents adopting vaccination. Insufficient knowledge about vaccines and targeted diseases, lack of advice from health professionals and, if provided, suspicions regarding the motivations for such advice were common issues. Vaccination cost was a major barrier for many new immigrant parents. CONCLUSIONS: Social norms play a key role influencing parental vaccination decision-making. Insight gained from this study will help inform healthcare providers in vaccination communication and policymakers in future vaccination programme.


A “Syndromic” Approach for Diagnosing and Managing Travel-Related Infectious Diseases in Children


title: Vaccination antivirale et immunité muqueuse respiratoire Un concept séduisant pour des résultats encore décevants

text: Points essentiels • Les surfaces muqueuses de l’arbre respiratoire constituent une porte d’entrée très importante et un site critique pour la réponse immune. Les principaux anticorps sécrétés localement appar-tiennent à l’isotype IgA (S-Ig A). Les cellules effectrices qui dominent au niveau de la muqueuse ne sont pas des cellules IgA de type B, mais les lymphocytes T qui peuvent représenter jusqu’à 80 % de la totalité des populations lymphocytaires de la muqueuse. • L’immunoprophylaxie par voie muqueuse constitue une approche intéressante pour contrôler les infections acquises par cette voie. Des immunoglobulines spécifiques administrées localement peuvent prévenir des infections virales comme cela a été démontré pour le virus respiratoire syncytial; mais les quantités d’anticorps nécessaires pour être actives sont très importantes et difficiles à obtenir. • Parmi les facteurs susceptibles d’induire une réponse immune muqueuse et une immunité à médiation cellulaire, on trouve la voie orale ou respiratoire et des virus réplicatifs. • Très peu de vaccins antiviraux muqueux ont été développés; le seul exemple pour les virus respiratoires reste le vaccin grippal atténué administré par voie nasale. D’autres vaccins commercialisés par voie parentérale ont été utilisés expérimentalement par voie nasale, qu’il s’agisse de vaccins vivants (varicelle, rougeole) ou inactivés (grippe injectable); ils n’induisent par cette voie inhabituelle qu’une réponse locale modérée. • La voie muqueuse ne constitue pas une voie essentielle et incontournable pour élaborer un vaccin actif contre des virus respiratoires. L’exemple du vaccin grippe atténué administré par voie nasale est prometteur pour l’avenir de la vaccination par voie muqueuse. Key points • Mucosal surfaces of the respiratory tract represent a major portal of entry for most human viruses and a critical component of the mammalian immunologic repertoire. The major antibody isotype in external secretions is secretory immunoglobin A (S-IgA). The major effector cells in mucosal surfaces, however, are not IgA B cells, but T lymphocytes, which may account for up to 80% of the mucosal lymphoid cell population. • Mucosal immunoprophylaxis is theoretically an important approach to control infections acquired through these portals. Passive antibodies can protect against mucosal viral infections, as shown for respiratory syncytial virus, but very high quantities of passive antibodies are needed to restrict virus replication on mucosal surface. • Factors likely to induce mucosal antibody and cell-mediated immune responses include oral or respiratory routes of immunization and active (effectively replicating) vaccine agents. • Very few antiviral vaccines have been developed to protect the mucosal surface of the respiratory tract, and only an attenuated influenza virus vaccine uses the nasal route. Other vaccines, approved for parenteral use, have been administered experimentally by the nasal route; these include active (replicating) and inactive (nonreplicating) vaccines. By this route they induce only a moderate local mucosal response. • Neither the development of mucosal immunity nor the administration of vaccines via the mucosal route is essential for control or prevention of most respiratory viral infections and diseases acquired through the respiratory tract. Nonetheless, the example of the live attenuated intranasal influenza vaccine, which induces both systemic and local immune response, is promising for the future of mucosal immunization against respiratory viral infections.


title: Evolution and resolution of brain involvement associated with SARS- CoV2 infection: A close Clinical – Paraclinical follow up study of a case

text: The new severe acute respiratory syndrome- coronavirus 2 is reported to affect the nervous system. Among the reports of the various neurological manifestations, there are a few documented specific processes to explain the neurological signs. We report a para-infectious encephalitis patient with clinical, laboratory, and imaging findings during evolution and convalescence phase of coronavirus infection. This comprehensive overview can illuminate the natural history of similar cases. As the two previously reported cases of encephalitis associated with this virus were not widely discussed regarding the treatment, we share our successful approach and add some recommendations about this new and scarce entity.


title: Neutrophil extracellular traps and thrombosis in COVID-19

text: Here, we report on four patients whose hospitalizations for COVID-19 were complicated by venous thromboembolism (VTE). All demonstrated high levels of D-dimer as well as high neutrophil-to-lymphocyte ratios. For three patients, we were able to test sera for neutrophil extracellular trap (NET) remnants and found significantly elevated levels of cell-free DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3. Neutrophil-derived S100A8/A9 (calprotectin) was also elevated. Given strong links between hyperactive neutrophils, NET release, and thrombosis in many inflammatory diseases, the potential relationship between NETs and VTE should be further investigated in COVID-19.


title: Towards a ‘virtual’ world: Social isolation and struggles during the COVID‐19 pandemic as single women living alone

text: This article is a personal reflection of how the current COVID‐19 pandemic affects our working lives and wellbeing, as single female academics who live alone in the UK. We offer a dialogue of our daily lives of being confined at home with lockdown measures extended. In particular, we focus on the experience of, and coping with, isolation and loneliness. Is isolation making us more socially connected? Through ‘virtual’ working and changing learning environments for us as teachers and learners, we explore changes in our working life and subsequent changes in the domestic environment. By capturing our lived experiences, we create an intellectual and safe space to voice our emotional struggles — as ‘invisible’ isolated individuals containing and consuming loneliness on our own. We foster alternative conversations as to how we might engender new perspectives from single female academics to combat social isolation in the workplace.


title: Outcome of trauma and orthopaedic surgery at a UK District General Hospital during the Covid-19 pandemic

text: INTRODUCTION: There are suggestions that elective surgery performed during the incubation period of COVID-19 infection may cause an immediate impairment of cell-mediated immunity, leading to high morbidity and mortality. However is contrasting data about the associated mortality. Since the outbreak, our unit has maintained a prospective database recording Trauma and Orthopaedic surgical activity. Our aim was to share our experience of the first 3 months with prospective data on outcome of essential surgery during the covid-19 peak. Our focus in this report was on the mortality rate as services begin to open. Methods: We prospectively collected data during the peak of the pandemic in the UK, for fracture neck of femur patients (NOF) the most commonly performed surgical procedure and the most vulnerable during this period. We compared this Covid-19 cohort of NOFs against a cohort of NOF's during the same time in 2019 and another cohort of NOF's in 2020 outside the lockdown period to compare mortality rates and give a broader perspective. RESULTS: During the period March 1, 2020 to May 31, 2020, total of 206 patients were operated. Ninety-four fracture NOF and another one hundred twelve essential surgical procedures were performed. In the NOF cohort, there were nine patients that died. Three of them were covid-19 positive, one was not tested and the rest five were covid-19 negative. There was no mortality reported in the non NOF group. Conclusion: In our unit, during the lock down period, mortality rate in patients undergoing fracture NOF was not significantly different from a similar cohort earlier in the year and similar period last year. We have not observed any mortality, to date in the Non NOF procedures carried out.


title: A discussion of irrational stockpiling behaviour during crisis

text: Abstract One of the ubiquitous human behaviours observed in natural disasters and humanitarian crisis is irrational stockpiling (also known as hoarding or panic buying). Limited, distorted and exaggerated information during crisis disturbs people's judgement and results in aberrant actions which can be explained with economics and psychology theories. The objective of this paper is to examine the perplexing stockpiling phenomena during disasters like COVID-19 pandemic and discuss its immediate and long-term impact on economy, society and local communities.


title: Acute lung injury and acute respiratory distress syndrome: experimental and clinical investigations

text: Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) can be associated with various disorders. Recent investigation has involved clinical studies in collaboration with clinical investigators and pathologists on the pathogenetic mechanisms of ALI or ARDS caused by various disorders. This literature review includes a brief historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the long-term experimental studies and clinical investigations from our laboratory, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS.


Paediatric airway infections


Made-to-measure Microbes


title: Detection and characterization of diverse alpha- and betacoronaviruses from bats in China

text: Bats have been implicated as important reservoir hosts of alpha- and betacoronaviruses. In this study, diverse coronaviruses (CoVs) were detected in 50 of 951 (positive rate 5.3%) intestinal specimens of eight bat species collected in four provinces and the Tibet Autonomous Region of China by pan-coronavirus RT-PCR screening. Based on 400-nt RNA-dependent RNA polymerase (RdRP) sequence analysis, eight belonged to genus Alphacoronavirus and 42 to Betacoronavirus. Among the 50 positive specimens, thirteen gave rise to CoV full-length RdRP gene amplification for further sequence comparison, of which three divergent sequences (two from a unreported province) were subjected to full genome sequencing. Two complete genomes of betacoronaviruses (JTMC15 and JPDB144) and one nearly-complete genome of alphacoronavirus (JTAC2) were sequenced and their genomic organization predicted. The present study has identified additional numbers of genetically diverse bat-borne coronaviruses with a wide distribution in China. Two new species of bat CoV, identified through sequence comparison and phylogenetic analysis, are proposed. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s12250-016-3727-3 and is accessible for authorized users.


The not-so-infinite malleability of RNA viruses: Viral and cellular determinants of RNA virus mutation rates


Letter from the United States: A New York experience with COVID‐19


title: Inhibition of genes expression of SARS coronavirus by synthetic small interfering RNAs

text: RNA interference (RNAi) is triggered by the presence of a double-stranded RNA (dsRNA), and results in the silencing of homologous gene expression through the specific degradation of an mRNA containing the same sequence. dsRNA-mediated RNAi can be used in a wide variety of eucaryotes to induce the sequence-specific inhibition of gene expression. Synthetic 21-23 nucleotide (nt) small interfering RNA (siRNA) with 2 nt 3′ overhangs was recently found to mediate efficient sequence-specific mRNA degradation in mammalian cells. Here, we studied the effects of synthetic siRNA duplexes targeted to SARS coronavirus structural proteins E, M, and N in a cell culture system. Among total 26 siRNA duplexes, we obtained 3 siRNA duplexes which could sequence-specifically reduce target genes expression over 80% at the concentration of 60 nM in Vero E6 cells. The downregulation effect was in correlation with the concentrations of the siRNA duplexes in a range of 0∼60 nM. Our results also showed that many inactive siRNA duplexes may be brought to life simply by unpairing the 5' end of the antisense strands. Results suggest that siRNA is capable of inhibiting SARS coronavirus genes expression and thus may be a new therapeutic strategy for treatment of SARS.


title: Overall synthesis and conclusions

text: Abstract This chapter first systematically summarizes the most important findings and policy implications of each of the chapters “Factors affecting traffic flow efficiency implications of connected and autonomous vehicles: A review and policy recommendations” by Narayanan et al.; “Automated bus systems in Europe: A systematic review of passenger experience and road user interaction” by Heikoop et al.; “Cyber security and its impact on CAV safety: Overview, policy needs and challenges” by Katrakazas et al.; “Cybersecurity certification and auditing of automotive industry” by Mateo Sanguino et al.; “The wider use of autonomous vehicles in non-commuting journeys” by Kimber et al.; “Policy implications of the potential carbon dioxide (CO2) emission and energy impacts of highly automated vehicles” by Annema; “Potential health and well-being implications of autonomous vehicles” by Singleton et al.; “Data protection in a GDPR era: An international comparison of implications for autonomous vehicles” by Costantini et al.; “Ethical issues concerning automated vehicles and their implications for transport” by Dogan et al.; “Governance cultures and sociotechnical imaginaries of self-driving vehicle technology: Comparative analysis of Finland, UK and Germany” by Mladenović et al.; “Wider implications of autonomous vessels for the maritime industry: Mapping the unprecedented challenges” by Ghaderi; “The potential for automation to transform urban deliveries: Drivers, barriers and policy priorities” by Paddeu and Parkhurst. Next it synthesizes the overall findings and policy implications, and discusses future avenues for policy making and research. A first conclusion is that the chapters make clear that the ranges in policy relevant implications of AVs, within the scope of each chapter/topic, are still relatively broad. Secondly we conclude that research that is conceptually rich is more valuable for policy making. Thirdly we hypothesize that context matters for the uptake, impacts, and specific system design characteristics of real world AV implementation. Fourth we conclude that research on the global south has been limited so far. Fifth we argue that AVs, shared vehicles and electric vehicles (EVs) might stimulate each other in a positive way, in all directions. Finally we conclude that AVs will have wider societal implications, such as in the area of land use, accessibility, social exclusion, governmental expenditures, the labor market, and the environment. The more indirect the effects of AVs are, the more difficult they are to understand. For policy making a first conclusion is that the issues of ethics, cyber security and data protection deserve way more attention than they currently get. We also conclude that future motorway network extensions might not be no-regret anymore, because of possible congestion reductions due to AVs, but also because of decreasing marginal values of time. Finally we argue that countries that introduce AVs later than other countries can learn a lot from the real world experiences elsewhere.


title: Model based approach for estimating the dosage regimen of indomethacin a potential antiviral treatment of patients infected with SARS CoV-2

text: To face SARS-CoV-2 pandemic various attempts are made to identify potential effective treatments by repurposing available drugs. Among them, indomethacin, an anti-inflammatory drug, was shown to have potent in-vitro antiviral properties on human SARS-CoV-1, canine CCoV, and more recently on human SARS-CoV-2 at low micromolar range. Our objective was to show that indomethacin could be considered as a promising candidate for the treatment of SARS-CoV-2 and to provide criteria for comparing benefits of alternative dosage regimens using a model-based approach. A multi-stage model-based approach was developed to characterize % of recovery and viral load in CCoV-infected dogs, to estimate the PK of indomethacin in dog and human using published data after administration of immediate (IR) and sustained-release (SR) formulations, and to estimate the expected antiviral activity as a function of different assumptions on the effective exposure in human. Different dosage regimens were evaluated for IR formulation (25 mg and 50 mg three-times-a-day, and 25 mg four-times-a-day), and SR formulation (75 mg once and twice-a-day). The best performing dosing regimens were: 50 mg three-times-a-day for the IR formulation, and 75 mg twice-a-day for the SR formulation. The treatment with the SR formulation at the dose of 75 mg twice-a-day is expected to achieve a complete response in three days for the treatment in patients infected by the SARS-CoV-2 coronavirus. These results suggest that indomethacin could be considered as a promising candidate for the treatment of SARS-CoV-2 whose potential therapeutic effect need to be further assessed in a prospective clinical trial. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10928-020-09690-4) contains supplementary material, which is available to authorized users.


title: Global stability for an epidemic model with applications to feline infectious peritonitis and tuberculosis

text: Abstract A general compartmental model of disease transmission is studied. The generality comes from the fact that new infections may enter any of the infectious classes and that there is an ordering of the infectious classes so that individuals can be permitted (or not) to pass from one class to the next. The model includes staged progression, differential infectivity, and combinations of the two as special cases. The exact etiology of feline infectious peritonitis and its connection to coronavirus is unclear, with two competing theories – mutation process vs multiple virus strains. We apply the model to each of these theories, showing that in either case, one should expect traditional threshold dynamics. A further application to tuberculosis with multiple progression routes through latency is also presented.


COVID‐19 and its implications for Dermatology and Venereology


title: CO-RADS – A categorical CT assessment scheme for patients with suspected COVID-19: definition and evaluation

text: PURPOSE: To introduce the COVID-19 Reporting and Data System (CO-RADS) for standardized assessment of pulmonary involvement of COVID-19 on non-enhanced chest CT and report its initial interobserver agreement and performance. METHODS: The Dutch Radiological Society (NVvR) developed CO-RADS based on other efforts for standardization, such as Lung-RADS or BI-RADS. CO-RADS assesses the suspicion for pulmonary involvement of COVID-19 on a scale from 1 (very low) to 5 (very high). The system is meant to be used in patients presenting with moderate to severe symptoms of COVID-19. The system was evaluated using 105 chest CTs of patients admitted to the hospital with clinical suspicion of COVID-19 in whom RT-PCR was performed (62 +/- 16 years, 61 men, 53 with positive RT-PCR). Eight observers assessed the scans using CO-RADS. Fleiss’ kappa was calculated, and scores of individual observers were compared to the median of the remaining seven observers. The resulting area under the receiver operating characteristics curve (AUC) was compared to results from RT-PCR and clinical diagnosis of COVID-19. RESULTS: There was absolute agreement among observers in 573 (68.2%) of 840 observations. Fleiss’ kappa was 0.47 (95% confidence interval (CI) 0.45-0.47), with the highest kappa for CO-RADS categories 1 (0.58, 95% CI 0.54-0.62) and 5 (0.68, 95% CI 0.65-0.72). The average AUC was 0.91 (95% CI 0.85-0.97) for predicting RT-PCR outcome and 0.95 (95% CI 0.91-0.99) for clinical diagnosis. The false negative rate for CO-RADS 1 was 9/161 (5.6%, 95% CI 1.0-10%), and the false positive rate for CO-RADS 5 was 1/286 (0.3%, 95% CI 0-1.0%). CONCLUSIONS: CO-RADS is a categorical assessment scheme for pulmonary involvement of COVID-19 on non-enhanced chest CT providing very good performance for predicting COVID-19 in patients with moderate to severe symptoms and has a substantial interobserver agreement, especially for categories 1 and 5.


Attenuation of antibody response to SARS-CoV-2 in a patient on ocrelizumab with hypogammaglobulinemia.


title: Development and Prospective Validation of a Transparent Deep Learning Algorithm for Predicting Need for Mechanical Ventilation

text: IMPORTANCE: Objective and early identification of hospitalized patients, and particularly those with novel coronavirus disease 2019 (COVID-19), who may require mechanical ventilation is of great importance and may aid in delivering timely treatment. OBJECTIVE: To develop, externally validate and prospectively test a transparent deep learning algorithm for predicting 24 hours in advance the need for mechanical ventilation in hospitalized patients and those with COVID-19. DESIGN: Observational cohort study SETTING: Two academic medical centers from January 01, 2016 to December 31, 2019 (Retrospective cohorts) and February 10, 2020 to May 4, 2020 (Prospective cohorts). PARTICIPANTS: Over 31,000 admissions to the intensive care units (ICUs) at two hospitals. Additionally, 777 patients with COVID-19 patients were used for prospective validation. Patients who were placed on mechanical ventilation within four hours of their admission were excluded. MAIN OUTCOME(S) and MEASURE(S): Electronic health record (EHR) data were extracted on an hourly basis, and a set of 40 features were calculated and passed to an interpretable deep-learning algorithm to predict the future need for mechanical ventilation 24 hours in advance. Additionally, commonly used clinical criteria (based on heart rate, oxygen saturation, respiratory rate, FiO2 and pH) was used to assess future need for mechanical ventilation. Performance of the algorithms were evaluated using the area under receiver-operating characteristic curve (AUC), sensitivity, specificity and positive predictive value. RESULTS: After applying exclusion criteria, the external validation cohort included 3,888 general ICU and 402 COVID-19 patients. The performance of the model (AUC) with a 24-hour prediction horizon at the validation site was 0.882 for the general ICU population and 0.918 for patients with COVID-19. In comparison, commonly used clinical criteria and the ROX score achieved AUCs in the range of 0.773 - 0.782 and 0.768 - 0.810 for the general ICU population and patients with COVID-19, respectively. CONCLUSIONS and RELEVANCE: A generalizable and transparent deep-learning algorithm improves on traditional clinical criteria to predict the need for mechanical ventilation in hospitalized patients, including those with COVID-19. Such an algorithm may help clinicians with optimizing timing of tracheal intubation, better allocation of mechanical ventilation resources and staff, and improve patient care.


title: Middle East respiratory syndrome coronavirus and bat coronavirus HKU9 both can utilize GRP78 for attachment onto host cells

text: Coronavirus tropism is predominantly determined by the interaction between coronavirus spikes and the host receptors. In this regard, coronaviruses have evolved a complicated receptor-recognition system through their spike proteins. Spikes from highly related coronaviruses can recognize distinct receptors, whereas spikes of distant coronaviruses can employ the same cell-surface molecule for entry. Moreover, coronavirus spikes can recognize a broad range of cell-surface molecules in addition to the receptors and thereby can augment coronavirus attachment or entry. The receptor of Middle East respiratory syndrome coronavirus (MERS-CoV) is dipeptidyl peptidase 4 (DPP4). In this study, we identified membrane-associated 78-kDa glucose-regulated protein (GRP78) as an additional binding target of the MERS-CoV spike. Further analyses indicated that GRP78 could not independently render nonpermissive cells susceptible to MERS-CoV infection but could facilitate MERS-CoV entry into permissive cells by augmenting virus attachment. More importantly, by exploring potential interactions between GRP78 and spikes of other coronaviruses, we discovered that the highly conserved human GRP78 could interact with the spike protein of bat coronavirus HKU9 (bCoV-HKU9) and facilitate its attachment to the host cell surface. Taken together, our study has identified GRP78 as a host factor that can interact with the spike proteins of two Betacoronaviruses, the lineage C MERS-CoV and the lineage D bCoV-HKU9. The capacity of GRP78 to facilitate surface attachment of both a human coronavirus and a phylogenetically related bat coronavirus exemplifies the need for continuous surveillance of the evolution of animal coronaviruses to monitor their potential for human adaptations.


The synthetic futures of vesicular stomatitis virus


title: Evidence for mutations in SARS‐CoV‐2 Italian isolates potentially affecting virus transmission

text: Italy is the first western country suffering heavy SARS‐CoV‐2 transmission and disease impact after Covid‐19 pandemia started in China. Even though the presence of mutations on spike glycoprotein and nucleocapsid in Italian isolates has been reported, the potential impact of these mutations on viral transmission has not been evaluated. We have compared SARS‐CoV‐2 genome sequences from Italian patients with virus sequences from Chinese patients. We focussed upon three non‐synonimous mutations of genes coding for S(one) and N (two) viral proteins present in Italian isolates and absent in Chinese ones, using various bio‐informatic tools. Amino acid analysis and changes in three‐dimensional protein structure suggests the mutations reduce protein stability and, particularly for S1 mutation, the enhanced torsional ability of the molecule could favour virus binding to cell receptor(s). This theoretical interpretation awaits experimental and clinical confirmation. This article is protected by copyright. All rights reserved.


title: Anti HSV-1 Activity of Halistanol Sulfate and Halistanol Sulfate C Isolated from Brazilian Marine Sponge Petromica citrina (Demospongiae)

text: The n-butanol fraction (BF) obtained from the crude extract of the marine sponge Petromica citrina, the halistanol-enriched fraction (TSH fraction), and the isolated compounds halistanol sulfate (1) and halistanol sulfate C (2), were evaluated for their inhibitory effects on the replication of the Herpes Simplex Virus type 1 (HSV-1, KOS strain) by the viral plaque number reduction assay. The TSH fraction was the most effective against HSV-1 replication (SI = 15.33), whereas compounds 1 (SI = 2.46) and 2 (SI = 1.95) were less active. The most active fraction and these compounds were also assayed to determine the viral multiplication step(s) upon which they act as well as their potential synergistic effects. The anti-HSV-1 activity detected was mediated by the inhibition of virus attachment and by the penetration into Vero cells, the virucidal effect on virus particles, and by the impairment in levels of ICP27 and gD proteins of HSV-1. In summary, these results suggest that the anti-HSV-1 activity of TSH fraction detected is possibly related to the synergic effects of compounds 1 and 2.


Human Sialome and Coronavirus Disease-2019 (COVID-19) Pandemic: An Understated Correlation?


title: Proteome and phosphoproteome analysis of honeybee (Apis mellifera) venom collected from electrical stimulation and manual extraction of the venom gland

text: BACKGROUND: Honeybee venom is a complicated defensive toxin that has a wide range of pharmacologically active compounds. Some of these compounds are useful for human therapeutics. There are two major forms of honeybee venom used in pharmacological applications: manually (or reservoir disrupting) extracted glandular venom (GV), and venom extracted through the use of electrical stimulation (ESV). A proteome comparison of these two venom forms and an understanding of the phosphorylation status of ESV, are still very limited. Here, the proteomes of GV and ESV were compared using both gel-based and gel-free proteomics approaches and the phosphoproteome of ESV was determined through the use of TiO(2) enrichment. RESULTS: Of the 43 proteins identified in GV, < 40% were venom toxins, and > 60% of the proteins were non-toxic proteins resulting from contamination by gland tissue damage during extraction and bee death. Of the 17 proteins identified in ESV, 14 proteins (>80%) were venom toxic proteins and most of them were found in higher abundance than in GV. Moreover, two novel proteins (dehydrogenase/reductase SDR family member 11-like and histone H2B.3-like) and three novel phosphorylation sites (icarapin (S43), phospholipase A-2 (T145), and apamin (T23)) were identified. CONCLUSIONS: Our data demonstrate that venom extracted manually is different from venom extracted using ESV, and these differences may be important in their use as pharmacological agents. ESV may be more efficient than GV as a potential pharmacological source because of its higher venom protein content, production efficiency, and without the need to kill honeybee. The three newly identified phosphorylated venom proteins in ESV may elicit a different immune response through the specific recognition of antigenic determinants. The two novel venom proteins extend our proteome coverage of honeybee venom.


title: Lycorine: A prospective natural lead for anticancer drug discovery

text: Abstract Nature is the most abundant source for novel drug discovery. Lycorine is a natural alkaloid with immense therapeutic potential. Lycorine is active in a very low concentration and with high specificity against a number of cancers both in vivo and in vitro and against various drug-resistant cancer cells. This review summarized the therapeutic effect and the anticancer mechanisms of lycorine. At the same time, we have discussed the pharmacology and comparative structure-activity relationship for the anticancer activity of this compound. The researches outlined in this paper serve as a foundation to explain lycorine as an important lead compound for new generation anticancer drug design and provide the principle for the development of biological strategies to utilize lycorine in the treatment of cancers.


title: Initial performance evaluation of a spotted array Mobile Analysis Platform (MAP) for the detection of influenza A/B, RSV, and MERS coronavirus

text: Abstract Clinical samples were evaluated with the Mobile Analysis Platform (MAP) to determine platform performance for detecting respiratory viruses in samples previously characterized using clinical reverse transcriptase polymerase chain reaction assays. The percent agreement between MAP and clinical results was 97% for influenza A (73/75), 100% (21/21) for influenza B, 100% (6/6) for respiratory syncytial virus (RSV), and 80% (4/5) for negative specimens. The approximate limit of detection of the MAP was 30 copies/assay for RSV and 1500 copies/assay for Middle East respiratory syndrome coronavirus.


title: Effects of metals on sperm quality, fertilization and hatching rates, and embryo and larval survival of pejerrey fish (Odontesthes bonariensis)

text: Some species of fish have been used as bioindicators of aquatic environmental pollution all over the world. Pejerrey (Odontesthes bonariensis) was selected for the current study due to its sensitivity to pollutants and because is one of the emblematic fish species that inhabits shallow lakes of the Pampa region (Argentina). Recently, in Chascomús lake were recorded concentrations of Cd, Cr, Cu and Zn with values above the Argentine National Guidelines for the Protection of the Aquatic life. Regarding this, the aim of the present study was to investigate the effects of environmental concentrations of these metals on the sperm quality, fertilization and hatching rates, and embryo and larval survival of pejerrey. Also, the same endpoints were analyzed with concentrations ten times higher to simulate a polluted worst-case scenario. The results showed that the presence of some metals in aquatic environments reduced pejerrey sperm motility (in ~50%) and velocity (in ~30%). These results were obtained using a computer assisted sperm analyzer enforcing the application of this analysis as a tool or bioindicator of aquatic pollution. In addition, fertilization rate was diminished (in ~40%) for all treatments. Besides, the hatching rate, and embryo and larval survival were drastically affected being zero for the highest metal concentrations assessed. All together these results, showed that even lower metal concentrations can negatively affect different reproductive parameters of one of the most emblematic fish species of the Argentinean water bodies.


Training Nurses to Better Deal With Ethical Dilemmas During Pandemics


"Strategic cardiac catheterization lab staffing in the era of COVID-19"


title: Structure-Based Design with Tag-Based Purification and In-Process Biotinylation Enable Streamlined Development of SARS-CoV-2 Spike Molecular Probes

text: Biotin-labeled molecular probes, comprising specific regions of the SARS-CoV-2 spike, would be helpful in the isolation and characterization of antibodies targeting this recently emerged pathogen. To develop such probes, we designed constructs incorporating an N-terminal purification tag, a site-specific protease-cleavage site, the probe region of interest, and a C-terminal sequence targeted by biotin ligase. Probe regions included full-length spike ectodomain as well as various subregions, and we also designed mutants to eliminate recognition of the ACE2 receptor. Yields of biotin-labeled probes from transient transfection ranged from ∼0.5 mg/L for the complete ectodomain to >5 mg/L for several subregions. Probes were characterized for antigenicity and ACE2 recognition, and the structure of the spike ectodomain probe was determined by cryo-electron microscopy. We also characterized antibody-binding specificities and cell-sorting capabilities of the biotinylated probes. Altogether, structure-based design coupled to efficient purification and biotinylation processes can thus enable streamlined development of SARS-CoV-2 spike-ectodomain probes.


title: On-farm biosecurity practices and causes of preweaning mortality in Canadian commercial mink kits

text: BACKGROUND: Mink are an important animal commodity group in Canada and excessive kit mortality represents a significant loss to production. National biosecurity standards have been developed for Canadian mink farms, but it is unclear how well these standards have been implemented as there are no studies correlating management practices of mink producers with causes of death in mink kits. To that end, we surveyed Ontario mink producers on their biosecurity and management practices and conducted almost 5660 post mortem examinations on found-dead, preweaned kits to characterize mink farm biosecurity practices and causes of death in preweaned kits. RESULTS: We found that very few biosecurity and management practices were uniformly used by producers, despite good awareness of appropriate practices. Use of personal protective equipment was implemented by fewer than 50% of respondents, while control of mink shed access, disinfection of feed containers after use, and use of a rodent control program were the only practices implemented by greater than 70% of respondents. Only 18% of producers reported regular use of antimicrobials in feed or water, although 91% stated they used antimicrobials for treatment of bacterial diseases on a regular basis. On post mortem examination, no gross abnormalities were noted in 71% of the kits, 45% were thought to be stillborn or aborted, 27% had some form of abnormal fluid distribution in the body, and 2% had a congenital malformation. A subset of 69 gastrointestinal tract samples was submitted for bacterial culture, of which 45 samples yielded sufficient growth. Most interesting was the identification of Salmonella enterica serovar Heidelberg in 11% of samples. CONCLUSIONS: The results of this study will provide a benchmark for Canadian mink producers and their veterinarians, defining the areas to which greater attention should be given to ensure more rigorous biosecurity practices are in place. Ultimately, these improvements in practices may contribute to increased mink production and animal well-being. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13028-017-0326-8) contains supplementary material, which is available to authorized users.


title: Molecular epidemiology of respiratory viruses in virus-induced asthma

text: Acute respiratory illness (ARI) due to various viruses is not only the most common cause of upper respiratory infection in humans but is also a major cause of morbidity and mortality, leading to diseases such as bronchiolitis and pneumonia. Previous studies have shown that respiratory syncytial virus (RSV), human rhinovirus (HRV), human metapneumovirus (HMPV), human parainfluenza virus (HPIV), and human enterovirus infections may be associated with virus-induced asthma. For example, it has been suggested that HRV infection is detected in the acute exacerbation of asthma and infection is prolonged. Thus it is believed that the main etiological cause of asthma is ARI viruses. Furthermore, the number of asthma patients in most industrial countries has greatly increased, resulting in a morbidity rate of around 10-15% of the population. However, the relationships between viral infections, host immune response, and host factors in the pathophysiology of asthma remain unclear. To gain a better understanding of the epidemiology of virus-induced asthma, it is important to assess both the characteristics of the viruses and the host defense mechanisms. Molecular epidemiology enables us to understand the pathogenesis of microorganisms by identifying specific pathways, molecules, and genes that influence the risk of developing a disease. However, the epidemiology of various respiratory viruses associated with virus-induced asthma is not fully understood. Therefore, in this article, we review molecular epidemiological studies of RSV, HRV, HPIV, and HMPV infection associated with virus-induced asthma.


The Use of Aspirated Consonants during Speech may Increase the Transmission of COVID-19


title: SARS: clinical virology and pathogenesis

text: Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus, called the SARS coronavirus (SARS‐CoV). Over 95% of well characterized cohorts of SARS have evidence of recent SARS‐CoV infection. The genome of SARS‐CoV has been sequenced and it is not related to any of the previously known human or animal coronaviruses. It is probable that SARS‐CoV was an animal virus that adapted to human‐human transmission in the recent past. The virus can be found in nasopharyngeal aspirate, urine and stools of SARS patients. Second generation reverse transcriptase polymerase chain reaction assays are able to detect SARS‐CoV in nasopharyngeal aspirates of approximately 80% of patients with SARS within the first 3 days of illness. Seroconversion for SARS‐CoV using immunofluorescence on infected cells is an excellent method of confirming the diagnosis, but antibody responses only appear around day 10 of the illness. Within the first 10 days the histological picture is that of acute phase diffuse alveolar damage (DAD) with a mixture of inflammatory infiltrate, oedema and hyaline membrane formation. Desquamation of pneumocytes is prominent and consistent. After 10 days of illness the picture changes to one of organizing DAD with increased fibrosis, squamous metaplasia and multinucleated giant cells. The role of cytokines in the pathogenesis of SARS is still unclear.


Preparedness for COVID-19 infection prevention in Korea: Single-center experience


title: Plant Viral Proteases: Beyond the Role of Peptide Cutters

text: Almost half of known plant viral species rely on proteolytic cleavages as key co- and post-translational modifications throughout their infection cycle. Most of these viruses encode their own endopeptidases, proteases with high substrate specificity that internally cleave large polyprotein precursors for the release of functional sub-units. Processing of the polyprotein, however, is not an all-or-nothing process in which endopeptidases act as simple peptide cutters. On the contrary, spatial-temporal modulation of these polyprotein cleavage events is crucial for a successful viral infection. In this way, the processing of the polyprotein coordinates viral replication, assembly and movement, and has significant impact on pathogen fitness and virulence. In this mini-review, we give an overview of plant viral proteases emphasizing their importance during viral infections and the varied functionalities that result from their proteolytic activities.


Community‐acquired pneumonia: An Asia Pacific perspective


Safety for all: coronavirus disease 2019 pandemic and cardiac surgery: a roadmap to ‘phase’ 2


title: Refined Estimate of the Incubation Period of Severe Acute Respiratory Syndrome and Related Influencing Factors

text: Many epidemiologists have agreed that a refined estimate of the incubation period of severe acute respiratory syndrome (SARS) would need a sample size of about 200 cases and appropriate statistical methods enabling the inclusion of cases with defined periods of exposure. However, no such studies have been reported so far. Besides, determinants of the SARS incubation period remain unclear. In this study, 209 probable SARS cases with documented episodes of exposure between March 1 and May 31, 2003, in mainland China were included. A nonparametric method was used to analyze these data with defined periods of exposure to obtain the refined estimate of the SARS incubation period. Furthermore, the authors also explored the influence of various factors on the SARS incubation period by analysis of variance, linear regression analysis, and analysis of covariance. The estimates of mean and variance of the SARS incubation period were 5.29 days and 12.33 days(2), respectively; 90% of patients would have an incubation period of less than 11.58 days with a probability of 0.8, and 99% of patients would have an incubation of less than 22.22 days with a probability of 0.9. The affected area showed a highly significant effect on the incubation period (p < 0.001), but the contact pattern, occupation, gender, and age did not.


title: Globalization of Communicable Diseases

text: Abstract Fueled by globalization and human behavior, communicable diseases pose a serious threat to humankind despite unparalleled technological advances. New viruses and devastating communicable diseases such as Ebola and Zika are emerging; diseases previously considered eradicated such as measles are reemerging, while antibiotic resistance is increasing to dangerously high levels worldwide. Increased human population and accelerated global travel make local outbreaks instant global threats. Researchers are concerned that an avian influenza outbreak could kill many more people when it emerges because of the absence of immunity and human travel interaction patterns. Yet the threat of communicable disease varies by geographic location—where you live matters. This entry examines the spatial patterns of familiar communicable diseases, including the syndemic of human immunodeficiency virus (HIV) and tuberculosis, as well as new diseases such as Ebola, Zika, and dengue. It highlights the huge potential of mapping communicable disease genotypes while raising the alarm on the urgent need for effective global disease surveillance systems and new tools for fighting communicable diseases. Because communicable diseases do not respect political boundaries, global cooperation is vital to prevent this threat to humankind.


title: Survival of Severe Acute Respiratory Syndrome Coronavirus

text: Background. The primary modes of transmission of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) appear to be direct mucus membrane contact with infectious droplets and through exposure to formites. Knowledge of the survival characteristics of the virus is essential for formulating appropriate infection-control measures. Methods. Survival of SARS-CoV strain GVU6109 was studied in stool and respiratory specimens. Survival of the virus on different environmental surfaces, including a laboratory request form, an impervious disposable gown, and a cotton nondisposable gown, was investigated. The virucidal effects of sodium hypochlorite, house detergent, and a peroxygen compound (Virkon S; Antec International) on the virus were also studied. Results. SARS-CoV GVU6109 can survive for 4 days in diarrheal stool samples with an alkaline pH, and it can remain infectious in respiratory specimens for >7 days at room temperature. Even at a relatively high concentration (10(4) tissue culture infective doses/mL), the virus could not be recovered after drying of a paper request form, and its infectivity was shown to last longer on the disposable gown than on the cotton gown. All disinfectants tested were shown to be able to reduce the virus load by >3 log within 5 min. Conclusions. Fecal and respiratory samples can remain infectious for a long period of time at room temperature. The risk of infection via contact with droplet-contaminated paper is small. Absorbent material, such as cotton, is preferred to nonabsorptive material for personal protective clothing for routine patient care where risk of large spillage is unlikely. The virus is easily inactivated by commonly used disinfectants.


title: Tratamiento farmacológico de las agudizaciones infecciosas de la EPOC

text: Las agudizaciones de la enfermedad pulmonar obstructiva crónica (EPOC) son episodios frecuentes y potencialmente graves, que dejan un impacto permanente en la calidad de vida y en la función pulmonar de los pacientes. Hasta un 75% de las agudizaciones tiene una etiología bacteriana, en ocasiones asociada a infección vírica. La tasa de fracaso del tratamiento ambulatorio de las agudizaciones alcanza el 20-25% y la gravedad de la enfermedad de base es el principal factor de riesgo de fracaso. La colonización bacteriana persistente es un factor de riesgo de agudizaciones frecuentes y graves, y de más rápida progresión de la EPOC. Por este motivo el tratamiento antibiótico de las agudizaciones debe perseguir no sólo la curación clínica, sino también la mejor erradicación posible para acelerar la recuperación y prevenir las recaídas. Nuevos ensayos clínicos han demostrado que el antibiótico que consigue una mejor erradicación puede prolongar el tiempo sin síntomas de agudización. Exacerbations of chronic obstructive pulmonary disease (COPD) are frequent and potentially serious episodes that permanently affect patients’ quality of life and lung function. Up to 75% of exacerbations are caused by bacteria, sometimes associated with viral infection. Outpatient treatment of exacerbations is unsuccessful in 20-25% of patients and the main risk factor for this lack of success is the severity of the underlying disease. Persistent bacterial colonization is a risk factor for frequent and severe exacerbations and for rapid progression of COPD. Therefore, antibiotic treatment should aim to achieve not only the resolution of symptons but also the best eradication possible to hasten recovery and prevent recurrences. New clinical trials have demonstrated that the antibiotic that best achieves bacterial eradication can prolong exacerbation-free periods.


title: Clinical evaluation of serological IgG antibody response on the Abbott Architect for established SARS-CoV-2 infection

text: OBJECTIVE: This study aimed to evaluated the diagnostic performance of the Abbott Architect SARS-CoV-2 IgG assay in COVID-19 patients. METHODS: Residual sera from 177 symptomatic COVID-19 positive patients, and 163 non-COVID-19 patients were tested for antibody with the Abbott SARS-CoV-2 IgG assay (Abbott Diagnostics, Chicago, US). Clinical records for COVID-19 patients were reviewed to determine the time from onset of clinical illness to testing. RESULTS: Specificity of the assay was 100.0% (95% CI: 97.1 – 100.0%). The clinical sensitivity of the assay varied depending on time from onset of symptoms, increasing with longer periods since onset of clinical illness. The clinical sensitivity at ≤6 days was 8.6% (7/81; 95% CI: 3.8 – 17.5%), 7-13 days: 43.6% (17/39; 95% CI: 28.2 – 60.2%), 14-20 days: 84.0% (21/25; 95% CI: 63.1 – 94.7%), and ≥21 days: 84.4% (27/32; 95% CI: 66.5 – 94.1%). Clinical sensitivity was higher in the ≥14 days group compared to <14. There were no differences between the 14-20 days and ≥21 days group; the combined clinical sensitivity for these groups (≥14 days) was 84.2% (49/57; 71.6 – 92.1%). CONCLUSION: The Abbott SARS-CoV-2 IgG test has high specificity. Clinical sensitivity was limited in early stages of disease but improved from 14 days after onset of clinical infection.


title: Novel 1,2,4-Oxadiazole Derivatives in Drug Discovery

text: Five-membered 1,2,4-oxadiazole heterocyclic ring has received considerable attention because of its unique bioisosteric properties and an unusually wide spectrum of biological activities. Thus, it is a perfect framework for the novel drug development. After a century since the 1,2,4-oxadiazole have been discovered, the uncommon potential attracted medicinal chemists’ attention, leading to the discovery of a few presently accessible drugs containing 1,2,4-oxadiazole unit. It is worth noting that the interest in a 1,2,4-oxadiazoles’ biological application has been doubled in the last fifteen years. Herein, after a concise historical introduction, we present a comprehensive overview of the recent achievements in the synthesis of 1,2,4-oxadiazole-based compounds and the major advances in their biological applications in the period of the last five years as well as brief remarks on prospects for further development.


title: Influenza and Influenza-like Viruses in Children in the Epidemic Season 2015/2016 in Poland

text: Influenza is an infectious disease caused by influenza A and B viruses. Children are the group which is the most exposed to influenza and influenza-like infections. They are considered as carriers of influenza infections in the population. In the epidemic season 2015/2016 more than 8000 samples were tested, of which over 30 % specimens were collected from patients aged 0–14 years. In 42.3 % cases the influenza or influenza-like viruses were confirmed. The most common subtype was A/H1N1/pdm09. Analysis of positive specimens was categorized into three smaller groups 0–4, 5–9, 10–14. Differences in the frequency of virus detections in younger age groups appeared. This study has shown that children are a very important group in the spread of the influenza virus in the population. A higher percentage of vaccinated children would decrease the number of infected patients in the whole population.


title: PSGL-1 inhibits the virion incorporation of SARS-CoV and SARS-CoV-2 spike glycoproteins and impairs virus attachment and infectivity

text: P-selectin glycoprotein ligand-1 (PSGL-1) is a cell surface glycoprotein that binds to P-, E-, and L-selectins to mediate the tethering and rolling of immune cells on the surface of the endothelium for cell migration into inflamed tissues. PSGL-1 has been identified as an interferon-γ (INF-γ)-regulated factor that restricts HIV-1 infectivity, and has recently been found to possess broad-spectrum antiviral activities. Here we report that the expression of PSGL-1 in virus-producing cells impairs the incorporation of SARS-CoV and SARS-CoV-2 spike (S) glycoproteins into pseudovirions and blocks virus attachment and infection of target cells. These findings suggest that PSGL-1 may potentially inhibit coronavirus replication in PSGL-1+ cells.


Hydroxychloroquine and “off-label” utilization in the treatment of oral conditions


SARS, Xenotransplantation and Bioterrorism: Preventing the Next Epidemic


title: Antiviral Chemotherapy

text: Over the past 20 years, antiviral therapy has undergone a revolution and is now making a significant impact on the treatment of major virus diseases, for example HIV and viral hepatitis B and C. Targets include viral reverse transcriptases and proteases. The use of interferon to boost host immunity has also proved effective. Our understanding of chemotherapeutic strategies and drug resistance has become considerably more sophisticated since the widespread introduction of routine genome sequencing of virus isolates.


title: Point-of-Care Microdevices for Blood Plasma Analysis in Viral Infectious Diseases

text: Each year, outbreaks of viral infections cause illness, disability, death, and economic loss. As learned from past incidents, the detrimental impact grows exponentially without effective quarantine. Therefore, rapid on-site detection and analysis are highly desired. In addition, for high-risk areas of viral contamination, close monitoring should be provided during the potential disease incubation period. As the epidemic progresses, a response protocol needs tobe rapidly implemented and the virus evolution fully tracked. For these scenarios, point-of-care microdevices can provide sensitive, accurate, rapid and low-cost analysis for a large population, especially in handling complex patient samples, such as blood, urine and saliva. Blood plasma can be considered as a mine of information containing sources and clues of biomarkers, including nucleic acids, immunoglobulin and other proteins, as well as pathogens for clinical diagnosis. However, blood plasma is also the most complicated body fluid. For targeted plasma biomarker detection or untargeted plasma biomarker discovery, the challenges can be as difficult as identifying a needle in a haystack. A useful platform must not only pursue single performance characteristics, but also excel at multiple performance parameters, such as speed, accuracy, sensitivity, selectivity, cost, portability, reliability, and user friendliness. Throughout the decades, tremendous progress has been made in point-of-care microdevices for viral infectious diseases. In this paper, we review fully integrated lab-on-chip systems for blood analysis of viral infectious disease.


Letter: Implementation of a Neurosurgery Telehealth Program Amid the COVID-19 Crisis—Challenges, Lessons Learned, and a Way Forward


Reply to “MRI evaluation of the olfactory clefts in patients with SARS-CoV-2 infection revealed an unexpected mechanism for olfactory function loss”