title: Pathogenic Neisseria meningitidis utilizes CD147 for vascular colonization

text: Neisseria meningitidis is a cause of meningitis epidemics worldwide and of rapidly progressing fatal septic shock. A crucial step in the pathogenesis of invasive meningococcal infections is the adhesion of bloodborne meningococci to both peripheral and brain endothelia, leading to major vascular dysfunction. Initial adhesion of pathogenic strains to endothelial cells relies on meningococcal type IV pili, but the endothelial receptor for bacterial adhesion remains unknown. Here, we report that the immunoglobulin superfamily member CD147 (also called extracellular matrix metalloproteinase inducer (EMMPRIN) or Basigin) is a critical host receptor for the meningococcal pilus components PilE and PilV. Interfering with this interaction potently inhibited the primary attachment of meningococci to human endothelial cells in vitro and prevented colonization of vessels in human brain tissue explants ex vivo and in humanized mice in vivo. These findings establish the molecular events by which meningococci target human endothelia, and they open new perspectives for treatment and prevention of meningococcus-induced vascular dysfunctions. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm.3563) contains supplementary material, which is available to authorized users.


Kawasaki Disease and Human Coronavirus


title: Good science, bad science

text: The pandemic has generated a dangerous infodemic


title: An atypical winter outbreak of hand, foot, and mouth disease associated with human enterovirus 71, 2010

text: BACKGROUND: To analyze the epidemiological characteristics and pathogenic molecular characteristics of an hand, foot, and mouth disease (HFMD) outbreak caused by enterovirus 71 in Linyi City, Shandong Province, China during November 30 to December 28, 2010. METHODS: One hundred and seventy three stool specimens and 40 throat samples were collected from 173 hospitalized cases. Epidemiologic and clinical investigations, laboratory testing, and genetic analyses were performed to identify the causal pathogen of the outbreak. RESULTS: Among the 173 cases reported in December 2010, the male–female ratio was 1.88: 1; 23 cases (13.3%) were severe. The majority of patients were children aged < 5 years (95.4%). Some patients developed respiratory symptoms including runny nose (38.2%), cough (20.2%), and sore throat (14.5%). One hundred and thirty eight EV71 positive cases were identified based on real time reverse-transcription PCR detection and 107 isolates were sequenced with the VP1 region. Phylogenetic analysis of full-length VP1 sequences of 107 Linyi EV71 isolates showed that they belonged to the C4a cluster of the C4 subgenotype and were divided into 3 lineages (Lineage I, II and III). The two amino acid substitutions (Gly and Gln for Glu) at position 145 within the VP1 region are more likely to appear in EV71 isolates from severe cases (52.2%) than those recovered from mild cases (8.3%). CONCLUSION: This outbreak of HMFD was caused by EV71 in an atypical winter. EV71 strains associated with this outbreak represented three separate chains of transmission. Substitution at amino acid position 145 of the VP1 region of EV71 might be an important virulence marker for severe cases. These findings suggest that continued surveillance for EV71 variants has the potential to greatly impact HFMD prevention and control.


title: Recombinant HcGAPDH Protein Expressed on Probiotic Bacillus subtilis Spores Protects Sheep from Haemonchus contortus Infection by Inducing both Humoral and Cell-Mediated Responses

text: Probiotic Bacillales are effective in controlling pathogens. Live probiotic bacteria improve the composition of the gastrointestinal microbiota, leading to a reduction in pathogen colonization. However, it remains largely unknown how probiotics regulate the host’s immunologic responses and protect the host from parasitic infection. In this study, we addressed whether Bacillales were effective against Haemonchus contortus, a parasitic nematode that infects small ruminants worldwide. Using 16S rRNA sequencing, we found that Bacillales were largely depleted in the abomasal microbiota of sheep infected with H. contortus. We constructed a recombinant Bacillus subtilis named rBS(CotB-HcG) that express the glyceraldehyde-3-phosphate dehydrogenase of H. contortus (HcGAPDH) on its spore surface using the Bacillus subtilis spore coat protein B (CotB) as a carrier. Mice receiving rBS(CotB-HcG) orally showed strong Th1-dominated immune responses. More importantly, sheep administered BS(CotB-HcG) per os showed increasing proliferation of the peripheral blood mononucleates, elevated anti-HcGAPDH IgG in sera, and higher anti-HcGAPDH sIgA in the intestinal mucus than the control sheep. The average weight gain of H. contortus-infected sheep treated with rBS(CotB-HcG) (Hc+rBS(CotB-HcG)) was 48.73% greater than that of unvaccinated sheep. Furthermore, these Hc+rBS(CotB-HcG) sheep had fewer eggs per gram of feces by 84.1% and adult worms by 71.5%. They also demonstrated greatly lessened abomasal damage by H. contortus with an abundance of probiotic species in the abomasal microbiota. Collectively, our data unequivocally demonstrate the protective roles of CotB-HcGAPDH-expressing B. subtilis spores in against H. contortus infection and showed great potential of using probiotic-based strategy in controlling parasitic nematodes of socioeconomic importance in general. IMPORTANCE Initial analyses of the abomasal microbiota of sheep using 16S rRNA sequencing suggested that probiotic bacteria played a protective role in against H. contortus infection. A recombinant Bacillus subtilis expressing a fusion protein CotB-HcGAPDH on its spore’s surface induced strong Th1 immune response in a murine model. The same probiotic recombinant, upon only one oral application, protected sheep against H. contortus infection by reducing egg shedding and decreasing adult worm loads of the parasite and increasing body weight gain of infected sheep. Both Th1 and Th2 immune responses were evident in these immunized sheep.


Social Isolation as a Means of Reducing Dysfunctional Coronavirus Anxiety and Increasing Psychoneuroimmunity


title: COVID-19 spreading in Rio de Janeiro, Brazil: do the policies of social isolation really work?

text: The recent Coronavirus has been spreading through all the world fastly. In this work we focus on the evolution of the COVID-19 in one of the most populous Brazilian states, namely the Rio de Janeiro state. The first case was reported in March 5, 2020, thus we have a considerable amount of available data to make a good analysis. We study the dynamics of COVID-19 through a Susceptible-Infectious-Quarantined-Recovered (SIQR) model with an additional mechanism that represents the implementation of public policies of social isolation. Based on the data collected from the Rio de Janeiro state Department of Health from March 5, 2020 through April 26, 2020, we observed that the implementation of social distancing policies changed the initial exponential growth to a sub-exponential one. The SIQR model with the above-mentioned mechanism is capable of reproducing the data of confirmed cases in Rio de Janeiro, and it explains how that change occurred. The model also predicts an important mitigation effect, namely the flattening effect, i.e., the considerably decrease of the maximum number of confirmed cases. Through the results of the model, this effect can be directly related to the social isolation policies. Finally, we consider the relaxation of such policies, and discuss about the ideal period of time to release people to return to their activities.


title: Evidence of recombination in coronaviruses implicating pangolin origins of nCoV-2019

text: A novel coronavirus (nCoV-2019) was the cause of an outbreak of respiratory illness detected in Wuhan, Hubei Province, China in December of 2019. Genomic analyses of nCoV-2019 determined a 96% resemblance with a coronavirus isolated from a bat in 2013 (RaTG13); however, the receptor binding motif (RBM) of these two genomes share low sequence similarity. This divergence suggests a possible alternative source for the RBM coding sequence in nCoV-2019. We identified high sequence similarity in the RBM between nCoV-2019 and a coronavirus genome reconstructed from a viral metagenomic dataset from pangolins possibly indicating a more complex origin for nCoV-2019.


title: Routine activity effects of the Covid-19 pandemic on burglary in Detroit, March, 2020

text: The spread of the coronavirus has led to containment policies in many places, with concomitant shifts in routine activities. Major declines in crime have been reported as a result. However, those declines depend on crime type and may differ by parts of a city and land uses. This paper examines burglary in Detroit, Michigan during the month of March, 2020, a period of considerable change in routine activities. We examine 879 block groups, separating those dominated by residential land use from those with more mixed land use. We divide the month into three periods: pre-containment, transition period, and post-containment. Burglaries increase in block groups with mixed land use, but not blocks dominated by residential land use. The impact of containment policies on burglary clarifies after taking land use into account.


title: Distinctive clinical features of human bocavirus in children younger than 2 years

text: BACKGROUND AND OBJECTIVE: Clinical characteristics of human bocavirus (HBoV) infection have been studied worldwide, but their importance of those characteristics remains unknown. We investigated distinctive clinical features of HBoV-positive children with lower respiratory tract infection (LRTI). METHODS AND RESULTS: During April 2007–July 2009, for 402 hospitalized children younger than 2 years with LRTI, we prospectively examined virus genomes in nasopharyngeal swabs for HBoV, respiratory syncytial virus (RSV), rhinovirus, metapneumovirus, parainfluenzavirus, and adenovirus. The HBoV genomes were identified in 34 patients (8.5%). Clinical and laboratory data of HBoV-positive and other virus/bacteria-negative patients (n = 18) were analyzed and compared with data of RSV-single positive patients (n = 99). The seasonal distribution of HBoV exhibits a concentration of cases during March–September, with most RSV cases occurring during winter in Japan. The minimum age of HBoV-positive patients was 5 months, although 44 patients (44%) with RSV were younger than 6 months. The main clinical features were respiratory distress and hypoxia. Hypoxia advances within 3 days after onset. The mean oxygen saturation on arrival was 92.8%, which was significantly lower than that in patients with RSV (p < 0.001). White blood cell counts were similar among groups. However, the percentage of neutrophils in white blood cells were significantly higher in HBoV-positive patients (62 vs. 45%, p < 0.001). Their prognoses were good. Their hospital stays were 6.6 days. CONCLUSIONS: HBoV-single positive patients show several clinical characteristics, such as seasonality, age, hypoxia, and neutrophilia, which differ from those with RSV infection.


Intubating Ebola Patients: Technical Limitations of Extensive Personal Protective Equipment


title: Entry of Rhabdoviruses Into Animal Cells

text: Entry is the first step in the infectious life cycle of a virus. In the case of rhabdoviruses, entry is facilitated exclusively by the envelope glycoprotein G and its interactions with the host cell. For vesicular stomatitis virus (VSV), attachment to the cell surface was thought to be facilitated by interactions with the lipid phosphatidylserine, however recent work suggests that it is in fact initiated by recognition of proteinaeous receptors. Clathrin-mediated endocytosis delivers the virions into endosomes where they have been proposed to traffic to multi-vesicular bodies. There, the viral envelope fuses with internal vesicles in a process mediated by glycoprotein G in a pH- and phosphatidylserine-dependent manner. A clear mechanistic understanding of glycoprotein G mediated fusion has yet to be obtained, however current data suggests that it is likely facilitated by events distinct from Class I or Class II fusion proteins of other viruses. Rhabdoviruses are also notable in that their fusion protein exists in a reversible pH-dependent equilibrium, which prevents irreversible preactivation during assembly, and may prove to be relevant in the mediation of cell-to-cell fusion - an alternate form of viral spread.


title: Molekulare Identifikation von Hantaviren in neuen Wirten

text: In addition to classical virus isolation in cell culture, the molecular detection of new virus variants by PCR techniques allows broader epidemiological insights into the world of viral pathogens. For the detection of hantaviruses–zoonotic viruses leading to fever and organ failure in humans–we developed a genus-wide nested RT-PCR format, which enables the discovery of new members within this virus genus. The methodological approach allowed the demonstration of first hantaviruses from Africa and revealed new hantavirus reservoir hosts, as shrews, moles, and bats.


title: Antibody Fragment Expression and Purification

text: Interest in the potential of monoclonal antibodies (mAbs) to serve as therapeutic agents has surged in the past decade with a major emphasis on human viral diseases. There has been much attention in this area directed towards the human immunodeficiency virus type-1 (HIV-1) and promising research developments have emerged on the inhibition of HIV-1 infection by mAbs and the identification of several highly conserved neutralizing epitopes. More recently, potent fully-human neutralizing mAbs have been developed against a variety of important human viral disease agents including the paramyxoviruses Hendra virus and Nipah virus, and human or humanized mAbs have been developed against severe acute respiratory syndrome coronavirus (SARS CoV), and West Nile virus, among others. Most of these more recently developed antiviral mAbs have come from the use of antibody phage-display technologies and the implementation of simplified, inexpensive yet efficient methods, for expressing and purifying the initially selected fragment antibodies is of prime importance in further facilitating this area of research.


title: Models of RNA virus evolution and their roles in vaccine design

text: Viruses are fast evolving pathogens that continuously adapt to the highly variable environments they live and reproduce in. Strategies devoted to inhibit virus replication and to control their spread among hosts need to cope with these extremely heterogeneous populations and with their potential to avoid medical interventions. Computational techniques such as phylogenetic methods have broadened our picture of viral evolution both in time and space, and mathematical modeling has contributed substantially to our progress in unraveling the dynamics of virus replication, fitness, and virulence. Integration of multiple computational and mathematical approaches with experimental data can help to predict the behavior of viral pathogens and to anticipate their escape dynamics. This piece of information plays a critical role in some aspects of vaccine development, such as viral strain selection for vaccinations or rational attenuation of viruses. Here we review several aspects of viral evolution that can be addressed quantitatively, and we discuss computational methods that have the potential to improve vaccine design.


title: Several enteropathogens are circulating in suckling and newly weaned piglets suffering from diarrhea in the province of Villa Clara, Cuba

text: Intestinal contents of suckling (n = 45) and newly weaned (n = 45) piglets, suffering from diarrhea in the province of Villa Clara in Cuba, were tested for viral, bacterial, and parasitic enteropathogens from May to June 2008. At least one enteropathogen was identified in 53.3 % of piglets and enterotoxigenic Escherichia coli (ETEC; 25.6 %) was the major pathogen; mostly STa(+)/STb(+) or F4(+)/STa(+)/STb(+) ETEC were isolated. The overall occurrence of the rest of pathogens was 10 % for transmissible gastroenteritis virus (TGEV) and Cryptosporidium parvum, 6.7 % for rotavirus A and Isospora suis, 5.6 % for α-toxigenic Clostridium perfringens, 3.3 % for verotoxigenic E. coli (VTEC), and 2.2 % for Salmonella enterica subspecies enterica serovar Newport. TGEV and α-toxigenic C. perfringens were only identified in suckling piglets, while Salmonella Newport and VTEC were only detected in weaned pigs. Porcine epidemic diarrhea virus (PEDV), β-toxigenic C. perfringens, Eimeria spp., and helminths were not identified. Eight kinds of mixed infections were detected in 25 % of enteropathogen positive piglets. ETEC was present in 10 of 12 mixed infections, and TGEV infections were never combined. This survey demonstrates that several enteropathogens are circulating in piggeries located in the province of Villa Clara in Cuba, and that is necessary to improve surveillance, prevention, and control of enteric infections in order to increase production efficiency.


title: PLGA nanoparticle entrapped killed porcine reproductive and respiratory syndrome virus vaccine helps in viral clearance in pigs

text: Abstract Porcine reproductive and respiratory syndrome (PRRS) is a chronic viral disease of pigs, has been posing a huge economic concern to pig industry worldwide. In this study, we developed biodegradable PLGA [poly(d,l-lactide-co-glycolide)] nanoparticle-entrapped killed PRRSV vaccine (Nano-KAg), and administered intranasally to pigs once and evaluated the immune correlates. In Nano-KAg vaccinated homologous virus challenged pigs, complete clearance of viremia was observed in 2 weeks, associated with a significant increase in virus neutralizing titers only in the lungs, compared to both unvaccinated and killed vaccine vaccinated pigs. The lung homogenate and sera of Nano-KAg vaccinated pigs had higher levels of IFN-γ and lower levels of TGF-β than control groups. Restimulation of mononuclear cells isolated from the lungs, blood, BAL, and TBLN of Nano-KAg vaccinated pigs’ secreted significantly increased levels of Th1 cytokines, IFN-γ and IL-12. In addition, higher frequencies of CD3+CD8+, CD4+CD8+, and γδ T cells, and reduced frequency of Foxp3+ T-regulatory cells were observed in Nano-KAg vaccinated pigs. Thus, intranasal delivery of Nano-KAg vaccine may be a suitable strategy to elicit anti-PRRSV immune response required to better clear viremia in pigs.


title: Infection by enteric adenoviruses, rotaviruses, and other agents in a rural african environment

text: From February 1985 to January 1986, 432 stool samples, 310 from rural African children with diarrhea and 122 from controls, were analysed for the presence of enteric viruses known to be associated with diarrhea. Group A rotavirus ELISA indicated 12.9% positivity among patients and 2.5% positivity among controls. Only 23 of the 43 rotavirus ELISA‐positive stools were also positive by electron microscopy. Nine children, three of whom were controls, were found to be shedding coronavirus‐like particles, detected by electron microscopy. Stools from all but one of the nine children had been taken within 1 month of each other. Dot‐blot hybridization tests for the presence of Ad40 or Ad41 DNA revealed 44 positive stools, 41 of which were from patients (13.2% positivity). Only three of the Ad40‐ or Ad41‐positive stools by DNA hybridization were positive by electron microscopy, and only these three strains could be grown in semipermissive Chang conjunctival cells and their identity checked by restriction enzyme analysis. Further attempts to rescue the other strains using a helper virus failed, but nine of the stools proved positive by ELISA using a subgroup F‐specific monoclonal antibody. On the basis of the DNA hybridization results alone, subgroup F adenoviruses were encountered as frequently as rotavirus in the study and were significantly associated with diarrhea, although the viability and intactness of virus particles by the time of laboratory analysis appeared to be very low.


title: Clinical management of respiratory syndrome in patients hospitalized for suspected Middle East respiratory syndrome coronavirus infection in the Paris area from 2013 to 2016

text: BACKGROUND: Patients with suspected Middle East respiratory syndrome coronavirus (MERS-CoV) infection should be hospitalized in isolation wards to avoid transmission. This suspicion can also lead to medical confusion and inappropriate management of acute respiratory syndrome due to causes other than MERS-CoV. METHODS: We studied the characteristics and outcome of patients hospitalized for suspected MERS-CoV infection in the isolation wards of two referral infectious disease departments in the Paris area between January 2013 and December 2016. RESULTS: Of 93 adult patients (49 male (52.6%), median age 63.4 years) hospitalized, 82 out of 93 adult patients had returned from Saudi Arabia, and 74 of them were pilgrims (Hajj). Chest X-ray findings were abnormal in 72 (77%) patients. The 93 patients were negative for MERS-CoV RT-PCR, and 70 (75.2%) patients had documented infection, 47 (50.5%) viral, 22 (23.6%) bacterial and one Plasmodium falciparum malaria. Microbiological analysis identified Rhinovirus (27.9%), Influenza virus (26.8%), Legionella pneumophila (7.5%), Streptococcus pneumoniae (7.5%), and non-MERS-coronavirus (6.4%). Antibiotics were initiated in 81 (87%) cases, with two antibiotics in 63 patients (67.7%). The median duration of hospitalization and isolation was 3 days (1–33) and 24 h (8–92), respectively. Time of isolation decreased over time (P < 0.01). Two patients (2%) died. CONCLUSION: The management of patients with possible MERS-CoV infection requires medical facilities with trained personnel, and rapid access to virological results. Empirical treatment with neuraminidase inhibitors and an association of antibiotics effective against S. pneumoniae and L. pneumophila are the cornerstones of the management of patients hospitalized for suspected MERS-CoV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3223-5) contains supplementary material, which is available to authorized users.


title: Chapter One Exploration of the Sialic Acid World

text: Abstract Sialic acids are cytoprotectors, mainly localized on the surface of cell membranes with multiple and outstanding cell biological functions. The history of their structural analysis, occurrence, and functions is fascinating and described in this review. Reports from different researchers on apparently similar substances from a variety of biological materials led to the identification of a 9-carbon monosaccharide, which in 1957 was designated “sialic acid.” The most frequently occurring member of the sialic acid family is N-acetylneuraminic acid, followed by N-glycolylneuraminic acid and O-acetylated derivatives, and up to now over about 80 neuraminic acid derivatives have been described. They appeared first in the animal kingdom, ranging from echinoderms up to higher animals, in many microorganisms, and are also expressed in insects, but are absent in higher plants. Sialic acids are masks and ligands and play as such dual roles in biology. Their involvement in immunology and tumor biology, as well as in hereditary diseases, cannot be underestimated. N-Glycolylneuraminic acid is very special, as this sugar cannot be expressed by humans, but is a xenoantigen with pathogenetic potential. Sialidases (neuraminidases), which liberate sialic acids from cellular compounds, had been known from very early on from studies with influenza viruses. Sialyltransferases, which are responsible for the sialylation of glycans and elongation of polysialic acids, are studied because of their significance in development and, for instance, in cancer. As more information about the functions in health and disease is acquired, the use of sialic acids in the treatment of diseases is also envisaged.


title: Characterization and Noncovalent Inhibition of the Deubiquitinase and deISGylase Activity of SARS-CoV-2 Papain-Like Protease

text: [Image: see text] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, is a novel human betacoronavirus that is rapidly spreading worldwide. The outbreak currently includes over 3.7 million cases and 260,000 fatalities. As a betacoronavirus, SARS-CoV-2 encodes for a papain-like protease (PLpro) that is likely responsible for cleavage of the coronavirus (CoV) viral polypeptide. The PLpro is also responsible for suppression of host innate immune responses by virtue of its ability to reverse host ubiquitination and ISGylation events. Here, the biochemical activity of SARS-CoV-2 PLpro against ubiquitin (Ub) and interferon-stimulated gene product 15 (ISG15) substrates is evaluated, revealing that the protease has a marked reduction in its ability to process K48 linked Ub substrates compared to its counterpart in SARS-CoV. Additionally, its substrate activity more closely mirrors that of the PLpro from the Middle East respiratory syndrome coronavirus and prefers ISG15s from certain species including humans. Additionally, naphthalene based PLpro inhibitors are shown to be effective at halting SARS-CoV-2 PLpro activity as well as SARS-CoV-2 replication.


title: Infectious complications after hematopoietic stem cell transplantation: current status and future perspectives in Korea

text: Hematopoietic stem cell transplantation (HSCT) is a treatment for hematologic malignancies, immune deficiencies, or genetic diseases, ect. Recently, the number of HSCTs performed in Korea has increased and the outcomes have improved. However, infectious complications account for most of the morbidity and mortality after HSCT. Post-HSCT infectious complications are usually classified according to the time after HSCT: pre-engraftment, immediate post-engraftment, and late post-engraftment period. In addition, the types and risk factors of infectious complications differ according to the stem cell source, donor type, conditioning intensity, region, prophylaxis strategy, and comorbidities, such as graft-versushost disease and invasive fungal infection. In this review, we summarize infectious complications after HSCT, focusing on the Korean perspectives.


title: Genomic characterization of equine coronavirus

text: Abstract The complete genome sequence of the first equine coronavirus (ECoV) isolate, NC99 strain was accomplished by directly sequencing 11 overlapping fragments which were RT–PCR amplified from viral RNA. The ECoV genome is 30,992 nucleotides in length, excluding the polyA tail. Analysis of the sequence identified 11 open reading frames which encode two replicase polyproteins, five structural proteins (hemagglutinin esterase, spike, envelope, membrane, and nucleocapsid) and four accessory proteins (NS2, p4.7, p12.7, and I). The two replicase polyproteins are predicted to be proteolytically processed by three virus-encoded proteases into 16 non-structural proteins (nsp1–16). The ECoV nsp3 protein had considerable amino acid deletions and insertions compared to the nsp3 proteins of bovine coronavirus, human coronavirus OC43, and porcine hemagglutinating encephalomyelitis virus, three group 2 coronaviruses phylogenetically most closely related to ECoV. The structure of subgenomic mRNAs was analyzed by Northern blot analysis and sequencing of the leader–body junction in each sg mRNA.


title: QM/QM studies for Michael reaction in coronavirus main protease (3CLPro)

text: Abstract Severe acute respiratory syndrome (SARS) is an illness caused by a novel corona virus wherein the main proteinase called 3CLPro has been established as a target for drug design. The mechanism of action involves nucleophilic attack by Cys145 present in the active site on the carbonyl carbon of the scissile amide bond of the substrate and the intermediate product is stabilized by hydrogen bonds with the residues of the oxyanion hole. Based on the X-ray structure of 3CLPro co-crystallized with a trans-α,β-unsaturated ethyl ester (Michael acceptor), a set of QM/QM and QM/MM calculations were performed, yielding three models with increasingly higher the number of atoms. A previous validation step was performed using classical theoretical calculation and PROCHECK software. The Michael reaction studies show an exothermic process with −4.5kcal/mol. During the reaction pathway, an intermediate is formed by hydrogen and water molecule migration from a histidine residue and solvent, respectively. In addition, similar with experimental results, the complex between N3 and 3CLPro is 578kcal/mol more stable than N1-3CLPro using Own N-layer Integrated molecular Orbital molecular Mechanics (ONIOM) approach. We suggest 3CLPro inhibitors need small polar groups to decrease the energy barrier for alkylation reaction. These results can be useful for the development of new compounds against SARS.


title: Study and interest of cellular load in respiratory samples for the optimization of molecular virological diagnosis in clinical practice

text: BACKGROUND: Respiratory viral diagnosis of upper respiratory tract infections has largely developed through multiplex molecular techniques. Although the sensitivity of different types of upper respiratory tract samples seems to be correlated to the number of sampled cells, this link remains largely unexplored. METHODS: Our study included 800 upper respiratory tract specimens of which 400 negative and 400 positive for viral detection in multiplex PCR. All samples were selected and matched for age in these 2 groups. For the positive group, samples were selected for the detected viral species. RESULTS: Among the factors influencing the cellularity were the type of sample (p < 0.0001); patient age (p < 0.001); viral positive or negative nature of the sample (p = 0.002); and, for the positive samples, the number of viral targets detected (0.004 < p < 0.049) and viral species. CONCLUSION: The cellular load of upper respiratory samples is multifactorial and occurs for many in the sensitivity of molecular detection. However it was not possible to determine a minimum cellularity threshold allowing molecular viral detection. The differences according to the type of virus remain to be studied on a larger scale.


title: Transcriptome and Comparative Gene Expression Analysis of Sogatella furcifera (Horváth) in Response to Southern Rice Black-Streaked Dwarf Virus

text: BACKGROUND: The white backed planthopper (WBPH), Sogatella furcifera (Horváth), causes great damage to many crops by direct feeding or transmitting plant viruses. Southern rice black-streaked dwarf virus (SRBSDV), transmitted by WBPH, has become a great threat to rice production in East Asia. METHODOLOGY/PRINCIPAL FINDINGS: By de novo transcriptome assembling and massive parallel pyrosequencing, we constructed two transcriptomes of WBPH and profiled the alternation of gene expression in response to SRBSDV infection in transcriptional level. Over 25 million reads of high-quality DNA sequences and 81388 different unigenes were generated using Illumina technology from both viruliferous and non-viruliferous WBPH. WBPH has a very similar gene ontological distribution to other two closely related rice planthoppers, Nilaparvata lugens and Laodelphax striatellus. 7291 microsatellite loci were also predicted which could be useful for further evolutionary analysis. Furthermore, comparative analysis of the two transcriptomes generated from viruliferous and non-viruliferous WBPH provided a list of candidate transcripts that potentially were elicited as a response to viral infection. Pathway analyses of a subset of these transcripts indicated that SRBSDV infection may perturb primary metabolism and the ubiquitin-proteasome pathways. In addition, 5.5% (181 out of 3315) of the genes in cell cytoskeleton organization pathway showed obvious changes. Our data also demonstrated that SRBSDV infection activated the immunity regulatory systems of WBPH, such as RNA interference, autophagy and antimicrobial peptide production. CONCLUSIONS/SIGNIFICANCE: We employed massively parallel pyrosequencing to collect ESTs from viruliferous and non-viruliferous samples of WBPH. 81388 different unigenes have been obtained. We for the first time described the direct effects of a Reoviridae family plant virus on global gene expression profiles of its insect vector using high-throughput sequencing. Our study will provide a road map for future investigations of the fascinating interactions between Reoviridae viruses and their insect vectors, and provide new strategies for crop protection.


title: HIV and SARS‐CoV‐2 co‐infection: A case report from Uganda

text: There are no reports of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and HIV co‐infection from sub‐Saharan Africa where 70% of people living with HIV are found. We report a case of HIV/SARS‐CoV‐2 co‐infection from Uganda. A 34 year old HIV‐positive female on antiretroviral therapy (tenofovir disoproxil fumarate, lamivudine and efavirenz) for 5 years, tested positive for SARS‐CoV‐2, the causative agent for coronavirus disease 19 (COVID‐19). She was asymptomatic at presentation but subsequently developed headache, chest pain, diarrhoea, anorexia and fatigue on day 3 of isolation without cough, fever or shortness of breath. Her CD4 count was 965 cells/mm(3), the HIV viral load was undetectable (<1,000 cells/mm(3)) and other laboratory work up was normal. She was successfully managed with hydroxychloroquine and broad spectrum antibiotics, and was discharged after 24 days. This case demonstrates an atypical clinical presentation of COVID – 19 in an HIV infected patient without other co‐morbidity. This article is protected by copyright. All rights reserved.


title: Analysis of Austrian COVID-19 deaths by age and sex

text: We analyze the age and sex distribution of the reported COVID-19 deaths in Austria. In accordance with international studies, the Austrian data also suggests that the risk of death increases substantially with age. The observed age dependency of the proportions of registered COVID-19 deaths in relation to the population sizes in the age groups is approximately exponential, similar to the age dependency of the general age specific mortality rate. Furthermore, we compare the general age specific mortality rate in Austria with the estimates of the SARS-CoV‑2 infection fatality rate by Ferguson et al. (2020). The parallels to the general age specific mortality rates do not imply that COVID-19 does not pose an additional risk. On the contrary, it follows from the structure and magnitude of the infection fatality rate that it is substantial, especially for higher age groups. However, since in many cases persons with severe pre-existing conditions are affected, it is not yet possible to estimate what effects COVID-19 will have on life expectancy.


title: Influenza associated mortality in the subtropics and tropics: Results from three Asian cities

text: Abstract Influenza has been well documented to significantly contribute to winter increase of mortality in the temperate countries, but its severity in the subtropics and tropics was not recognized until recently and geographical variations of disease burden in these regions remain poorly understood. In this study, we applied a standardized modeling strategy to the mortality and virology data from three Asian cities: subtropical Guangzhou and Hong Kong, and tropical Singapore, to estimate the disease burden of influenza in these cities. We found that influenza was associated with 10.6, 13.4 and 8.3 deaths per 100,000 population in Guangzhou, Hong Kong and Singapore, respectively. The annual rates of excess deaths in the elders were estimated highest in Guangzhou and lowest in Singapore. The excess death rate attributable to A/H1N1 subtype was found slightly higher than the rates attributable to A/H3N2 during the study period of 2004–2006 based on the data from Hong Kong and Guangzhou. Our study revealed a geographical variation in the disease burden of influenza in these subtropical and tropical cities. These results highlight a need to explore the determinants for severity of seasonal influenza.


title: Tocilizumab: A Therapeutic Option for the Treatment of Cytokine Storm Syndrome in COVID-19

text: Abstract Presently, we need more therapeutic molecules for this COVID-19 outbreak. The severity and mortality of the disease is associated with a high level of release of cytokine in the patients which is known as CRS (cytokine release syndrome) or cytokine storm syndrome. IL-6 is a type of pro-inflammatory cytokine which release in the severe COVID-19 patients. This cytokine initiates CRS the JAK-STAT pathway. Tocilizumab, a humanized monoclonal antibody, is designed to bind both mIL-6R (membrane bound receptor for IL-6) and sIL-6R (soluble receptor for IL-6) and inhibit the JAK-STAT signaling pathway. It finally stops the cytokine storm syndrome. However, we need to understand that how tocilizumab is bound with mIL-6R or sIL-6R. Similarly, we also need to understand more about the real molecular mechanism of activity of tocilizumab.


title: Emerging zoonoses: responsible communication with the media—lessons learned and future perspectives

text: Abstract Emerging zoonotic disease outbreaks are inevitable and often unpredictable events. The environment surrounding an outbreak is unique in public health, and outbreaks are frequently marked by uncertainty, confusion and a sense of urgency. Good communication at this time, generally through the media, is essential, but examples unfortunately abound of communication failures that have delayed outbreak control, undermined public trust and compliance, and unnecessarily prolonged economic, social and political turmoil. With this paper we hope to disseminate the idea that communication expertise has become as essential to outbreak control as epidemiological training and laboratory analysis. The paper presents the best practices for communicating with the public and discusses future aspects of communicating through the mass media during an outbreak.


title: Phage display of a CTL epitope elicits a long-term in vivo cytotoxic response

text: The Ovalbumin(257–264) CTL epitope on the major coat protein of the filamentous bacteriophage in different antigen formulations was displayed and the immune response in C57BL6/J mice studied. The display of single cytotoxic epitope on the surface of the virion is sufficient to induce priming and sustain long-term major histocompatibility complex class I restricted cytotoxic T lymphocytes response in vivo. The filamentous bacteriophage is a versatile carrier able to display simultaneously either single or multiple epitopes and can elicit a cellular response carrying very little peptide (<1.5 µg).


Risque sanitaire infectieux


title: Clinical course and predictors of 60-day mortality in 239 critically ill patients with COVID-19: a multicenter retrospective study from Wuhan, China

text: BACKGROUND: The global numbers of confirmed cases and deceased critically ill patients with COVID-19 are increasing. However, the clinical course, and the 60-day mortality and its predictors in critically ill patients have not been fully elucidated. The aim of this study is to identify the clinical course, and 60-day mortality and its predictors in critically ill patients with COVID-19. METHODS: Critically ill adult patients admitted to intensive care units (ICUs) from 3 hospitals in Wuhan, China, were included. Data on demographic information, preexisting comorbidities, laboratory findings at ICU admission, treatments, clinical outcomes, and results of SARS-CoV-2 RNA tests and of serum SARS-CoV-2 IgM were collected including the duration between symptom onset and negative conversion of SARS-CoV-2 RNA. RESULTS: Of 1748 patients with COVID-19, 239 (13.7%) critically ill patients were included. Complications included acute respiratory distress syndrome (ARDS) in 164 (68.6%) patients, coagulopathy in 150 (62.7%) patients, acute cardiac injury in 103 (43.1%) patients, and acute kidney injury (AKI) in 119 (49.8%) patients, which occurred 15.5 days, 17 days, 18.5 days, and 19 days after the symptom onset, respectively. The median duration of the negative conversion of SARS-CoV-2 RNA was 30 (range 6–81) days in 49 critically ill survivors that were identified. A total of 147 (61.5%) patients deceased by 60 days after ICU admission. The median duration between ICU admission and decease was 12 (range 3–36). Cox proportional-hazards regression analysis revealed that age older than 65 years, thrombocytopenia at ICU admission, ARDS, and AKI independently predicted the 60-day mortality. CONCLUSIONS: Severe complications are common and the 60-day mortality of critically ill patients with COVID-19 is considerably high. The duration of the negative conversion of SARS-CoV-2 RNA and its association with the severity of critically ill patients with COVID-19 should be seriously considered and further studied.


title: Exacerbations of chronic obstructive pulmonary disease and chronic mucus hypersecretion

text: Abstract Chronic obstructive pulmonary disease (COPD) exacerbations are an important cause of the considerable morbidity and mortality found in COPD. COPD exacerbations increase with increasing severity of COPD, and some patients are prone to frequent exacerbations leading to hospital admission and readmission. These frequent exacerbations may have considerable impact on quality of life and activities of daily living. Factors that increase the risk for COPD exacerbations are associated with increased airway inflammation caused by common pollutants and bacterial and/or viral infections. These inflammatory responses cause mucus hypersecretion and, thereby, airway obstruction and associated exacerbations. While chronic mucus hypersecretion is a significant risk factor for frequent and severe exacerbations, patients with chronic mucus hypersecretion have a lower rate of relapse after initial treatment for acute exacerbation. The benefit of antibiotics for treatment of COPD exacerbations is small but significant. While the mechanisms of actions are not clear, mucolytic agents reduce the number of days of disability in subjects with exacerbations. Reducing mucous cell numbers in small airways could be a useful way to reduce chronic mucus hypersecretion. Our studies suggest that programmed cell death is crucial in the resolution of metaplastic mucous cells, and understanding these mechanisms may provide novel therapies to reduce the risk of COPD exacerbations.


title: COVID-19: A Geriatric Emergency

text: The older Italian population is posing a challenge in the number of deaths for coronavirus disease 2019 (COVID-19). According to previous data from China, pre-existing health conditions dramatically increase the risk of dying from COVID-19. The presence of multiple diseases in older patients may be considered as a mark of frailty, which increases the person’s vulnerability to stress and impairs the multisystemic compensatory effort to restore homeostasis. The clinical complexity associated with the management of frailty may increase the risk of complications during infection as well as the lack of the early recognition of atypical symptoms. There is an urgent need to share expertise and clinical management skills with geriatricians as well as the need for early diagnosis to start treatment at the earliest convenience in the community, with the aim to avoid the collapse of intensive care units.


title: Treating ecological deficit with debt: The practical and political concerns with green bonds

text: Recent years have witnessed calls to ‘unlock’ private capital and unleash a wave of green finance that can address the global environmental crisis. To this end, ample resources are being invested in the rapidly growing market for green bonds: a debt security that links finance to projects that claim environmental benefits. This has placed green bonds in the vanguard of green finance, with a promise of treating our ecological deficit with debt. Such positioning demands close scrutiny of their obstacles, opportunities, and socio-environmental impacts. This paper contributes to this task with a multi-disciplinary review of green bond media articles, grey literature, and academic research. The paper has three key aims. It seeks to provide an introduction to green bonds for scholars who are not fluent in finance. Secondly, it attempts to provide a platform for further green finance research by delineating the major practical and political concerns with green bonds. Finally, it aims to widen our view of the green bond market by putting applied and critical research agendas into direct conversation. The paper concludes by calling for more explicit analysis of what green bonds can actually do; centring an expanded notion of greenwashing in green bond discourse; and pursuing more comparative, case driven research on green bond market development.


title: The performance of RT-PCR compared with a rapid serological assay for acute dengue fever in a diagnostic laboratory

text: Summary The laboratory diagnosis of dengue has largely relied on serological assays, although many different RT-PCR protocols have been reported. Owing to its limited use, the value of RT-PCR in the clinical laboratory has not been fully evaluated. During the outbreak of severe acute respiratory syndrome (SARS) in Singapore in 2003, RT-PCR to detect dengue viral RNA was used as a rapid diagnostic tool to differentiate dengue from SARS among patients who presented to a hospital designated to manage and quarantine SARS cases. A total of 343 results for RT-PCR and 439 results for serology were analysed and compared with the final discharge diagnosis. Our experience indicates that RT-PCR for dengue can be set up rapidly in a clinical laboratory, with very sensitive and specific results for the diagnosis of dengue, particularly in the first 5 days from onset of symptoms.


One size does not fit all – Patterns of vulnerability and resilience in the COVID-19 pandemic and why heterogeneity of disease matters


title: The Long Noncoding RNA NEAT1 Exerts Antihantaviral Effects by Acting as Positive Feedback for RIG-I Signaling

text: Hantavirus infection, which causes zoonotic diseases with a high mortality rate in humans, has long been a global public health concern. Over the past decades, accumulating evidence suggests that long noncoding RNAs (lncRNAs) play key regulatory roles in innate immunity. However, the involvement of host lncRNAs in hantaviral control remains uncharacterized. In this study, we identified the lncRNA NEAT1 as a vital antiviral modulator. NEAT1 was dramatically upregulated after Hantaan virus (HTNV) infection, whereas its downregulation in vitro or in vivo delayed host innate immune responses and aggravated HTNV replication. Ectopic expression of NEAT1 enhanced beta interferon (IFN-β) production and suppressed HTNV infection. Further investigation suggested that NEAT1 served as positive feedback for RIG-I signaling. HTNV infection activated NEAT1 transcription through the RIG-I–IRF7 pathway, whereas NEAT1 removed the transcriptional inhibitory effects of the splicing factor proline- and glutamine-rich protein (SFPQ) by relocating SFPQ to paraspeckles, thus promoting the expression of RIG-I and DDX60. RIG-I and DDX60 had synergic effects on IFN production. Taken together, our findings demonstrate that NEAT1 modulates the innate immune response against HTNV infection, providing another layer of information about the role of lncRNAs in controlling viral infections. IMPORTANCE Hantaviruses have attracted worldwide attention as archetypal emerging pathogens. Recently, increasing evidence has highlighted long noncoding RNAs (lncRNAs) as key regulators of innate immunity; however, their roles in hantavirus infection remain unknown. In the present work, a new unexplored function of lncRNA NEAT1 in controlling HTNV replication was found. NEAT1 promoted interferon (IFN) responses by acting as positive feedback for RIG-I signaling. This lncRNA was induced by HTNV through the RIG-I–IRF7 pathway in a time- and dose-dependent manner and promoted HTNV-induced IFN production by facilitating RIG-I and DDX60 expression. Intriguingly, NEAT1 relocated SFPQ and formed paraspeckles after HTNV infection, which might reverse inhibitive effects of SFPQ on the transcription of RIG-I and DDX60. To the best of our knowledge, this is the first study to address the regulatory role of the lncRNA NEAT1 in host innate immunity after HTNV infection. In summary, our findings provide additional insights regarding the role of lncRNAs in controlling viral infections.


title: Bacterial and fungal colonization of the respiratory tract in COVID-19 patients should not be neglected

text: • We conducted a retrospective study on 61 patients admitted to the ICU; • We investigated the relationship among SARS-CoV-2 and bacterial/fungal colonization; • Among positive bronchial aspirates, 80 % were colonized by fungi or P. aeruginosa; • No multidrug-resistant bacteria or fungi were isolated; • The failure in the regulation of defenses against pathogens other than SARS-CoV-2.


title: An effective docking strategy for virtual screening based on multi-objective optimization algorithm

text: BACKGROUND: Development of a fast and accurate scoring function in virtual screening remains a hot issue in current computer-aided drug research. Different scoring functions focus on diverse aspects of ligand binding, and no single scoring can satisfy the peculiarities of each target system. Therefore, the idea of a consensus score strategy was put forward. Integrating several scoring functions, consensus score re-assesses the docked conformations using a primary scoring function. However, it is not really robust and efficient from the perspective of optimization. Furthermore, to date, the majority of available methods are still based on single objective optimization design. RESULTS: In this paper, two multi-objective optimization methods, called MOSFOM, were developed for virtual screening, which simultaneously consider both the energy score and the contact score. Results suggest that MOSFOM can effectively enhance enrichment and performance compared with a single score. For three different kinds of binding sites, MOSFOM displays an excellent ability to differentiate active compounds through energy and shape complementarity. EFMOGA performed particularly well in the top 2% of database for all three cases, whereas MOEA_Nrg and MOEA_Cnt performed better than the corresponding individual scoring functions if the appropriate type of binding site was selected. CONCLUSION: The multi-objective optimization method was successfully applied in virtual screening with two different scoring functions that can yield reasonable binding poses and can furthermore, be ranked with the potentially compromised conformations of each compound, abandoning those conformations that can not satisfy overall objective functions.


title: Development of a reverse transcription-loop-mediated isothermal amplification as a rapid early-detection method for novel SARS-CoV-2

text: The previous outbreaks of SARS-CoV and MERS-CoV have led researchers to study the role of diagnostics in impediment of further spread and transmission. With the recent emergence of the novel SARS-CoV-2, the availability of rapid, sensitive, and reliable diagnostic methods is essential for disease control. Hence, we have developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the specific detection of SARS-CoV-2. The primer sets for RT-LAMP assay were designed to target the nucleocapsid gene of the viral RNA, and displayed a detection limit of 10(2) RNA copies close to that of qRT-PCR. Notably, the assay has exhibited a rapid detection span of 30 min combined with the colorimetric visualization. This test can detect specifically viral RNAs of the SARS-CoV-2 with no cross-reactivity to related coronaviruses, such as HCoV-229E, HCoV-NL63, HCoV-OC43, and MERS-CoV as well as human infectious influenza viruses (type B, H1N1pdm, H3N2, H5N1, H5N6, H5N8, and H7N9), and other respiratory disease-causing viruses (RSVA, RSVB, ADV, PIV, MPV, and HRV). Furthermore, the developed RT-LAMP assay has been evaluated using specimens collected from COVID-19 patients that exhibited high agreement to the qRT-PCR. Our RT-LAMP assay is simple to perform, less expensive, time-efficient, and can be used in clinical laboratories for preliminary detection of SARS-CoV-2 in suspected patients. In addition to the high sensitivity and specificity, this isothermal amplification conjugated with a single-tube colorimetric detection method may contribute to the public health responses and disease control, especially in the areas with limited laboratory capacities.


title: The impact of SARS‐Cov‐2 pandemic on stroke care: A warning message

text: The recent coronavirus disease (COVID‐19) pandemic intensely impacted the health systems worldwide, which had to deal with the challenge of contemporarily answering to the needs of COVID‐19 patients and managing other life threatening disorders. Several European countries such as Italy, France and Spain, particularly hit by the pandemic, had to deeply reorganize healthcare and to redistribute personnel, resources and beds to deal with the demands of the uncontrolled spreading of the COVID‐19 infection.


title: The duty to treat in the context of an influenza pandemic

text: Abstract The recent influenza pandemic proved that an influenza pandemic is no longer a future scenario. It may urge health care workers to undergo certain or even large risks. According to the WHO as well as commentators, a strong case can be made for adopting a duty to treat during a disease outbreak. Many current professional codes of ethics, however, fail to provide explicit guidance sufficient to set policy or assure the public in the event of an infectious disease outbreak. This paper aims to assess whether there is a duty to treat in the case of an influenza pandemic. As we conclude that there are valid reasons that support the duty to treat in this specific context, we will subsequently explore its scope and limits.


title: Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19

text: Abstract Background The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, December 2019, and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. Objective To identify biomarkers for disease severity and progression of COVID-19. Methods Forty-eight cytokines in the plasma samples from 50 COVID-19 cases including 11 critically ill, 25 severe and 14 moderate patients were measured and analyzed in combination with clinical data. Results Fourteen cytokines were found to be significantly elevated in COVID-19 cases and showed different expression profiles in patients with different disease severity. Moreover, expression levels of IP-10, MCP-3, HGF, MIG and MIP-1α, which were shown to be highly associated with disease severity during disease progression, were remarkably higher in critically ill patients, followed by severe and then the moderate patients. Serial detection of the five cytokines in 16 cases showed that continuously high levels were associated with deteriorated progression of disease and fatal outcome. Furthermore, IP-10 and MCP-3 were excellent predictors for the progression of COVID-19, and the combination of the two cytokines showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations with a value of 0.99. Conclusion In this study, we report biomarkers that highly associated with disease severity and progression of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, and provide potential therapeutic targets and strategies.


title: PCR for Detection of Oseltamivir Resistance Mutation in Influenza A(H7N9) Virus

text: Sensitive molecular techniques are needed for rapid detection of the R292K oseltamivir-resistant mutant of influenza A(H7/N9) virus strain to monitor its transmission and guide antiviral treatment. We developed a real-time reverse transcription PCR and single nucleotide polymorphism probes to differentiate this mutant strain in mixed virus populations in human specimens.


title: Respiratory viruses associated with severe pneumonia in children under 2 years old in a rural community in Pakistan

text: The objective of this study was to determine the incidence of respiratory viruses associated with severe pneumonia among children less than 2 years of age in the rural district of Matiari in Sindh, Pakistan. This study was a community‐based prospective cohort active surveillance of infants enrolled at birth and followed for 2 years. Cases were identified using the World Health Organization's Integrated Management of Childhood Illnesses’ definition of severe pneumonia. Nasopharyngeal swabs were obtained for assessment by multiplex RT‐PCR for eight viruses and their subtypes, including RSV, influenza virus, human metapneumovirus, enterovirus/rhinovirus, coronavirus, parainfluenza virus, adenovirus, and human bocavirus. Blood cultures were collected from febrile participants. A total of 817 newborns were enrolled and followed with fortnightly surveillance for 2 years, accounting for a total of 1,501 child‐years of follow‐up. Of the nasopharyngeal swabs collected, 77.8% (179/230) were positive for one or more of the above mentioned respiratory viruses. The incidence of laboratory confirmed viral‐associated pneumonia was 11.9 per 100 child‐years of follow‐up. Enterovirus/rhinovirus was detected in 51.7% patients, followed by parainfluenza virus type III (8.3%), and RSV (5.7%). Of the uncontaminated blood cultures, 1.4% (5/356) were positive. Respiratory viruses are frequently detected during acute respiratory infection episodes in children under 2 years old in a rural community in Pakistan. However, causal association is yet to be established and the concomitant role of bacteria as a co‐infection or super‐infection needs further investigation. J. Med. Virol. 88:1882–1890, 2016. © 2016 Wiley Periodicals, Inc.


Into the looking glass: Post-viral syndrome post COVID-19


title: Angiotensin Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Use Among Outpatients Diagnosed with COVID-19

text: Coronavirus disease 2019 (COVID-19) is a viral pandemic precipitated by the severe acute respiratory syndrome coronavirus 2. Since previous reports suggested that viral entry into cells may involve angiotensin converting enzyme 2, there has been growing concern that angiotensin converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) use may exacerbate the disease severity. In this retrospective, single-center US study of adult patients diagnosed with COVID-19, we evaluated the association of ACEI/ARB use with hospital admission. Secondary outcomes included: ICU admission, mechanical ventilation, length of hospital stay, use of inotropes, and all-cause mortality. Propensity score matching was performed to account for potential confounders. Among 590 unmatched patients diagnosed with COVID-19, 78 patients were receiving ACEI/ARB (median age 63 years and 59.7% male) and 512 patients were non-users (median age 42 years and 47.1% male). In the propensity matched population, multivariate logistic regression analysis adjusting for age, gender and comorbidities demonstrated that ACEI/ARB use was not associated with hospital admission (OR 1.2, 95% CI 0.5-2.7, p = 0.652). CAD and CKD/ESRD remained independently associated with admission to hospital. All-cause mortality, ICU stay, need for ventilation, and inotrope use was not significantly different between the 2 study groups. In conclusion, among patients who were diagnosed with COVID-19, ACEI/ARB use was not associated with increased risk of hospital admission.


title: Multiplex Molecular Detection of Respiratory Pathogens in Children With Asthma Exacerbation

text: Background Up to 80% of asthma exacerbations in white children are associated with viral upper respiratory infections. The relative importance of different respiratory pathogens and relevant microbiological data in Asian children are unclear. This study elucidated the epidemiology of respiratory infections in Hong Kong children with asthma exacerbation. Methods A total of 209 children aged 3-18 years with asthma exacerbations and 77 controls with stable asthma were recruited. The severity of asthma exacerbations was assessed according to Global Initiative for Asthma guideline, and subjects aged 6 years or older performed exhaled nitric oxide and spirometric measurements. Nested multiplex polymerase chain reaction was used to detect 20 different respiratory pathogens. Results Respiratory pathogens were detected in 105 (51.0%) subjects. The presence of any respiratory pathogen was associated with asthma exacerbation (odds ratio [OR], 2.77; 95% CI, 1.51–5.11; P < .001). Specifically, human rhinovirus (HRV) infection was more common among children with asthma exacerbation (OR, 2.38; 95% CI, 1.09–5.32; P = .018). All other pathogens or coinfections were not associated with asthmatic attacks. None of these respiratory infections was associated with the severity of asthma exacerbation (P > .15 for all). During peak HRV season in the winter of 2007 to 2008, this virus was detected in 46.4% of children with asthma exacerbations. Conclusions Respiratory viral infections are commonly found in children with asthma exacerbation, with HRV being the most important pathogen in our patients. Respiratory viral infection is a triggering factor for asthma exacerbation but does not correlate with its severity.


title: Clinical trial analysis of 2019‐nCoV therapy registered in China

text: So far, there is a lack of effective drugs for the new coronavirus pneumonia. With more and more patients diagnosed, China has carried out more than 100 clinical studies of new coronavirus infection, including antiviral drugs, antimalarial drugs, glucocorticoids, plasma therapy, virus vaccine, and other Western drugs, while Chinese medicine research accounted for half of the studies. Most of the trials were initiated by investigators and the study period would last for 1 to 11 months. The primary endpoints included symptom improvement and virus nucleic acid turning negative, but the optimal endpoint has not been determined. Although the final results of studies will take a long time to complete, the interim research data may provide some help for the current urgent demand for drug treatment. Compared with that of during SARS period in 2003, China has the stronger capability to carry out clinical trials of new drugs in emergency period.


title: Pathogenicity study of Iranian genotype of avian infectious bronchitis virus (IR-1)

text: Avian infectious bronchitis (IB) is a major cause of economic losses in poultry industry. The IB virus primarily affects respiratory tract, but various strains differ in their tropism for other target organs such as kidney and alimentary tract. The objective of this study was to estimate the pathogenicity of Iranian IBV variant (IR-1), which is limited exclusively to Iran. Specific pathogen free chicks were inoculated intranasally. Sera, fecal swabs and different tissue samples were collected on different days post infection (DPI). Clinical signs, gross pathology and histological changes were recorded. The viral load was quantified in the RNA extractions from different tissue samples using real-time PCR. Anti-IBV antibodies were detected in serum samples. The IgG antibody were found on 21 and 28 DPI. Severe histological lesions were observed in the trachea and lung while the lesions in kidney were appeared to be milder. Viral RNA was detected in all tested tissues from 1 DPI to the last day of the experiment. The highest viral load was measured in the trachea and feces on 1(st) and 5(th) DPI, respectively. It can be concluded the IR-1 had broad tropism for respiratory tract, digestive system, and renal tissue, reflecting its epitheliotropic nature, but it caused the most severe lesions in the respiratory tract. This was the first pathogenicity study of Iranian IR-1 IBV. Further knowledge of IBV pathogenesis provides the groundwork to inform more effective prevention practices.


title: Retrospective analysis of nosocomial infections in the intensive care unit of a tertiary hospital in China during 2003 and 2007

text: BACKGROUND: Nosocomial infections are a major threat to patients in the intensive care unit (ICU). Limited data exist on the epidemiology of ICU-acquired infections in China. This retrospective study was carried out to determine the current status of nosocomial infection in China. METHODS: A retrospective review of nococomial infections in the ICU of a tertiary hospital in East China between 2003 and 2007 was performed. Nosocomial infections were defined according to the definitions of Centers for Disease Control and Prevention. The overall patient nosocomial infection rate, the incidence density rate of nosocomial infections, the excess length of stay, and distribution of nosocomial infection sites were determined. Then, pathogen and antimicrobial susceptibility profiles were further investigated. RESULTS: Among 1980 patients admitted over the period of time, the overall patient nosocomial infection rate was 26.8% or 51.0 per 1000 patient days., Lower respiratory tract infections (LRTI) accounted for most of the infections (68.4%), followed by urinary tract infections (UTI, 15.9%), bloodstream (BSI, 5.9%), and gastrointestinal tract (GI, 2.5%) infections. There was no significant change in LRTI, UTI and BSI infection rates during the 5 years. However, GI rate was significantly decreased from 5.5% in 2003 to 0.4% in 2007. In addition, A. baumannii, C. albicans and S. epidermidis were the most frequent pathogens isolated in patients with LRTIs, UTIs and BSIs, respectively. The rates of isolates resistant to commonly used antibiotics ranged from 24.0% to 93.1%. CONCLUSION: There was a high and relatively stable rate of nosocomial infections in the ICU of a tertiary hospital in China through year 2003–2007, with some differences in the distribution of the infection sites, and pathogen and antibiotic susceptibility profiles from those reported from the Western countries. Guidelines for surveillance and prevention of nosocomial infections must be implemented in order to reduce the rate.


title: Lifting the lid on toilet plume aerosol: A literature review with suggestions for future research

text: BACKGROUND: The potential risks associated with “toilet plume” aerosols produced by flush toilets is a subject of continuing study. This review examines the evidence regarding toilet plume bioaerosol generation and infectious disease transmission. METHODS: The peer-reviewed scientific literature was searched to identify articles related to aerosol production during toilet flushing, as well as epidemiologic studies examining the potential role of toilets in infectious disease outbreaks. RESULTS: The studies demonstrate that potentially infectious aerosols may be produced in substantial quantities during flushing. Aerosolization can continue through multiple flushes to expose subsequent toilet users. Some of the aerosols desiccate to become droplet nuclei and remain adrift in the air currents. However, no studies have yet clearly demonstrated or refuted toilet plume-related disease transmission, and the significance of the risk remains largely uncharacterized. CONCLUSION: Research suggests that toilet plume could play a contributory role in the transmission of infectious diseases. Additional research in multiple areas is warranted to assess the risks posed by toilet plume, especially within health care facilities.


title: Applications of nanotechnology in food packaging and food safety: Barrier materials, antimicrobials and sensors

text: Abstract In this article, several applications of nanomaterials in food packaging and food safety are reviewed, including: polymer/clay nanocomposites as high barrier packaging materials, silver nanoparticles as potent antimicrobial agents, and nanosensors and nanomaterial-based assays for the detection of food-relevant analytes (gasses, small organic molecules and food-borne pathogens). In addition to covering the technical aspects of these topics, the current commercial status and understanding of health implications of these technologies are also discussed. These applications were chosen because they do not involve direct addition of nanoparticles to consumed foods, and thus are more likely to be marketed to the public in the short term.


title: Review on the global epidemiological situation and the efficacy of chloroquine and hydroxychloroquine for the treatment of COVID-19

text: Covid-19 disease is caused by SARS-CoV-2, a virus belonging to the coronavirus family. Covid-19 is so new that there is currently no specific vaccine or treatment. Clinical trials are currently underway. In vitro tests are also being conducted to assess the efficacy of chloroquine and hydroxychloroquine for the treatment of this epidemic, which is considered a pandemic by the WHO. We note that the content of this review is dated. The information it contains is subject to change and modification as the epidemic progresses.


Ethical reflections on the COVID‐19 pandemic: The epidemiology of panic


Brève : Vivre avec un cancer en période d'épidémie


title: Overexpression of a wheat jasmonate-regulated lectin increases pathogen resistance

text: Abstract Jasmonates are known to induce the transcriptional activation of plant defense genes, which leads to the production of jasmonate-regulated proteins (JRP). We previously cloned and characterized a novel jacalin-like lectin gene (Ta-JA1) from wheat (Triticum aestivum L.), which codes a modular JRP with disease response and jacalin-related lectin (JRL) domains and is present only in the Gramineae family. The function of this protein is still unclear. Phylogenetic analysis indicated that Ta-JA1 and related proteins from cereals grouped together, which diverged from JRL with an additional N-terminal disease response domain. The recombinant Ta-JA1 proteins agglutinated rabbit erythrocytes, and this hemagglutination activity was preferentially inhibited by mannose. The Ta-JA1 protein was able to inhibit E. coli cell growth. Overexpression of Ta-JA1 in transgenic tobacco plants increased their resistance to infection by tobacco bacterial, fungal and viral pathogens. Our results suggest that Ta-JA1 belongs to a mannose-specific lectin, which may confer a basal but broad-spectrum resistance to plant pathogens. Ta-JA1 and its homologues in maize, rice, sorghum and creeping bentgrass may represent a new type of monocot lectin with a modular structure and diversity of physiological functions in biotic and abiotic stress responses.


title: Detection of Airborne Severe Acute Respiratory Syndrome (SARS) Coronavirus and Environmental Contamination in SARS Outbreak Units

text: Severe acute respiratory syndrome (SARS) is characterized by a risk of nosocomial transmission; however, the risk of airborne transmission of SARS is unknown. During the Toronto outbreaks of SARS, we investigated environmental contamination in SARS units, by employing novel air sampling and conventional surface swabbing. Two polymerase chain reaction (PCR)–positive air samples were obtained from a room occupied by a patient with SARS, indicating the presence of the virus in the air of the room. In addition, several PCR-positive swab samples were recovered from frequently touched surfaces in rooms occupied by patients with SARS (a bed table and a television remote control) and in a nurses’ station used by staff (a medication refrigerator door). These data provide the first experimental confirmation of viral aerosol generation by a patient with SARS, indicating the possibility of airborne droplet transmission, which emphasizes the need for adequate respiratory protection, as well as for strict surface hygiene practices


title: A cause for concern

text: The UK government has released the scientific advice it has received on covid-19, and independent experts aren't impressed, reports Jessica Hamzelou


title: Children and adolescents in the CoVid-19 pandemic: Schools and daycare centers are to be opened again without restrictions. The protection of teachers, educators, carers and parents and the general hygiene rules do not conflict with this

text: In the opinion of the medical societies of hygiene and pediatrics undersigning the present statement, the analyses published to date regarding transmission of SARS-CoV-2 and the course of CoVid-19 show that children play a much less significant role in the spread of the virus than do adults. According to the findings available to date, not only do children and adolescents less frequently fall ill with CoVid-19, they also generally become less severely ill than do adults. The vast majority of infections in children and adolescents are asymptomatic or oligosymptomatic. Even the first analyses from China demonstrated that children and adolescents play a subordinate role in the transmission of the virus – not only to other children and adolescents, but also to adults. Taking into account regional infection rates and available resources, daycare centers, kindergartens and elementary schools promptly should be reopened. For children, this should be possible without excessive restrictions, such as clustering into very small groups, implementation of barrier precautions, maintaining appropriate distance from others or wearing masks. A factor more decisive than individual group size is the issue of sustaining the constancy of respective group members and the avoidance of intermixing. Children can be taught basic rules of hygiene such as handwashing and careful hygiene behavior when coming into contact with others during mealtimes and/or when using sanitary facilities. Independent of the prevention measures implemented for children and adolescents, the protection of teachers, educators and caregivers is crucial, (e.g., the maintenance of appropriate distance from others, use of medical masks, situation-dependent hand disinfection, when necessary, supported by regular pool testing). Children over the age of 10 and adolescents up to school graduation age are more capable of actively understanding and conforming to specific hygiene rules. For this group, maintaining appropriate distance from others (1.5 meters), wearing a mouth-and-nose protection (whenever they are not sitting in their assigned classroom seats) and consistent education regarding the basic rules of infection prevention may provide increased options for normalizing teaching activities. Children and adolescents suspected of infection with SARS-CoV-2 should be tested immediately in order to either confirm or rule out such an infection. Evidence of individual infections in children or students must not automatically lead to the closure of the entire daycare center or school. A detailed analysis of the chain of infection is a prerequisite for a balanced approach to infection control. The opening of schools and children’s facilities should be accompanied by specifically structured, model surveillance studies that further clarify outstanding questions about infectious disease events and hygiene control. These prospective, concomitant examinations will be essential for the purpose of evaluating and verifying the effectiveness of the required hygiene measures.


title: Inflammation and changes in cytokine levels in neurological feline infectious peritonitis

text: Abstract Feline infectious peritonitis (FIP) is a progressive, fatal, predominantly Arthus-type immune-mediated disease that is triggered when cats are infected with a mutant enteric coronavirus. The disease presents variably with multiple organ failure, seizures, generalized effusion, or shock. Neurological FIP is clinically and pathologically more homogeneous than systemic ‘wet’ or ‘dry’ FIP; thus, comparison of cytokine profiles from cats with neurological FIP, wet FIP, and non-FIP neurological disease may provide insight into some baseline characteristics relating to the immunopathogenesis of neurological FIP. This study characterizes inflammation and changes in cytokines in the brain tissue of FIP-affected cats. Cellular infiltrates in cats with FIP included lymphocytes, plasma cells, neutrophils, macrophages, and eosinophils. IL-1β, IL-6, IL-12, IL-18, TNF-α, macrophage inhibitory protein (MIP)-1α, and RANTES showed no upregulation in the brains of control cats, moderate upregulation in neurological FIP cats, and very high upregulation in generalized FIP cats. Transcription of IFN-γ appeared upregulated in cats with systemic FIP and slightly downregulated in neurological FIP. In most cytokines tested, variance was extremely high in generalized FIP and much less in neurological FIP. Principal components analysis was performed in order to find the least number of ‘components’ that would summarize the cytokine profiles in cats with neurological FIP. A large component of the variance (91.7%) was accounted for by levels of IL-6, MIP-1α, and RANTES. These findings provide new insight into the immunopathogenesis of FIP and suggest targets for immune therapy of this disease.


title: epic2: National Evidence-Based Guidelines for Preventing Healthcare-Associated Infections in NHS Hospitals in England

text: Executive Summary National evidence-based guidelines for preventing healthcare-associated infections (HCAI) in National Health Service (NHS) hospitals in England were commissioned by the Department of Health (DH) and developed during 1998-2000 by a nurse-led multi-professional team of researchers and specialist clinicians. Following extensive consultation, they were published in January 2001.1 These guidelines describe the precautions healthcare workers should take in three areas: standard principles for preventing HCAI, which include hospital environmental hygiene, hand hygiene, the use of personal protective equipment, and the safe use and disposal of sharps; preventing infections associated with the use of short-term indwelling urethral catheters; and preventing infections associated with central venous catheters. The evidence for these guidelines was identified by multiple systematic reviews of experimental and non-experimental research and expert opinion as reflected in systematically identified professional, national and international guidelines, which were formally assessed by a validated appraisal process. In 2003, we developed complementary national guidelines for preventing HCAI in primary and community care on behalf of the National Collaborating Centre for Nursing and Supportive Care (National Institute for Healthand Clinical Excellence).2 A cardinal feature of evidence-based guidelines is that they are subject to timely review in order that new research evidence and technological advances can be identified, appraised and, if shown to be effective in preventing HCAI, incorporated into amended guidelines. Periodically updating the evidence base and guideline recommendations is essential in order to maintain their validity and authority. Consequently, the DH commissioned a review of new evidence published following the last systematic reviews. We have now updated the evidence base for making infection prevention and control recommendations. A critical assessment of the updated evidence indicated that the original epic guidelines published in 2001 remain robust, relevant and appropriate but that adjustments need to be made to some guideline recommendations following a synopsis of the evidence underpinning the guidelines. These updated national guidelines (epic2) provide comprehensive recommendations for preventing HCAI in hospitals and other acute care settings based on the best currently available evidence. Because this is not always the best possible evidence, we have included a suggested agenda for further research in each section of the guidelines. National evidence-based guidelines are broad principles of best practice which need to be integrated into local practice guidelines. To monitor implementation, we have suggested key audit criteria for each section of recommendations. Clinically effective infection prevention and control practice is an essential feature of protecting patients. By incorporating these guidelines into routine daily clinical practice, patient safety can be enhanced and the risk of patients acquiring an infection during episodes of healthcare in NHS hospitals in England can be minimised.


title: Experimental screening studies on rabies virus transmission and oral rabies vaccination of the Greater Kudu (Tragelaphus strepsiceros)

text: Rabies in the Greater Kudu (Tragelaphus strepsiceros) in Namibia is unique and found in such magnitude as has not been reported elsewhere in southern Africa. Reasons as to why Kudus appear to be exceptionally susceptible to rabies still remain speculative at best. Because the current severe rabies endemic in Kudus continues to have an enormous negative impact on the Namibian agricultural sector, we set out to question existing dogmas regarding the epidemiology of the disease in a unique experimental setting. In addition, we explored effective measures to protect these antelopes. Although we were able to confirm high susceptibly of kudus for rabies and sporadic horizontal rabies virus transmission to contact animals, we contend that these observations cannot plausibly explain the rapid spread of the disease in Kudus over large territories. Since parenteral vaccination of free-roaming Kudus is virtually impossible, oral rabies vaccination using modified life virus vaccines with a high safety profile would be the ultimate solution to the problem. In a proof-of-concept study using a 3rd generation oral rabies virus vaccine construct (SPBN GASGAS) we found evidence that Kudus can be vaccinated by the oral route and protected against a subsequent rabies infection. In a second phase, more targeted studies need to be initiated by focusing on optimizing oral vaccine uptake and delivery.


title: Novel adenovirus detected in captive bottlenose dolphins (Tursiops truncatus) suffering from self-limiting gastroenteritis

text: BACKGROUND: Adenoviruses are common pathogens in vertebrates, including humans. In marine mammals, adenovirus has been associated with fatal hepatitis in sea lions. However, only in rare cases have adenoviruses been detected in cetaceans, where no clear correlation was found between presence of the virus and disease status. CASE PRESENTATION: A novel adenovirus was identified in four captive bottlenose dolphins with self-limiting gastroenteritis. Viral detection and identification were achieved by: PCR-amplification from fecal samples; sequencing of partial adenovirus polymerase (pol) and hexon genes; producing the virus in HeLa cells, with PCR and immunofluorescence detection, and with sequencing of the amplified pol and hexon gene fragments. A causative role of this adenovirus for gastroenteritis was suggested by: 1) we failed to identify other potential etiological agents; 2) the exclusive detection of this novel adenovirus and of seropositivity for canine adenoviruses 1 and 2 in the four sick dolphins, but not in 10 healthy individuals of the same captive population; and 3) the virus disappeared from feces after clinical signs receded. The partial sequences of the amplified fragments of the pol and hexon genes were closest to those of adenoviruses identified in sea lions with fatal adenoviral hepatitis, and to a Genbank-deposited sequence obtained from a harbour porpoise. CONCLUSION: These data suggest that adenovirus can cause self-limiting gastroenteritis in dolphins. This adenoviral infection can be detected by serology and by PCR detection in fecal material. Lack of signs of hepatitis in sick dolphins may reflect restricted tissue tropism or virulence of this adenovirus compared to those of the adenovirus identified in sea lions. Gene sequence-based phylogenetic analysis supports a common origin of adenoviruses that affect sea mammals. Our findings suggest the need for vigilance against adenoviruses in captive and wild dolphin populations.


title: Can artificial intelligence identify effective COVID‐19 therapies?

text: In this issue of EMBO Molecular Medicine, Stebbing et al (2020b) validate an artificial intelligence‐assisted prediction that a drug used to treat rheumatoid arthritis could be a potent weapon against COVID‐19. Using liver organoids infected with SARS‐CoV‐2, they confirm dual antiviral and anti‐inflammatory activities and show that its administration in four COVID‐19 patients is correlated with disease improvement, paving the way for more rigorous placebo‐controlled trials.


title: Pitfalls in telemedicine consultations in the era of COVID 19 and how to avoid them

text: BACKGROUND AND AIMS: With restrictions on face to face clinical consultations in the COVID-19 pandemic, Telemedicine has become an essential tool in providing continuity of care to patients. We explore the common pitfalls in remote consultations and strategies that can be adopted to avoid them. METHODS: We have done a comprehensive review of the literature using suitable keywords on the search engines of PubMed, SCOPUS, Google Scholar and Research Gate in the first week of May 2020 including ‘COVID-19’, ‘telemedicine’ and ‘remote consultations’. RESULTS: Telemedicine has become an integral part to support patient's clinical care in the current COVID-19 pandemic now and will be in the future for both primary and secondary care. Common pitfalls can be identified and steps can be taken to prevent them. CONCLUSION: Telemedicine it is going to play a key role in future of health medicine, however, telemedicine technology should be applied in appropriate settings and situations. Suitable training, enhanced documentations, communication and observing information governance guidelines will go a long way in avoiding pitfalls associated with remote consultations.


title: Psychiatric Aspects of Chloroquine and Hydroxychloroquine Treatment in the Wake of COVID-19: Psychopharmacological Interactions and Neuropsychiatric Sequelae

text: BACKGROUND: Chloroquine and hydroxychloroquine are among several experimental treatments being investigated in the urgent response to the COVID-19. With increased use of these medications, physicians need to become knowledgeable of these drugs’ neuropsychiatric side effects and interactions with psychiatric medications. METHODS: Literature review was performed in PubMed from 1950-2020 regarding psychiatric topics and targeted pharmacological properties of chloroquine and hydroxychloroquine. REVIEW: First, chloroquine and hydroxychloroquine may mildly inhibit CYP2D6 metabolism of psychiatric medications, and psychiatric medications that interfere with CYP2D6 or CYP3A4 activity could alter chloroquine and hydroxychloroquine levels. Second, they may prolong the QT interval, warranting caution with concomitant prescription of other QT prolonging agents. Finally, neuropsychiatric side effects are very uncommon but possible, and include a potentially prolonged phenomenon of “psychosis following chloroquine.” Hydroxychloroquine has less information available about its neuropsychiatric side effects than chloroquine, with psychosis literature limited to several case reports. It is not clear whether patients with psychiatric illness are more vulnerable to neuropsychiatric sequela of these medications, however, overdose on these medications by suicidal patients has high risk of mortality. CONCLUSION: The risk of neuropsychiatric side effects of chloroquine and hydroxychloroquine when used for COVID-19 treatment is not known. Best practice may include suicide risk assessment for patients treated with hydroxychloroquine. However, delirium is expected to be a more likely etiology of neuropsychiatric symptoms in critically ill patients treated for COVID-19, and adjustment disorder is a much more likely etiology of anxiety and depression symptoms than the side effects of chloroquine or hydroxychloroquine.


title: Severe acute diarrhea

text: Acute diarrhea is commonly caused by an infection. Severe acute diarrhea warrants immediate medical evaluation and hospitalization. Indications for stool studies include fever; bloody diarrhea; recent travel to an endemic area; recent antibiotics; immunosuppression; and occupational risks, such as food handlers. Noninfectious causes include inflammatory bowel disease, radiation enteritis, and intestinal ischemia. Management of severe acute diarrhea includes intravenous fluid rehydration and empiric antibiotics. Use of antidiarrheal agents is controversial when invasive pathogens are suspected.


Quelle conduite à tenir pour prendre en charge des pathologies médicales de la surface oculaire pendant l’épidémie de COVID-19?


title: Insights into DNA substrate selection by APOBEC3G from structural, biochemical, and functional studies

text: Human apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3 (A3) proteins are a family of cytidine deaminases that catalyze the conversion of deoxycytidine (dC) to deoxyuridine (dU) in single-stranded DNA (ssDNA). A3 proteins act in the innate immune response to viral infection by mutating the viral ssDNA. One of the most well-studied human A3 family members is A3G, which is a potent inhibitor of HIV-1. Each A3 protein prefers a specific substrate sequence for catalysis—for example, A3G deaminates the third dC in the CCCA sequence motif. However, the interaction between A3G and ssDNA is difficult to characterize due to poor solution behavior of the full-length protein and loss of DNA affinity of the truncated protein. Here, we present a novel DNA-anchoring fusion strategy using the protection of telomeres protein 1 (Pot1) which has nanomolar affinity for ssDNA, with which we captured an A3G-ssDNA interaction. We crystallized a non-preferred adenine in the -1 nucleotide-binding pocket of A3G. The structure reveals a unique conformation of the catalytic site loops that sheds light onto how the enzyme scans substrate in the -1 pocket. Furthermore, our biochemistry and virology studies provide evidence that the nucleotide-binding pockets on A3G influence each other in selecting the preferred DNA substrate. Together, the results provide insights into the mechanism by which A3G selects and deaminates its preferred substrates and help define how A3 proteins are tailored to recognize specific DNA sequences. This knowledge contributes to a better understanding of the mechanism of DNA substrate selection by A3G, as well as A3G antiviral activity against HIV-1.


title: Genome Information Broker for Viruses (GIB-V): database for comparative analysis of virus genomes

text: Genome Information Broker for Viruses (GIB-V) is a comprehensive virus genome/segment database. We extracted 18 418 complete virus genomes/segments from the International Nucleotide Sequence Database Collaboration (INSDC, ) by DNA Data Bank of Japan (DDBJ), EMBL and GenBank and stored them in our system. The list of registered viruses is arranged hierarchically according to taxonomy. Keyword searches can be performed for genome/segment data or biological features of any virus stored in GIB-V. GIB-V is equipped with a BLAST search function, and search results are displayed graphically or in list form. Moreover, the BLAST results can be used online with the ClustalW feature of the DDBJ. All available virus genome/segment data can be collected by the GIB-V download function. GIB-V can be accessed at no charge at .


VIRAL POLYMERASES


On COVID-19 and Matters Arising


title: Operative team checklist for aerosol generating procedures to minimise exposure of healthcare workers to SARS-CoV-2

text: Abstract Objectives In many countries around the world, the COVID-19 pandemic has resulted in health services being diverted to manage patients with the condition. There are situations however that still require the undertaking of aerosol generating procedures (AGP) with potentially high exposure of healthcare workers to SARS-CoV-2 transmission through droplet, contact and possibly airborne routes. The objective of this paper is to explore a structured way for the operative team to approach AGP to reduce aerosolisation of secretions, decrease open airway time and minimise staff exposure. Methods The authors (otolaryngologists, anaesthetists and nursing staff) created a unified operative team checklist based on collation of national and international specialty society statements, local state government recommendations, hospital policies and literature review. Simulation was undertaken and the checklist was refined after performing AGP on patients with unknown (presumed positive) COVID-19 status. Results An 8 step operative team checklist is provided describing details for the immediate pre-operative, intra-operative and post-operative journey of the patient to encourage healthcare workers to reflect upon and modify usual practice during AGP to mitigate exposure to SARS-CoV-2. The example of paediatric laryngo-bronchoscopy for diagnostic purposes or retrieval of an inhaled airway foreign body is used to illustrate the steps however the checklist structure is modifiable for other AGP and adaptable for local needs. Conclusions At a time of overwhelming and changing information and recommendations, an operative team checklist may provide some structure to healthcare workers undertaking AGP to reduce anxiety, maintain focus, prompt consideration of alternatives and potentially reduce risk.


The underrecognized prothrombotic vascular disease of COVID‐19


title: Predicting the severity of acute bronchiolitis in infants: Should we use a clinical score or a biomarker?

text: Krebs von den Lungen 6 antigen (KL‐6) has been shown to be a useful biomarker of the severity of Respiratory syncytial virus bronchiolitis. To assess the correlation between the clinical severity of acute bronchiolitis, serum KL‐6, and the causative viruses, 222 infants with acute bronchiolitis presenting at the Pediatric Emergency Department of Estaing University Hospital, Clermont‐Ferrand, France, were prospectively enrolled from October 2011 to May 2012. Disease severity was assessed with a score calculated from oxygen saturation, respiratory rate, and respiratory effort. A nasopharyngeal aspirate was collected to screen for a panel of 20 respiratory viruses. Serum was assessed and compared with a control group of 38 bronchiolitis‐free infants. No significant difference in KL‐6 levels was found between the children with bronchiolitis (mean 231 IU/mL ± 106) and those without (230 IU/mL ± 102), or between children who were hospitalized or not, or between the types of virus. No correlation was found between serum KL‐6 levels and the disease severity score. The absence of Human Rhinovirus was a predictive factor for hospitalization (OR 3.4 [1.4–7.9]; P = 0.006). Older age and a higher oxygen saturation were protective factors (OR 0.65[0.55–0.77]; P < 0.0001 and OR 0.67 [0.54–0.85] P < 0.001, respectively). These results suggest that in infants presenting with bronchiolitis for the first time, clinical outcome depends more on the adaptive capacities of the host than on epithelial dysfunction intensity. Many of the features of bronchiolitis are affected by underlying disease and by treatment. J. Med. Virol. 86:1944–1952, 2014. © 2013 Wiley Periodicals, Inc.


title: Genetic analysis of calf health in Charolais beef cattle

text: The objective of this study was to investigate the factors that influence calf health and survival in Charolais cattle. Data from 2,740 calves, originating from 16 French farms and observed from birth until 30 d of age, were analyzed using models that took account of direct genetic, maternal genetic, and common environmental effects. Both direct and maternal genetic parameters were estimated for birth weight (BW), calving ease (CE), neonatal vitality (NV), survival at 30 d (Surv), and umbilical infection and diarrhea at different ages (0 to 5 d: Umb1 and Diar1; 6 to 20 d: Umb2 and Diar2; and 21 to 30 d: Umb3 and Diar3). The heritability values for direct and maternal genetic effects were, 0.026 (SE = 0.027) and 0.096 (SE = 0.042) for Surv, 0.280 (SE = 0.063) and 0.063 (SE = 0.038) for BW, 0.129 (SE = 0.041) and 0 for CE, 0.073 (SE = 0.035) and 0 for NV, 0.071 (SE = 0.038) and 0.017 (SE = 0.026) for Umb1, 0 and 0.082 (SE = 0.029) for Umb2, 0 and 0.044 (SE = 0.030) for Diar1, 0.016 (SE = 0.022) and 0.012 (SE = 0.026) for Diar2, and 0.016 (SE = 0.028) and 0 for Diar3, respectively. Significant genetic variability in beef cattle was thus revealed for five calf health traits: NV, Surv, Diar1, Umb1, and Umb2. In addition, for three traits (Surv, Diar1, and Umb2), maternal genetic effects clearly contributed more to health performance than direct genetic effects. Estimates of genetic correlation between traits varied markedly (from 0 to 1 in absolute values) depending on the traits in question, the age for a given trait, and the type (direct or maternal) of the genetic effects considered. These results suggest that not all health traits in Charolais cattle can be improved simultaneously, and breeders will therefore have to prioritize certain traits of interest in their breeding objectives. Overall, our results demonstrate the potential utility of collecting and integrating data on calf diseases, NV and survival in future beef cattle breeding programs. To ensure appropriate biological and genetic evaluations of calf health performance, it is important to accurately describe the phenotypes for diarrhea and umbilical infections (in terms of age ranges) and account for maternal genetic and common environmental effects that explain calf health performance traits. Further investigation and improved data collection are now necessary to maximize the efficiency of breeding schemes designed to simultaneously improve production and health traits.