title: Prevalence of viral, bacterial and parasitological diseases in rats and mice used in research environments in Australasia over a 5-y period

text: Viral, bacterial and parasitological infections in rats and mice used in biomedical research continue to occur despite improved housing and biosurveillance. The presence of disease in laboratory animals can lead to spurious results for research undertaken in universities, research institutes and the pharmaceutical industry. Here the authors report the results of serological, microbiological, parasitological and molecular tests done on mice and rats from Australasia submitted to a rodent health monitoring laboratory (Cerberus Sciences) from 2004 to 2009. In tested mice, norovirus was the most prevalent virus and ectromelia virus was the least prevalent virus. In tested rats, pneumonia virus of mice was the most prevalent virus and adenoviruses 1 and 2 were the least prevalent viruses. In mice, Helicobacter hepaticus was the most prevalent bacterium, and in rats, Proteus spp. were the most prevalent bacteria. The most common positive helminthological finding in mice and rats was the presence of all pinworms (including Aspicularis spp. and Syphacia spp.). The most common positive protozoan findings in mice and rats were Chilomastix spp. and Trichomonads.


title: Weighted multifractal cross-correlation analysis based on Shannon entropy

text: Abstract In this paper, we propose a modification of multifractal cross-correlation analysis based on statistical moments (MFSMXA) method, called weighted MFSMXA method based on Shannon entropy (W-MFSMXA), to investigate cross-correlations and cross-multifractality between time series. Robustness of this method is verified by numerical experiments with both artificial and stock returns series. Results show that the proposed W-MFSMXA method not only keep the multifractal structure unchanged, but contains more significant information of series compared to the previous MFSMXA method. Furthermore, analytic formulas of the binomial multifractal model are generated for W-MFSMXA. Theoretical analysis and finite-size effect test demonstrate that W-MFSMXA slightly outperforms MFSMXA for relatively shorter series. We further generate the scaling exponent ratio to describe the relation of two methods, whose profile is found approximating a centrosymmetric hyperbola. Cross-multifractality is found in returns series but then destroyed after being shuffled as a consequence of the removed long memory in separate series.


title: Key data for outbreak evaluation: building on the Ebola experience

text: Following the detection of an infectious disease outbreak, rapid epidemiological assessment is critical for guiding an effective public health response. To understand the transmission dynamics and potential impact of an outbreak, several types of data are necessary. Here we build on experience gained in the West African Ebola epidemic and prior emerging infectious disease outbreaks to set out a checklist of data needed to: (1) quantify severity and transmissibility; (2) characterize heterogeneities in transmission and their determinants; and (3) assess the effectiveness of different interventions. We differentiate data needs into individual-level data (e.g. a detailed list of reported cases), exposure data (e.g. identifying where/how cases may have been infected) and population-level data (e.g. size/demographics of the population(s) affected and when/where interventions were implemented). A remarkable amount of individual-level and exposure data was collected during the West African Ebola epidemic, which allowed the assessment of (1) and (2). However, gaps in population-level data (particularly around which interventions were applied when and where) posed challenges to the assessment of (3). Here we highlight recurrent data issues, give practical suggestions for addressing these issues and discuss priorities for improvements in data collection in future outbreaks. This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.


title: Middle East respiratory syndrome coronavirus (MERS-CoV): Impact on Saudi Arabia, 2015

text: Middle East respiratory syndrome is the acute respiratory syndrome caused by betacoronavirus MERS-CoV. The first case of this disease was reported from Saudi Arabia in 2012. This virus is lethal and is a close relative of a severe acute respiratory syndrome (SARS), which is responsible for more than 3000 deaths in 2002–2003. According to Ministry of Health, Saudi Arabia. The number of new cases is 457 in 2015. Riyadh has the highest number of reports in comparison to the other cities. According to this report, males are more susceptible than female, especially after the age of 40. Because of the awareness and early diagnosis the incidence is falling gradually. The pre-existence of another disease like cancer or diabetic etc. boosts the infection. MERS is a zoonotic disease and human to human transmission is low. The MERS-CoV is a RNA virus with protein envelope. On the outer surface, virus has spike like glycoprotein which is responsible for the attachment and entrance inside host cells. There is no specific treatment for the MERS-CoV till now, but drugs are in pipeline which bind with the spike glycoprotein and inhibit its entrance host cells. MERS-CoV and SAR-CoV are from the same genus, so it was thought that the drugs which inhibit the growth of SARS-CoV can also inhibit the growth of MERS-CoV but those drugs are not completely inhibiting virus activity. Until we don’t have proper structure and the treatment of MERS-CoV, We should take precautions, especially the health care workers, Camel owners and Pilgrims during Hajj and Umrah, because they are at a higher risk of getting infected.


title: The profile of peripheral blood lymphocyte subsets and serum cytokines in children with 2019 novel coronavirus pneumonia

text: Abstract Objectives The study was aimed at investigating the characteristics of peripheral blood lymphocyte subsets and serum cytokines in children with 2019 novel coronavirus (2019-nCoV) pneumonia. Methods Children with 2019-nCoV pneumonia or with respiratory syncytial virus (RSV) pneumonia were included. Data including lymphocyte subsets and serum cytokines were collected and analyzed. Results : 56 patients were included in the study, 40 children with 2019-nCoV pneumonia and 16 children with RSV pneumonia. Compared with children with RSV pneumonia, patients with 2019-nCoV pneumonia had higher count of CD3+8+ lymphocyte, higher percentages of CD3+, CD3+8+ lymphocytes and a lower percentage of CD19+ lymphocyte. The serum IL-10 level was significantly higher in children with RSV pneumonia. One 2019-nCoV pneumonia child who was with an obvious increase of IL-10 developed severe pneumonia. Conclusions Immune response played a very important role in the development of 2019-nCoV pneumonia. The effective CD8+ T cell response might influence the severity of 2019-nCoV pneumonia. The adaptable change in IL-10 level might contribute to the relatively mild pneumonia symptoms in children with 2019-nCoV pneumonia and bacterial co-infection might be a risk factor of severe 2019-nCoV pneumonia.


docid: pirblwuq

title: Detection of HHV-6B in post-mortem central nervous system tissue of a post-bone marrow transplant recipient: a multi-virus array analysis

text: Abstract Background HHV-6 has been implicated in a number of neurological disorders. Recent evidence has suggested high incidence of HHV-6 infection in patients (46%) undergoing allogeneic bone marrow transplant (BMT). Objective To investigate whether HHV-6 plays a role in the development of fatal encephalopathy in an allogeneic post-BMT patient using an unbiased approach. Results Detection of HHV-6 viral DNA sequence and RNA expression were demonstrated in fresh frozen post-mortem autopsy material derived from the insular cortex using a multi-virus array platform. In addition, PCR analysis by real-time quantitative TaqMan demonstrated high viral burden in multiple brain regions tested. Sequencing analysis of PCR product confirmed the virus to be HHV-6 variant B. Conclusions Active infection as demonstrated by expression of viral RNA and high viral load in the CNS suggest a possible pathogenic role of HHV-6 in development neurologic complications post-BMT.


title: “The Most Dangerous Strain”

text: Socioeconomic inequities have direct implications in COVID presentation, severity of illness and prognosis. From practice of prophylactic measures to availability of personal protective equipment, from access to diagnostic tests to treatment resources, there are many facets and distinct disease processes of a virus that, among many things, serves to expose and highlight our global disparities.


title: Placebo: Its action and place in health research today* — Summary and conclusions

text: The material presented at this conference pointed to a new dimension in the prosecution of activities that seek to relieve people of disease. While the simple instrument of the placebo may show those interested in the efficacy of physiologically active chemicals the extent to which the chemical of interest is actually active, the surprising outcome of such studies is that the placebo per se is worthy of more general study. This, when taken further, points to the ways in which mind can influence the matter of the body. Of course, mind itself is an activity of matter, so we may retain the experimental approach that has told us about the world outside ourselves to examine the world that is inside our brains. New techniques and approaches to these once intractable problems are now in train. Where they will lead us we cannot predict, but as with the emergence of all new tools, we have to adopt those ethics that will carry us forward with the expectation that we will maximise benefits and minimise harms.


title: A Novel Bacterium-Like Particle Vaccine Displaying the MERS-CoV Receptor-Binding Domain Induces Specific Mucosal and Systemic Immune Responses in Mice

text: Middle East respiratory syndrome coronavirus (MERS-CoV), a new coronavirus that has been causing severe and fatal acute respiratory illnesses in humans since its outbreak in 2012, has raised public fear worldwide. The development of prophylactics and therapeutics is urgently needed to prevent and control MERS-CoV infections. In this study, a bacterium (Lactococcus lactis)-like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). The designs included different numbers of lysin motif (LysM) repeats in the PAs linked by linkers (RBD-linker-PA2 (RLP(2)), RBD-linker-PA3 (RLP(3)) and RBD-PA3 (RP(3))), and three LysM repeats and a linker in the fusion proteins increased the binding activity to the RBD. The specific immune responses were tested by intranasally immunizing mice with RLP(3)-GEM with or without the adjuvant GEL01. The results showed that GEL01-adjuvanted RLP(3)-GEM increased the systemic humoral, cellular and local mucosal immune responses in the mouse model, especially in the intestinal tract. The above results indicate that the MERS-CoV BLP product has the potential to be developed into a promising mucosal candidate vaccine to protect against MERS-CoV infections.


title: In the fight against the new coronavirus outbreak, we must also struggle with human bias

text: A compounding factor of the outbreak is the potential for the general public to misunderstand the facts and design conspiracy theories.


title: In silico disease model: from simple networks to complex diseases

text: In this chapter we consider in silico modeling of diseases starting from some simple to some complex (and mathematical) concepts. Examples and applications of in silico modeling for some important categories of diseases (such as for cancers, infectious diseases, and neuronal diseases) are also given.


Covid-19 Pandemic and Comments From Miami, Florida


title: Virtual screening and dynamics of potential inhibitors targeting RNA binding domain of nucleocapsid phosphoprotein from SARS-CoV-2

text: The emergence of the coronavirus disease-2019 pandemic has led to an outbreak in the world. The SARS-CoV-2 is seventh and latest in coronavirus family with unique exonucleases for repairing any mismatches in newly transcribed genetic material. Therefore, drugs with novel additional mechanisms are required to simultaneously target and eliminate the virus. Thus, a newly deciphered N protein is taken as a target that belongs to SARS-CoV-2. They play a vital role in RNA transcription, viral replication and new virion formation. This study used virtual screening, molecular modeling and docking of the 8987 ligands from Asinex and PubChem databases against this novel target protein. Three hotspot sites having DScore ≥1 (Site 1, Site 2 and Site 3) for ligand binding were selected. Subsequently, high throughput screening, standard precision and extra precision docking process and molecular dynamics concluded three best drugs from two libraries. Two antiviral moieties from Asinex databases (5817 and 6799) have docking scores of −10.29 and −10.156; along with their respective free binding energies (ΔG bind) of −51.96 and −64.36 on Site 3. The third drug, Zidovudine, is from PubChem database with docking scores of −9.75 with its binding free energies (ΔG bind) of −59.43 on Site 3. The RMSD and RMSF were calculated for all the three drugs through molecular dynamics simulation studies for 50 ns. Zidovudine shows a very stable interaction with fluctuation starting at 2.4 Å on 2 ns and remained stable at 3 Å from 13 to 50 ns. Thus, paving the way for further biological validation as a potential treatment. Communicated by Ramaswamy H. Sarma


Hypofractionation in COVID-19 Radiotherapy: A Mix of Evidence Based Medicine and of Opportunities


title: Can indoor sports centers be allowed to re-open during the COVID-19 pandemic based on a certificate of equivalence?

text: Within a time span of only a few months, the SARS-CoV-2 virus has managed to spread across the world. This virus can spread by close contact, which includes large droplet spray and inhalation of microscopic droplets, and by indirect contact via contaminated objects. While in most countries, supermarkets have remained open, due to the COVID-19 pandemic, authorities have ordered many other shops, restaurants, bars, music theaters and indoor sports centers to be closed. As part of COVID-19 (semi)lock-down exit strategies, many government authorities are now (May 2020) allowing a gradual re-opening, where sometimes indoor sport centers are last in line to be permitted to re-open. This technical note discusses the challenges in re-opening these facilities and the measures already suggested by some to tackle these challenges. It also elaborates three potential additional measures and based on these additional measures, it suggests the concept of a certificate of equivalence that could allow indoor sports centers with such a certificate to re-open more rapidly. It also attempts to stimulate increased preparedness of indoor sports centers for potential next waves of SARS-CoV-2 as well as future pandemics. It is concluded that fighting situations such as the COVID-19 pandemic and limiting economic damage requires increased collaboration and research by virologists, epidemiologists, microbiologists, aerosol scientists, building physicists, building services engineers and sports scientists.


title: The S proteins of human coronavirus NL63 and severe acute respiratory syndrome coronavirus bind overlapping regions of ACE2

text: The cellular receptor for human coronavirus NL63 (HCoV-NL63), a group I coronavirus, is angiotensin-converting enzyme2 (ACE2). ACE2 is also the receptor for the SARS coronavirus (SARS-CoV), a group II coronavirus. Here we describe the ability of HCoV-NL63 to utilize a number of ACE2 variants previously characterized as SARS-CoV receptors. Several ACE2 variants that reduced SARS-CoV S-protein association similarly reduced that of HCoV-NL63, whereas alteration of a number of solvent-exposed ACE2 residues did not interfere with binding by either S protein. One notable exception is ACE2 residue 354, at the boundary of the SARS-CoV binding site, whose alteration markedly inhibited utilization by the HCoV-NL63 but not SARS-CoV S proteins. In addition, the SARS-CoV S-protein receptor-binding domain inhibited entry mediated by the HCoV-NL63 S protein. These studies indicate that HCoV-NL63, like SARS-CoV, associates region of human ACE2 that includes a key loop formed by β-strands 4 and 5.


title: Non-invasive bioluminescence imaging of HCoV-OC43 infection and therapy in the central nervous system of live mice

text: Abstract Human coronaviruses (HCoVs) are important pathogens that cause upper respiratory tract infections and have neuroinvasive abilities; however, little is known about the dynamic infection process of CoVs in vivo, and there are currently no specific antiviral drugs to prevent or treat HCoV infection. Here, we verified the replication ability and pathogenicity of a reporter HCoV-OC43 strain expressing Renilla luciferase (Rluc; rOC43-ns2DelRluc) in mice with different genetic backgrounds (C57BL/6 and BALB/c). Additionally, we monitored the spatial and temporal progression of HCoV-OC43 through the central nervous system (CNS) of live BALB/c mice after intranasal or intracerebral inoculation with rOC43-ns2DelRluc. We found that rOC43-ns2DelRluc was fatal to suckling mice after intranasal inoculation, and that viral titers and Rluc expression were detected in the brains and spinal cords of mice infected with rOC43-ns2DelRluc. Moreover, viral replication was initially observed in the brain by non-invasive bioluminescence imaging before the infection spread to the spinal cord of BALB/c mice, consistent with its tropism in the CNS. Furthermore, the Rluc readout correlated with the HCoV replication ability and protein expression, which allowed quantification of antiviral activity in live mice. Additionally, we validated that chloroquine strongly inhibited rOC43-ns2DelRluc replication in vivo. These results provide new insights into the temporal and spatial dissemination of HCoV-OC43 in the CNS, and our methods provide an extremely sensitive platform for evaluating the efficacy of antiviral therapies to treat neuroinvasive HCoVs in live mice.


docid: clxtuxoq

title: The intestinal microbiome in dogs and cats with diarrhoea as detected by a faecal polymerase chain reaction‐based panel in Perth, Western Australia

text: This study reports the prevalence of potential faecal pathogens in the microbiome detected in a cohort of cats and dogs with diarrhoea in Perth, Western Australia. Records from a commercial diagnostic laboratory using faecal PCR testing between July 2014 and August 2015 were reviewed.Of 289 feline faecal samples reviewed, Salmonella spp. (1.7%), Campylobacter spp. (47.6%), Clostridium perfringens (81.3%), Giardia spp. (11.1%), Toxoplasma gondii (1.2%), Tritrichomonas foetus (4.8%), panleukopenia virus (6.5%) and coronavirus (39.5%) were detected. In dogs, Salmonella spp. (5.4%), Campylobacter spp. (36.3%), C. perfringens (85.4%), Giardia spp. (6.2%), parvovirus (9.4%), coronavirus (4.7%) and distemper virus (1.5%) were detected.


Dysgeusia in COVID-19: possible mechanisms and implications


A Brewing Storm: The Neuropsychological Sequelae of Hyperinflammation due to COVID-19


title: MERS coronavirus: diagnostics, epidemiology and transmission

text: The first known cases of Middle East respiratory syndrome (MERS), associated with infection by a novel coronavirus (CoV), occurred in 2012 in Jordan but were reported retrospectively. The case first to be publicly reported was from Jeddah, in the Kingdom of Saudi Arabia (KSA). Since then, MERS-CoV sequences have been found in a bat and in many dromedary camels (DC). MERS-CoV is enzootic in DC across the Arabian Peninsula and in parts of Africa, causing mild upper respiratory tract illness in its camel reservoir and sporadic, but relatively rare human infections. Precisely how virus transmits to humans remains unknown but close and lengthy exposure appears to be a requirement. The KSA is the focal point of MERS, with the majority of human cases. In humans, MERS is mostly known as a lower respiratory tract (LRT) disease involving fever, cough, breathing difficulties and pneumonia that may progress to acute respiratory distress syndrome, multiorgan failure and death in 20 % to 40 % of those infected. However, MERS-CoV has also been detected in mild and influenza-like illnesses and in those with no signs or symptoms. Older males most obviously suffer severe disease and MERS patients often have comorbidities. Compared to severe acute respiratory syndrome (SARS), another sometimes- fatal zoonotic coronavirus disease that has since disappeared, MERS progresses more rapidly to respiratory failure and acute kidney injury (it also has an affinity for growth in kidney cells under laboratory conditions), is more frequently reported in patients with underlying disease and is more often fatal. Most human cases of MERS have been linked to lapses in infection prevention and control (IPC) in healthcare settings, with approximately 20 % of all virus detections reported among healthcare workers (HCWs) and higher exposures in those with occupations that bring them into close contact with camels. Sero-surveys have found widespread evidence of past infection in adult camels and limited past exposure among humans. Sensitive, validated reverse transcriptase real-time polymerase chain reaction (RT-rtPCR)-based diagnostics have been available almost from the start of the emergence of MERS. While the basic virology of MERS-CoV has advanced over the past three years, understanding of the interplay between camel, environment, and human remains limited. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0439-5) contains supplementary material, which is available to authorized users.


docid: ggomuomb

title: Cellular Proteins Associated with the Interior and Exterior of Vesicular Stomatitis Virus Virions

text: Virus particles (virions) often contain not only virus-encoded but also host-encoded proteins. Some of these host proteins are enclosed within the virion structure, while others, in the case of enveloped viruses, are embedded in the host-derived membrane. While many of these host protein incorporations are likely accidental, some may play a role in virus infectivity, replication and/or immunoreactivity in the next host. Host protein incorporations may be especially important in therapeutic applications where large numbers of virus particles are administered. Vesicular stomatitis virus (VSV) is the prototypic rhabdovirus and a candidate vaccine, gene therapy and oncolytic vector. Using mass spectrometry, we previously examined cell type dependent host protein content of VSV virions using intact (“whole”) virions purified from three cell lines originating from different species. Here we aimed to determine the localization of host proteins within the VSV virions by analyzing: i) whole VSV virions; and ii) whole VSV virions treated with Proteinase K to remove all proteins outside the viral envelope. A total of 257 proteins were identified, with 181 identified in whole virions and 183 identified in Proteinase K treated virions. Most of these proteins have not been previously shown to be associated with VSV. Functional enrichment analysis indicated the most overrepresented categories were proteins associated with vesicles, vesicle-mediated transport and protein localization. Using western blotting, the presence of several host proteins, including some not previously shown in association with VSV (such as Yes1, Prl1 and Ddx3y), was confirmed and their relative quantities in various virion fractions determined. Our study provides a valuable inventory of virion-associated host proteins for further investigation of their roles in the replication cycle, pathogenesis and immunoreactivity of VSV.


title: Find the right sample: A study on the versatility of saliva and urine samples for the diagnosis of emerging viruses

text: BACKGROUND: The emergence of different viral infections during the last decades like dengue, West Nile, SARS, chikungunya, MERS-CoV, Ebola, Zika and Yellow Fever raised some questions on quickness and reliability of laboratory diagnostic tests for verification of suspected cases. Since sampling of blood requires medically trained personal and comprises some risks for the patient as well as for the health care personal, the sampling by non-invasive methods (e.g. saliva and/ or urine) might be a very valuable alternative for investigating a diseased patient. MAIN BODY: To analyse the usefulness of alternative noninvasive samples for the diagnosis of emerging infectious viral diseases, a literature search was performed on PubMed for alternative sampling for these viral infections. In total, 711 papers of potential relevance were found, of which we have included 128 in this review. CONCLUSIONS: Considering the experience using non-invasive sampling for the diagnostic of emerging viral diseases, it seems important to perform an investigation using alternative samples for routine diagnostics. Moreover, during an outbreak situation, evaluation of appropriate sampling and further processing for laboratory analysis on various diagnostic platforms are very crucial. This will help to achieve optimal diagnostic results for a good and reliable case identification. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3611-x) contains supplementary material, which is available to authorized users.


One lung ventilation during COVID-19 pandemic


title: Diagnostic Accuracy of FebriDx: A Rapid Test to Detect Immune Responses to Viral and Bacterial Upper Respiratory Infections

text: C-reactive protein (CRP) and myxovirus resistance protein A (MxA) are associated with bacterial and viral infections, respectively. We conducted a prospective, multicenter, cross-sectional study of adults and children with febrile upper respiratory tract infections (URIs) to evaluate the diagnostic accuracy of a rapid CRP/MxA immunoassay to identify clinically significant bacterial infection with host response and acute pathogenic viral infection. The reference standard for classifying URI etiology was an algorithm that included throat bacterial culture, upper respiratory PCR for viral and atypical pathogens, procalcitonin, white blood cell count, and bandemia. The algorithm also allowed for physician override. Among 205 patients, 25 (12.2%) were classified as bacterial, 53 (25.9%) as viral, and 127 (62.0%) negative by the reference standard. For bacterial detection, agreement between FebriDx and the reference standard was 91.7%, with FebriDx having a sensitivity of 80% (95% CI: 59–93%), specificity of 93% (89–97%), positive predictive value (PPV) of 63% (45–79%), and a negative predictive value (NPV) of 97% (94–99%). For viral detection, agreement was 84%, with a sensitivity of 87% (75–95%), specificity of 83% (76–89%), PPV of 64% (63–75%), and NPV of 95% (90–98%). FebriDx may help to identify clinically significant immune responses associated with bacterial and viral URIs that are more likely to require clinical management or therapeutic intervention, and has potential to assist with antibiotic stewardship.


title: 25 Host Defenses to Viruses

text: Abstract Virus infections continue to pose a substantial threat to human health. Unravelling the intricacies of immune defenses against viruses should lead to improved control of infections through the design of new vaccines and therapies. Our understanding of the fundamental cellular and molecular mechanisms involved in the immune systems response to virus infection has improved substantially in recent years. This wealth of new information and the promise of new insight from systems biology approaches continue to drive research in this field. Such knowledge has revealed why viruses sometimes induce immune dysfunction or trigger disastrous pathology and has paved the way for new therapies being tested against chronic and emerging infections. In this chapter, we briefly summarize the general concepts in immunity to virus infections and highlight some of the key challenges remaining for the future. Virus infections continue to pose a substantial threat to human health.


title: Quantitative and qualitative flow cytometric analysis of nanosized cell-derived membrane vesicles

text: Abstract Nanosized cell-derived membrane vesicles are increasingly recognized as therapeutic vehicles and high-potential biomarkers for several diseases. Currently available methods allow bulk analysis of vesicles but are not suited for accurate quantification and fail to reveal phenotypic heterogeneity in membrane vesicle populations. For such analyses, single vesicle-based, multiparameter, high-throughput methods are needed. We developed a fluorescence-based, high-resolution flow cytometric method for quantitative and qualitative analysis of nanosized membrane vesicles. Proof of principle was obtained by single-particle analysis of virions and liposomes. Further validation was obtained by quantification of cell-derived nanosized membrane vesicles from cell cultures and body fluids. An important aspect was that the technology was extended to detect specific proteins on individual vesicles. This allowed identification of exosome subsets and phenotyping of individual exosomes produced by dendritic cells (DCs) undergoing different modes of activation. The described technology allows quantitative, multiparameter, and high-throughput analysis of a wide variety of nanosized particles and has broad applications. From the Clinical Editor The authors developed a fluorescence-based, high-resolution flow cytometric method for quantitative and qualitative analysis of nanosized cell-derived membrane vesicles that are increasingly recognized both as therapeutic vehicles and high-potential biomarkers for several diseases. A high throughput, easily available, and sensitive detection method such as the one discussed here is a critically important prerequisite for further refinements of this technology.


title: Less expression of CD4(+) and CD8(+) T cells might reflect the severity of infection and predict worse prognosis in patients with COVID-19: evidence from a pooled analysis

text: This study mainly focused on the very serious COVID-19 epidemic situation at present and provided a new insight for the treatment and monitor of patients with COVID-19. Through this meta-analysis, we could draw a conclusion that less expression of blood CD4(+) and CD8(+) T cells count might reflect the severity of infection and often accompanied by a poor prognosis. Hence, we inferred blood CD4+ and CD8+ T cells count could be a promising biomarker for disease assessment and monitor of patients with COVID-19.


title: Susceptibility of human and rat neural cell lines to infection by SARS-coronavirus

text: Abstract Pathological characterization of autopsied tissues from patients with SARS revealed severe damage in restricted tissues, such as lung, with no apparent cell damage in other tissues, such as intestine and brain. Here, we examined the susceptibility of neural cell lines of human (OL) and rat (C6) origins to SARS-associated coronavirus. Both of the neural cell lines showed no apparent cytopathic effects (CPE) by infection but produced virus with infectivity of 102–5 per ml, in sharp contrast to the production by infected Vero E6 cells of >109 per ml that showed a lytic infection with characteristic rounding CPE. Interestingly, the infection of intestinal cell line CaCo-2 also induced no apparent CPE, with production of the virus at a slightly lower level as that of the Vero E6 cell culture. Notably, the cellular receptor for the virus, angiotensin-converting enzyme 2 was expressed at similar levels on Vero E6 and CaCo-2 cells, but at undetectable levels on OL and C6 cells.


SIMILARITIES OF IMMUNE REACTIONS BETWEEN HEPATITIS C AND SEVERE ACUTE RESPIRATORY SYNDROME‐ASSOCIATED CORONAVIRUS INFECTIONS


title: Challenges, Learning Curve, and Safety of Endoscopic Endonasal Surgery of Sellar-Suprasellar Lesions in a Community Hospital

text: Background and Objective Endoscopic endonasal surgery (EES) for the management of sellar, suprasellar, and anterior skull base lesions is gaining popularity. Our aim was to analyze and present the clinical outcomes of EES for the management of these lesions in a community hospital setting. Methods We retrospectively reviewed the charts of 56 patients with sellar, suprasellar, and anterior skull base lesions who underwent EES between 2010 and 2018. Results There was male predominance (53.6%) with a mean age of 54.9 ± 13.7 years. Lesions were 45 pituitary adenomas, 5 meningiomas, 3 metastatic, 1 craniopharyngioma, 1 Rathke cyst, and 1 mucocele. Gross total excision was achieved in 57.1%, subtotal excision occurred in 37.5%, and decompression and biopsy were achieved in 5.4% patients. Postoperative vision normalized or improved in 27 patients (86.1%) and was stable in 4 patients (13.9%). Recovery of a preexisting hormonal deficit occurred in 13 (23.2%) patients, and a new hormonal deficit occurred in 9 patients (16.1%). The mean hospital stay was 6.1 ± 4.9 days. Postoperative complications included cerebrospinal fluid leak in 8 patients (14.3%). Four patients (7.1%) had meningitis. Diabetes insipidus was present in 19 patients (33.9%), and postoperative intracranial hematoma requiring evacuation was necessary in 2 patients (3.6%). The mean follow-up duration was 47.5 ± 25.8 months. Lesion progression or recurrence requiring redo surgery occurred in 5 patients (8.9%). Regarding the learning curve, the postoperative cerebrospinal fluid leak, meningitis, new hormonal deficits, and diabetes insipidus decreased in the second half of the patients. Conclusions EES provides an effective and safe surgical option with low morbidity and mortality for the treatment of sellar, suprasellar, and anterior skull base lesions in a community hospital setting.


title: The association between laryngopharyngeal reflux and COVID‐19 is still not demonstrated

text: We read with interest the paper entitled «The impact of laryngopharyngeal reflux disease on 95 hospitalized patients with COVID-19 in Wuhan, China: A retrospective study.»1 The authors retrospectively reported that hospitalized patients with laryngopharyngeal reflux (LPR) had poorer clinical outcomes compared with those without LPR according to Reflux Symptom Index (RSI). The LPR diagnosis was based on RSI>13, which is the threshold used by Belafsky et al. to suspect LPR.2 This article is protected by copyright. All rights reserved.


title: COVID-19 response in northwest Syria: innovation and community engagement in a complex conflict

text: Despite lacking capacity and resources, the health system in the northwest Syria is using innovative approaches for the containment of COVID-19. Lessons drawn from previous outbreaks in the region, such as the polio outbreak in 2013 and the annual seasonal influenza, have enabled the Early Warning and Response Network, a surveillance system to develop mechanisms of predicting risk and strengthening surveillance for the new pandemic. Social media tools such as WhatsApp are effectively collecting health information and communicating health messaging about COVID-19. Community engagement has also been scaled up, mobilizing local resources and encouraging thousands of volunteers to join the ‘Volunteers against Corona’ campaign. Bottom-up local governance technical entities, such as Idleb Health Directorate and the White Helmets, have played key leadership role in the response. These efforts need to be scaled up to prevent the transmission of COVID-19 in a region chronically affected by a complex armed conflict.


title: Construction and characterization of recombinant human adenovirus type 5 expressing foot-and-mouth disease virus capsid proteins of Indian vaccine strain, O/IND/R2/75

text: AIM: Generation of recombinant human adenovirus type 5 expressing foot-and-mouth disease virus (FMDV) capsid protein genes along with full-length 2B, 3B and 3C(pro) and its characterization. MATERIALS AND METHODS: FMD viral RNA isolation, cDNA synthesis, and polymerase chain reaction were performed to synthesize expression cassettes (P1-2AB3BC(wt) and P1-2AB3BC(m)) followed by cloning in pShuttle-CMV vector. Chemically competent BJ5183-AD-1 cells were transformed with the recombinant pShuttle-CMV to produce recombinant adenoviral plasmids. HEK-293 cells were transfected with the recombinant adenoviral plasmids to generate recombinant adenoviruses (hAd5/P1-2AB3BC(wt) and hAd5/P1-2AB3BC(m)). Expression of the target proteins was analyzed by sandwich ELISA and indirect immunofluorescence assay. The recombinant adenoviruses were purified and concentrated by CsCl density gradient ultracentrifugation. Growth kinetics and thermostability of the recombinant adenoviruses were compared with that of non-recombinant replication-defective adenovirus (dAd5). RESULTS: The recombinant adenoviruses containing capsid protein genes of the FMDV O/IND/R2/75 were generated and amplified in HEK-293 cells. The titer of the recombinant adenoviruses was approximately 10(8), 10(9.5) and 10(11) TCID(50)/ml in supernatant media, cell lysate and CsCl purified preparation, respectively. Expression of the FMDV capsid protein was detectable in sandwich ELISA and confirmed by immunofluorescence assay. Growth kinetics of the recombinant adenoviruses did not reveal a significant difference when compared with that of dAd5. A decrement of up to 10-fold at 4°C and 21-fold at 37°C was recorded in the virus titers during 60 h incubation period and found to be statistically significant (p<0.01). CONCLUSION: Recombinant adenoviruses expressing capsid proteins of the FMDV O/IND/R2/75 were constructed and produced in high titers. In vitro expression of the target proteins in the adenovirus vector system was detected by sandwich ELISA and immunofluorescence assay.


docid: inzzywps

title: Managing ophthalmic practices in a referral emergency COVID‐19 hospital in north‐east Italy


docid: garchpin

title: 2,6-Bis-arylmethyloxy-5-hydroxychromones with antiviral activity against both hepatitis C virus (HCV) and SARS-associated coronavirus (SCV)

text: In this study, as a bioisosteric alternative scaffold of the antiviral aryl diketoacids (ADKs), we used 5-hydroxychromone on which two arylmethyloxy substituents were installed. The 5-hydroxychromones (5b–5g) thus prepared showed anti-HCV activity and, depending on the aromatic substituents on the 2-arylmethyloxy moiety, some of the derivatives (5b–5f) were also active against SCV. In addition, unlike the ADKs which showed selective inhibition against the helicase activity of the SCV NTPase/helicase, the 5-hydroxychromones (5b–5f) were active against both NTPase and helicase activities of the target enzyme. Among those, 3-iodobenzyloxy-substituted derivative 5e showed the most potent activity against HCV (EC(50) = 4 μM) as well as SCV (IC(50) = 4 μM for ATPase activity, 11 μM for helicase activity) and this might be used as a platform structure for future development of the multi-target or broad-spectrum antivirals.


title: Public Health Crisis Preparedness and Response in Korea

text: Since the 2006 Pandemic Influenza Preparedness and Response Plan according to the World Health Organization’s recommendation, the Republic of Korea has prepared and periodically evaluated the plan to respond to various public health crises including pandemic influenza. Korea has stockpiled 13,000,000 doses of antiviral drugs covering 26% of the Korean population and runs 519 isolated beds in 16 medical institutions. The division of public health crisis response in Korea Centers for Disease Control and Prevention are in charge of responding to public health crises caused by emerging infectious diseases including severe acute respiratory syndrome, avian influenza human infection, and pandemic influenza. Its job description includes preparing for emerging infectious diseases, securing medical resources during a crisis, activating the emergency response during the crisis, and fortification of capabilities of public health personnel. It could evolve into a comprehensive national agency to deal with public health crisis based on the experience of previous national emerging infectious diseases.


“Pandemic fear” and COVID-19: mental health burden and strategies


title: Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy

text: Abstract Background Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19. Methods We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020–10.04.2020). The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI). Secondary outcome was overt disseminated intravascular coagulation (DIC). Results We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]). Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward. Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%–11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward). Half of the thromboembolic events were diagnosed within 24 h of hospital admission. Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%). Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA). The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively. Overt DIC was present in 8 (2.2%) patients. Conclusions The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.


title: Plasma therapy against infectious pathogens, as of yesterday, today and tomorrow

text: Abstract Plasma therapy consists in bringing to a patient in need – in general suffering a severe, resistant to current therapy, and even lethal infection – plasma or specific, fractioned, antibodies, along with other immunoglobulins and possibly healing factors that can be obtained from immunized blood donors; donors (voluntary and benevolent) can be either actively immunized individuals or convalescent persons. Plasma therapy has been used since the Spanish flu in 1917–1918, and regularly then when viral epidemics threatened vulnerable populations, the last reported occurrence being the 2013–2015 Ebola virus outbreak in West Africa. The precise action mechanism of plasma therapy is not fully delineated as it may function beyond purified, neutralizing antibodies.


title: COVID-19 and Individual Genetic Susceptibility/Receptivity: Role of ACE1/ACE2 Genes, Immunity, Inflammation and Coagulation. Might the Double X-Chromosome in Females Be Protective against SARS-CoV-2 Compared to the Single X-Chromosome in Males?

text: In December 2019, a novel severe acute respiratory syndrome (SARS) from a new coronavirus (SARS-CoV-2) was recognized in the city of Wuhan, China. Rapidly, it became an epidemic in China and has now spread throughout the world reaching pandemic proportions. High mortality rates characterize SARS-CoV-2 disease (COVID-19), which mainly affects the elderly, causing unrestrained cytokines-storm and subsequent pulmonary shutdown, also suspected micro thromboembolism events. At the present time, no specific and dedicated treatments, nor approved vaccines, are available, though very promising data come from the use of anti-inflammatory, anti-malaria, and anti-coagulant drugs. In addition, it seems that males are more susceptible to SARS-CoV-2 than females, with males 65% more likely to die from the infection than females. Data from the World Health Organization (WHO) and Chinese scientists show that of all cases about 1.7% of women who contract the virus will die compared with 2.8% of men, and data from Hong Kong hospitals state that 32% of male and 15% of female COVID-19 patients required intensive care or died. On the other hand, the long-term fallout of coronavirus may be worse for women than for men due to social and psychosocial reasons. Regardless of sex- or gender-biased data obtained from WHO and those gathered from sometimes controversial scientific journals, some central points should be considered. Firstly, SARS-CoV-2 has a strong interaction with the human ACE2 receptor, which plays an essential role in cell entry together with transmembrane serine protease 2 (TMPRSS2); it is interesting to note that the ACE2 gene lays on the X-chromosome, thus allowing females to be potentially heterozygous and differently assorted compared to men who are definitely hemizygous. Secondly, the higher ACE2 expression rate in females, though controversial, might ascribe them the worst prognosis, in contrast with worldwide epidemiological data. Finally, several genes involved in inflammation are located on the X-chromosome, which also contains high number of immune-related genes responsible for innate and adaptive immune responses to infection. Other genes, out from the RAS-pathway, might directly or indirectly impact on the ACE1/ACE2 balance by influencing its main actors (e.g., ABO locus, SRY, SOX3, ADAM17). Unexpectedly, the higher levels of ACE2 or ACE1/ACE2 rebalancing might improve the outcome of COVID-19 in both sexes by reducing inflammation, thrombosis, and death. Moreover, X-heterozygous females might also activate a mosaic advantage and show more pronounced sex-related differences resulting in a sex dimorphism, further favoring them in counteracting the progression of the SARS-CoV-2 infection.


title: Occurrence of SARS‐CoV‐2 during mycophenolate mofetil treatment for pemphigus

text: we read with great interest the article entitled “Should SARS‐CoV‐2 influence immunosuppressive therapy for autoimmune blistering diseases?” published by Di Altobrando A. et al. in the JEADV. This is the first report of COronaVIrus DIsease 2019 (COVID‐19) in a patient affected by autoimmune blistering disease (ABD) during immunosuppressive treatment (i.e. azathioprine). The authors conclude that it is crucial to learn of more cases of ABD patients under immunosuppressive treatment who have developed COVID‐19, in order to better quantify the risk of infection under immunosuppressive therapy.


COVID-19 and Individuals with Mental Illness in Psychiatric Facilities


title: Molecular Diagnostics for Detection of Bacterial and Viral Pathogens in Community-Acquired Pneumonia

text: Traditional microbiological methods for detection of respiratory tract pathogens can be slow, are often not sensitive, may not distinguish infection from colonization, and are influenced by previous antibiotic therapy. Molecular diagnostic tests for common and atypical causative pathogens of community-acquired pneumonia have the potential to dramatically increase the diagnostic yield and decrease the time required to render results. Unfortunately, these tests often lack standardization and are not widely available. Consideration should be given to the development and evaluation of companion molecular diagnostic tests for detection of respiratory pathogens in future clinical trials of antimicrobials intended to treat community-acquired pneumonia.


Keep “time is brain,” even in the crisis of COVID-19


docid: pwsvhitd

title: Detection of hepatitis C virus in the nasal secretions of an intranasal drug-user

text: BACKGROUND: One controversial source of infection for hepatitis C virus (HCV) involves the sharing of contaminated implements, such as straws or spoons, used to nasally inhale cocaine and other powdered drugs. An essential precondition for this mode of transmission is the presence of HCV in the nasal secretions of intranasal drug users. METHODS: Blood and nasal secretion samples were collected from five plasma-positive chronic intranasal drug users and tested for HCV RNA using RT-PCR. RESULTS: HCV was detected in all five blood samples and in the nasal secretions of the subject with the highest serum viral load. CONCLUSIONS: This study is the first to demonstrate the presence of HCV in nasal secretions. This finding has implications for potential transmission of HCV through contact with contaminated nasal secretions.


title: CT manifestations of the coronavirus disease 2019 of imported infection versus second-generation infection in patients outside the original district (Wuhan, China) of this disease: An observational study

text: To explore the discrepancy in computed tomography (CT) manifestations of the coronavirus disease 2019 (COVID-19) in patients outside the original district (Wuhan, China) between cases with imported infection and second-generation infection, 22 patients with COVID-19 from 2 hospitals in Nanchong, China, 938 km away from the original district (Wuhan, China) of this disease were enrolled. All patients underwent initial and follow-up CT after admission during the treatment, and were divided into 2 groups. Group A and B were composed of 15 patients with a history of exposure to the original district (Wuhan, China) in short-term (i.e., imported infection), and 7 with a close contact with the patients with confirmed COVID-19 or with the healthy individuals from the original district (i.e., second-generation infection), respectively. Initial CT features including extent score and density score between groups were statistically compared. We found that all patients in group A and 3 of 7 patients in group B had abnormal CT findings while 4 of 7 patients in group B had not. Patients with abnormal CT findings were more frequent in group A than in group B (P < .05). On initial CT, pure ground glass opacity (GGO), and GGO with consolidation and/or other abnormalities were found in 20% (3/15) and 80% (12/15) patients in group A, respectively, while 1 (14.3%), 2 (28.6%), and 4 (57.1%) had pure GGOs, GGO with focal consolidation, and normal CT appearances in Group B, respectively. Patients with extent and density scores of ≥5 were more frequent in group A than in group B (all P-values < .01). Additionally, 3 of 4 (75%) patients with normal initial CT findings had focal pure GGO lesions on follow-up. In conclusion, COVID-19 in patients with a history of exposure to the original district can be severer than with the second-generation infection on CT.


title: Quasispecies and its impact on viral hepatitis

text: Abstract Quasispecies dynamics mediates adaptability of RNA viruses through a number of mechanisms reviewed in the present article, with emphasis on the medical implications for the hepatitis viruses. We discuss replicative and non-replicative molecular mechanisms of genome variation, modulating effects of mutant spectra, and several modes of viral evolution that can affect viral pathogenesis. Relevant evolutionary events include the generation of minority virus variants with altered functional properties, and alterations of mutant spectrum complexity that can affect disease progression or response to treatment. The widespread occurrence of resistance to antiviral drugs encourages new strategies to control hepatic viral disease such as combination therapies and lethal mutagenesis. In particular, ribavirin may be exerting in some cases its antiviral activity with participation of its mutagenic action. Despite many unanswered questions, here we document that quasispecies dynamics has provided an interpretation of the adaptability of the hepatitis viruses, with features conceptually similar to those observed with other RNA viruses, a reflection of the common underlying Darwinian principles.


title: Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection

text: The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naïve hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.


title: Chapter 28 Experimental Infections of the Common Marmoset (Callithrix jacchus)

text: Abstract Interest in the use of marmosets for experimental infectious disease has dramatically increased in the last decade. These animals are native to the Atlantic coastal forests in northeastern Brazil. The majority of experimental animals come from the National Primate Research Centers and other breeding facilities. They are advantageous because of their relative small size, weighting 350–400g as adults, their life span is compact compared with other nonhuman primate (NHP), and they produce offspring by 3years of age. They are free of Herpes B virus and, it is believed, to date, other dangerous human pathogens (Abbot et al., 2003) [1]. We describe here the experimental infections of marmosets to human pathogens. While it is always interesting to compare various NHPs with each other, the importance of an animal model is always in comparing its similarities to human infections.


title: COVID-19 STEMI 2020: It’s Not What You Know, It’s How You Think

text: [Figure: see text]


title: Ion channel activity of the CSFV p7 viroporin in surrogates of the ER lipid bilayer

text: [Figure: see text]


title: Single dose of an adenovirus vectored mouse interferon-α protects mice from lethal EV71 challenge

text: Abstract Enterovirus 71 (EV71) causes hand-foot-and-mouth diseases as well as neurological complications in young children. Interferon (IFN) can inhibit the replication of many viruses with low cytotoxic effects. Previously, an adenovirus vectored mouse interferon-α (DEF201), subtype 5, was generated by Wu et al, 2007. In this study, the antiviral effects of DEF201 against EV71 were evaluated in a murine model. 6–day-old BALB/c mice were administered a single dose of DEF201 before or after infection with lethal dose of EV71. The survival rate, clinical symptoms, tissue viral loads and histology pathogenesis were evaluated. IFN gene expression following a single dose of DEF201 maintained high concentrations of 100–9000 pg/mL for more than 7 days in mice serum. Pre-infection administration of a single dose of 106 PFU of DEF201 offered full protection of the mice against EV71 infection compared with the empty Ad5 vector control. In addition, virus load in DEF201-treated mice muscle tissue was significantly decreased as compared with empty vector control. Histopathology analysis revealed that DEF201 significantly prevented the development of severe tissue damage with reduction of viral antigen in the murine muscle tissue. Post-infection treatment at 6 h offered full protection and partial protection at 12 h, indicating that DEF201 could be used as an anti-EV71 therapeutic agent in early stage of EV71 infection. In addition, our study showed that DEF201 enhanced the neutralization ability of serum in EV71-vaccinated mice, implying that DEF201 could promote the production of specific anti-EV71 antibodies. In conclusion, single dose of DEF201 is highly efficacious as a prophylactic agent against EV71 infection in vivo.


title: Validating a Widely Implemented Deterioration Index Model Among Hospitalized COVID-19 Patients

text: Introduction: The coronavirus disease 2019 (COVID-19) pandemic is straining the capacity of U.S. healthcare systems. Accurately identifying subgroups of hospitalized COVID-19 patients at high- and low-risk for complications would assist in directing resources. Objective: To validate the Epic Deterioration Index (EDI), a predictive model implemented in over 100 U.S. hospitals that has been recently promoted for use in COVID-19 patients. Methods: We studied adult patients admitted with COVID-19 to non-ICU level care at a large academic medical center from March 9 through April 7, 2020. We used the EDI, calculated at 15-minute intervals, to predict a composite adverse outcome of ICU-level care, mechanical ventilation, or death during the hospitalization. In a subset of patients hospitalized for at least 48 hours, we also evaluated the ability of the EDI (range 0-100) to identify patients at low risk of experiencing this composite outcome during their remaining hospitalization. We evaluated model discrimination and calibration using both raw EDI scores and their slopes. Results: Among 174 COVID-19 patients meeting inclusion criteria, 61 (35%) experienced the composite outcome. Area under the receiver-operating-characteristic curve (AUC) of the EDI was 0.76 (95% CI 0.68-0.84). Patients who met or exceeded an EDI of 64.8 made up 17% of the study cohort and had an 80% probability of experiencing the outcome during their hospitalization with a median lead time of 28 hours from when the threshold was first exceeded to the outcome. Employing the EDI slope lowered the AUCs to 0.68 (95% CI 0.60-0.77) and 0.67 (95% CI 0.59-0.75) for slopes calculated over 4 and 8 hours, respectively. In a subset of 109 patients hospitalized for at least 48 hours and who had not experienced the composite outcome, 14 (13%) patients who never exceeded an EDI of 37.9 had a 93% probability of not experiencing the outcome throughout the rest of their hospitalization, suggesting low risk. Conclusion: In this validation study, we found the EDI identifies small subsets of high- and low-risk patients with fair discrimination. These findings highlight the need for hospitals to carefully evaluate prediction models before widespread operational use among COVID-19 patients.


title: The coming plague

text: A killer pandemic is now more likely than ever. Where will it come from and how can we beat it, asks Debora MacKenzie


docid: vvchfyuu

title: Temporal trends in the incidence and demographics of cancers, communicable diseases, and non-communicable diseases in Saudi Arabia over the last decade

text: OBJECTIVES: To describe the trends in the incidence rates of 5 most common cancers, communicable diseases, and non-communicable diseases in Saudi Arabia over the last decade. METHODS: The incidence rates of cancers (2001-2014), communicable diseases (2003-2016), and non-communicable diseases (1990-2017) were retrieved, classified, and analyzed retrospectively during November 2017, based on data available with the Ministry of Health and were analyzed at the Imam Abdulrahman Bin Faisal University in Dammam, Kingdom of Saudi Arabia. RESULTS: Age-standardized incidence rate (ASR) (per 100,000 population) of breast cancer among women increased dramatically from 11.8 in 2001 to 22.7 in 2014, indicating a 92.4% increase over the decade. Colorectal cancer incidence was the highest among men, and its ASR per 100,000 population increased from 5.0 to 10.6 in men and from 5.0 to 8.2 in women. Among communicable diseases, incidences of hepatitis B, measles, chickenpox, and brucellosis decreased while dengue fever increased. An alarming increase was observed in the incidence rate of non-communicable diseases namely, obesity, diabetes, and hypertension. CONCLUSION: The incidence rate of non-communicable diseases increased over the decade and was associated with increased mortality and disability, reduced quality of life, and increased health-care costs, indicating an urgent need to establish prevention and control programs. The rising trend in the incidence of cancers may also become a health care issue in Saudi Arabia in the coming years.


title: Integrated urban services: Experience from four cities on different continents

text: Abstract Rapid urbanization combined with climate change necessitates new types of urban services that make best use of science and technology. The Integrated Urban Hydro-Meteorological, Climate and Environmental Services and systems are a new initiative from the World Meteorological Organization (WMO) that seeks to provide science-based integrated urban services supporting safe, healthy and resilient cities. Various cities have already started development and implementation of such Integrated Urban Services and successfully test and use them following specific requirements of local stakeholders. This paper demonstrates the novel concept and approach of Integrated Urban Hydro-Meteorological, Climate and Environmental Services (IUS) from a set of four case study cities: Hong Kong, Toronto, Mexico City and Paris, that use different IUS configurations with good existing practice. These cities represent a range of countries, climates and geophysical settings. The aggregate main joint similarities of the IUS in these cities and synergy of the cities' experience, achievements and research findings are presented, as well as identification of existing gaps in knowledge and further research needs. A list of potential criteria for identifying and classifying IUS demonstration cities is proposed. It will aid future, more detailed analysis of the IUS experience, and selection of additional demonstration cities.


title: Charged PVDF multilayer nanofiber filter in filtering simulated airborne novel coronavirus (COVID-19) using ambient nano-aerosols

text: Abstract The novel coronavirus (COVID-19), average size 100 nm, can be aerosolized by cough, sneeze, speech and breath of infected persons. The airborne carrier for the COVID-19 can be tiny droplets and particulates from infected person, fine suspended mists (humidity) in air, or ambient aerosols in air. To-date, unfortunately there are no test standards for nano-aerosols (≤100 nm). A goal in our study is to develop air filters (e.g. respirator, facemask, ventilator, medical breathing filter/system) with 90% capture on 100-nm airborne COVID-19 with pressure drop of less than 30 Pa (3.1 mm water). There are two challenges. First, this airborne bio-nanoaerosol (combined virus and carrier) is amorphous unlike cubic NaCl crystals. Second, unlike standard laboratory tests on NaCl and test oil (DOP) droplets, these polydispersed aerosols all challenge the filter simultaneously and they are of different sizes and can interact among themselves complicating the filtration process. For the first time, we have studied these two effects using ambient aerosols (simulating the bio-nanoaerosols of coronavirus plus carrier of different shapes and sizes) to challenge electrostatically charged multilayer/multimodule nanofiber filters. This problem is fundamentally complicated due to mechanical and electrostatic interactions among aerosols of different sizes with induced charges of different magnitudes. The test filters were arranged in 2, 4, and 6 multiple-modules stack-up with each module having 0.765 g/m2 of charged PVDF nanofibers (mean diameter 525 ± 191 nm). This configuration minimized electrical interference among neighboring charged nanofibers and reduced flow resistance in the filter. For ambient aerosol size>80 nm (applicable to the smallest COVID-19), the electrostatic effect contributes 100–180% more efficiency to the existing mechanical efficiency (due to diffusion and interception) depending on the number of modules in the filter. By stacking-up modules to increase fiber basis weight in the filter, a 6-layer charged nanofiber filter achieved 88%, 88% and 96% filtration efficiency for, respectively, 55-nm, 100-nm and 300-nm ambient aerosol. This is very close to attaining our set goal of 90%-efficiency on the 100-nm ambient aerosol. The pressure drop for the 6-layer nanofiber filter was only 26 Pa (2.65 mm water column) which was below our limit of 30 Pa (3.1 mm water). For the test multi-module filters, a high ‘quality factor’ (efficiency-to-pressure-drop ratio) of about 0.1 to 0.13 Pa−1 can be consistently maintained, which was far better than conventional filters. Using the same PVDF 6-layer charged nanofiber filter, laboratory tests results using monodispersed NaCl aerosols of 50, 100, and 300 nm yielded filtration efficiency, respectively, 92%, 94% and 98% (qualified for 'N98 standard') with same pressure drop of 26 Pa. The 2–6% discrepancy in efficiency for the NaCl aerosols was primarily attributed to the absence of interaction among aerosols of different sizes using monodispersed NaCl aerosols in the laboratory. This discrepancy can be further reduced with increasing number of modules in the filter and for larger 300-nm aerosol. The 6-layer charged nanofiber filter was qualified as a 'N98 respirator' (98% capture efficiency for 300-nm NaCl aerosols) but with pressure drop of only 2.65-mm water which was 1/10 below conventional N95 with 25-mm (exhaling) to 35-mm (inhaling) water column! The 6-layer charged PVDF nanofiber filter provides good personal protection against airborne COVID-19 virus and nano-aerosols from pollution based on the N98 standard, yet it is at least 10X more breathable than a conventional N95 respirator.


Fetal Interventions in the Setting of COVID-19 Pandemic: Statement from the North American Fetal Therapy Network (NAFTNet)


The story of the pandemic: navigating our way between optimism and pessimism


title: COVID-19 pandemic in sub-Saharan Africa: preparedness, response, and hidden potentials

text: After the detection of coronavirus disease 2019 (COVID-19) first reported case in Nigeria, the virus has spread to all sub-Saharan Africa (SSA). Through different initiatives, SSA countries came together to create goal-driven taskforces to improve their responses against the virus. As COVID-19 raises major concerns over the scarcity of medical supplies, numbers of SSA countries adopted innovative solutions to fill in their shortage. This health crisis may come as an opportunity for SSA to demonstrate its pandemic readiness, responses, and reveal unknown potential.


title: Fear and Stigma: The Epidemic within the SARS Outbreak

text: Because of their evolving nature and inherent scientific uncertainties, outbreaks of emerging infectious diseases can be associated with considerable fear in the general public or in specific communities, especially when illness and deaths are substantial. Mitigating fear and discrimination directed toward persons infected with, and affected by, infectious disease can be important in controlling transmission. Persons who are feared and stigmatized may delay seeking care and remain in the community undetected. This article outlines efforts to rapidly assess, monitor, and address fears associated with the 2003 severe acute respiratory syndrome (SARS) epidemic in the United States. Although fear, stigmatization, and discrimination were not widespread in the general public, Asian-American communities were particularly affected.


title: Fine Tuning the Cytokine Storm by IFN and IL-10 Following Neurotropic Coronavirus Encephalomyelitis

text: The central nervous system (CNS) is vulnerable to several viral infections including herpes viruses, arboviruses and HIV to name a few. While a rapid and effective immune response is essential to limit viral spread and mortality, this anti-viral response needs to be tightly regulated in order to limit immune mediated tissue damage. This balance between effective virus control with limited pathology is especially important due to the highly specialized functions and limited regenerative capacity of neurons, which can be targets of direct virus cytolysis or bystander damage. CNS infection with the neurotropic strain of mouse hepatitis virus (MHV) induces an acute encephalomyelitis associated with focal areas of demyelination, which is sustained during viral persistence. Both innate and adaptive immune cells work in coordination to control virus replication. While type I interferons are essential to limit virus spread associated with early mortality, perforin, and interferon-γ promote further virus clearance in astrocytes/microglia and oligodendrocytes, respectively. Effective control of virus replication is nonetheless associated with tissue damage, characterized by demyelinating lesions. Interestingly, the anti-inflammatory cytokine IL-10 limits expansion of tissue lesions during chronic infection without affecting viral persistence. Thus, effective coordination of pro- and anti-inflammatory cytokines is essential during MHV induced encephalomyelitis in order to protect the host against viral infection at a limited cost.


Colorectal cancer surgery during the COVID‐19 pandemic


title: COVID-19: beta-thalassemia subjects immunised?

text: The novel coronavirus pneumonia (COVID-19) is a contagious acute respiratory infectious disease whose causative agent has been demonstrated to be a novel virus of the coronavirus family, SARSCoV-2. A recent PRE-print study has showed a heme attack on the 1-beta chain of hemoglobin by COVID19. Beta-thalassemia results of a default in the hemoglobin beta- chain synthesis. 1,5% global population are heterozygotes for this disease. In this study, by a multiple linear regression, we have analyzed the evolution of COVID-19 infection in three Italian regions (Puglia, Sardinia, Sicilia) with different beta-thalassemic prevalences, in order to search a link. The results have showed that betathalassemic heterozygote population prevalence is correlated to immunity against COVID-19, by a regression. This paper is only for academic discussion, the hypotheses and conclusions needs to be confirmed by further research .


Leptomeningeal involvement in a patient with systemic lupus erythematosus infecting by COVID-19


title: Involvement of caveolin-1 in the Jak–Stat signaling pathway and infectious spleen and kidney necrosis virus infection in mandarin fish (Siniperca chuatsi)

text: Abstract Caveolae, the major source of caveolin-1 protein, are specialized invaginated microdomains of the plasma membrane that act as organizing centers for signaling molecules in the immune system. In the present study, we report the cloning and characterization of caveolin-1 (mCav-1) from mandarin fish (Siniperca chuatsi) and study on the roles of mCav-1 in the fish Jak–Stat signaling pathway and in virus infection. The cDNA sequence of mCav-1 was 707bp in size, encoding a protein of 181 amino acids, which was different from the mammalian protein (178 amino acids). The deduced amino acid sequence of mCav-1 shared similar architecture with vertebrate caveolin-1 proteins, but mCav-1 lacked a phosphorylation site (y14). The major subcellular location of mCav-1 was in the caveolae, where the protein appeared to have major functions. Real-time PCR revealed that the expression of the mandarin fish Mx, IRF-1, SOCS1, and SOCS3 genes involved in the poly(I:C)-induced Jak–Stat signaling pathway was impaired by the mCav-1 scaffolding domain peptide (mSDP). In mandarin fish fry (MFF-1) cells, the protein levels of mCav-1 were markedly up-regulated at 12 and 24h post-infection with ISKNV (infectious spleen and kidney necrosis virus). In addition, ISKNV entry into MFF-1 cells was significantly inhibited by mSDP, and the inhibition was dose-dependent. Thus, ISKNV infection was apparently associated with mCav-1 protein and may utilize the caveolae-related endocytosis pathway. The findings reported here further our understanding of the function of caveolin-1 in the complex signal transduction network in fish immune systems and in the cellular entry mechanism of iridoviruses.


title: The evolution of codon usage in structural and non-structural viral genes: The case of Avian coronavirus and its natural host Gallus gallus

text: Abstract To assess the codon evolution in virus–host systems, Avian coronavirus and its natural host Gallus gallus were used as a model. Codon usage (CU) was measured for the viral spike (S), nucleocapsid (N), nonstructural protein 2 (NSP2) and papain-like protease (PLpro) genes from a diverse set of A. coronavirus lineages and for G. gallus genes (lung surfactant protein A, intestinal cholecystokinin, oviduct ovomucin alpha subunit, kidney vitamin D receptor and the ubiquitary beta-actin) for different A. coronavirus replicating sites. Relative synonymous codon usage (RSCU) trees accommodating all virus and host genes in a single topology showed a higher proximity of A. coronavirus CU to the respiratory tract for all genes. The codon adaptation index (CAI) showed a lower adaptation of S to G. gallus compared to NSP2, PLpro and N. The effective number of codons (Nc) and GC3% revealed that natural selection and genetic drift are the evolutionary forces driving the codon usage evolution of both A. coronavirus and G. gallus regardless of the gene being considered. The spike gene showed only one 100% conserved amino acid position coded by an A. coronavirus preferred codon, a significantly low number when compared to the three other genes (p <0.0001). Virus CU evolves independently for each gene in a manner predicted by the protein function, with a balance between natural selection and mutation pressure, giving further molecular basis for the viruses’ ability to exploit the host's cellular environment in a concerted virus–host molecular evolution.


The COVID Surgery Service (CSS) within the Salzburg COVID‐Emergency Plan (SCEP)


title: Leading Change to Address the Needs and Well-being of Trainees During the COVID-19 Pandemic

text: The coronavirus disease 2019 (COVID-19) pandemic challenged program leaders to respond rapidly to changes in healthcare delivery, protect trainee safety, and transform educational activities. The pandemic demanded that program directors prioritize and address myriad threats to trainees’ well-being. In this paper, we adapt Maslow's needs framework to systematically address trainee well-being during the COVID-19 pandemic and identify potential interventions to meet trainee needs at the program, institution, and extra-institutional levels. Transforming education to effectively respond to trainee well-being needs requires leadership, and we use Kotter's 8 step change management model as an example of a framework to effectively lead change. Program leaders can take this opportunity to reflect upon their training programs and take the opportunity to improve them. Some of the systems of education we develop during the COVID-19 pandemic, such as telehealth, tele-education, and ways to stay connected may provide advantages and will be important to continue and expand upon post-COVID-19.


title: Development and application of a simple recombinase polymerase amplification assay for rapid point-of-care detection of feline herpesvirus type 1

text: Feline herpesvirus type 1 (FHV-1) is a highly contagious pathogen of domestic cats and other members of the family Felidae. Point-of-care diagnosis of persistent infection in cats is essential for control of its spread. A recombinase polymerase amplification (RPA) assay (RPA-LFD-FHV) combined with a lateral flow dipstrip (LFD) was developed that uses human body heat for incubation. Sensitivity was evaluated by testing a serial dilution of a control plasmid, and specificity was evaluated by testing related viruses. Swab samples from cats with suspected infection were tested by RPA-LFD-FHV, and the results were compared to those obtained by PCR to evaluate its clinical performance. The RPA-FLD-FHV assay was carried out successfully within 20 min, using body heat for incubation. The RPA-FLD-FHV had a detection limit of 10(3) copies of the FHV-1 gD gene, which was lower than that of PCR, which was 10(4) copies. The assay could detect templates of FHV-1 but not those of other feline and canine viruses. Viruses in boiled samples could be efficiently detected by the RPA-FLD-FHV. Thirty-one out of the 80 samples were positive by the RPA-FLD-FHV assay, whereas only 27 were positive by PCR. DNA sequencing confirmed that the four samples that were positive by RPA-FLD-FHV but negative by PCR were indeed positive. These results indicate that RPA-FLD-FHV is applicable for clinical use. The RPA-FLD-FHV assay is a simple, rapid, and reliable method for point-of-care diagnosis of FHV-1 infection.


Latest updates on COVID‐2019: A changing paradigm shift


title: Rianimazione e prevenzione delle infezioni nosocomiali

text: I servizi di rianimazione devono organizzare la prevenzione delle infezioni nei loro pazienti in modo minuzioso, in quanto i pazienti sono spesso immunodepressi e subiscono gesti invasivi molteplici, realizzati da personale differente, spesso in situazioni di urgenza e a qualsiasi ora del giorno o della notte. Le principali infezioni che bisogna tentare di prevenire sono le polmoniti batteriche acquisite sotto ventilazione meccanica (PAVM), le infezioni su cateteri intravascolari e le infezioni urinarie su catetere vescicale. L’incidenza di queste infezioni è diminuita nella maggior parte dei servizi che ne effettuano un monitoraggio su base numerica, in particolare nel quadro di programmi di miglioramento della qualità. Le tecniche di prevenzione sono molteplici e devono essere applicate simultaneamente. Esse riguardano delle misure globali, come le modalità di prevenzione della trasmissione crociata (igiene delle mani, in particolare) o di utilizzo degli antibiotici nella prospettiva di ridurre la pressione di selezione di batteri resistenti agli antibiotici, così come delle misure specifiche relative al posizionamento e all’utilizzo di ciascuno dei dispositivi invasivi. Numerose tecniche si sono dimostrate efficaci in studi di buon livello metodologico (igiene delle mani, medicazioni dei cateteri, ecc.) mentre altre sono ancora oggetto di controversie, portando a raccomandazioni nazionali e internazionali regolarmente aggiornate in funzione dei nuovi dati scientifici. Queste misure, implementate in modo ragionato nel quadro di programmi di miglioramento della qualità, consentono di ottenere dei tassi molto bassi per quanto riguarda le infezioni dei cateteri vascolari e dei risultati meno buoni per le PAVM, illustrando la necessità di proseguire la ricerca in questo settore.


title: Antivirals and antiviral strategies

text: In recent years, the demand for new antiviral strategies has increased markedly. There are many contributing factors to this increased demand, including the ever-increasing prevalence of chronic viral infections such as HIV and hepatitis B and C, and the emergence of new viruses such as the SARS coronavirus. The potential danger of haemorrhagic fever viruses and eradicated viruses such as variola virus being used as bioterrorist weapons has also increased the profile of antiviral drug discovery. Here, the virus infections for which antiviral therapy is needed and the compounds that are available, or are being developed, for the treatment of these infections are described. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro975) contains supplementary material, which is available to authorized users.


title: Detection of porcine respiratory coronavirus and transmissible gastroenteritis virus by an enzyme-linked immunosorbent assay

text: Abstract An enzyme-linked immunosorbent assay (ELISA) for the detection of transmissible gastroenteritis virus (TGEV) and porcine respiratory coronavirus (PRCV) was developed. A bovine TGEV-specific polyclonal antibody was purified by affinity chromatography with the TRIO Bioprocessing System and was used as the capture antibody, at a concentration of 1.5 μg/well. The F5.39 monoclonal antibody was obtained by the fusion of spleen lymphocytes from TGEV immunized mice with NS-1 myeloma cells. This mAb was used as a second antibody for the ELISA to detect TGEV in field cases, 53 intestinal samples were taken from pigs exhibiting clinical signs of transmissible gastroenteritis. All the positive samples detected by the ELISA were confirmed as positive by immunofluorescence or cell culture immunofluorescence. To study the ability of this ELISA to detect PRCV in nasal swabs and lung samples, 20 seven-day-old piglets were inoculated with a Quebec strain of PRCV. The ELISA was able to detect PRCV in both kinds of samples.


docid: gyvlikye

title: Pérdida del sentido del olfato durante la pandemia COVID-19


title: Immunoglobulin Fc binding activity is associated with the mouse hepatitis virus E2 peplomer protein

text: Abstract Antigenic variation among murine coronaviruses is associated primarily with the surface peplomer protein E2 (180,000 Dal. E2 is responsible for attachment of the virus to the host cell, MHV-induced cell fusion, and eliciting neutralizing antibody. We report here the molecular mimicry between E2 and Fc γ receptor (FcγR). Molecular mimicry between E2 and FcyR may allow the escape of virus-infected cells from destruction by immunological mechanisms. Rabbit IgG, monoclonal rat IgG1 and IgG2b, monoclonal mouse IgG2a and IgG2b, and the rat anti-mouse FcγR monoclonal antibody 2.4132 immunoprecipitated from MHV-JHM-infected cells a polypeptide with a molecular mass identical to that immunoprecipitated by anti-E2 antibodies. F(ab′)2 fragments of rabbit IgG did not immunoprecipitate any proteins from MHV-infected cells. All of these antibodies did not immunoprecipitate any proteins from uninfected cells. The anti-mouse FcyR monoclonal antibody 2.4132 immunoprecipitated from MHV-JHM-, MHV-3-, or MHV-A59-infected L-2 cells and 17CL-1 cells, or MHV-JHM-infected cultures of neonatal BALB/c brain cells, a protein with a molecular weight identical to that of MHV-JHM E2. The anti-FcyR monoclonal antibody did not immunoprecipitate any proteins from uninfected cells. Furthermore, the 2.4132 monoclonal antibody (mab), unrelated rat and mouse monoclonal antibodies, and a goat antiserum against E2, but not normal goat serum, immunoprecipitated a 75,000- to 77,000-Da molecule from uninfected WEHI-3 cells, a FcγR bearing cell line. Several lines of evidence demonstrated that the protein immunoprecipitated by the anti-FcγR mab from MHV-JHM-infected cells is the E2 glycoprotein: (1) Partial proteolytic maps obtained by Staphylococcus aureus V-8 protease treatment of the 180,000-Da proteins immunoprecipitated by the anti FcγR mab and the anti-E2 mab were identical. (2) Sequential immunoprecipitation experiments from MHV-JHM-infected cells revealed that the same polypeptide chain was recognized by the anti-E2 mab and by the anti-FcγR mab 2.41G2. (3) Actinomycin D did not influence the induction and expression of the 180,000-Da polypeptide chain that was immunoprecipitated by the anti-FcγR mab, demonstrating that this protein is of viral origin.


title: Diagnosis and Treatment of Undifferentiated and Infectious Acute Diarrhea in the Adult Horse

text: Acute, infectious, diarrhea in adult horses is a major cause of morbidity and is associated with numerous complications. Common causes include salmonellosis, clostridiosis, Coronavirus, and infection with Neorickettsia risticii (Potomac horse fever). Treatment is empirical and supportive until results of specific diagnostic tests are available. Supportive care is aimed at restoring hydration, correcting electrolyte imbalances, and limiting the systemic inflammatory response. The mainstays of therapy are intravenous fluid therapy, electrolyte supplementation where necessary, nonsteroidal anti-inflammatory agents, and nutritional support. Specific therapies include colloid oncotic support, antibiotics, hyperimmune plasma, polymyxin B, pentoxifylline, probiotics, binding agents, gastroprotectants, laminitis prevention, and coagulation prophylaxis.


title: Variation of the sequence in the gene encoding for transmembrane protein M of canine coronavirus (CCV)

text: Abstract A nucleotide variability in the sequence of the gene encoding for the transmembrane protein M of canine coronavirus (CCV) is described. A total of 177 faecal samples from pups with enteritis were analysed by a PCR and n-PCR specific for CCV. Four samples, collected from a dog presenting a long-duration shedding of CCV, and a sample from another diarrhoeic dog, were found positive by PCR but negative by n-PCR. Sequence analysis of the samples revealed silent nucleotide substitutions in the binding site of the internal primer used for the n-PCR. Moreover, the nucleotide substitutions occurring over the whole fragment of the five samples analysed were similar.


title: Practical Strategies Against the Novel Coronavirus and COVID-19—the Imminent Global Threat

text: The last month of 2019 harbingered the emergence of a viral outbreak that is now a major public threat globally. COVID-19 was first diagnosed and confirmed in a couple of cases with unknown pneumonia; the patients lived in, or travelled to, Wuhan, the capital of China's Hubei province. People now face a complex challenge that deserves urgent intervention by all involved in medical healthcare globally. Conventional antiviral therapies or vaccines are the most referred means of tackling the virus, but we think establishing these ideal management strategies is presently far-fetched. In-house isolation or quarantine of suspected cases to keep hospital admissions manageable and prevent in-hospital spread of the virus, and promoting general awareness about transmission routes are the practical strategies used to tackle the spread of COVID-19. Cases with weakened or compromised immune systems—for example, elderly individuals, young children, and those with pre-existing conditions such as diabetes, cancer, hypertension, and chronic respiratory diseases—are particularly more susceptible to COVID-19. Hopefully, cumulative data using whole-genome sequencing of the SARS-CoV-2 genome in parallel with mathematical modeling will help the molecular biologists to understand unknown features of the pathogenesis and epidemiology of COVID-19.


title: TNF-α − 308 G/A and IFN-γ + 874 A/T gene polymorphisms in Saudi patients with cutaneous leishmaniasis

text: BACKGROUND: Cutaneous leishmaniasis (CL) is well linked with immunogenetic factors. This study was undertaken to test the association of TNF-α − 308 and IFN-γ + 874 gene polymorphisms with the susceptibility of Leishmania (L) species among CL patients in central region of Saudi Arabia. METHODS: This is a case-control study involved 169 Saudi subjects with different L. species and 199 healthy controls from central region of Saudi Arabia. All subjects were characterized by TNF-α − 308 G/A and IFN-γ + 874 A/T gene polymorphisms using PCR. RESULTS: Evaluation of genotyping and allelic frequency of TNF-α − 308 G/A in different L. species showed no significant association compared to controls (p > 0.05). Except, in cases of L. tropica that showed significantly higher TNF-α − 308 A versus G allele frequency (p = 0.0004). Evaluation of genotyping of IFN-γ + 874 (TT versus AA+AT recessive) and allelic frequency of IFN-γ + 874 (T versus A) showed significant higher in L. major and also in total CL cases as compared to healthy controls (p < 0.05). Furthermore, a strong association was observed between the susceptibility of L. major, L. tropica or total CL cases with synergistically combined high TNF-α 308/INF-γ 874 alleles. CONCLUSIONS: This is the first report that shows the gene polymorphisms of TNF-α − 308 G/A and IFN-γ + 874 A/T in Saudi patients with different L. species infections. Data showed that the TNF-α-308 G/A gene polymorphism is not associated with the susceptibility of CL in Saudi subjects. The only correlation was found in between A versus G allelic frequency in L. tropica. Importantly, IFN-γ + 874 A/T polymorphism was found to be associated with the susceptibility of L. major and also with total CL subjects. Moreover, data from synergistically combined high TNF-α 308/INF-γ 874 alleles strongly suggest their potential role in the susceptibility of leishmania infection.


title: A junior doctor’s experience of critical illness: from treating patients to becoming a patient with COVID‐19

text: When the coronavirus disease 2019 (COVID‐19) pandemic was declared, it was clear that severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) would have far‐reaching impacts on medicine, society and everyday life. As a junior doctor working closely with patients with SARS‐CoV‐2 infection, I was aware of my personal risk of exposure to the virus. I assumed that as a fit and well 26‐year‐old with no comorbidities, if I were to become infected, it was unlikely that COVID‐19 would be severe. However, I became critically unwell following a week of clinical work, necessitating hospital admission, tracheal intubation and mechanical ventilation. I remained mechanically ventilated for 6 days and was then transferred to a medical ward 2 days later. After two further days of rehabilitation, I was discharged home. This reflection is not a junior doctor’s view of how COVID‐19 was managed by the NHS, but a personal view of my illness from ‘the other side of the curtain’. My reflections focus upon the psychological aspects of my experiences, exploring the memories that I formed around the time of critical care, how the fears that I possessed were managed with exceptional communication, and the importance of the wider healthcare team in my recovery.


title: Taking social support into account regarding the mental health of healthcare practitioners involved in treating COVID-19 patients

text: While the WHO has already published its mental health and psychosocial considerations during the COVID-19 outbreak, there has been almost no discussion of the specific measures that healthcare institutions should take with regard to the mental health of healthcare practitioners. We would like to take this occasion to propose a perspective on this matter from research on social support. Social support can be classified in various ways such as informational, appraisal, instrumental, and emotional. When battling an unknown virus such as this one, having correct informational support is necessary above all else. It is also important that appropriate evaluation for the contribution of practitioners in the institutions as appraisal support. Instrumental support, meanwhile, refers to guaranteeing a system where practitioners can get adequate rest and not excessively strain themselves, and emotional support is when practitioners are shown adequate understanding and appreciation by those around them. There is another view that categorizes social support by how it is given and received: received support and perceived support. It is important for practitioners to receive perceived support, because perceived support is confirmed to have a positive effect on physical and mental health. For the sake of the physical and mental health of healthcare practitioners, it is important for healthcare sites and organizations to take social support into account and for healthcare institutions to adopt the perspective of social support in their day-to-day operations.


docid: bfqzjvkx

title: Datenschutzrechtliche Informationen im Zusammenhang mit der Corona-Pandemie


Substantial direct medical costs for symptomatic COVID-19 cases in the US


title: Unravelling lead antiviral phytochemicals for the inhibition of SARS-CoV-2 M(pro) enzyme through in silico approach

text: A new SARS coronavirus (SARS-CoV-2) belonging to the genus Betacoronavirus has caused a pandemic known as COVID-19. Among coronaviruses, the main protease (M(pro)) is an essential drug target which, along with papain-like proteases catalyzes the processing of polyproteins translated from viral RNA and recognizes specific cleavage sites. There are no human proteases with similar cleavage specificity and therefore, inhibitors are highly likely to be nontoxic. Therefore, targeting the SARS-CoV-2 M(pro) enzyme with small molecules can block viral replication. The present study is aimed at the identification of promising lead molecules for SARS-CoV-2 M(pro) enzyme through virtual screening of antiviral compounds from plants. The binding affinity of selected small drug-like molecules to SARS-CoV-2 M(pro), SARS-CoV M(pro) and MERS-CoV M(pro) were studied using molecular docking. Bonducellpin D was identified as the best lead molecule which shows higher binding affinity (−9.28 kcal/mol) as compared to the control (−8.24 kcal/mol). The molecular binding was stabilized through four hydrogen bonds with Glu166 and Thr190 as well as hydrophobic interactions via eight residues. The SARS-CoV-2 M(pro) shows identities of 96.08% and 50.65% to that of SARS-CoV M(pro) and MERS-CoV M(pro) respectively at the sequence level. At the structural level, the root mean square deviation (RMSD) between SARS-CoV-2 M(pro) and SARS-CoV M(pro) was found to be 0.517 Å and 0.817 Å between SARS-CoV-2 M(pro) and MERS-CoV M(pro). Bonducellpin D exhibited broad-spectrum inhibition potential against SARS-CoV M(pro) and MERS-CoV M(pro) and therefore is a promising drug candidate, which needs further validations through in vitro and in vivo studies.


title: Tetralogy of fallot palliation in a COVID-19 positive neonate

text: • Although severe multisystemic manifestations have been defined in adults, there is limited data on the disease burden of COVID-19 in infants and children. • We present the case of a 15-day-old infant who was born with Tetralogy of Fallot (TOF), and was found to be COVID-19 positive on day 7 of life. • Although the majority of children with COVID-19 may be asymptomatic, among symptomatic children, 5% have dyspnea or hypoxemia, and 0.6% progress to acute respiratory distress or multi organ dysfunction. • In the face of this sustained public health crisis, the concomitant occurrence of SARS-CoV-2 with pediatric congenital heart disease may become more and more common; guidance on appropriate management of patients in such a situation is imperative to ensure patient safety.


title: Monophyletic Relationship between Severe Acute Respiratory Syndrome Coronavirus and Group 2 Coronaviruses

text: Although primary genomic analysis has revealed that severe acute respiratory syndrome coronavirus (SARS CoV) is a new type of coronavirus, the different protein trees published in previous reports have provided no conclusive evidence indicating the phylogenetic position of SARS CoV. To clarify the phylogenetic relationship between SARS CoV and other coronaviruses, we compiled a large data set composed of 7 concatenated protein sequences and performed comprehensive analyses, using the maximum-likelihood, Bayesian-inference, and maximum-parsimony methods. All resulting phylogenetic trees displayed an identical topology and supported the hypothesis that the relationship between SARS CoV and group 2 CoVs is monophyletic. Relationships among all major groups were well resolved and were supported by all statistical analyses.


title: The Human Sodium Iodide Symporter as a Reporter Gene for Studying Middle East Respiratory Syndrome Coronavirus Pathogenesis

text: Single photon emission computed tomography (SPECT) is frequently used in oncology and cardiology to evaluate disease progression and/or treatment efficacy. Such technology allows for real-time evaluation of disease progression and when applied to studying infectious diseases may provide insight into pathogenesis. Insertion of a SPECT-compatible reporter gene into a virus may provide insight into mechanisms of pathogenesis and viral tropism. The human sodium iodide symporter (hNIS), a SPECT and positron emission tomography reporter gene, was inserted into Middle East respiratory syndrome coronavirus (MERS-CoV), a recently emerged virus that can cause severe respiratory disease and death in afflicted humans to obtain a quantifiable and sensitive marker for viral replication to further MERS-CoV animal model development. The recombinant virus was evaluated for fitness, stability, and reporter gene functionality. The recombinant and parental viruses demonstrated equal fitness in terms of peak titer and replication kinetics, were stable for up to six in vitro passages, and were functional. Further in vivo evaluation indicated variable stability, but resolution limits hampered in vivo functional evaluation. These data support the further development of hNIS for monitoring infection in animal models of viral disease. IMPORTANCE Advanced medical imaging such as single photon emission computed tomography with computed tomography (SPECT/CT) enhances fields such as oncology and cardiology. Application of SPECT/CT, magnetic resonance imaging, and positron emission tomography to infectious disease may enhance pathogenesis studies and provide alternate biomarkers of disease progression. The experiments described in this article focus on insertion of a SPECT/CT-compatible reporter gene into MERS-CoV to demonstrate that a functional SPECT/CT reporter gene can be inserted into a virus.