title: Benefits of random‐priming: Exhaustive survey of a cDNA library from lung tissue of a SARS patient

text: The severe acute respiratory syndrome (SARS) leads to severe injury in the lungs with multiple factors, though the pathogenesis is still largely unclear. This paper describes the particular analyses of the transcriptome of human lung tissue that was infected by SARS‐associated coronavirus (SARS‐CoV). Random primers were used to produce ESTs from total RNA samples of the lung tissue. The result showed a high diversity of the transcripts, covering much of the human genome, including loci which do not contain protein coding sequences. 10,801 ESTs were generated and assembled into 267 contigs plus 7,659 singletons. Sequences matching to SARS‐CoV RNAs and other pneumonia‐related microbes were found. The transcripts were well classified by functional annotation. Among the 7,872 assembled sequences that were identified as from human genome, 578 non‐coding genes were revealed by BLAST search. The transcripts were mapped to the human genome with the restriction of identity = 100%, which found a candidate pool of 448 novel transcriptional loci where EST transcriptional signal was never found before. Among these, 13 loci were never reported to be transcriptional by other detection methods such as gene chips, tiling arrays, and paired‐end ditags (PETs). The result showed that random‐priming cDNA library is valid for the investigation of transcript diversity in the virus‐infected tissue. The EST data could be a useful supplemental source for SARS pathology researches. J. Med. Virol. 83:574–586, 2011. © 2011 Wiley‐Liss, Inc.


title: Acute respiratory failure in COVID-19: is it “typical” ARDS?

text: In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) was identified in Wuhan, China. The World Health Organization (WHO) declared this outbreak a significant threat to international health. COVID-19 is highly infectious and can lead to fatal comorbidities especially acute respiratory distress syndrome (ARDS). Thus, fully understanding the characteristics of COVID-19-related ARDS is conducive to early identification and precise treatment. We aimed to describe the characteristics of COVID-19-related ARDS and to elucidate the differences from ARDS caused by other factors. COVID-19 mainly affected the respiratory system with minor damage to other organs. Injury to the alveolar epithelial cells was the main cause of COVID-19-related ARDS, and endothelial cells were less damaged with therefore less exudation. The clinical manifestations were relatively mild in some COVID-19 patients, which was inconsistent with the severity of laboratory and imaging findings. The onset time of COVID-19-related ARDS was 8–12 days, which was inconsistent with ARDS Berlin criteria, which defined a 1-week onset limit. Some of these patients might have a relatively normal lung compliance. The severity was redefined into three stages according to its specificity: mild, mild-moderate, and moderate-severe. HFNO can be safe in COVID-19-related ARDS patients, even in some moderate-severe patients. The more likely cause of death is severe respiratory failure. Thus, the timing of invasive mechanical ventilation is very important. The effects of corticosteroids in COVID-19-related ARDS patients were uncertain. We hope to help improve the prognosis of severe cases and reduce the mortality.


title: Epidemic spreading in multiplex networks influenced by opinion exchanges on vaccination

text: Through years, the use of vaccines has always been a controversial issue. People in a society may have different opinions about how beneficial the vaccines are and as a consequence some of those individuals decide to vaccinate or not themselves and their relatives. This attitude in face of vaccines has clear consequences in the spread of diseases and their transformation in epidemics. Motivated by this scenario, we study, in a simultaneous way, the changes of opinions about vaccination together with the evolution of a disease. In our model we consider a multiplex network consisting of two layers. One of the layers corresponds to a social network where people share their opinions and influence others opinions. The social model that rules the dynamic is the M-model, which takes into account two different processes that occurs in a society: persuasion and compromise. This two processes are related through a parameter r, r < 1 describes a moderate and committed society, for r > 1 the society tends to have extremist opinions, while r = 1 represents a neutral society. This social network may be of real or virtual contacts. On the other hand, the second layer corresponds to a network of physical contacts where the disease spreading is described by the SIR-Model. In this model the individuals may be in one of the following four states: Susceptible (S), Infected(I), Recovered (R) or Vaccinated (V). A Susceptible individual can: i) get vaccinated, if his opinion in the other layer is totally in favor of the vaccine, ii) get infected, with probability β if he is in contact with an infected neighbor. Those I individuals recover after a certain period t(r) = 6. Vaccinated individuals have an extremist positive opinion that does not change. We consider that the vaccine has a certain effectiveness ω and as a consequence vaccinated nodes can be infected with probability β(1 − ω) if they are in contact with an infected neighbor. In this case, if the infection process is successful, the new infected individual changes his opinion from extremist positive to totally against the vaccine. We find that depending on the trend in the opinion of the society, which depends on r, different behaviors in the spread of the epidemic occurs. An epidemic threshold was found, in which below β* and above ω* the diseases never becomes an epidemic, and it varies with the opinion parameter r.


title: Wastewater and public health: the potential of wastewater surveillance for monitoring COVID-19

text: Pathogenic viruses represent one of the greatest threats to human wellbeing. As evidenced by the COVID-19 global pandemic, however, halting the spread of highly contagious diseases is notoriously difficult. Successful control strategies therefore have to rely on effective surveillance. Here we describe how monitoring wastewater from urban areas can be used to detect the arrival and subsequent decline of pathogens, such as SARS-CoV-2. As the amount of virus shed in faeces and urine varies largely from person to person, it is very difficult to quantitatively determine the number of people who are infected in the population. More research on the surveillance of viruses in wastewater using accurate and validated methods and subsequent risk analysis and modelling is paramount in understanding the dynamics of viral outbreaks.


title: Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study

text: BACKGROUND: An important feature of severe acute respiratory syndrome coronavirus 2 pathogenesis is COVID-19-associated coagulopathy, characterised by increased thrombotic and microvascular complications. Previous studies have suggested a role for endothelial cell injury in COVID-19-associated coagulopathy. To determine whether endotheliopathy is involved in COVID-19-associated coagulopathy pathogenesis, we assessed markers of endothelial cell and platelet activation in critically and non-critically ill patients admitted to the hospital with COVID-19. METHODS: In this single-centre cross-sectional study, hospitalised adult (≥18 years) patients with laboratory-confirmed COVID-19 were identified in the medical intensive care unit (ICU) or a specialised non-ICU COVID-19 floor in our hospital. Asymptomatic, non-hospitalised controls were recruited as a comparator group for biomarkers that did not have a reference range. We assessed markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes. We compared the level of each marker in ICU patients, non-ICU patients, and controls, where applicable. We assessed correlations between these laboratory results with clinical outcomes, including hospital discharge and mortality. Kaplan–Meier analysis was used to further explore the association between biochemical markers and survival. FINDINGS: 68 patients with COVID-19 were included in the study from April 13 to April 24, 2020, including 48 ICU and 20 non-ICU patients, as well as 13 non-hospitalised, asymptomatic controls. Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen (mean 565% [SD 199] in ICU patients vs 278% [133] in non-ICU patients; p<0·0001) and soluble P-selectin (15·9 ng/mL [4·8] vs 11·2 ng/mL [3·1]; p=0·0014). VWF antigen concentrations were also elevated above the normal range in 16 (80%) of 20 non-ICU patients. We found mortality to be significantly correlated with VWF antigen (r = 0·38; p=0·0022) and soluble thrombomodulin (r = 0·38; p=0·0078) among all patients. In all patients, soluble thrombomodulin concentrations greater than 3·26 ng/mL were associated with lower rates of hospital discharge (22 [88%] of 25 patients with low concentrations vs 13 [52%] of 25 patients with high concentrations; p=0·0050) and lower likelihood of survival on Kaplan–Meier analysis (hazard ratio 5·9, 95% CI 1·9–18·4; p=0·0087). INTERPRETATION: Our findings show that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death. Early identification of endotheliopathy and strategies to mitigate its progression might improve outcomes in COVID-19. FUNDING: This work was supported by a gift donation from Jack Levin to the Benign Hematology programme at Yale, and the National Institutes of Health.


title: Severe acute respiratory syndrome coronavirus protein 7a interacts with hSGT

text: Abstract Severe acute respiratory syndrome coronavirus (SARS-CoV) 7a is an accessory protein with no known homologues. In this study, we report the interaction of a SARS-CoV 7a and small glutamine-rich tetratricopeptide repeat-containing protein (SGT). SARS-CoV 7a and human SGT interaction was identified using a two-hybrid system screen and confirmed with interaction screens in cell culture and cellular co-localization studies. The SGT domain of interaction was mapped by deletion mutant analysis and results indicated that tetratricopeptide repeat 2 (aa 125-158) was essential for interaction. We also showed that 7a interacted with SARS-CoV structural proteins M (membrane) and E (envelope), which have been shown to be essential for virus-like particle formation. Taken together, our results coupled with data from studies of the interaction between SGT and HIV-1 vpu indicated that SGT could be involved in the life-cycle, possibly assembly of SARS-CoV.


title: Current Status of Point-of-Care Diagnostic Devices in the Indian Healthcare System with an Update on COVID-19 Pandemic

text: Abstract Point-of-care (POC) diagnostic device is an instrument that is used to acquire particular clinical information of patients in clinical as well as resource-limited settings. The conventional clinical diagnostic procedure requires high-end and costly instruments, an expert technician for operation and result interpretation, longer time, etc. that ultimately makes it exhausting and expensive. Although there are a lot of improvements in the medical facilities in the Indian healthcare system, the use of POC diagnostic devices is still in its nascent phase. This review illustrates the status of POC diagnostic devices currently used in clinical setups along with constraints in their use. The devices and technologies that are in the research and development phase across the country that has tremendous potential to elevate the clinical diagnostics scenario along with the diagnosis of ongoing COVID-19 pandemic are emphasized. The implications of using POC diagnostic devices and the future objectives for technological advancements that may eventually uplift the status of healthcare and related sectors in India are also discussed here.


title: Evaluating respiratory cryptosporidiosis in pediatric diarrheal disease: protocol for a prospective, observational study in Malawi

text: BACKGROUND: Cryptosporidium is among the most common causes of severe diarrhea in African children 0–23 months old. It is associated with excess mortality, stunting and malnutrition. The most common manifestation of cryptosporidium is intestinal diarrheal disease. However, respiratory cryptosporidiosis has been documented in up to a third of children presenting with diarrhea. It is unclear whether respiratory involvement is a transient phenomenon or a reservoir for gastrointestinal (GI) disease. This study aims to evaluate the role of respiratory cryptosporidiosis in pediatric diarrheal disease. METHODS: This is a prospective, observational study conducted at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi. Young children aged 2–24 months hospitalized with diarrhea will be enrolled. Enrolled children will have induced sputum, nasopharyngeal (NP) swab and stool samples collected. All participants positive for cryptosporidium on sputum/NP/stool PCR testing will be followed up fortnightly after discharge from the hospital up to 8 weeks post-discharge. Sputum/NP/stool sample collection will be done at each visit. The primary outcomes will be presence of Cryptosporidium spp. in sputum/NP/stool. The secondary outcome will be presence of respiratory and GI symptoms, mortality and stunting. Ethical approval was obtained from the University of Malawi College of Medicine Research Ethics Committee (COMREC) and the Liverpool School of Tropical Medicine (LSTM) research ethics committee. DISCUSSION: The study began recruitment activities at QECH in February 2019. The protocol allows for expansion of recruitment to secondary sites within Blantyre and Chikwawa districts in the event that targets are not met at QECH. Study recruitment is expected to continue until early 2020.


title: Virus–host interactomes — antiviral drug discovery

text: One of the key questions in virology is how viruses, encoding relatively few genes, gain temporary or constant control over their hosts. To understand pathogenicity of a virus it is important to gain knowledge on the function of the individual viral proteins in the host cell, on their interactions with viral and cellular proteins and on the consequences of these interactions on cellular signaling pathways. A combination of transcriptomics, proteomics, high-throughput technologies and the bioinformatical analysis of the respective data help to elucidate specific cellular antiviral drug target candidates. In addition, viral and human interactome analyses indicate that different viruses target common, central human proteins for entering cellular signaling pathways and machineries which might constitute powerful broad-spectrum antiviral targets.


title: The new scope of virus taxonomy: partitioning the virosphere into 15 hierarchical ranks

text: Virus taxonomy emerged as a discipline in the middle of the twentieth century. Traditionally, classification by virus taxonomists has been focussed on the grouping of relatively closely related viruses. However, during the past few years, the International Committee on Taxonomy of Viruses (ICTV) has recognized that the taxonomy it develops can be usefully extended to include the basal evolutionary relationships among distantly related viruses. Consequently, the ICTV has changed its Code to allow a 15-rank classification hierarchy that closely aligns with the Linnaean taxonomic system and may accommodate the entire spectrum of genetic divergence in the virosphere. The current taxonomies of three human pathogens, Ebola virus, severe acute respiratory syndrome coronavirus and herpes simplex virus 1 are used to illustrate the impact of the expanded rank structure. This new rank hierarchy of virus taxonomy will stimulate further research on virus origins and evolution, and vice versa, and could promote crosstalk with the taxonomies of cellular organisms.


title: Why are HIV-1 fusion inhibitors not effective against SARS-CoV? Biophysical evaluation of molecular interactions

text: Abstract The envelope spike (S) glycoprotein of the severe acute respiratory syndrome associated coronavirus (SARS-CoV) mediates the entry of the virus into target cells. Recent studies point out to a cell entry mechanism of this virus similar to other enveloped viruses, such as HIV-1. As it happens with other viruses peptidic fusion inhibitors, SARS-CoV S protein HR2-derived peptides are potential therapeutic drugs against the virus. It is believed that HR2 peptides block the six-helix bundle formation, a key structure in the viral fusion, by interacting with the HR1 region. It is a matter of discussion if the HIV-1 gp41 HR2-derived peptide T20 (enfuvirtide) could be a possible SARS-CoV inhibitor given the similarities between the two viruses. We tested the possibility of interaction between both T20 (HIV-1 gp41 HR2-derived peptide) and T-1249 with S protein HR1- and HR2-derived peptides. Our biophysical data show a significant interaction between a SARS-CoV HR1-derived peptide and T20. However, the interaction is only moderate (K B =(1.1±0.3)×105 M−1). This finding shows that the reasoning behind the hypothesis that T20, already approved for clinical application in AIDS treatment, could inhibit the fusion of SARS-CoV with target cells is correct but the effect may not be strong enough for application.


title: Immunogenicity and protective efficacy of orally administered recombinant Lactobacillus plantarum expressing VP2 protein against IBDV in chicken

text: AIM: To develop an effective oral vaccine against the very virulent infectious bursal disease virus (vvIBDV), we generated two recombinant Lactobacillus plantarum strains (pPG612‐VP2/LP and pPG612‐T7g10‐VP2/LP, which carried the T7g10 translational enhancer) that displayed the VP2 protein on the surface, and compared the humoral and cellular immune responses against vvIBDV in chickens. METHODS AND RESULTS: We genetically engineered the L. plantarum strains pPG612‐VP2/LP and pPG612‐T7g10‐VP2/LP constitutively expressing the VP2 protein of vvIBDV. We found that the T7g10 enhancer efficiently upregulates VP2 expression in pPG612‐T7g10‐VP2/LP. Orally administered, pPG612‐T7g10‐VP2/LP exhibited significant levels of protection (87·5%) against vvIBDV in chickens, indicating improved immunogenicity. Chickens in the pPG612‐T7g10‐VP2/LP group produced higher levels of interferons (IFN‐γ) and interleukins (IL‐2 and IL‐4) than those in the pPG612‐VP2/LP group. CD8+ and CD4+ lymphocyte counts indicated greater stimulation in the pPG612‐T7g10‐VP2/LP group (13·3 and 21·0% respectively) than in the pPG612‐VP2/LP group (10·4 and 14·0% respectively). Thus, pPG612‐T7g10‐VP2/LP could induce strong humoral and cellular immune responses against vvIBDV. CONCLUSIONS: The recombinant L. plantarum that expresses pPG612‐T7g10‐VP2 is a promising candidate for oral vaccine development against vvIBDV. SIGNIFICANCE AND IMPACT OF THE STUDY: The recombinant Lactobacillus delivery system provides a promising strategy for vaccine development against vvIBDV in chickens.


title: Prevalence and socio-demographic correlates of psychological health problems in Chinese adolescents during the outbreak of COVID-19

text: Psychological health problems, especially emotional disorders, are common among adolescents. The epidemiology of emotional disorders is greatly influenced by stressful events. This study sought to assess the prevalence rate and socio-demographic correlates of depressive and anxiety symptoms among Chinese adolescents affected by the outbreak of COVID-19. We conducted a cross-sectional study among Chinese students aged 12–18 years during the COVID-19 epidemic period. An online survey was used to conduct rapid assessment. A total of 8079 participants were involved in the study. An online survey was used to collect demographic data, assess students’ awareness of COVID-19, and assess depressive and anxiety symptoms with the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) questionnaire, respectively. The prevalence of depressive symptoms, anxiety symptoms, and a combination of depressive and anxiety symptoms was 43.7%, 37.4%, and 31.3%, respectively, among Chinese high school students during the COVID-19 outbreak. Multivariable logistic regression analysis revealed that female gender was the higher risk factor for depressive and anxiety symptoms. In terms of grades, senior high school was a risk factor for depressive and anxiety symptoms; the higher the grade, the greater the prevalence of depressive and anxiety symptoms. Our findings show there is a high prevalence of psychological health problems among adolescents, which are negatively associated with the level of awareness of COVID-19. These findings suggest that the government needs to pay more attention to psychological health among adolescents while combating COVID-19. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00787-020-01541-4) contains supplementary material, which is available to authorized users.


title: Specificity in Ubiquitination Triggered by Virus Infection

text: Ubiquitination is a prominent posttranslational modification, in which the ubiquitin moiety is covalently attached to a target protein to influence protein stability, interaction partner and biological function. All seven lysine residues of ubiquitin, along with the N-terminal methionine, can each serve as a substrate for further ubiquitination, which effectuates a diverse combination of mono- or poly-ubiquitinated proteins with linear or branched ubiquitin chains. The intricately composed ubiquitin codes are then recognized by a large variety of ubiquitin binding domain (UBD)-containing proteins to participate in the regulation of various pathways to modulate the cell behavior. Viruses, as obligate parasites, involve many aspects of the cell pathways to overcome host defenses and subjugate cellular machineries. In the virus-host interactions, both the virus and the host tap into the rich source of versatile ubiquitination code in order to compete, combat, and co-evolve. Here, we review the recent literature to discuss the role of ubiquitin system as the infection progresses in virus life cycle and the importance of ubiquitin specificity in the regulation of virus-host relation.


title: Extracellular cysteines define ectopeptidase (APN, CD13) expression and function

text: Abstract Alanyl aminopeptidase (APN) is a surface-bound metallopeptidase that processes the N-terminals of biologically active peptides such as enkephalins, angiotensins, neurokinins, and cytokines. It exerts profound activity on vital processes such as immune response, cellular growth, and blood pressure control. Inhibition of either APN gene expression or its enzymatic activity severely affects leukocyte growth and function. We show here that oxidoreductase-mediated modulations of the cell surface thiol status affect the enzymatic activity of APN. Additional evidence for the pivotal role of extracellular cysteines in the APN molecule was obtained when substitution of any of these six cysteines caused complete loss of surface expression and enzymatic activity. In contrast, the transmembrane Cys24 appears to have no similar function. Enzymatically inactive cysteine mutants were retained in the endoplasmic reticulum as shown by high-resolution imaging and Endoglycosidase H digestion. In the absence of any crystal-structure data, the demonstration that individual extracellular cysteines contribute to APN expression and function appears to be of particular importance. The data are the first to show thiol-dependent modulation of the activity of a typical surface-bound peptidase at the cell surface, probably reflecting a general regulating mechanism. This may relate to various disease processes such as inflammation or malignant transformation.


title: Identification of enteric viruses circulating in a dog population with low vaccine coverage

text: Although the use of vaccines has controlled enteric diseases in dogs in many developed countries, vaccine coverage is still under optimal situation in Brazil. There is a large population of nonimmunized dogs and few studies about the identification of the viruses associated with diarrhea. To address this situation, stool samples from 325 dogs were analyzed by polymerase chain reaction for the detection of common enteric viruses such as Canine adenovirus (CAdV), Canine coronavirus (CCoV), Canine distemper virus (CDV), Canine rotavirus (CRV) and Carnivorous protoparvovirus 1 (canine parvovirus 2; CPV-2). At least one of these species was detected in 56.6% (184/325) of the samples. The viruses detected most frequently in either diarrheic or nondiarrheic dog feces were CPV-2 (54.3% of the positive samples), CDV (45.1%) and CCoV (30.4%), followed by CRV (8.2%) and CAdV (4.9%). Only one agent was detected in the majority of the positive samples (63%), but co-infections were present in 37% of the positive samples and mainly included CDV and CPV-2. The data presented herein can improve the clinical knowledge in regions with low vaccine coverage and highlight the need to improve the methods used to control these infectious diseases in domestic dogs.


title: Virtual screening, ADME/T, and binding free energy analysis of anti-viral, anti-protease, and anti-infectious compounds against NSP10/NSP16 methyltransferase and main protease of SARS CoV-2

text: Recently, a pathogen has been identified as a novel coronavirus (SARS-CoV-2) and found to trigger novel pneumonia (COVID-19) in human beings and some other mammals. The uncontrolled release of cytokines is seen from the primary stages of symptoms to last acute respiratory distress syndrome (ARDS). Thus, it is necessary to find out safe and effective drugs against this deadly coronavirus as soon as possible. Here, we downloaded the three-dimensional model of NSP10/NSP16 methyltransferase (PDB-ID: 6w6l) and main protease (PDB-ID: 6lu7) of COVID-19. Using these molecular models, we performed virtual screening with our anti-viral, inti-infectious, and anti-protease compounds, which are attractive therapeutics to prevent infection of the COVID-19. We found that top screened compound binds with protein molecules with good dock score with the help of hydrophobic interactions and hydrogen bonding. We observed that protease complexed with Cyclocytidine hydrochloride (anti-viral and anti-cancer), Trifluridine (anti-viral), Adonitol, and Meropenem (anti-bacterial), and Penciclovir (anti-viral) bound with a good docking score ranging from −6.8 to −5.1 (Kcal/mol). Further, NSP10/NSP16 methyltransferase complexed with Telbivudine, Oxytetracycline dihydrate (anti-viral), Methylgallate (anti-malarial), 2-deoxyglucose and Daphnetin (anti-cancer) from the docking score of −7.0 to −5.7 (Kcal/mol). In conclusion, the selected compounds may be used as a novel therapeutic agent to combat this deadly pandemic disease, SARS-CoV-2 infection, but needs further experimental research. HIGHLIGHTS: NSP10/NSP16 methyltransferase and main protease complex of SARS CoV-2 bind with selected drugs. NSP10/NSP16 methyltransferase and protease interacted with drugs by hydrophobic interactions. Compounds show good DG binging free energy with protein complexes. Ligands were found to follow the Lipinski rule of five.


Statewide Stay‐At‐Home Directives on the Spread of COVID‐19 in Metropolitan and Nonmetropolitan Counties in the United States


title: A primer for pediatric radiologists on infection control in an era of COVID-19

text: Pediatric radiology departments across the globe face unique challenges in the midst of the current COVID-19 pandemic that have not been addressed in professional guidelines. Providing a safe environment for personnel while continuing to deliver optimal care to patients is feasible when abiding by fundamental recommendations. In this article, we review current infection control practices across the multiple pediatric institutions represented on the Society for Pediatric Radiology (SPR) Quality and Safety committee. We discuss the routes of infectious transmission and appropriate transmission-based precautions, in addition to exploring strategies to optimize personal protective equipment (PPE) supplies. This work serves as a summary of current evidence-based recommendations for infection control, and current best practices specific to pediatric radiologists. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00247-020-04713-1) contains supplementary material, which is available to authorized users.


title: Plasma Metabolomic and Lipidomic Alterations Associated with COVID-19

text: The pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. The symptoms of COVID-19 range from mild to severe conditions. However, the physiological changes associated with COVID-19 are barely understood. In this study, we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of COVID-19 patients who had experienced different symptoms. We found the metabolite and lipid alterations exhibit apparent correlation with the course of disease in these COVID-19 patients, indicating that the development of COVID-19 affected whole-body metabolism of the patients. In particular, malic acid of the TCA cycle and carbamoyl phosphate of urea cycle reveal the altered energy metabolism and hepatic dysfunction, respectively. It should be noted that carbamoyl phosphate is profoundly down-regulated in fatal patients compared with mild patients. And more importantly, guanosine monophosphate (GMP), which is mediated by not only GMP synthase but also CD39 and CD73, is significantly changed between healthy subjects and COVID-19 patients, as well as between the mild and fatal groups. In addition, the dyslipidaemia was observed in COVID-19 patients. Overall, the disturbed metabolic patterns have been found to align with the progress and severity of COVID-19. This work provides valuable knowledge about plasma biomarkers associated with COVID-19 and potential therapeutic targets, as well as important resource for further studies of COVID-19 pathogenesis.


title: Infectious Bronchitis Virus S2 Gene Sequence Variability May Affect S1 Subunit Specific Antibody Binding

text: The S2 gene of several strains of infectious bronchitis virus (IBV) belonging to the Arkansas, Connecticut, and Florida serotypes was sequenced. Phylogenetic analysis of the S2 gene nucleotide and deduced amino acid sequence data resulted in groups of strains that were the same as groupings observed when S1 sequence data was used. Thus, it appears that S2 subunits are conserved within a serotype but not between serotypes. Although the sequence differences were small, we found that only a few amino acid differences were responsible for different secondary structure predictions for the S2 subunit. It is likely that these changes create different interactions between the S1 and S2 subunits, which could affect the conformation of the S1 subunit where serotype specific epitopes are located. Based on this sequence data, we hypothesize that the S2 subunit can affect specific antibody binding to the S1 subunit of the IBV spike glycoprotein.


title: Animal Models of Cystic Fibrosis Pathology: Phenotypic Parallels and Divergences

text: Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The resultant characteristic ion transport defect results in decreased mucociliary clearance, bacterial colonisation, and chronic neutrophil-dominated inflammation. Much knowledge surrounding the pathophysiology of the disease has been gained through the generation of animal models, despite inherent limitations in each. The failure of certain mouse models to recapitulate the phenotypic manifestations of human disease has initiated the generation of larger animals in which to study CF, including the pig and the ferret. This review will summarise the basic phenotypes of three animal models and describe the contributions of such animal studies to our current understanding of CF.


title: Hypermetabolism and COVID‐19

text: BACKGROUND: Hypermetabolism has been described in stress states such as trauma, sepsis, ARDS, and severe burn injuries. We hypothesize that patients with COVID‐19 may develop a hypermetabolic state which may be a major contributing factor to the extraordinary ventilatory and oxygenation demands in patients with COVID‐19. METHOD: Resting energy expenditure (REE), carbon dioxide production (VCO2) and oxygen consumption (VO2) were measured by indirect calorimetry on seven critically ill patients with COVID‐19. RESULTS: The median measured REE was 4044 Kcal/day which was 235.7% ± 51.7% of predicted. The median VCO2 was 452 mL/min (range 295–582 mL/min) and the median VO2 was 585 mL/min (range 416–798 mL/min). CONCLUSION: Critically ill patients with COVID‐19 are in an extreme hypermetabolic state. This may explain the high failure rates for mechanical ventilation for these patients and highlights the potential need for increased nutritional requirements for such patients. This article is protected by copyright. All rights reserved


title: Potential covalent drugs targeting the main protease of the SARS-CoV-2 coronavirus

text: MOTIVATION: Since December 2019, the newly identified coronavirus SARS-CoV-2 has caused a massive health crisis worldwide and resulted in over 70,000 COVID-19 infections so far. Clinical drugs targeting SARS-CoV-2 are urgently needed to decrease the high fatality rate of confirmed COVID-19 patients. Traditional de novo drug discovery needs more than 10 years, so drug repurposing seems the best option currently to find potential drugs for treating COVID-19. RESULTS: Compared with traditional non-covalent drugs, covalent drugs have attracted escalating attention recent years due to their advantages in potential specificity upon careful design, efficiency, and patient burden. We recently developed a computational protocol named as SCAR for discovering covalent drugs. In this work, we used the SCAR protocol to identify possible covalent drugs (approved or clinically tested) targeting the main protease (3CLpro) of SARS-CoV-2. We identified 11 potential hits, among which at least 6 hits were exclusively enriched by the SCAR protocol. Since the preclinical or clinical information of these identified drugs is already available, they might be ready for being clinically tested in the treatment of COVID-19.


title: High fatality rates and associated factors in two hospital outbreaks of MERS in Daejeon, the Republic of Korea

text: Abstract Objectives To explore the epidemiological and clinical factors predictive of the case fatality rate (CFR) of Middle East respiratory syndrome-coronavirus (MERS-CoV) infection in an outbreak in Daejeon, the Republic of Korea. Methods We reviewed the outbreak investigation reports and medical records of 1 index case and 25 additional MERS cases in hospitals A (14 cases) and B (11 cases), and conducted an in-depth interview with the index case. Results The CFR in hospital B was higher than that in hospital A (63.6% vs. 28.6%, respectively). Higher MERS-CoV exposure conditions were also found in hospital B, including aggravated pneumonia in the index case and nebulizer use in a six-bed admission room. The host factors associated with high CFR were pre-existing pneumonia, smoking history, an incubation period of less than 5 days, leukocytosis, abnormal renal function at diagnosis, and respiratory symptoms such as sputum and dyspnea. Conclusions The conditions surrounding MERS-CoV exposure and the underlying poor pulmonary function due to a smoking history or pre-existing pneumonia may explain the high CFR in hospital B. The clinical features described above may enable prediction of the prognosis of MERS cases.


title: The use of face masks during the COVID‐19 pandemic in Poland: A survey study of 2315 young adults

text: Face masks wearing during the coronavirus disease 2019 (COVID‐19) pandemic became ubiquitous. The aim of our study was to assess the use of face masks among young adults during the current viral pandemic. The survey was based on specially created Google Forms and posted on numerous Facebook groups for young people in Poland. Seven days were considered as a recall period. A total of 2315 answers were obtained, 2307 were finally analysis, as eight questionnaires were removed because of data incompleteness. 60.4% of responders declared using the face masks. Those who reported an atopic predisposition wore face masks significantly (P = .007) more commonly (65.5% and 57.7%, respectively). Cloth masks (46.2%) appeared to be most popular ones, followed by surgical masks (39.2%), respirators (N95 and FFP) (13.3%), half‐face elastomeric respirators (0.8%) and full‐face respirators (0.4%). Females significantly more frequently (P = .0001) used cloth masks; respirators, half‐face elastomeric respirators and full‐face respirators were used more commonly by males (P < .0001, P = .001 and P = .001, respectively). 23.9% of responders who used single‐use mask wore it again. Moreover, 73.6% participants declared mask decontamination; however, the procedures were not always appropriate. We suggest that our results may be of help in construction of general public education campaigns on the proper use of face masks.


title: Serological patterns of Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae, Pasteurella multocida and Streptococcus suis in pig herds affected by pleuritis

text: BACKGROUND: Respiratory illness is traditionally regarded as the disease of the growing pig, and has historically mainly been associated to bacterial infections with focus on Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae. These bacteria still are of great importance, but continuously increasing herd sizes have complicated the scenario and the influence of secondary invaders may have been increased. The aim of this study was to evaluate the presence of A. pleuropneumoniae and M. hyopneumoniae, as well as that of the secondary invaders Pasteurella multocida and Streptococcus suis by serology in four pig herds (A–D) using age segregated rearing systems with high incidences of pleuritic lesions at slaughter. RESULTS: Pleuritic lesions registered at slaughter ranged from 20.5 to 33.1 % in the four herds. In herd A, the levels of serum antibodies to A. pleuropneumoniae exceeded A(450) > 1.5, but not to any other microbe searched for. The seroconversion took place early during the fattening period. Similar levels of serum antibodies to A. pleuropneumoniae were also recorded in herd B, with a subsequent increase in levels of antibodies to P. multocida. Pigs seroconverted to both agents during the early phase of the fattening period. In herd C, pigs seroconverted to P. multocida during the early phase of the fattening period and thereafter to A. pleuropneumoniae. In herd D, the levels of antibodies to P. multocida exceeded A(450) > 1.0 in absence (A(450) < 0.5) of antibodies to A. pleuropneumoniae. The levels of serum antibodies to M. hyopneumoniae and to S. suis remained below A(450) < 1.0 in all four herds. Pigs seroconverted to M. hyopneumoniae late during the rearing period (herd B–D), or not at all (herd A). CONCLUSION: Different serological patterns were found in the four herds with high levels of serum antibodies to A. pleuropneumoniae and P. multocida, either alone or in combination with each other. Seroconversion to M. hyopneumoniae late during the rearing period or not at all, confirmed the positive effect of age segregated rearing in preventing or delaying infections with M. hyopneumoniae. The results obtained highlight the necessity of diagnostic investigations to define the true disease pattern in herds with a high incidence of pleuritic lesions.


title: Assembly of HCV E1 and E2 glycoproteins into coronavirus VLPs

text: Hepatitis C virus (HCV) is believed to assemble by budding into membranes of the early secretory pathway, consistent with the membrane location where the viral envelope glycoproteins E1 and E2 accumulate when expressed. Coronavirus assembly also takes place at pre-Golgi membranes. Here, we generated coronavirus-like particles carrying in their envelope chimeric HCV glycoproteins composed of the ectodomains of E1 and E2, each fused to the transmembrane plus endodomain of the mouse hepatitis coronavirus spike glycoprotein. The chimeric particle system will enable structural and functional studies of the HCV glycoproteins.


title: Risk of travel-related cases of Zika virus infection is predicted by transmission intensity in outbreak-affected countries

text: BACKGROUND: Zika virus (ZIKV) infection is emerging globally, currently causing outbreaks in the Caribbean, and Central and South America, and putting travellers to affected countries at risk. Model-based estimates for the basic reproduction number (R (0)) of ZIKV in affected Caribbean and Central and South American countries, obtained from 2015 to 2016 human case surveillance data, were compared by logistic regression and Receiver-Operating Characteristic (ROC), with the prevalence of ZIKV-positive test results in Canadians who travelled to them. RESULTS: Estimates of R (0) for each country were a good predictor of the ZIKV test result (ROC area under the curve = 0.83) and the odds of testing positive was 11-fold greater for travellers visiting countries with estimated R (0) ≥ 2.76, compared to those visiting countries with R (0) < 2.76. CONCLUSIONS: Risk to travellers varies widely amongst countries affected by ZIKV outbreaks. Estimates of R (0) from surveillance data can assist in assessing levels of risk for travellers and may help improve travel advice. They may also allow better prediction of spread of ZIKV from affected countries by travellers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-017-1977-z) contains supplementary material, which is available to authorized users.


title: Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study

text: BACKGROUND: Scientific evidence suggests that dromedary camels are the intermediary host for the Middle East respiratory syndrome coronavirus (MERS-CoV). However, the actual number of infections in people who have had contact with camels is unknown and most index patients cannot recall any such contact. We aimed to do a nationwide serosurvey in Saudi Arabia to establish the prevalence of MERS-CoV antibodies, both in the general population and in populations of individuals who have maximum exposure to camels. METHODS: In the cross-sectional serosurvey, we tested human serum samples obtained from healthy individuals older than 15 years who attended primary health-care centres or participated in a national burden-of-disease study in all 13 provinces of Saudi Arabia. Additionally, we tested serum samples from shepherds and abattoir workers with occupational exposure to camels. Samples were screened by recombinant ELISA and MERS-CoV seropositivity was confirmed by recombinant immunofluorescence and plaque reduction neutralisation tests. We used two-tailed Mann Whitney U exact tests, χ(2), and Fisher's exact tests to analyse the data. FINDINGS: Between Dec 1, 2012, and Dec 1, 2013, we obtained individual serum samples from 10 009 individuals. Anti-MERS-CoV antibodies were confirmed in 15 (0·15%; 95% CI 0·09–0·24) of 10 009 people in six of the 13 provinces. The mean age of seropositive individuals was significantly younger than that of patients with reported, laboratory-confirmed, primary Middle Eastern respiratory syndrome (43·5 years [SD 17·3] vs 53·8 years [17·5]; p=0·008). Men had a higher antibody prevalence than did women (11 [0·25%] of 4341 vs two [0·05%] of 4378; p=0·028) and antibody prevalence was significantly higher in central versus coastal provinces (14 [0·26%] of 5479 vs one [0·02%] of 4529; p=0·003). Compared with the general population, seroprevalence of MERS-CoV antibodies was significantly increased by 15 times in shepherds (two [2·3%] of 87, p=0·0004) and by 23 times in slaughterhouse workers (five [3·6%] of 140; p<0·0001). INTERPRETATION: Seroprevalence of MERS-CoV antibodies was significantly higher in camel-exposed individuals than in the general population. By simple multiplication, a projected 44 951 (95% CI 26 971–71 922) individuals older than 15 years might be seropositive for MERS-CoV in Saudi Arabia. These individuals might be the source of infection for patients with confirmed MERS who had no previous exposure to camels. FUNDING: European Union, German Centre for Infection Research, Federal Ministry of Education and Research, German Research Council, and Ministry of Health of Saudi Arabia.


title: Elucidation of the stability and functional regions of the human coronavirus OC43 nucleocapsid protein

text: Human coronavirus OC43 (HCoV-OC43) is one of the causes of the “common cold” in human during seasons of cold weather. The primary function of the HCoV-OC43 nucleocapsid protein (N protein) is to recognize viral genomic RNA, which leads to ribonucleocapsid formation. Here, we characterized the stability and identified the functional regions of the recombinant HCoV-OC43 N protein. Circular dichroism and fluorescence measurements revealed that the HCoV-OC43 N protein is more highly ordered and stabler than the SARS-CoV N protein previously studied. Surface plasmon resonance (SPR) experiments showed that the affinity of HCoV-OC43 N protein for RNA was approximately fivefold higher than that of N protein for DNA. Moreover, we found that the HCoV-OC43 N protein contains three RNA-binding regions in its N-terminal region (residues 1–173) and central-linker region (residues 174–232 and 233–300). The binding affinities of the truncated N proteins and RNA follow the order: residues 1–173–residues 233–300 > residues 174–232. SPR experiments demonstrated that the C-terminal region (residues 301–448) of HCoV-OC43 N protein lacks RNA-binding activity, while crosslinking and gel filtration analyses revealed that the C-terminal region is mainly involved in the oligomerization of the HCoV-OC43 N protein. This study may benefit the understanding of the mechanism of HCoV-OC43 nucleocapsid formation.


title: Crystal structure of RlmM, the 2′O-ribose methyltransferase for C2498 of Escherichia coli 23S rRNA

text: RlmM (YgdE) catalyzes the S-adenosyl methionine (AdoMet)-dependent 2′O methylation of C2498 in 23S ribosomal RNA (rRNA) of Escherichia coli. Previous experiments have shown that RlmM is active on 23S rRNA from an RlmM knockout strain but not on mature 50S subunits from the same strain. Here, we demonstrate RlmM methyltransferase (MTase) activity on in vitro transcribed 23S rRNA and its domain V. We have solved crystal structures of E. coli RlmM at 1.9 Å resolution and of an RlmM–AdoMet complex at 2.6 Å resolution. RlmM consists of an N-terminal THUMP domain and a C-terminal catalytic Rossmann-like fold MTase domain in a novel arrangement. The catalytic domain of RlmM is closely related to YiiB, TlyA and fibrillarins, with the second K of the catalytic tetrad KDKE shifted by two residues at the C-terminal end of a beta strand compared with most 2′O MTases. The AdoMet-binding site is open and shallow, suggesting that RNA substrate binding may be required to form a conformation needed for catalysis. A continuous surface of conserved positive charge indicates that RlmM uses one side of the two domains and the inter-domain linker to recognize its RNA substrate.


title: Drawing on disorder: How viruses use histone mimicry to their advantage

text: Humans carry trillions of viruses that thrive because of their ability to exploit the host. In this exploitation, viruses promote their own replication by suppressing the host antiviral response and by inducing changes in host biosynthetic processes, often with extremely small genomes of their own. In the review, we discuss the phenomenon of histone mimicry by viral proteins and how this mimicry allows the virus to dial in to the cell’s transcriptional processes and establish a cell state that promotes infection. We suggest that histone mimicry is part of a broader viral strategy to use intrinsic protein disorder as a means to overcome the size limitations of its own genome and to maximize its impact on host protein networks. In particular, we discuss how intrinsic protein disorder may enable viral proteins to interfere with phase-separated host protein condensates, including those that contribute to chromatin-mediated control of gene expression.


title: An optimised silicon piezoresistive microcantilever sensor for surface stress studies

text: Surface stress is a versatile and efficient means to study various physical, chemical, biochemical and biological processes. This work focuses on developing high sensitive piezoresistive microcantilever designs to study surface stress. The cantilevers are made of silicon with rectangular holes at their base that also circumscribe a piezoresistor sensing element. To find the optimum design, the effects of change in cantilever width, rectangular hole length and type of dopant on mechanical properties like deflection, frequency and maximum stress are characterised using finite element analysis software. The surface stress sensitivity characteristics of the different cantilever designs is ascertained by applying a surface stress on their top surfaces. Results show that the sensitivity is increased by increasing the cantilever width as well as the length of the hole and the sensitivity of p-type designs is more than two times the n-type.


title: Viral nucleases induce an mRNA degradation-transcription feedback loop in mammalian cells

text: Gamma-herpesviruses encode a cytoplasmic mRNA-targeting endonuclease, SOX, that cleaves most cellular mRNAs. Cleaved fragments are subsequently degraded by the cellular 5′-3′ mRNA exonuclease Xrn1, thereby suppressing cellular gene expression and facilitating viral evasion of host defenses. We reveal that mammalian cells respond to this widespread cytoplasmic mRNA decay by altering RNA polymerase II (RNAPII) transcription in the nucleus. Measuring RNAPII recruitment to promoters and nascent mRNA synthesis revealed that the majority of affected genes are transcriptionally repressed in SOX-expressing cells. The transcriptional feedback does not occur in response to the initial viral endonuclease-induced cleavage, but instead to degradation of the cleaved fragments by cellular exonucleases. In particular, Xrn1 catalytic activity is required for transcriptional repression. Notably, viral mRNA transcription escapes decay-induced repression, and this escape requires Xrn1. Collectively, these results indicate that mRNA decay rates impact transcription, and that gamma-herpesviruses use this feedback mechanism to facilitate viral gene expression.


title: Strongly Heterogeneous Transmission of COVID-19 in Mainland China: Local and Regional Variation

text: Background: The outbreak of novel coronavirus disease 2019 (COVID-19) started in the city of Wuhan, China, with a period of rapid initial spread. Transmission on a regional and then national scale was promoted by intense travel during the holiday period of the Chinese New Year. We studied the variation in transmission of COVID-19, locally in Wuhan, as well as on a larger spatial scale, among different cities and even among provinces in mainland China. Methods: In addition to reported numbers of new cases, we have been able to assemble detailed contact data for some of the initial clusters of COVID-19. This enabled estimation of the serial interval for clinical cases, as well as reproduction numbers for small and large regions. Findings: We estimated the average serial interval was 4.8 days. For early transmission in Wuhan, any infectious case produced as many as four new cases, transmission outside Wuhan was less intense, with reproduction numbers below two. During the rapid growth phase of the outbreak the region of Wuhan city acted as a hot spot, generating new cases upon contact, while locally, in other provinces, transmission was low. Interpretation: COVID-19 is capable of spreading very rapidly. The sizes of outbreak in provinces of mainland China mainly depended on the numbers of cases imported from Wuhan as the local reproduction numbers were low. The COVID-19 epidemic should be controllable with appropriate interventions (suspension of public transportation, cancellation of mass gatherings, implementation of surveillance and testing, and promotion of personal hygiene and face mask use).


title: Investing in Public Health Microbiology Laboratories in Western Balkan Countries Enhances Health Security From Communicable Disease Threats in Europe

text: The European Centre for Disease Prevention and Control (ECDC), under the EU enlargement policy, has supported national efforts of Western Balkan countries to strengthen their communicable disease prevention and control systems. The new EU strategy “A credible enlargement perspective for and enhanced EU engagement with the Western Balkans” advocates transformation processes that will build the foundation of EU-oriented national reforms. Well-functioning public health microbiology laboratories are key for early detection and control of infectious diseases, and thus maintaining and enhancing health security in Europe. In order to help Western Balkan countries to improve their national capacities, ECDC facilitated needs assessments and identified key areas for advancement toward effective public health microbiology systems. Countries identified gaps in their laboratory data reporting and exchange systems. Harmonized and effective procedures for handling of highly contagious agents and cross-border transportation of biological samples were often lacking, as well as the systematic use of diagnostic testing at the primary care level or referral of patients, in particular for detection of antimicrobial resistance. There is a clear need to address the financial investment required for sustaining sufficient numbers of skilled laboratory workforce, laboratory supplies, and the development of new methods and techniques, including investment in emerging laboratory technologies, such as molecular typing by whole genome sequencing. This article highlights the key areas for investing in public health microbiology laboratories in Western Balkan countries needed to strengthen health security in Europe.


title: Detection of rhinovirus RNA in middle turbinate of patients with common colds by in situ hybridization

text: Human rhinovirus 14 RNA was determined by in situ hybridization from middle turbinate biopsies in 32 patients with diagnosed common colds and in five control individuals. Twenty‐two (69%) biopsies from common colds patients but none of the five control biopsies showed reactivity for human rhinovirus 14 antisense probe. The signal was detected both in the respiratory epithelium and in mucosal inflammatory cells. In situ hybridization of the middle turbinate tissue yielded more positive results than RT‐PCR (47%) or virus culture (34%) assayed from nasopharyngeal aspirates, but no statistical significant differences were observed (P = 0.265, P = 0.425, respectively). The results indicated that in situ hybridization procedure was slightly more sensitive than PCR assays and classical culture for the detection of human rhinovirus infection of upper respiratory tract. However, in situ hybridization procedure appeared to be an interesting methodology to investigate the physiopathology of respiratory tract infection by rhinoviruses. J. Med. Virol. 70: 319–323, 2003. © 2003 Wiley‐Liss, Inc.


title: Why the WHO won't use the p-word

text: There are no criteria for a pandemic, but covid-19 looks like one, says Debora MacKenzie


title: Recomendaciones para el manejo de la faringoamigdalitis aguda del adulto()

text: Acute pharyngitis in adults is one of the most common infectious diseases seen in general practitioners’ consultations. Viral aetiology is the most common. Among bacterial causes, the main agent is Streptococcus pyogenes or group A β-haemolytic streptococcus (GABHS), which causes 5%-30% of the episodes. In the diagnostic process, clinical assessment scales can help clinicians to better predict suspected bacterial aetiology by selecting patients who should undergo a rapid antigen detection test. If these techniques are not performed, an overdiagnosis of streptococcal pharyngitis often occurs, resulting in unnecessary prescriptions of antibiotics, most of which are broad spectrum. Consequently, management algorithms that include the use of predictive clinical rules and rapid tests have been set up. The aim of the treatment is speeding up symptom resolution, reducing the contagious time span and preventing local suppurative and non-suppurative complications. Penicillin and amoxicillin are the antibiotics of choice for the treatment of pharyngitis. The association of amoxicillin and clavulanate is not indicated as the initial treatment of acute infection. Neither are macrolides indicated as first-line therapy; they should be reserved for patients allergic to penicillin. The appropriate diagnosis of bacterial pharyngitis and proper use of antibiotics based on the scientific evidence available are crucial. Using management algorithms can be helpful in identifying and screening the cases that do not require antibiotic therapy.


title: The Long Road of Immunotherapeutics against Multiple Sclerosis †

text: This commentary highlights novel immunomodulation and vaccine-based research against multiple sclerosis (MS) and reveals the amazing story that triggered this cutting-edge MS research in Greece and worldwide. It further reveals the interest and solid support of some of the world’s leading scientists, including sixteen Nobel Laureates who requested from European leadership to take action in supporting Greece and its universities in the biggest ever financial crisis the country has encountered in the last decades. This support endorsed vaccine-based research on MS, initiated in Greece and Australia, leading to a worldwide network aiming to treat or manage disease outcomes. Initiatives by bright and determined researchers can result in frontiers science. We shed light on a unique story behind great research on MS which is a step forward in our efforts to develop effective treatments for MS.


title: Balancing cancer immunotherapy efficacy and toxicity

text: Abstract Anti-programmed death-1/ligand-1 (PD-1/PD-L1) directed therapies are transforming cancer care, with durable anti-tumor responses observed in multiple cancer types. Toxicities arising from therapy are autoimmune in nature and may affect essentially any organ system. The immunologic basis of such toxities is complex, with contributions from T cell activation and autoantibody generation. Though less recognized, hypersensitivity reactions are also possible. Although most toxicities resolve with systemic corticosteroids, some require second-line immunosuppression. Further, the safety of drug rechallenge is not well-characterized, with variable rates of toxicity flares arising with re-exposure. Herein, we review toxicities of immune checkpoint inhibitor therapies, particularly focusing on issues that allergists/immunologists may clinically encounter, including interstitial nephritis, skin toxicity, and risks associated with immunotherapy rechallenge.


title: Outpatient Otolaryngology in the Era of COVID-19: A Data-Driven Analysis of Practice Patterns

text: INTRODUCTION: Coronavirus disease 2019 (COVID-19) has induced a prioritization of acute care and telehealth, affecting the quantity of patients seen and the modality of their care. STUDY DESIGN: Retrospective review. SETTING: Single-institution study conducted within the Division of Otolaryngology at the Yale School of Medicine. SUBJECTS AND METHODS: Data on all outpatient appointments within the Division of Otolaryngology were obtained from administrative records of billing and scheduling from March 16 to April 10, 2020. For comparison, a corresponding period from 2019 was also utilized. RESULTS: Of 5913 scheduled visits, 3665 (62.0%) were seen between March 18 and April 12, 2019, in comparison with 649 of 5044 (12.9%) during the corresponding COVID-19–affected period. The majority of completed visits performed in weeks 1 and 2 were in person, while the majority in weeks 3 and 4 were via telehealth. Among subspecialties, a larger proportion of completed visits in 2020 were performed by pediatric and head and neck oncology otolaryngologists as compared with general/specialty otolaryngologists (P < .001). Older adults (≥65 years) were less likely to have telehealth visits than younger adults (18-64 years; 45.6% vs 59.6%, P = .003). CONCLUSIONS: A major decrease in the completion rates of scheduled visits was seen in the COVID-19–affected period, though this was not proportional among subspecialties. An associated increase in telehealth visits was observed. After COVID-19–related hospital policy changes, approximately 2 weeks passed before telehealth visits surpassed in-person visits, though this was not true among older adults.


title: COVID-19 lockdown: de-risking exit by protecting the lung with leukaemia inhibitory factor (LIF)

text: There are two key needs in COVID-19 management: (i) to reduce SARS-CoV-2 viral infection rate; and (ii) to reduce death rate of those infected - the subject of this commentary. The current WHO estimated global mortality rate is 3.4% (March 2020) and the global death toll has now past 200,000 (April 2020). Without therapy the COVID-19 pandemic is escalating exponentially: from the first reported death in Wuhan China 10th January 2020, it took 91 days for the global death toll to pass 100,000 - then a further 16 days to reach 200,000. A vaccination program will take 1–2 years to roll out, once safety and efficacy is proven. Anti-virals are being sought mainly amongst repurposed drug candidates but also with combinatorial screening of libraries, for example to block virus binding angiotensin converting enzyme 2 (ACE2) - ACE2 providing the receptor on cells that allows viral entry. Cell-based approaches include stem cells and exosomes but these will never meet scale of need whilst also carrying risk of viral transmission if contaminated. Countries have introduced Population control with social distancing and lockdown to isolate individuals: this has reduced infectivity rate - “R” - where R denotes the average number of people an infected person will spread the illness to. But, after lockdown, the virus remains: the probability of R increasing again is high. The new danger is exit from lockdown. Here, leukaemia inhibitory factor (LIF) represents an untapped resource to boost the lung's own resistance to developing COVID-19 - reducing risk of severe disease as nations cautiously leave lockdown to return to normality.


Prioritizing the ‘Dormant’ Flaviviruses


title: Applying evolutionary concepts to wildlife disease ecology and management

text: Existing and emerging infectious diseases are among the most pressing global threats to biodiversity, food safety and human health. The complex interplay between host, pathogen and environment creates a challenge for conserving species, communities and ecosystem functions, while mediating the many known ecological and socio-economic negative effects of disease. Despite the clear ecological and evolutionary contexts of host–pathogen dynamics, approaches to managing wildlife disease remain predominantly reactionary, focusing on surveillance and some attempts at eradication. A few exceptional studies have heeded recent calls for better integration of ecological concepts in the study and management of wildlife disease; however, evolutionary concepts remain underused. Applied evolution consists of four principles: evolutionary history, genetic and phenotypic variation, selection and eco-evolutionary dynamics. In this article, we first update a classical framework for understanding wildlife disease to integrate better these principles. Within this framework, we explore the evolutionary implications of environment–disease interactions. Subsequently, we synthesize areas where applied evolution can be employed in wildlife disease management. Finally, we discuss some future directions and challenges. Here, we underscore that despite some evolutionary principles currently playing an important role in our understanding of disease in wild animals, considerable opportunities remain for fostering the practice of evolutionarily enlightened wildlife disease management.


title: Ecological Factors Associated with European Bat Lyssavirus Seroprevalence in Spanish Bats

text: Bats have been proposed as major reservoirs for diverse emerging infectious viral diseases, with rabies being the best known in Europe. However, studies exploring the ecological interaction between lyssaviruses and their natural hosts are scarce. This study completes our active surveillance work on Spanish bat colonies that began in 1992. Herein, we analyzed ecological factors that might affect the infection dynamics observed in those colonies. Between 2001 and 2011, we collected and tested 2,393 blood samples and 45 dead bats from 25 localities and 20 bat species. The results for dead confirmed the presence of EBLV-1 RNA in six species analyzed (for the first time in Myotis capaccinii). Samples positive for European bat lyssavirus-1 (EBLV-1)–neutralizing antibodies were detected in 68% of the localities sampled and in 13 bat species, seven of which were found for the first time (even in Myotis daubentonii, a species to date always linked to EBLV-2). EBLV-1 seroprevalence (20.7%) ranged between 11.1 and 40.2% among bat species and seasonal variation was observed, with significantly higher antibody prevalence in summer (July). EBLV-1 seroprevalence was significantly associated with colony size and species richness. Higher seroprevalence percentages were found in large multispecific colonies, suggesting that intra- and interspecific contacts are major risk factors for EBLV-1 transmission in bat colonies. Although bat-roosting behavior strongly determines EBLV-1 variability, we also found some evidence that bat phylogeny might be involved in bat-species seroprevalence. The results of this study highlight the importance of life history and roost ecology in understanding EBLV-1–prevalence patterns in bat colonies and also provide useful information for public health officials.


title: Novel Chikungunya Virus Variant in Travelers Returning from Indian Ocean Islands

text: Chikungunya virus (CHIKV) emerged in Indian Ocean islands in 2005 and is causing an ongoing outbreak that involves >260,000 patients, including travelers returning home from these islands. We investigated cases in 4 patients returning from Mayotte and Reunion Islands with CHIKV infection and a nurse infected in metropolitan France after direct contact with the blood of a traveler. Four patients had tenosynovitis and pain at wrist pressure, and 1 had life-threatening manifestations. Four CHIKV strains were isolated, including 1 from the patient with the autochthonous case. The complete genomic sequence identified a new CHIKV variant emerging from the East/central African evolutionary lineage. Aedes albopictus, the implicated vector of CHIKV in Indian Ocean islands, has dispersed worldwide in recent decades. High viral loads in patients returning from Indian Ocean islands to countries where Ae. albopictus is prevalent may be a source of epidemics.


title: Severe acute respiratory syndrome: global initiatives for disease diagnosis

text: We present a retrospective analysis of the available articles on severe acute respiratory syndrome (SARS) published since the outbreak of the disease. SARS is a new infectious disease caused by a novel coronavirus. Originating in Guangdong, Southern China, at the end of 2002, it has spread to regions all over the world, affecting more than 8000 people. With high morbidity and mortality, SARS is an important respiratory disease which may be encountered world-wide. The causative virus was identified by a WHO-led network of laboratories, which identified the genome sequence and developed the first molecular assays for diagnosis. For the respiratory physician, detecting SARS in its earliest stages, identifying pathways of transmission, and implementing preventive and therapeutic strategies are all important. The WHO and the CDC have published helpful definitions of ‘suspected’ and ‘probable’ cases. However, the symptoms of the disease may change, and laboratory tests and definitions are still limited. Even in a situation of no new cases of infection, SARS remains a major respiratory health hazard. As with influenza virus outbreaks, new epidemics may arise at the end of each year.


title: Crimean–Congo haemorrhagic fever virus: Past, present and future insights for animal modelling and medical countermeasures

text: Crimean–Congo haemorrhagic fever (CCHF) is a widespread tick‐borne viral zoonosis with a case‐fatality rate ranging from 9% to 50% in humans. Although a licensed vaccine to prevent infection by the CCHF virus (CCHFV) exists, its ability to induce neutralizing antibodies is limited and its efficacy against CCHFV remains undetermined. In addition, controlling CCHF infections by eradication of the tick reservoir has been ineffective, both economically and logistically, and the treatment options for CCHF remain limited. In this review, we first critically discuss the existing animal models to evaluate therapeutics for CCHF. We then review the therapeutic options for CCHF that have been investigated in human cases, followed by investigational drugs that have been evaluated in pre‐clinical studies. We highlight the importance of understanding human prognostic factors in developing an animal model for CCHF that recapitulates hallmarks of human disease and its implication for selecting therapeutic candidates.


title: Surveillance of 16 respiratory viruses in patients with influenza‐like illness in Nanjing, China

text: Much less is known about the etiology of influenza‐like illness in China. A continuous surveillance of 16 respiratory viruses was conducted from November 2010 to October 2011 of outpatients with influenza‐like illness in Nanjing, China. The two largest general hospitals and a provincial virus laboratory in Nanjing participated in this study. Throat swabs were collected from outpatients during medical visits for influenza‐like illness and were tested for 16 respiratory viruses using PCR. Three hundred seventeen viruses were detected in samples from 246 (50.6%) patients with influenza‐like illness. The viruses found mostly commonly were influenza, rhinovirus, hCoV HKU1, and adenovirus. The identification rates of respiratory viruses differed significantly among different sampling seasons (P = 0.0002). The rates of influenza A and hCoV HKU1 were much higher during the influenza‐like illness winter peak than during the influenza‐like illness summer peak and other months. Co‐infections were detected in 57 (11.7%) patients and were found most commonly in adults older than 60 years. RSV was detected in 5.9% and 2.6% of patients who were 0–5 and 6–15 years old, respectively, but was not detected in other age groups. This study confirmed that multiple respiratory viruses may circulate concurrently in the population and account for a large proportion of influenza‐like illness. In addition to influenza virus, hCoV HKU1 may be associated with the influenza‐like illness winter peak in Nanjing, China. J. Med. Virol. 84:1980–1984, 2012. © 2012 Wiley Periodicals, Inc.


title: Organ donation during the coronavirus pandemic: an evolving saga in uncharted waters

text: Coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic of respiratory illness, known as coronavirus disease 2019 (COVID-19).[1] The risk of developing COVID-19 from a SARS-CoV-2 infected organ donor is unknown. Therefore, extreme caution is necessary when considering transplantation. Transmission is affected by epidemiological risk factors, incubation period, degree of viraemia, and viability of SARS-CoV-2 in blood and organ compartments. Recent guidelines from NHSBT[2] recommend that all potential donors be tested for SARS-CoV-2 and donation suspended from those who test positive. Donation is discouraged for asymptomatic individuals who have been in a COVID-19-affected area in the last 28 days.


title: Potential Intermediate Hosts for Coronavirus Transmission: No Evidence of Clade 2c Coronaviruses in Domestic Livestock from Ghana

text: The emergence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV), nearly a decade ago with worldwide distribution, was believed to be of zoonotic origin from bats with dromedary camels as intermediate hosts. There is a likelihood of other domestic livestock serving as intermediate hosts for this virus. The presence of coronaviruses, closely related to MERS-CoV in Ghanaian bats, presented the opportunity to test the hypothesis of transmissibility of this virus through domestic livestock species. The possible interactions between livestock and bats in 31 household farms were accessed by observation and interviews with farmers. Rectal swabs and serum from cattle, sheep, goats, donkeys, and swine from commercial and household farms were tested for MERS-CoV and a Nycteris sp. bat coronavirus, previously detected in Ghana. A pan-PCR assay to detect clade 2c viruses and recombinant immunofluorescence assay to detect anti-spike IgG antibodies against the target viruses were used. Likely contact between livestock and bats was determined for 13 farms (41.9%) that reported confining their livestock and also observing bats in their homes. Livestock were left unconfined on eight farms (25.8%) that also observed bats roosting in trees close to their homes. No viral RNA or antibodies against the two coronaviruses were detected in any of the livestock species tested. Cattle, sheep, goats, donkeys, and swine are not likely hosts of clade 2c coronaviruses.


title: Impact Of Sars-Cov-2 And Its Reverberation In Global Higher Education And Mental Health

text: BACKGROUND: : According to UNESCO's monitoring, more than 160 countries implemented nationwide closures, which impacted over 87% of the world's student population. Several other countries implemented localized school closures; should these closures become nationwide, millions of additional learners will experience education disruption. Universities from around the world have been uncertain about how long the coronavirus crisis will last and how it might affect the mental health of students and faculty. The psychological impact has been a critical disruptor, creating anxiety and uncertainty. METHOD: : The data were cross-checked with information from the main international newspapers. RESULTS: : By discussing online and distance education, the coronavirus opens an important and urgent issue that affects mental health – these are virtually unexplored topics, and their results have not been validated yet. Online education is not limited to distance education, as it regards a grouping of learning/teaching procedures completed in cyberspace. Blended learning was, thus, introduced as a tool in personalized learning to adjust to new realities. These are unprecedented circumstances, and we understand they create stress, favoring anguish and a fierce search for new knowledge acquisition. CONCLUSIONS: : Current research highlights that anxiety and depression, exacerbated by uncertainties and intensification of the information flow, will grow extensively. Negative physiological consequences of stress will manifest. For instance, loneliness, which will increase under these circumstances, seems to have a negative impact on education and, therefore, on psychological pain and suffering.


Emerging infections in Asia and its possible global effects


title: Distinct Viral Clades of SARS‐CoV‐2: Implications for Modeling of Viral Spread

text: Distinct viral clades have a likely impact on COVID‐19 pathogenesis and spread. Sequence analysis from 2310 viral isolates from Nexstrain reveals that residue at 614 of the viral spike protein is changed from a putative ancestral aspartic acid (D) to a glycine (G) between two viral clades. The G strain is predominantly on the East Coast of the United States, and the D strain is predominantly on the West Coast. This mutation of the SARS‐CoV‐2 S protein spike is conserved in coronaviruses. Point mutations in a murine coronavirus spike protein can result in increased virulence through instability of the viral machinery and altered viral to cell membrane fusion. This observation may partially explain the discrepancy in predicted deaths from COVID‐19 between the East Coast and West Coast, and possibly explain that other factors aside from social distance, such as competition between two strains of differing virulence, may be at play. This article is protected by copyright. All rights reserved.


title: Syndromic Surveillance System for MERS-CoV as New Early Warning and Identification Approach [Corrigendum]

text: [This corrects the article DOI: 10.2147/RMHP.S239984.].


title: Does comorbidity increase the risk of patients with COVID-19: evidence from meta-analysis

text: Currently, the number of patients with coronavirus disease 2019 (COVID-19) has increased rapidly, but relationship between comorbidity and patients with COVID-19 still not clear. The aim was to explore whether the presence of common comorbidities increases COVID-19 patients’ risk. A literature search was performed using the electronic platforms (PubMed, Cochrane Library, Embase, and other databases) to obtain relevant research studies published up to March 1, 2020. Relevant data of research endpoints in each study were extracted and merged. All data analysis was performed using Stata12.0 software. A total of 1558 patients with COVID-19 in 6 studies were enrolled in our meta-analysis eventually. Hypertension (OR: 2.29, P<0.001), diabetes (OR: 2.47, P<0.001), chronic obstructive pulmonary disease (COPD) (OR: 5.97, P<0.001), cardiovascular disease (OR: 2.93, P<0.001), and cerebrovascular disease (OR:3.89, P=0.002)were independent risk factors associated with COVID-19 patients. The meta-analysis revealed no correlation between increased risk of COVID-19 and liver disease, malignancy, or renal disease. Hypertension, diabetes, COPD, cardiovascular disease, and cerebrovascular disease are major risk factors for patients with COVID-19. Knowledge of these risk factors can be a resource for clinicians in the early appropriate medical management of patients with COVID-19.


title: Intermittent Suction of Oral Secretions Before Each Positional Change may Reduce Ventilator-Associated Pneumonia: A Pilot Study

text: ABSTRACT Background That ventilator-associated pneumonia (VAP) can be reduced by continuous and/or intermittent subglottic suction highlights the importance of clearance of oropharyngeal secretions. We prospectively evaluated the usefulness of intermittent suction of oral secretions before each positional change in reducing VAP. Methods A time-sequence nonrandomized intervention design was used. The study consisted of a 9-month observation phase (control group, 237 patients), a 6-month education phase, followed by a 7-month intervention phase (studied group, 227 patients). The occurrence of VAP, duration of mechanical ventilation, length of intensive care unit (ICU) stay, and mortality were recorded. Results VAP occurred less frequently in the studied group (6 of 227 patients, 2.6%) than in the control group (26 of 237 patients, 11.0%; P < 0.001). The incidence rate of VAP in control and studied groups was 6.51 and 2.04 per 1000 ventilator days, respectively (P =0.002). For VAP patients, the ventilator days were 28.8 ± 17.2days and 20.2 ± 4.0days (P =0.009), respectively, and the length of ICU stay was 27.6 ± 17.0days and 20.3 ± 4.0days (P =0.012), respectively, in the control and studied groups. Intermittent suction of oral secretions before each positional change was the only independent factor responsible for a decrease of VAP in the studied group after stepwise logistic regression analysis (P =0.003). Conclusions Intermittent suction of oral secretions before each positional change may reduce VAP occurrence in ICU patients.


title: Unpolarized Release of Vaccinia Virus and HIV Antigen by Colchicine Treatment Enhances Intranasal HIV Antigen Expression and Mucosal Humoral Responses

text: The induction of a strong mucosal immune response is essential to building successful HIV vaccines. Highly attenuated recombinant HIV vaccinia virus can be administered mucosally, but even high doses of immunization have been found unable to induce strong mucosal antibody responses. In order to solve this problem, we studied the interactions of recombinant HIV vaccinia virus Tiantan strain (rVTT-gagpol) in mucosal epithelial cells (specifically Caco-2 cell layers) and in BALB/c mice. We evaluated the impact of this virus on HIV antigen delivery and specific immune responses. The results demonstrated that rVTT-gagpol was able to infect Caco-2 cell layers and both the nasal and lung epithelia in BALB/c mice. The progeny viruses and expressed p24 were released mainly from apical surfaces. In BALB/c mice, the infection was limited to the respiratory system and was not observed in the blood. This showed that polarized distribution limited antigen delivery into the whole body and thus limited immune response. To see if this could be improved upon, we stimulated unpolarized budding of the virus and HIV antigens by treating both Caco-2 cells and BALB/c mice with colchicine. We found that, in BALB/c mice, the degree of infection and antigen expression in the epithelia went up. As a result, specific immune responses increased correspondingly. Together, these data suggest that polarized budding limits antigen delivery and immune responses, but unpolarized distribution can increase antigen expression and delivery and thus enhance specific immune responses. This conclusion can be used to optimize mucosal HIV vaccine strategies.


Clinical features of atypical 2019 novel coronavirus pneumonia with an initially negative RT-PCR assay


title: Interaction Behavior Between Niclosamide and Pepsin Determined by Spectroscopic and Docking Methods

text: The interaction between niclosamide (NIC) and pepsin was investigated using multispectroscopic and molecular docking methods. Binding constant, number of binding sites, and thermodynamic parameters at different temperatures were measured. Results of fluorescence quenching and synchronous fluorescence spectroscopy in combination with three-dimensional fluorescence spectroscopy showed that changes occurred in the microenvironment of tryptophan residues and the molecular conformation of pepsin. Molecular interaction distance and energy-transfer efficiency between pepsin and NIC were determined based on Förster nonradiative energy-transfer mechanism. Furthermore, the binding of NIC inhibited pepsin activity in vitro. All these results indicated that NIC bound to pepsin mainly through hydrophobic interactions and hydrogen bonds at a single binding site. In conclusion, this study provided substantial molecular-level evidence that NIC could induce changes in pepsin structure and conformation.


title: Psychiatrist in post-COVID-19 era – Are we prepared?

text: • First communication from India with psychiatry residents perspective. • Authors had first-hand experience of working in the COVID designated areas. • Highlights the need of the hour.


title: Risk Perception, Preventive Behaviors, and Vaccination Coverage in the Korean Population during the 2009–2010 Pandemic Influenza A (H1N1): Comparison between High-Risk Group and Non–High-Risk Group

text: BACKGROUND: This study was carried out to estimate the vaccination coverage, public perception, and preventive behaviors against pandemic influenza A (H1N1) and to understand the motivation and barriers to vaccination between high-risk and non–high-risk groups during the outbreak of pandemic influenza A (H1N1). METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional nationwide telephone survey of 1,650 community-dwelling Korean adults aged 19 years and older was conducted in the later stage of the 2009–2010 pandemic influenza A (H1N1) outbreak. The questionnaire identified the demographics, vaccination status of participants and all household members, barriers to non-vaccination, perceived threat, and preventive behaviors. In Korea, the overall rate of pandemic influenza vaccination coverage in the surveyed population was 15.5%; vaccination coverage in the high-risk group and non–high-risk group was 47.3% and 8.0%, respectively. In the high-risk group, the most important triggering event for vaccination was receiving a notice from a public health organization. In the non–high-risk group, vaccination was more strongly influenced by previous experience with influenza or mass media campaigns. In both groups, the most common reasons for not receiving vaccination was that their health was sufficient to forgo the vaccination, and lack of time. There was no significant difference in how either group perceived the threat or adopted preventive behavior. The predictive factors for pandemic influenza vaccination were being elderly (age ≥65 years), prior seasonal influenza vaccination, and chronic medical disease. CONCLUSIONS/SIGNIFICANCE: With the exception of vaccination coverage, the preventive behaviors of the high-risk group were not different from those of the non–high-risk group during the 2009–2010 pandemic. For future pandemic preparedness planning, it is crucial to reinforce preventive behaviors to avoid illness before vaccination and to increase vaccination coverage in the high-risk group.


Why the United States failed to contain COVID‐19


The Importance of Scientific Publications in Times of Pandemic Crisis


Type et impact des mesures de contrôle des épidémies d’infections nosocomiales


title: Disorders of the Urinary and Reproductive Systems in Ferrets

text: Urogenital lesions are relatively common in ferrets. Renal disease is diagnosed as in traditional small animal medicine; however, peculiarities in ferrets include physiologically low levels of creatinine. Renal cysts are very common in ferrets but are usually incidental findings. Uroliths are usually composed of struvite or cystine. Urethral obstruction in male ferrets is predominantly caused by adrenal-associated prostatic disease. Spontaneous cystitis is rare in ferrets. Primary reproductive disease is uncommon in ferrets in the United States where animals are usually neutered at 6 weeks of age. In other countries, ferrets either remain unneutered or are neutered at 5 to 6 months of age. Ferrets are seasonal breeders, and female are induced ovulators. Prolonged estrus and hyperestrogenism often causes profound bone marrow suppression.


title: Online faculty development using cognitive apprenticeship in response to COVID‐19

text: Despite the COVID 19 pandemic, it is still necessary to develop good assessment materials to assure the competence of our students. Our medical education department, therefore, changed its face-to-face workshops on "how to create Multiple choice questions (MCQs)" into online ones. It was our first time training faculty on the creation of questions online.


title: Relación entre asma e infecciones virales

text: A pesar de que las infecciones respiratorias virales son el factor asociado con más frecuencia con la expresión del asma (independientemente del fenotipo, edad y fase de la historia natural asmática en la cual la infección ocurre) y de la fuerte asociación temporal existente entre las infecciones y las crisis obstructivas/asmáticas, el rol de los virus en la patogénesis del asma no está aún bien dilucidado. Los factores que explicarían esta conexión son heterogéneos y, a veces, contradictorios. Probablemente las alteraciones en la función y tamaño de la vía aérea, la desregulación (congénita y adquirida) del tono de la vía aérea, las alteraciones en la respuesta inmunitaria a las infecciones y las variantes genéticas en dicha respuesta sean los cuatro mecanismos principales implicados en la asociación entre las infecciones respiratorias virales y el posterior desarrollo del asma o sibilancias en los niños. Futuras estrategias terapéuticas y de prevención deberían considerar estos mecanismos. Viral respiratory infections are the factor most frequently associated with asthma (independently of phenotype, age, and phase of the natural history of asthma during which the infection occurs) and there is a strong temporal association between viral respiratory infections and acute obstructive/asthmatic episodes. Nevertheless, the role of viral infections in the pathogenesis of asthma remains poorly characterized. The factors that could explain this association are heterogeneous and sometimes contradictory. The four main causative mechanisms implicated in the association between viral respiratory infections and the subsequent development of asthma or wheezing in children are alterations in airway function and size, dysregulation (congenital and acquired) of airway tone, alterations in the immune response to infections, and the genetic variants involved in immune response. These mechanisms should be taken into account in future preventive and therapeutic strategies.


title: Impact of the SARS-CoV-2 epidemic on private ENT consulting practice during the first month of lockdown in Réunion Island in 2020

text: Abstract Objective To analyze the impact of the first month of lockdown related to the 2020 SARS-Cov-2 epidemic on the consulting activity of private ENT physicians in Réunion Island. Material and Methods A multicenter prospective study analyzed the consulting activity of 12 ENT physicians in full-time private practice. The main endpoints were the number, characteristics and conditions of consultations. Secondary endpoints comprised presenting symptoms, diagnosis, prescriptions, adverse effects, and progression of monthly consulting turnover. Results 693 consultations were performed during the study period (Appendix 1), with 50% emergency consultations. In 57.9% were face-to-face, 28.4% by phone and 13.7% video. In face-to-face consultation, the physician wore gloves in 53.8% of cases and a mask in 92.2%: surgical mask in 71.6% of cases and FFP2 in 28.4%. The three most frequent symptoms (48.5% of cases) were otalgia, hearing impairment, and vertigo. The three most frequent diagnoses (60.6% of cases) were otitis, intra-auricular foreign body (including wax), and pharyngeal infection. The three most frequently prescribed complementary exams (74.3% of cases) were imaging, hearing work-up, and specialist opinion. The three most frequently prescribed treatments (52.7% of cases) were intra-auricular drops, oral antibiotics, and nasal spray. The incidence of adverse effects was 0.001%. None of the physicians or patients seemed to have been infected by Covid-19 during the study period. There was a 47.3-91% (median, 75.6%) drop in monthly consultation turnover. Conclusion The present study underscored the availability and adaptability of ENT physicians in the Réunion Island in an epidemic context, although economic impact was detrimental.


title: Recommandations pour la prise en charge chirurgicale des cancers gynécologiques en période de pandémie COVID-19 – Groupe FRANCOGYN pour le CNGOF

text: Résumé Introduction Proposer des recommandations de prise en charge des patientes atteintes de cancer gynécologique dans la période de pandémie du COVID-19. Matériel et méthode Recommandations sur le modèle des conférences de consensus. Résultats En cas de patiente positive COVID-19, il convient de différer la prise en charge chirurgicale d’au moins 15jours. Pour le cancer du col, la place de la chirurgie doit être ré-évaluée par rapport à la radiothérapie et la radio-chimiothérapie-concomitante et l’intérêt des chirurgies de stadification ganglionnaire doit être revu au cas par cas. Pour les cancers de l’ovaire de stade avancé, il convient de privilégier la chimiothérapie néo-adjuvante même si la chirurgie de cytoréduction première pourrait être envisageable. Il est licite de ne pas proposer la chimiothérapie hyperthermique intra-péritonéale en période de pandémie COVID-19. Pour les cas des patientes qui doivent bénéficier d’une chirurgie d’intervalle, il est possible de poursuivre la chimiothérapie et de proposer une chirurgie de clôture après 6 cycles de chimiothérapie. Pour le cancer de l’endomètre de stade précoce, en cas de risque ESMO préopératoire faible et intermédiaire, il faut privilégier une hystérectomie totale avec annexectomie bilatérale associée à une procédure du ganglion sentinelle. Il est licite d’envisager le report de 1 à 2 mois de la chirurgie dans les cancers de l’endomètre de bas risque (stade FIGO Ia sur l’IRM et cancer endométrioïde de grade 1-2 sur la biopsie endométriale). Pour les risques ESMO élevés, il semble légitime de privilégier l’algorithme du MSKCC (associant TEP TDM et procédure du GS) afin d’omettre les lympahdénectomies pelviennes et lomboaortiques. Conclusion En période de pandémie COVID-19, il convient de ne pas faire perdre de chance aux patientes atteintes de cancer, tout en limitant les risques liés au virus. Abstract Introduction Recommendations for the management of patients with gynecological cancer during the COVID-19 pandemic period. Material and method Recommendations based on the consensus conference model. Results In the case of a COVID-19 positive patient, surgical management should be postponed for at least 15 days. For cervical cancer, the place of surgery must be re-evaluated in relation to radiotherapy and Radio-Chemotherapy-Concomitant and the value of lymph node staging surgeries must be reviewed on a case-by-case basis. For advanced ovarian cancers, neo-adjuvant chemotherapy should be favored even if primary cytoreduction surgery could be envisaged. It is lawful not to offer hyperthermic intraperitoneal chemotherapy during a COVID-19 pandemic. In the case of patients who must undergo interval surgery, it is possible to continue the chemotherapy and to offer surgery after 6 cycles of chemotherapy. For early stage endometrial cancer, in case of low and intermediate preoperative ESMO risk, hysterectomy with bilateral annexectomy associated with a sentinel lymph node procedure should be favored. It is possible to consider postponing surgery for 1 to 2 months in low-risk endometrial cancers (FIGO Ia stage on MRI and grade 1-2 endometrioid cancer on endometrial biopsy). For high ESMO risk, it ispossible to favor the MSKCC algorithm (combining PET-CT and sentinel lymph node biopsy) in order to omit pelvic and lumbar-aortic lymphadenectomies. Conclusion During COVID-19 pandemic, patients suffering from cancer should not lose life chance, while limiting the risks associated with the virus.


title: Low-dose Interferon-α Treatment Improves Survival and Inflammatory Responses in a Mouse Model of Fulminant Acute Respiratory Distress Syndrome

text: Acute respiratory distress syndrome (ARDS) is accompanied by severe lung inflammation induced by various diseases. Despite the severity of symptoms, therapeutic strategies for this pathologic condition are still poorly developed. Interferon (IFN)-α is well known as an antiviral cytokine and low-dose IFN-α has been reported to show antiinflammatory effects. Therefore, we investigated how this cytokine affected ARDS in a mouse model. C57BL/6 mice received sequential intratracheal administration of α-galactosylceramide (α-GalCer) and lipopolysaccharide (LPS), which resulted in the development of fulminant ARDS. These mice were then treated intranasally with IFN-α and their survival, lung weight, pathological findings, and cytokine production were evaluated. Administration of low-dose IFN-α prolonged survival of fulminant ARDS mice, but higher doses of IFN-α did not. Histological analysis showed that low-dose IFN-α treatment improved findings of diffuse alveolar damage in fulminant ARDS mice, which was associated with reduction in the wet/dry (W/D) lung weight ratio. Furthermore, IFN-γ production in the lungs was significantly reduced in IFN-α-treated mice, compared with control mice, but tumor necrosis factor (TNF)-α production was almost equivalent for both groups. Low-dose IFN-α shows antiinflammatory and therapeutic effects in a mouse model of fulminant ARDS, and reduced production of IFN-γ in the lung may be involved in the beneficial effect of this treatment.


title: Chapter 49 Cotton Rat

text: The cotton rat (Sigmodon) species has long been recognized as a significant animal model for numerous human and rodent pathogens. This chapter provides a general description of the model, its natural distribution habitat and use in research. Additionally there is information about the unique anatomy, physiology, reproduction, and growth of this research model. Finally there will be a discussion on husbandry, diseases, and experimental procedures.


title: The use of nanolipoprotein particles to enhance the immunostimulatory properties of innate immune agonists against lethal influenza challenge

text: Abstract Recent studies have demonstrated that therapies targeting the innate immune system have the potential to provide transient, non-specific protection from a variety of infectious organisms; however, the potential of enhancing the efficacy of such treatments using nano-scale delivery platforms requires more in depth evaluation. As such, we employed a nanolipoprotein (NLP) platform to enhance the efficacy of innate immune agonists. Here, we demonstrate that the synthetic Toll-like receptor (TLR) agonists monophosphoryl lipid A (MPLA) and CpG oligodeoxynucleotides (CpG) can be readily incorporated into NLPs. Conjugation of MPLA and CpG to NLPs (MPLA:NLP and CpG:NLP, respectively) significantly enhanced their immunostimulatory profiles both in vitro and in vivo compared to administration of agonists alone, as evidenced by significant increases in cytokine production, cell surface expression of activation markers, and upregulation of immunoregulatory genes. Importantly, enhancement of cytokine production by agonist conjugation to NLPs was also observed in primary human dendritic cells. Furthermore, BALB/c mice pretreated with CpG:NLP constructs survived a lethal influenza challenge whereas pretreatment with CpG alone had no effect on survival.


Care and Community Revalued During the COVID‐19 Pandemic ‐ A Feminist Couple Perspective