Adaptation to the Plastic Barrier Sheet to Facilitate Intubation During the COVID-19 Pandemic


title: Differential innate immune response programs in neuronal subtypes determine susceptibility to infection in the brain by positive stranded RNA viruses

text: Although susceptibility of neurons in the brain to microbial infection is a major determinant of clinical outcome, little is known about the molecular factors governing this. Here, we show that two types of neurons from distinct brain regions exhibited differential permissivity to replication of several positive-stranded RNA viruses. Granule cell neurons (GCN) of the cerebellum and cortical neurons (CN) from the cerebral cortex have unique innate immune programs that confer differential susceptibility to viral infection ex vivo and in vivo. By transducing CN with genes that were expressed more highly in GCN, we identified three interferon-stimulated genes (ISGs; Ifi27, Irg1, and Rsad2/Viperin) that mediated antiviral effects against different neurotropic viruses. Moreover, we found that the epigenetic state and microRNA-mediated regulation of ISGs correlates with enhanced antiviral response in GCN. Thus, neurons from evolutionarily distinct brain regions have unique innate immune signatures, which likely contribute to their relative permissiveness to infection.


title: Murine coronavirus-induced encephalomyelitides in rats: Analysis of immunoglobulins and virus-specific antibodies in serum and cerebrospinal fluid

text: Abstract The humoral intrathecal immune response in coronavirus-induced demyelinating encephalomyelitis in rats associated with an autoimmune reaction to brain antigen, was analysed. The CSF of these animals revealed immune reactions which were directed against coronavirus and other, unknown, antigens. In general, no direct correlation between the disease, the state of the blood-brain barrier (BBB), intrathecal synthesis of Ig and the presence of virus-specific antibodies was detectable, suggesting that the humoral, in contrast to the cellular, immune response does not play a significant pathogenetic role in this CNS disease.


title: Necrotizing pneumonia: an emerging problem in children?

text: BACKGROUND: In children, necrotizing pneumonia (NP) is an uncommon, severe complication of pneumonia. It is characterized by destruction of the underlying lung parenchyma resulting in multiple small, thin-walled cavities and is often accompanied by empyema and bronchopleural fistulae. REVIEW: NP in children was first reported in children in 1994, and since then there has been a gradual increase in cases, which is partially explained by greater physician awareness and use of contrast computed tomography (CT) scans, and by temporal changes in circulating respiratory pathogens and antibiotic prescribing. The most common pathogens detected in children with NP are pneumococci and Staphylococcus aureus. The underlying disease mechanisms are poorly understood, but likely relate to multiple host susceptibility and bacterial virulence factors, with viral–bacterial interactions also possibly having a role. Most cases are in previously healthy young children who, despite adequate antibiotic therapy for bacterial pneumonia, remain febrile and unwell. Many also have evidence of pleural effusion, empyema, or pyopneumothorax, which has undergone drainage or surgical intervention without clinical improvement. The diagnosis is generally made by chest imaging, with CT scans being the most sensitive, showing loss of normal pulmonary architecture, decreased parenchymal enhancement and multiple thin-walled cavities. Blood culture and culture and molecular testing of pleural fluid provide a microbiologic diagnosis in as many as 50% of cases. Prolonged antibiotics, draining pleural fluid and gas that causes mass effects, and maintaining ventilation, circulation, nutrition, fluid, and electrolyte balance are critical components of therapy. Despite its serious nature, death is uncommon, with good clinical, radiographic and functional recovery achieved in the 5–6 months following diagnosis. Increased knowledge of NP’s pathogenesis will assist more rapid diagnosis and improve treatment and, ultimately, prevention. CONCLUSION: It is important to consider that our understanding of NP is limited to individual case reports or small case series, and treatment data from randomized-controlled trials are lacking. Furthermore, case series are retrospective and usually confined to single centers. Consequently, these studies may not be representative of patients in other locations, especially when allowing for temporal changes in pathogen behaviour and differences in immunization schedules and antibiotic prescribing practices.


title: Generality of the Final Size Formula for an Epidemic of a Newly Invading Infectious Disease

text: The well-known formula for the final size of an epidemic was published by Kermack and McKendrick in 1927. Their analysis was based on a simple susceptible-infected-recovered (SIR) model that assumes exponentially distributed infectious periods. More recent analyses have established that the standard final size formula is valid regardless of the distribution of infectious periods, but that it fails to be correct in the presence of certain kinds of heterogeneous mixing (e.g., if there is a core group, as for sexually transmitted diseases). We review previous work and establish more general conditions under which Kermack and McKendrick's formula is valid. We show that the final size formula is unchanged if there is a latent stage, any number of distinct infectious stages and/or a stage during which infectives are isolated (the durations of each stage can be drawn from any integrable distribution). We also consider the possibility that the transmission rates of infectious individuals are arbitrarily distributed—allowing, in particular, for the existence of super-spreaders—and prove that this potential complexity has no impact on the final size formula. Finally, we show that the final size formula is unchanged even for a general class of spatial contact structures. We conclude that whenever a new respiratory pathogen emerges, an estimate of the expected magnitude of the epidemic can be made as soon the basic reproduction number ℝ(0) can be approximated, and this estimate is likely to be improved only by more accurate estimates of ℝ(0), not by knowledge of any other epidemiological details.


title: Efficacy of orally administered porcine epidemic diarrhea vaccine-loaded hydroxypropyl methylcellulose phthalate microspheres and RANKL-secreting L. lactis

text: Abstract Here, we examined the efficacy of are combinant subunit antigen-based oral vaccine for preventing porcine epidemic diarrhea virus (PEDV). First, we generated a soluble recombinant partial spike S1 protein (aP2) from PEDV in E. coli and then evaluated the utility of aP2 subunit vaccine-loaded hydroxypropyl methylcellulose phthalate microspheres (HPMCP) and RANKL-secreting L. lactis (LLRANKL) as a candidate oral vaccine in pregnant sows. Pregnant sows were vaccinated twice (with a 2 week interval between doses) at 4 weeks before farrowing. Titers of virus-specific IgA antibodies in colostrum, and neutralizing antibodies in serum, of sows vaccinated with HPMCP (aP2) plus LL RANKL increased significantly at 4 weeks post-first vaccination. Furthermore, the survival rate of newborn suckling piglets delivered by sows vaccinated with HPMCP (aP2) plus LL RANKL was similar to that of piglets delivered by sows vaccinated with a commercial killed porcine epidemic diarrhea virus (PED) vaccine. The South Korean government promotes a PED vaccine program (live-killed-killed) to increase the titers of IgA and IgG antibodies in pregnant sows and prevent PEDV. The oral vaccine strategy described herein, which is based on a safe and efficient recombinant subunit antigen, is an alternative PED vaccination strategy that could replace the traditional strategy, which relies on attenuated live oral vaccines or artificial infection with virulent PEDV.


title: Differential regulation of the monocytic calcium-binding peptides macrophage-inhibiting factor related protein-8 (MRP8/S100A8) and allograft inflammatory factor-1 (AIF-1) following human traumatic brain injury

text: Intracellular calcium (Ca(2+)) has been shown to function as second messenger and to be associated with activation of different cell types including microglia. Previously, in human focal cerebral infarctions an early expression of macrophage-related protein-8 (MRP8/ S100A8), a member of the Ca(2+)-binding S100-protein family, in microglia has been reported. On the other hand, a delayed activation of microglia was observed following traumatic brain injury (TBI). We therefore examined immunohistochemically microglial expression of MRP8 and allograft inflammatory factor-1 (AIF-1), identical to microglial response factor-1 (mrf-1) and ionized calcium binding adaptor molecule-1 (iba1) in human brains after TBI and in control brains. Both, MRP8 and AIF-1 are Ca(2+)-binding peptides which have been associated with microglial activation in experimental models and in human cerebral infarctions. Detection of AIF-1 in controls confirmed constitutive expression of this peptide in a subset of microglial cells. After TBI, the density of AIF-1(+) microglia did not increase significantly. Lesional expression of AIF-1 did not significantly differ from other brain regions. Furthermore, following TBI, we found no significant differences in the density of AIF-1(+) microglia as compared to controls. Microglial MRP8 expression was not detectable in controls and within the first 3 days post TBI, but increased rapidly after 3 days post TBI, suggesting a subpopulation of microglial cells to be AIF-1(–)/MRP8(+). We conclude that the delayed expression of MRP8 and the lack of AIF-1 up-regulation in microglia after TBI is in contrast to ischemic brain lesions and might reflect different activation cascades of microglia.


title: Phosphatidic Acid Produced by Phospholipase D Promotes RNA Replication of a Plant RNA Virus

text: Eukaryotic positive-strand RNA [(+)RNA] viruses are intracellular obligate parasites replicate using the membrane-bound replicase complexes that contain multiple viral and host components. To replicate, (+)RNA viruses exploit host resources and modify host metabolism and membrane organization. Phospholipase D (PLD) is a phosphatidylcholine- and phosphatidylethanolamine-hydrolyzing enzyme that catalyzes the production of phosphatidic acid (PA), a lipid second messenger that modulates diverse intracellular signaling in various organisms. PA is normally present in small amounts (less than 1% of total phospholipids), but rapidly and transiently accumulates in lipid bilayers in response to different environmental cues such as biotic and abiotic stresses in plants. However, the precise functions of PLD and PA remain unknown. Here, we report the roles of PLD and PA in genomic RNA replication of a plant (+)RNA virus, Red clover necrotic mosaic virus (RCNMV). We found that RCNMV RNA replication complexes formed in Nicotiana benthamiana contained PLDα and PLDβ. Gene-silencing and pharmacological inhibition approaches showed that PLDs and PLDs-derived PA are required for viral RNA replication. Consistent with this, exogenous application of PA enhanced viral RNA replication in plant cells and plant-derived cell-free extracts. We also found that a viral auxiliary replication protein bound to PA in vitro, and that the amount of PA increased in RCNMV-infected plant leaves. Together, our findings suggest that RCNMV hijacks host PA-producing enzymes to replicate.


title: Coronavirus endoribonuclease targets viral polyuridine sequences to evade activating host sensors

text: Coronaviruses (CoVs) are positive-sense RNA viruses that can emerge from endemic reservoirs and infect zoonotically, causing significant morbidity and mortality. CoVs encode an endoribonuclease designated EndoU that facilitates evasion of host pattern recognition receptor MDA5, but the target of EndoU activity was not known. Here, we report that EndoU cleaves the 5′-polyuridines from negative-sense viral RNA, termed PUN RNA, which is the product of polyA-templated RNA synthesis. Using a virus containing an EndoU catalytic-inactive mutation, we detected a higher abundance of PUN RNA in the cytoplasm compared to wild-type−infected cells. Furthermore, we found that transfecting PUN RNA into cells stimulates a robust, MDA5-dependent interferon response, and that removal of the polyuridine extension on the RNA dampens the response. Overall, the results of this study reveal the PUN RNA to be a CoV MDA5-dependent pathogen-associated molecular pattern (PAMP). We also establish a mechanism for EndoU activity to cleave and limit the accumulation of this PAMP. Since EndoU activity is highly conserved in all CoVs, inhibiting this activity may serve as an approach for therapeutic interventions against existing and emerging CoV infections.


title: The Ubiquitin-Conjugating System: Multiple Roles in Viral Replication and Infection

text: Through the combined action of ubiquitinating and deubiquitinating enzymes, conjugation of ubiquitin to a target protein acts as a reversible post-translational modification functionally similar to phosphorylation. Indeed, ubiquitination is more and more recognized as a central process for the fine regulation of many cellular pathways. Due to their nature as obligate intracellular parasites, viruses rely on the most conserved host cell machineries for their own replication. Thus, it is not surprising that members from almost every viral family are challenged by ubiquitin mediated mechanisms in different steps of their life cycle and have evolved in order to by-pass or exploit the cellular ubiquitin conjugating system to maximize their chance to establish a successful infection. In this review we will present several examples of the complex interplay that links viruses and the ubiquitin conjugation machinery, with a special focus on the mechanisms evolved by the human immunodeficiency virus to escape from cellular restriction factors and to exit from infected cells.


title: Is povidone‐iodine mouthwash effective against SARS‐CoV‐2? First in vivo tests

text: The detection of SARS-CoV-2 in the saliva of patients with coronavirus disease (COVID-19) has made this biological fluid relevant in terms of the diagnosis and transmission of the infection (To et al, 2020a; Azzi et al, 2020a). As a result, the dental clinic is considered an environment of risk for dental healthcare personnel and their patients, particularly due to the potential transmission of the virus through droplets and aerosols (Peng et al, 2020).


title: S1 gene sequence analysis of a nephropathogenic strain of avian infectious bronchitis virus in Egypt

text: BACKGROUND: Infectious bronchitis is highly contagious and constitutes one of the most common and difficult poultry diseases to control. IBV is endemic in probably all countries that raise chickens. It exists as dozens of serotypes/genotypes. Only a few amino acid differences in the S1 protein of vaccine and challenge strains of IBV may result in poor protection. Tropism of IBV includes the respiratory tract tissues, proventriculus and caecal tonsils of the alimentary tract, the oviduct and the kidney. RESULTS: Infectious bronchitis virus (IBV) strain closely related to Massachusetts (Mass) serotype was isolated from broiler chickens suffering from severe renal and respiratory distresses. The isolate was serologically identified by Dot-ELISA and further characterized by RT-PCR then genotyped using S1 gene sequence analysis. Alignment of the S1 sequence of the isolate with 16 IBV strains revealed high homology to isolates related to Mass serotype. Inoculation with the strain reproduced the disease in experimental 1-day-old chickens and resulted in 20% mortality, severe renal and moderate respiratory distresses. Marked histopathological changes in both kidney and trachea were observed in experimentally infected chickens. A protection study using the H120 live attenuated vaccine showed low protection rate in spite of high S1 sequence homology (97%). Protection based criteria were: virus re-isolation attempts from trachea, tracheal and renal histopathology as well as IBV antigens detection by immunofluorescent antibody technique in kidney sections. CONCLUSION: Periodical evaluation of cross-protective capabilities of IBV vaccine(s) versus recently recovered field isolates should be performed to ensure optimum control of IBV.


title: Immunization with a poly (lactide co-glycolide) encapsulated plasmid DNA expressing antigenic regions of HPV 16 and 18 results in an increase in the precursor frequency of T cells that respond to epitopes from HPV 16, 18, 6 and 11

text: Abstract A phase II trial was conducted in subjects with human papillomavirus (HPV) associated high-grade cervical dysplasia testing the safety and efficacy of a microparticle encapsulated pDNA vaccine. Amolimogene expresses T cell epitopes from E6 and E7 proteins of HPV types 16 and 18. An analysis was performed on a subset of HLA-A2+ subjects to test whether CD8+ T cells specific to HPV 16, 18, 6 and 11 were increased in response to amolimogene immunization. Of the 21 subjects receiving amolimogene, 11 had elevated CD8+ T cell responses to HPV 16 and/or 18 peptides and seven of these also had increases to corresponding HPV 6 and/or 11 peptides. In addition, T cells primed and expanded in vitro with an HPV 18 peptide demonstrated cross-reactivity to the corresponding HPV 11 peptide. These data demonstrate that treatment with amolimogene elicits T cell responses to HPV 16, 18, 6 and 11.


title: Crisis Prevention and Management during SARS Outbreak, Singapore

text: We discuss crisis prevention and management during the first 3 months of the severe acute respiratory syndrome (SARS) outbreak in Singapore. Four public health issues were considered: prevention measures, self-health evaluation, SARS knowledge, and appraisal of crisis management. We conducted telephone interviews with a representative sample of 1,201 adults, ≥21 years of age. We found that sex, age, and attitude (anxiety and perception of open communication with authorities) were associated with practicing preventive measures. Analysis of Singapore’s outbreak improves our understanding of the social dimensions of infectious disease outbreaks.


Modeling and forecasting of epidemic spreading: The case of Covid-19 and beyond


title: Herbal drug BNO 1016 is safe and effective in the treatment of acute viral rhinosinusitis

text: Conclusion: Daily intake of 480 mg of BNO 1016 for 15 days is an effective treatment in acute viral rhinosinusitis. Objectives: The pooled efficacy data of two similar randomized placebo-controlled clinical trials were analyzed. Safety was evaluated on the basis of the individual trials. Methods: The efficacy analysis was based on 589 patients. Treatment was performed orally with either 3 × 160 mg BNO 1016 (n = 294) or 3 × placebo (n = 295) for 15 days. In both trials patients underwent five visits to the investigational sites. Symptoms were evaluated according to the EPOS 2012 guideline. Ultrasonography was used to confirm the diagnosis at onset of treatment and the remission of symptoms at the last visit. Efficacy was evaluated by the investigator as the mean major symptom score (MSS) at the end of treatment (visit 5, day 14). Patients reported symptoms and social/emotional consequences of rhinosinusitis using a quality of life questionnaire (SNOT-20 GAV). Results: MSS improved during the treatment period by a mean of 10.02 ± 1.61 score points to 2.47 ± 2.55 for BNO 1016 and of 9.87 ± 1.52 to 3.63 ± 3.63 for placebo. Differences between treatment groups at end of therapy (1.16 ± 3.14 score points; p < 0.0001) and patient-assessed quality of life (p = 0.0015) were statistically significant in favor of BNO 1016.


title: Morphological Cell Profiling of SARS-CoV-2 Infection Identifies Drug Repurposing Candidates for COVID-19

text: The global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated disease COVID-19, requires therapeutic interventions that can be rapidly translated to clinical care. Unfortunately, traditional drug discovery methods have a >90% failure rate and can take 10–15 years from target identification to clinical use. In contrast, drug repurposing can significantly accelerate translation. We developed a quantitative high-throughput screen to identify efficacious single agents and combination therapies against SARS-CoV-2. Quantitative high-content morphological profiling was coupled with an AI-based machine learning strategy to classify features of cells for infection and stress. This assay detected multiple antiviral mechanisms of action (MOA), including inhibition of viral entry, propagation, and modulation of host cellular responses. From a library of 1,425 FDA-approved compounds and clinical candidates, we identified 16 dose-responsive compounds with antiviral effects. In particular, we discovered that lactoferrin is an effective inhibitor of SARS-CoV-2 infection with an IC(50) of 308 nM and that it potentiates the efficacy of both remdesivir and hydroxychloroquine. Lactoferrin also stimulates an antiviral host cell response and retains inhibitory activity in iPSC-derived alveolar epithelial cells, a model for the primary site of infection. Given its safety profile in humans, these data suggest that lactoferrin is a readily translatable therapeutic adjunct for COVID-19. Additionally, several commonly prescribed drugs were found to exacerbate viral infection and warrant clinical investigation. We conclude that morphological profiling for drug repurposing is an effective strategy for the selection and optimization of drugs and drug combinations as viable therapeutic options for COVID-19 pandemic and other emerging infectious diseases.


title: Ultrastructural characterization of membranous torovirus replication factories

text: Plus‐stranded RNA viruses replicate in the cytosol of infected cells, in membrane‐bound replication complexes containing the replicase proteins, the viral RNA and host proteins. The formation of the replication and transcription complexes (RTCs) through the rearrangement of cellular membranes is currently being actively studied for viruses belonging to different viral families. In this work, we identified double‐membrane vesicles (DMVs) in the cytoplasm of cells infected with the equine torovirus Berne virus (BEV), the prototype member of the Torovirus genus (Coronaviridae family, Nidovirales order). Using confocal microscopy and transmission electron microscopy, we observed a close relationship between the RTCs and the DMVs of BEV. The examination of BEV‐infected cells revealed that the replicase proteins colocalize with each other and with newly synthesized RNA and are associated to the membrane rearrangement induced by BEV. However, the double‐stranded RNA, an intermediate of viral replication, is exclusively limited to the interior of DMVs. Our results with BEV resemble those obtained with other related viruses in the Nidovirales order, thus providing new evidence to support the idea that nidoviruses share a common replicative structure based on the DMV arranged clusters.


title: Communicable Diseases, Globalization of

text: This article examines the spatial distribution of leading infectious causes of morbidity and mortality worldwide. Beginning with simple models explaining the spatial pattern of infectious diseases, the epidemiologic transition, and disease ecology models, the article focuses on HIV/AIDS, tuberculosis, polio, SARS, and influenza as well as sexually transmitted infections such as gonorrhea. It addresses the problem of disease strain mutation and especially drug resistance, and argues for the application of genotyping in medical geography research. The article emphasizes how migration and increased global interaction are producing a globalization of infectious diseases while at the same time, ethnic residential segregation is producing spatial concentrations of infectious disease or different strains of disease.


title: Big data analytics for preventive medicine

text: Medical data is one of the most rewarding and yet most complicated data to analyze. How can healthcare providers use modern data analytics tools and technologies to analyze and create value from complex data? Data analytics, with its promise to efficiently discover valuable pattern by analyzing large amount of unstructured, heterogeneous, non-standard and incomplete healthcare data. It does not only forecast but also helps in decision making and is increasingly noticed as breakthrough in ongoing advancement with the goal is to improve the quality of patient care and reduces the healthcare cost. The aim of this study is to provide a comprehensive and structured overview of extensive research on the advancement of data analytics methods for disease prevention. This review first introduces disease prevention and its challenges followed by traditional prevention methodologies. We summarize state-of-the-art data analytics algorithms used for classification of disease, clustering (unusually high incidence of a particular disease), anomalies detection (detection of disease) and association as well as their respective advantages, drawbacks and guidelines for selection of specific model followed by discussion on recent development and successful application of disease prevention methods. The article concludes with open research challenges and recommendations.


title: An approach to the photocatalytic mechanism in the TiO(2)-nanomaterials microorganism interface for the control of infectious processes

text: The approach of this timely review considers the current literature that is focused on the interface nanostructure/cell-wall microorganism to understand the annihilation mechanism. Morphological studies use optical and electronic microscopes to determine the physical damage on the cell-wall and the possible cell lysis that confirms the viability and microorganism death. The key parameters of the tailoring the surface of the photoactive nanostructures such as the metal functionalization with bacteriostatic properties, hydrophilicity, textural porosity, morphology and the formation of heterojunction systems, can achieve the effective eradication of the microorganisms under natural conditions, ranging from practical to applications in environment, agriculture, and so on. However, to our knowledge, a comprehensive review of the microorganism/nanomaterial interface approach has rarely been conducted. The final remarks point the ideal photocatalytic way for the effective prevention/eradication of microorganisms, considering the resistance that the microorganism could develop without the appropriate regulatory aspects for human and ecosystem safety.


title: Should patients with acute exacerbation of chronic bronchitis be treated with antibiotics? Advantages of the use of fluoroquinolones

text: The pathological changes in chronic bronchitis (CB) produce airflow obstruction, reduce the effectiveness of the mucocilliary drainage system and lead to bacterial colonisation of bronchial secretion. The presence of bacteria induces an inflammatory response mediated by leukocytes. There is a direct relationship between the degree of impairment of the mucocilliary drainage system, the density of bacteria in mucus and the number of leukocytes in the sputum. Purulent sputum is a good marker of a high bacterial load. Eventually, if the number of leukocytes is high, their normal activity could decrease the effectiveness of the drainage system, increase the bronchial obstruction and probably damage the lung parenchyma. Whenever the density of bacteria in the bronchial lumen is ≥ 10(6) CFU/mL, there is a high probability that the degree of inflammatory response will lead to a vicious cycle which in turn tends to sustain the process. This situation can arise during the clinical course of any acute exacerbation of CB, independently of its aetiology, provided the episode is sufficiently severe and/or prolonged. Fluoroquinolones of the third and fourth generation are bactericidal against most microorganisms usually related to acute exacerbations of CB. Their diffusion to bronchial mucus is adequate. When used in short (5-day) treatment they reduce the bacterial load in a higher proportion than is achieved by βlactam or macrolide antibiotics given orally. Although the clinical cure rate is similar to that obtained with other antibiotics, the time between exacerbations could be increased.


title: Comparison of Infrared Thermal Detection Systems for mass fever screening in a tropical healthcare setting

text: Abstract Objectives Fever screening systems, such as Infrared Thermal Detection Systems (ITDS), have been used for rapid identification of potential cases during respiratory disease outbreaks for public health management. ITDS detect a difference between the subject and ambient temperature, making deployment in hot climates more challenging. This study, conducted in Singapore, a tropical city, evaluates the accuracy of three different ITDS for fever detection compared with traditional oral thermometry and self-reporting in a clinical setting. Study design This study is a prospective operational evaluation conducted in the Singapore military on all personnel seeking medical care at a high-volume primary healthcare centre over a one week period in February 2014. Methods Three ITDS, the STE Infrared Fever Screening System (IFSS), the Omnisense Sentry MKIII and the handheld Quick Shot Infrared Thermoscope HT-F03B, were evaluated. Temperature measurements were taken outside the healthcare centre, under a sheltered walkway and compared to oral temperature. Subjects were asked if they had fever. Results There were 430 subjects screened, of whom 34 participants (7.9%) had confirmed fever, determined by oral thermometer measurement. The handheld infrared thermoscope had a very low sensitivity (29.4%), but a high specificity (96.8%). The STE ITDS had a moderate sensitivity (44.1%), but a very high specificity (99.1%). Self-reported fevers showed good sensitivity (88.2%) and specificity (93.9%). The sensitivity of the Omnisense ITDS (89.7%) was the highest among the three methods with good specificity (92.0%). Conclusion The new generation Omnisense ITDS displayed a relatively high sensitivity and specificity for fever. Though it has a lower sensitivity, the old generation STE ITDS system showed a very high specificity. Self-reporting of fever was reliable. The handheld thermograph should not be used as a fever-screening tool under tropical conditions.


title: A mathematical model to guide the re-opening of economies during the COVID-19 pandemic

text: Despite rigorous global containment and quarantine efforts, the incidence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), also known as COVID-19, continues to surge, with more than 12 million laboratory-confirmed cases and over 500,000 deaths worldwide (as of 11 July 2020). Aside from the continued surge in cases and the imperatives of public health concern and saving lives, economic devastation is also mounting with a global depression now seeming inevitable. There is limited attention directed towards people who have recovered from the virus and whether this metric can be useful in guiding when the economy can be re-opened. In this paper, a simpler model is presented in order to guide various countries on the (possible) re-opening of the economy (or re-opening in stages/phases) alongside risk categories and ratios. Factors that need to be considered when applying the model include the healthcare capacity in terms of the number of hospitals, beds and healthcare workers that are available to capacitate this virus. In addition, population size, physical distancing measures, socio-economic disparities, lockdown regulations in each country, and more importantly - the amount and accuracy of testing conducted, is also imperative to consider. Decisions adopted by leaders around the world have the most difficult decision to make (yet), and have to weigh up on what really matters; health or wealth. It is suggested that this model be applied in a number of states/counties and countries in order to gauge the risk of their location being re-opened, by observing their total number of recoveries in proximity to total number of cases.


title: An ORF-2a protein is not present at a significant level in virions of the arterivirus lactate dehydrogenase-elevating virus

text: Abstract MRNA2 of the arteriviruses lactate dehydrogenase-elevating virus (LDV) and equine arteritis virus (EAV) encodes two proteins that are read in different frames, an about 26 kDa minor envelope glycoprotein and an about 8 kDa protein that lacks N-glycosylation sites and a signal peptide, but possesses a central hydrophobic segment. Recent studies have shown that both proteins of EAV are translated from mRNA 2 in EAV infected BHK cells, that the 8 kDa protein is membrane associated and that small amounts of it are recovered in purified virions (Snijder, E.J., van Tol, H., Pederson, K.W., Raamsman, M.J.B., de Vries, A.A.F., 1999. Identification of a novel structural protein of arteriviruses. J. Virol. 73, 6335–6345). The authors concluded that the 8 kDa protein is another arterivirus envelope protein and designated it E protein. However, we have not detected a significant level of an 8 kDa protein in LDV virions and thus conclude that it is not a structural virion component.


title: Incidence of COVID‐19 in patients with rheumatic diseases treated with targeted immunosuppressive drugs: what can we learn from observational data?

text: OBJECTIVES: To describe the incidence and severity of coronavirus disease 2019 (COVID‐19) in rheumatic patients treated with targeted synthetic or biological anti‐rheumatic drugs (ts/bDMARDs) compared with the general population living in the same Italian region. METHODS: Patients followed at two referral rheumatology centres in Lombardy from 25(th) February to 10(th) April 2020 were invited to participate in a survey to detect patients with confirmed COVID‐19, close contacts with known COVID‐19 cases, symptoms of infection, working, behavioural and disease management changes applied to prevent the contagion. The incidence of COVID‐19 in the Lombardy population was obtained from the National Institute of Statistics. Confirmed COVID‐19 was defined by nasopharyngeal swab. RESULTS: The survey was circulated amongst 955 patients (531 rheumatoid arthritis, 203 psoriatic arthritis, 181 spondyloarthritis, and 40 of connective tissue diseases/vasculitides/autoinflammatory diseases; mean age 53.7 years; female: 67.4%). The rate of responders was 98.05%. The incidence of confirmed COVID‐19 is consistent with the general population (0.62% vs 0.66%; p=0.92). None of the patients had severe complications or required intensive care treatment, and all of them temporarily discontinued ongoing ts/bDMARDs therapy. Almost all patients adopted precautions to prevent the contagion (90.6%) and maintained the ongoing treatment with ts/bDMARDs (93.2%). The disease activity remained stable in 89.5% of patients. CONCLUSIONS: Our results highlight the attitude from rheumatic patients to prevent the contagion while maintaining their chronic treatments. The incidence and severity of COVID‐19 in patients treated with ts/bDMARDs was not significantly different from that of the general population in the same region.


Middle East respiratory syndrome coronavirus (MERS-CoV) shows poor replication and weak induction of antiviral responses in human monocyte-derived macrophages and dendritic cells


title: A Data-informed Public Health Policy-Makers Platform

text: Hearing loss is a disease exhibiting a growing trend due to a number of factors, including but not limited to the mundane exposure to the noise and ever-increasing size of the older population. In the framework of a public health policymaking process, modeling of the hearing loss disease based on data is a key factor in alleviating the issues related to the disease and in issuing effective public health policies. First, the paper describes the steps of the data-driven policymaking process. Afterward, a scenario along with the part of the proposed platform responsible for supporting policymaking are presented. With the aim of demonstrating the capabilities and usability of the platform for the policy-makers, some initial results of preliminary analytics are presented in the framework of a policy-making process. Ultimately, the utility of the approach is validated throughout the results of the survey which was presented to the health system policy-makers involved in the policy development process in Croatia.


title: Emerging Zoonoses in Domesticated Livestock of Southeast Asia

text: Abstract Southeast Asia, identified as one of the hotspot for emerging and reemerging diseases is an area of emerging market with doubling population size within the next few years. The livestock industry is growing rapidly to cater for the population need via intensification and various diversification methods. This article discusses a few relevant emerging and emerging zoonoses within the past two decades and highlights the impact of these diseases to the animal industry and public health in the region.


title: Disparities in Coronavirus 2019 Reported Incidence, Knowledge, and Behavior Among US Adults

text: IMPORTANCE: Data from the coronavirus disease 2019 (COVID-19) pandemic in the US show large differences in hospitalizations and mortality across race and geography. However, there are limited data on health information, beliefs, and behaviors that might indicate different exposure to risk. OBJECTIVE: To determine the association of sociodemographic characteristics with reported incidence, knowledge, and behavior regarding COVID-19 among US adults. DESIGN, SETTING, AND PARTICIPANTS: A US national survey study was conducted from March 29 to April 13, 2020, to measure differences in knowledge, beliefs, and behavior about COVID-19. The survey oversampled COVID-19 hotspot areas. The survey was conducted electronically. The criteria for inclusion were age 18 years or older and residence in the US. Data analysis was performed in April 2020. MAIN OUTCOMES AND MEASURES: The main outcomes were incidence, knowledge, and behaviors related to COVID-19 as measured by survey response. RESULTS: The survey included 5198 individuals (mean [SD] age, 48 [18] years; 2336 men [45%]; 3759 white [72%], 830 [16%] African American, and 609 [12%] Hispanic). The largest differences in COVID-19–related knowledge and behaviors were associated with race/ethnicity, sex, and age, with African American participants, men, and people younger than 55 years showing less knowledge than other groups. African American respondents were 3.5 percentage points (95% CI, 1.5 to 5.5 percentage points; P = .001) more likely than white respondents to report being infected with COVID-19, as were men compared with women (3.2 percentage points; 95% CI, 2.0 to 4.4 percentage points; P < .001). Knowing someone who tested positive for COVID-19 was more common among African American respondents (7.2 percentage points; 95% CI, 3.4 to 10.9 percentage points; P < .001), people younger than 30 years (11.6 percentage points; 95% CI, 7.5 to 15.7 percentage points; P < .001), and people with higher incomes (coefficient on earning ≥$100 000, 12.3 percentage points; 95% CI, 8.7 to 15.8 percentage points; P < .001). Knowledge of potential fomite spread was lower among African American respondents (−9.4 percentage points; 95% CI, −13.1 to −5.7 percentage points; P < .001), Hispanic respondents (−4.8 percentage points; 95% CI, −8.9 to −0.77 percentage points; P = .02), and people younger than 30 years (−10.3 percentage points; 95% CI, −14.1 to −6.5 percentage points; P < .001). Similar gaps were found with respect to knowledge of COVID-19 symptoms and preventive behaviors. CONCLUSIONS AND RELEVANCE: In this survey study of US adults, there were gaps in reported incidence of COVID-19 and knowledge regarding its spread and symptoms and social distancing behavior. More effort is needed to increase accurate information and encourage appropriate behaviors among minority communities, men, and younger people.


title: An investigation of susceptibility to porcine reproductive and respiratory syndrome virus between two genetically diverse commercial lines of pigs(1)

text: The objective of this study was to determine whether host genetics play a role in susceptibility to the respiratory disease in growing pigs caused by the porcine reproductive and respiratory syndrome virus (PRRSV). Based on a previous study, 2 genetically diverse commercial lines of pigs that also were divergent in the susceptibility of monocyte-derived macrophages to PRRSV infection in vitro were selected for an in vivo challenge study. Based on the average percentage of infected macrophages for each line, a line derived from the Large White breed was characterized as fluorescence-activated cell sorting(hi) (FACS(hi)), and a line derived from Duroc and Pietrain breeds was characterized as FACS(lo). Pigs from each line were challenged at 6 wk of age with PRRSV VR-2385 and necropsied at 10 or 21 d after infection. Data collected included clinical evaluation of disease, virus titration in serum and lung lavage fluid, macroscopic lung lesion scores, and microscopic lung lesion scores. The FACS(lo) line had consistently more severe clinical disease compared with the FACS(hi) line in the early stages of infection. Differences between line means were significant (P < 0.05) at 10 d after infection for all variables just described, and the FACS(lo) line showed more severe signs of disease. By 21 d after infection, clinical signs and lesions were resolving, and the differences between lines were significant (P < 0.04) only for microscopic lung lesion scores but approached significance (P < 0.08) for virus titer in serum. At 21 d after infection, the relationship between the lines reversed; the FACS(hi) line had higher serum virus titers than the FACS(lo) line. This report provides evidence that strongly suggests the existence of a host genetic component in disease susceptibility to PRRSV and indicates that further study is warranted to define the cellular mechanisms that affect disease susceptibility.


title: A key player in biomedical sciences and clinical service in China, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)

text: The Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC) is the largest medical institution in China and has a leading high-level multidisciplinary medical research and medial service. Under the CAMS and PUMC infrastructure, there are 17 biomedical institutes and 6 large hospitals, which cover most fields of the human disease-related research. CAMS and PUMC has always attached great emphasis on the control and cure of severe diseases, as well as a series of innovative drug researches, and has made significant progress in those fields. The long-term goals for CAMS and PUMC in the future development are: reaching the international advanced level in the areas of severe disease prediction, prevention, control, diagnosis, and research on drug innovation; establishing theoretical and technological system for explanation of the mechanism of severe diseases, which possesses Chinese style and represents the frontier level in the world, and at the same time, providing scientific support for the prevention and treatment of severe disease and making contribution to the establishment and development of a harmonious society in China.


title: Ethical Issues in the Response to Ebola Virus Disease in US Emergency Departments: A Position Paper of the American College of Emergency Physicians, the Emergency Nurses Association and the Society for Academic Emergency Medicine

text: The 2014 outbreak of Ebola Virus Disease (EVD) in West Africa has presented a significant public health crisis to the international health community and challenged US emergency departments to prepare for patients with a disease of exceeding rarity in developed nations. With the presentation of patients with Ebola to US acute care facilities, ethical questions have been raised in both the press and medical literature as to how US emergency departments, emergency physicians, emergency nurses and other stakeholders in the healthcare system should approach the current epidemic and its potential for spread in the domestic environment. To address these concerns, the American College of Emergency Physicians, the Emergency Nurses Association and the Society for Academic Emergency Medicine developed this joint position paper to provide guidance to US emergency physicians, emergency nurses and other stakeholders in the healthcare system on how to approach the ethical dilemmas posed by the outbreak of EVD. This paper will address areas of immediate and potential ethical concern to US emergency departments in how they approach preparation for and management of potential patients with EVD.


title: Multifunctional viral protein γ34.5 manipulates nucleolar protein NOP53 for optimal viral replication of HSV-1

text: To ensure efficient virus replication, herpes simplex virus type 1 (HSV-1) encodes several viral proteins to counter host defense response upon infection. Among these proteins, the multifunctional viral protein γ34.5 crucially interferes with or disrupts several antiviral pathways at multiple levels. The current study shows that γ34.5 utilizes nucleolar protein NOP53 to facilitate the dephosphorylation of eukaryotic initiation factor eIF2α for efficient viral translation. Our study shows that: (1) ectopic expression of NOP53 greatly increases the intracellular and extracellular viral yields of HSV-1 (wild strain F) in type I interferon-deficient Vero cells, and more subtly promotes viral replication of γ34.5 deletion mutant virus HSV-1/Δγ34.5. (2) NOP53 is migrated from nuclei in HSV-1/F infected cells, but is redistributed incompletely after infection by either HSV-1/Δγ34.5 or ICP4 deletion mutant virus HSV-1/d120 (replication inadequate). Ectopic expression of γ34.5, consequently, induces cytoplasmic translocation of NOP53 in response to HSV-1/Δγ34.5 infection. (3) Increase of NOP53, in two forms of transient transfection and in vitro expression, attenuates the phosphorylation level of eIF2α in HSV-1/F infected cells, but fails to affect eIF2α phosphorylation induced by HSV-1/Δγ34.5 infection. (4) Knockdown of NOP53, which impairs the specific interaction between γ34.5 and protein phosphatase PP1α, disrupts the ability of γ34.5 to maintain HSV-1 virulence. (5) NOP53 knockdown also significantly reduces tissue damage and decreases viral yield in livers of HSV-1 infected mice. Our findings expand the understanding of the underlying mechanism by which viral protein γ34.5 induces NOP53 redistribution; cytoplasmic NOP53 facilitates γ34.5 recruitment of PP1α to dephosphorylate eIF2α, for optimal viral replication. This paper also demonstrates that blocking the specific interaction between γ34.5 and PP1α would be a useful approach for the development of antiviral agents.


title: Insight into the activity of SARS main protease: Molecular dynamics study of dimeric and monomeric form of enzyme

text: The phenomenon that SARS coronavirus main protease (SARS M(pro)) dimer is the main functional form has been confirmed by experiment. However, because of the absence of structural information of the monomer, the reasons for this remain unknown. To investigate it, two molecular dynamics (MD) simulations in water for dimer and monomer models have been carried out, using the crystal structure of protomer A of the dimer as the starting structure for the monomer. During the MD simulation of dimer, three interest phenomena of protomer A have been observed: (i) the distance between NE2 of His41 and SG of Cys145 averages 3.72 Å, which agrees well with the experimental observations made by X‐ray crystallography; (ii) His163 and Glu166 form the “tooth” conformational properties, resulting in the specificity for glutamine at substrate P1 site; and (iii) the substrate‐binding pocket formed by loop 140–146 and loop 184–197 is large enough to accommodate the substrate analog. However, during the MD simulation of the monomer complex, the three structural characteristics are all absent, which results directly in the inactivation of the monomer. Throughout the MD simulation of the dimer, the N‐terminus of protomer B forms stable hydrogen bonds with Phe140 and Glu166, through which His163, Glu166, and loop 140–146 are kept active form. Furthermore, a water‐bridge has been found between the N‐terminus of protomer B and Gly170, which stabilizes His172 and avoids it moving toward Tyr161 to disrupt the H‐bond between Tyr161 and His163, stabilizing the conformation of His163. The interactions between the N‐terminus and another monomer maintain the activity of dimer. Proteins 2007. © 2006 Wiley‐Liss, Inc.


Emerging respiratory viruses: is it ‘much ado about nothing’? (Shakespeare)


Coccidiosis


title: Development of a Device to Reduce Oropharyngeal Aerosol Transmission

text: The world-wide COVID-19 pandemic has greatly impacted dental practice. Issues confronting practicing dentists include possible transmission of disease by droplets/ aerosol or contact with contaminated surfaces. Dentists are at increased risk due to their proximity to the oropharynx. In an effort to reduce potential exposure to aerosols generated during treatment, a device has been developed in which a polycarbonate shield is mounted to the dental operating microscope with an attached high velocity vacuum hose. Anemometer measurements demonstrate an exhaust outflow of 3.9 ft/min at a position approximating the patient’s oropharynx. More research may be warranted using this or similar approaches to mitigate aerosol transmission.


title: Emergence of Arboviruses in the United States: The Boom and Bust of Funding, Innovation, and Capacity

text: Mosquito-borne viruses will continue to emerge and generate a significant public health burden around the globe. Here, we provide a longitudinal perspective on how the emergence of mosquito-borne viruses in the Americas has triggered reactionary funding by sponsored agencies, stimulating a number of publications, innovative development of traps, and augmented capacity. We discuss the return on investment (ROI) from the oscillation in federal funding that influences demand for surveillance and control traps and leads to innovation and research productivity.


title: Feline blood transfusions A pinker shade of pale

text: Practical relevance Blood transfusions are a potentially life-saving procedure that are within the reach of most small animal practitioners. Only minimal equipment is required. Patient group Any cat with clinical signs attributable to a reduced red blood cell mass that is affecting oxygen transport (as a result of reduced packed cell volume or acute blood loss) is a potential candidate for a transfusion. Clinical challenges Although the principles of transfusion medicine are not complicated, there can be fatal consequences if certain steps are omitted. Diagnostics Blood typing kits and blood filters are readily available from veterinary wholesalers, laboratories and blood banking services. Evidence base Over the past three decades, a substantial body of clinical research and reports has built up covering feline blood types and transfusion medicine. This article draws on that research to provide clinical guidance aimed at all veterinarians in feline or small animal practice who either currently practise transfusion medicine or plan to do so.


title: Complete Genome Sequence of a Novel Swine Acute Diarrhea Syndrome Coronavirus, CH/FJWT/2018, Isolated in Fujian, China, in 2018

text: The full-length genome sequence of a novel swine acute diarrhea syndrome coronavirus (SADS-CoV), CH/FJWT/2018, was determined, which was genetically most closely related to CN/GDWT/2017, recently discovered in Fujian, China. The indel sites of the spike (S) gene of CH/FJWT/2018 were most similar to those of bat-origin SADS-related coronaviruses.


Lower mortality of COVID-19 by early recognition and intervention: experience from Jiangsu Province


title: Incorporation fidelity of the viral RNA-dependent RNA polymerase: a kinetic, thermodynamic and structural perspective

text: Abstract Positive-strand RNA viruses exist as a quasi-species due to the incorporation of mutations into the viral genome during replication by the virus-encoded RNA-dependent RNA polymerase (RdRP). Therefore, the RdRP is often described as a low-fidelity enzyme. However, until recently, a complete description of the kinetic, thermodynamic and structural basis for the nucleotide incorporation fidelity of the RdRP has not been available. In this article, we review the following: (i) the steps employed by the RdRP to incorporate a correct nucleotide; (ii) the steps that are employed by the RdRP for nucleotide selection; (iii) the structure-based hypothesis for nucleotide selection; (iv) the impact of sites remote from the active site on polymerase fidelity. Given the recent observation that RNA viruses exist on the threshold of error catastrophe, the studies reviewed herein suggest novel strategies to perturb RdRP fidelity that may lead ultimately to the development of antiviral agents to treat RNA virus infection.


title: Analysis of the Host Transcriptome from Demyelinating Spinal Cord of Murine Coronavirus-Infected Mice

text: Persistent infection of the mouse central nervous system (CNS) with mouse hepatitis virus (MHV) induces a demyelinating disease pathologically similar to multiple sclerosis and is therefore used as a model system. There is little information regarding the host factors that correlate with and contribute to MHV-induced demyelination. Here, we detail the genes and pathways associated with MHV-induced demyelinating disease in the spinal cord. High-throughput sequencing of the host transcriptome revealed that demyelination is accompanied by numerous transcriptional changes indicative of immune infiltration as well as changes in the cytokine milieu and lipid metabolism. We found evidence that a Th1-biased cytokine/chemokine response and eicosanoid-derived inflammation accompany persistent MHV infection and that antigen presentation is ongoing. Interestingly, increased expression of genes involved in lipid transport, processing, and catabolism, including some with known roles in neurodegenerative diseases, coincided with demyelination. Lastly, expression of several genes involved in osteoclast or bone-resident macrophage function, most notably TREM2 and DAP12, was upregulated in persistently infected mouse spinal cord. This study highlights the complexity of the host antiviral response, which accompany MHV-induced demyelination, and further supports previous findings that MHV-induced demyelination is immune-mediated. Interestingly, these data suggest a parallel between bone reabsorption by osteoclasts and myelin debris clearance by microglia in the bone and the CNS, respectively. To our knowledge, this is the first report of using an RNA-seq approach to study the host CNS response to persistent viral infection.


title: The nucleocapsid protein of the SARS coronavirus is capable of self-association through a C-terminal 209 amino acid interaction domain

text: Abstract Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) caused a severe outbreak in several regions of the world in 2003. The virus is a novel coronavirus isolated from patients exhibiting atypical pneumonia and may have originated from wild animals such as civet cats in southern China. The genome of SARS-CoV is a positive-sense, single-stranded RNA whose sequence is distantly related to all known coronaviruses that infect humans and animals. Like other known coronaviruses, SARS-CoV is an enveloped virus containing three outer structural proteins, namely the membrane (M), envelope (E), and spike (S) proteins. The nucleocapsid (N) protein together with the viral RNA genome presumably form a helical core located within the viral envelope. The SARS-CoV nucleocapsid (N) protein is a 423 amino-acid, predicted phospho-protein of 46kDa that shares little homology with other members of the coronavirus family. A short serine-rich stretch, and a putative bipartite nuclear localization signal are unique to it, thus suggesting its involvement in many important functions during the viral life cycle. In this report we have cloned the N gene of the SARS coronavirus, and studied its property of self-association to form dimers. We expressed the N protein as a fusion protein in the yeast two-hybrid system to demonstrate self-association and confirmed dimerization of the N protein from mammalian cell lysates by coimmunoprecipitation. Furthermore, via deletion analysis, we have shown that the C-terminal 209 amino-acid region constitutes the interaction domain responsible for self-association of the N protein to form dimers.


title: Viral nucleolar localisation signals determine dynamic trafficking within the nucleolus

text: Abstract Localisation of both viral and cellular proteins to the nucleolus is determined by a variety of factors including nucleolar localisation signals (NoLSs), but how these signals operate is not clearly understood. The nucleolar trafficking of wild type viral proteins and chimeric proteins, which contain altered NoLSs, were compared to investigate the role of NoLSs in dynamic nucleolar trafficking. Three viral proteins from diverse viruses were selected which localised to the nucleolus; the coronavirus infectious bronchitis virus nucleocapsid (N) protein, the herpesvirus saimiri ORF57 protein and the HIV-1 Rev protein. The chimeric proteins were N protein and ORF57 protein which had their own NoLS replaced with those from ORF57 and Rev proteins, respectively. By analysing the sub-cellular localisation and trafficking of these viral proteins and their chimeras within and between nucleoli using confocal microscopy and photo-bleaching we show that NoLSs are responsible for different nucleolar localisations and trafficking rates.


Autophagy inhibition by chloroquine and hydroxychloroquine could adversely affect AKI and other organ injury in critically ill patients with COVID-19


Implementing clinical pharmacy services in France: one of the key points to minimise the effect of the shortage of pharmaceutical products in anaesthesia or intensive care units?


title: Intraruminal administration of milk in the calf as a model for ruminal drinking: Morphological and enzymatical changes in the jejunal mucosa

text: In order to develop a calf model for studying the syndrome of ruminal drinking (RD) in veal calves, three dual-fistulated calves were used to test the effect of intraruminal administration of milk replacer on the jejunal mucosa. Biopsies of the proximal jejunal mucosa were taken through a jejunal fistula and the mucosal morphology and the activities of two brush border enzymes, lactase and alkaline phosphatase, were determined. Means of villus length and brush border enzyme activities decreased during the period of intraruminal administration of milk. The hyperplastic villus atrophy in this model was similar to that found in chronic RD patients in previous studies. This could not be associated with isolation of pathogenic micro-organisms from the faeces and is probably the consequence of the intraruminal milk feeding procedure itself. Clinical recovery from the signs of RD occurred rapidly after intraruminal administration of milk ceased and was followed by restoration of villus length and brush border enzyme activities 3–4 weeks later.


Immunofluorescence in Diagnostic Virology


title: Association between passive immunity and health status of dairy calves under 30 days of age

text: Abstract Calves are highly susceptible to disease and mortality occurrence within the first month of life. Even if failed transfer of passive immunity (FTPI) is commonly recognized as a main factor affecting calf health and survival, conflicting results are reported in literature about the association between passive immunity (PI) and calf health, especially regarding enteric diseases. Therefore, a prospective cohort study was conducted on 78 calves of three Italian dairy farms during winters of years 2014–2016, with the specific aim of evaluating the association between PI and health status of calves within 30 days of age under field conditions. Blood samples were collected between 1 and 5 days of age from each calf included in the study, and disease and mortality occurrence was monitored throughout the first month of life. Additionally, fecal samples were collected from calves with scours before treatment. Blood serum samples were tested by an electrophoretic method for the assessment of immunoglobulin (Ig) concentration, whereas fecal samples were submitted to ELISA test for positivity to Escherichia coli K99, rotavirus, coronavirus, and Cryptosporidium spp. Only enteric diseases occurred in calves of this study. Calves that suffered from diarrhea or died within the first month of life had lower serum Ig concentrations than those that remained healthy or survived (P < .05). Even if not significantly (P = .127), lower serum Ig concentrations were observed in sick calves that had been treated with antibiotics compared to those that had not been treated. The odds of disease and mortality occurrence were 24 (95% CI = 3–231) and 11 (95% CI = 1–111) times higher, respectively, for calves with FTPI (serum Ig concentration <10.0 g/L) than for those with an adequate PI transfer (P < .05). Calves with adequate PI transfer had also a 6-day delay in the age at first disease onset compared to those with FTPI (P < .01). Even if estimated on a small number of calves, those with FTPI had higher risks of enteric infections by rotavirus (odds ratio = 12; 95% CI = 1–137) and Cryptosporidium spp. (odds ratio = 9; 95% CI = 1–72) (P < .05). In this study, the PI level influenced the occurrence of enteric diseases and mortality in calves under one month of age, confirming the importance of a proper colostrum provision to calf health and, consequently, to the reduction of antimicrobial use in dairy farming. However, further investigations are needed, particularly focusing on the relationship between PI and specific enteropathogen infections in calves.


title: A quantitative risk assessment of exposure to adventitious agents in a cell culture-derived subunit influenza vaccine

text: Abstract A risk-assessment model has demonstrated the ability of a new cell culture-based vaccine manufacturing process to reduce the level of any adventitious agent to a million-fold below infectious levels. The cell culture-derived subunit influenza vaccine (OPTAFLU®, Novartis Vaccines and Diagnostics) is produced using Madin–Darby canine kidney (MDCK) cells to propagate seasonal viral strains, as an alternative to embryonated chicken-eggs. As only a limited range of mammalian viruses can grow in MDCK cells, similar to embryonated eggs, MDCK cells can act as an effective filter for a wide range of adventitious agents that might be introduced during vaccine production. However, the introduction of an alternative cell substrate (for example, MDCK cells) into a vaccine manufacturing process requires thorough investigations to assess the potential for adventitious agent risk in the final product, in the unlikely event that contamination should occur. The risk assessment takes into account the entire manufacturing process, from initial influenza virus isolation, through to blending of the trivalent subunit vaccine and worst-case residual titres for the final vaccine formulation have been calculated for >20 viruses or virus families. Maximum residual titres for all viruses tested were in the range of 10−6 to 10−16 infectious units per vaccine dose. Thus, the new cell culture-based vaccine manufacturing process can reduce any adventitious agent to a level that is unable to cause infection.


title: A Precision Medicine Approach to Rhinitis Evaluation and Management

text: PURPOSE OF REVIEW: Precision medicine (PM) represents a new paradigm in disease diagnosis, prevention, and treatment. The PM approach focuses on the characterization of different phenotypes and pathogenic pathways in order to allow the selection of specific biomarkers that will be useful in disease management. Rhinitis is a highly prevalent and heterogeneous disease, both in terms of underlying endotypes and clinical presentations. Therefore, to apply the PM principles to the various rhinitis subtypes rise as a meaningful strategy to improve evaluation and treatment. RECENT FINDINGS: The technology of recombinant allergens has allowed molecular characterization of IgE reactivity of specific individual components of allergenic extracts. Recently published and ongoing clinical trials based on component resolved diagnosis (CRD) bring more precision to allergen immunotherapy for allergic rhinitis. Monoclonal antibodies against various cytokines involved in inflammatory allergic and nonallergic rhinitis endotypes show promissory results. SUMMARY: Better understanding of pathogenic pathways together with an accurate phenotype classification of patients presented with rhinitis symptoms contributes to point out clinical usefulness of biomarkers and other diagnostic tools, which leads to more accurate environmental control measures, personalized pharmacologic options, and new biological therapy developments.


title: RNA-GPS Predicts SARS-CoV-2 RNA Residency to Host Mitochondria and Nucleolus

text: Abstract/Summary SARS-CoV-2 genomic and subgenomic RNA (sgRNA) transcripts hijack the host cell's machinery. Subcellular localization of its viral RNA could thus play important roles in viral replication and host antiviral immune response. We perform computational modeling of SARS-CoV-2 viral RNA subcellular residency across eight subcellular neighborhoods. We compare hundreds of SARS-CoV-2 genomes to the human transcriptome and other coronaviruses. We predict the SARS-CoV-2 RNA genome and sgRNAs to be enriched towards the host mitochondrial matrix and nucleolus, and that the 5’ and 3’ viral untranslated regions contain the strongest, most distinct localization signals. We interpret the mitochondrial residency signal as an indicator of intracellular RNA trafficking with respect to double-membrane vesicles, a critical stage in the coronavirus life cycle. Our computational analysis serves as a hypothesis generation tool to suggest models for SARS-CoV-2 biology and inform experimental efforts to combat the virus. A record of this paper’s Transparent Peer Review process is included in the Supplemental Information.


title: Effect of diethylcarbamazine on serum antibodies to feline infectious peritonitis in cats

text: Abstract In preceding studies by the author, use of the immunomodulator drug diethylcarbamazine resulted in the detection of antibodies to feline oncornavirus-associated cell membrane antigen in nine feline leukaemia virus infected cats that had previously given negative results to this antibody. In the present report, seven diethylcarbamazine-treated cats developed higher serum antibody titres to feline infectious peritonitis more frequently than did seven untreated controls. Since feline infectious peritonitis is caused by a coronavirus, these results suggest that diethylcarbamazine treatment could be exploited for vaccination and treatment strategies for non-retroviral in addition to retroviral infections.


title: Modeling Vaccine Trials in Epidemics with Mild and Asymptomatic Infection

text: Background Vaccine efficacy against susceptibility to infection (VES), regardless of symptoms, is an important endpoint of vaccine trials for pathogens with a high proportion of asymptomatic infection, as such infections may contribute to onward transmission and outcomes such as Congenital Zika Syndrome. However, estimating VES is resource-intensive. We aim to identify methods to accurately estimate VES when only a limited amount of information is available and resources are constrained. Methods We model an individually randomized vaccine trial by generating a network of individuals and simulating an epidemic. The disease natural history follows a Susceptible, Exposed, Infectious and Symptomatic or Infectious and Asymptomatic, Recovered model. The vaccine is leaky, meaning it reduces the probability of infection upon exposure. We then use seven approaches to estimate VES, and we also estimate vaccine efficacy against progression to symptoms (VEP). Results A corrected relative risk and an interval censored Cox model accurately estimate VES and only require serologic testing of participants once at the end of the trial, while a Cox model using only symptomatic infections returns biased estimates. Only acquiring serological endpoints in a 10% sample and imputing the remaining infection statuses yields unbiased VES estimates across values of R0 and accurate estimates of VEP for higher values of R0. Conclusion Identifying resource-preserving methods for accurately estimating VES is important in designing trials for diseases with a high proportion of asymptomatic infection. Understanding potential sources of bias can allow for more accurate VE estimates in epidemic settings.


title: A cross-sectional study on mental health among health care workers during the outbreak of Corona Virus Disease 2019

text: Abstract The spread of Corona Virus Disease 2019 (COVID-19) has become a global major public health event, threatening people's physical and mental health and even life safety. This study is to investigate the psychological abnormality in health care workers battling the COVID-19 epidemic and to explore the associations among social support, resilience and mental health. A total of 1521 health care workers, of whom 147 had public health emergency experience while 1374 showed no experience, completed the Symptom Check-List-90 (SCL-90), Chinese version of Connor-Davidson resilience scale (CD-RISC) and Social Support Rating Scale (SSRS). χ2 test, t test and multiple regression analyses were used in statistical analysis. The results showed that people without public health emergency treatment experience showed worse performance in mental health, resilience and social support, and tended to suffer from psychological abnormality on interpersonal sensitivity and photic anxiety. This finding suggested that high levels of training and professional experience, resilience and social support were necessary to health care workers who are first taking part in public health emergence.


title: Galectin-related protein: An integral member of the network of chicken galectins 1. From strong sequence conservation of the gene confined to vertebrates to biochemical characteristics of the chicken protein and its crystal structure

text: BACKGROUND: Endogenous lectins are multifunctional effectors in cell physiology. Adding the sixth member of the galectin family in chicken, a model organism for systematic profiling of these adhesion/growth-regulatory proteins, is a step toward comprehensive network monitoring. METHODS: Database mining and computational data processing are applied for gene detection, chromosomal location and sequence alignments. Cloning, recombinant production and fusion-protein technology gain access to the protein, mass spectrometry and gel electrophoresis/filtration provide analytical data. Haemagglutination, glycan microarray and cell assays assess binding capacity, and crystallography of a shortened variant (also analyzed by ultracentrifugation and small angle X-ray scattering) determines its structure. RESULTS: The gene for the galectin-related protein (GRP) is present exclusively in vertebrates with high-level sequence conservation and similar chromosomal positioning. The chicken protein is monomeric and has lost the canonical galectin property of binding lactose. The crystal structure of the variant without the 36-amino-acid extension at the start provides explanations for this lack of binding. CONCLUSIONS: Chicken GRP is special within this family of six proteins by being unable to bind lactose. The documented high degree of sequence conservation among vertebrate orthologues confers the status of a model for delineating an assumedly shared functionality to this GRP. GENERAL SIGNIFICANCE: Biochemical characterization of a product of a gene under strong positive selection is a prerequisite for functional characterization. It is also essential for network monitoring by adding a new member to this lectin family.


title: CD26/dipeptidylpeptidase IV—chemokine interactions: double‐edged regulation of inflammation and tumor biology

text: Post‐translational modification of chemokines is an essential regulatory mechanism to enhance or dampen the inflammatory response. CD26/dipeptidylpeptidase IV, ubiquitously expressed in tissues and blood, removes NH(2)‐terminal dipeptides from proteins with a penultimate Pro or Ala. A large number of human chemokines, including CXCL2, CXCL6, CXCL9, CXCL10, CXCL11, CXCL12, CCL3L1, CCL4, CCL5, CCL11, CCL14, and CCL22, are cleaved by CD26; however, the efficiency is clearly influenced by the amino acids surrounding the cleavage site and although not yet proven, potentially affected by the chemokine concentration and interactions with third molecules. NH(2)‐terminal cleavage of chemokines by CD26 has prominent effects on their receptor binding, signaling, and hence, in vitro and in vivo biologic activities. However, rather than having a similar result, the outcome of NH(2)‐terminal truncation is highly diverse. Either no difference in activity or drastic alterations in receptor recognition/specificity and hence, chemotactic activity are observed. Analogously, chemokine‐dependent inhibition of HIV infection is enhanced (for CCL3L1 and CCL5) or decreased (for CXCL12) by CD26 cleavage. The occurrence of CD26‐processed chemokine isoforms in plasma underscores the importance of the in vitro‐observed CD26 cleavages. Through modulation of chemokine activity, CD26 regulates leukocyte/tumor cell migration and progenitor cell release from the bone marrow, as shown by use of mice treated with CD26 inhibitors or CD26 knockout mice. As chemokine processing by CD26 has a significant impact on physiologic and pathologic processes, application of CD26 inhibitors to affect chemokine function is currently explored, e.g., as add‐on therapy in viral infection and cancer.


Neonatal viral diarrhoeas


title: Half of Rural Residents at High Risk of Serious Illness Due to COVID‐19, Creating Stress on Rural Hospitals

text: PURPOSE: During the COVID‐19 epidemic, it is critical to understand how the need for hospital care in rural areas aligns with the capacity across states. METHODS: We analyzed data from the 2018 Behavioral Risk Factor Surveillance System to estimate the number of adults who have an elevated risk of serious illness if they are infected with coronavirus in metropolitan, micropolitan, and rural areas for each state. Study data included 430,949 survey responses representing over 255.2 million noninstitutionalized US adults. For data on hospital beds, aggregate survey data were linked to data from the 2017 Area Health Resource Files by state and metropolitan status. FINDINGS: About 50% of rural residents are at high risk for hospitalization and serious illness if they are infected with COVID‐19, compared to 46.9% and 40.0% in micropolitan and metropolitan areas, respectively. In 19 states, more than 50% of rural populations are at high risk for serious illness if infected. Rural residents will generate an estimated 10% more hospitalizations for COVID‐19 per capita than urban residents given equal infection rates. CONCLUSION: More than half of rural residents are at increased risk of hospitalization and death if infected with COVID‐19. Experts expect COVID‐19 burden to outpace hospital capacity across the country, and rural areas are no exception. Policy makers need to consider supply chain modifications, regulatory changes, and financial assistance policies to assist rural communities in caring for people affected by COVID‐19.


title: Upper Respiratory Tract Infections in Athletes

text: Upper respiratory tract infections (URTIs) represent the most common acute illnesses in the general population and account for the leading acute diagnoses in the outpatient setting. Given the athlete's expectation to return to activity as soon as possible, the sports medicine physician should be able to accurately diagnose and aggressively treat these illnesses. This article discusses the common pathogens, diagnosis, treatment options, and return-to-play decisions for URTIs, with a focus on the common cold, sinusitis, pharyngitis, and infectious mononucleosis in the athlete.


title: Laboratory haemostasis monitoring in COVID‐19

text: We thank the authors for their very useful and constructive criticisms about laboratory monitoring of haemostatic variables detailed in the ISTH guidance document for coagulopathy in COVID-19. We still believe that the use of simple and easily available laboratory markers both at admission and whilst in the hospital is necessary in the management of COVID-19 patients. Since the writing of this guidance and the letter from the experts being sent to us, there have been several reports of very high incidence of both arterial and venous thromboembolism (TE) in patients with COVID-19.1,2,3 In one report published in the Journal of Thrombosis and Haemostasis, the incidence of venous TE was 25%, some of whom died from this complication.2 Laboratory markers including D-dimer were relevant in these patients. The authors used D-dimer cut-off of 1.5 µg/mL for predicting venous TE and demonstrated sensitivity of 85.0% and specificity of 88.5% and negative predictive value of 94.7%.2 They also suggested D-dimers may be used to monitor the effectiveness of anticoagulants although this practice is not universally accepted.


title: Rhinovirus Outbreak in a Long Term Care Facility for Elderly Persons Associated with Unusually High Mortality

text: During a 6-week period in 2003, 56 residents and 26 staff developed respiratory illness in a long-term facility; 12 residents died. Seven of 13 respiratory specimens were culture-positive for rhinovirus; 6 of the isolates were serotype 82. In elderly populations, severe illness may be associated with organisms typically considered to be “benign,” such as rhinovirus.


title: Contamination of healthcare workers' mobile phones by epidemic viruses

text: Abstract Mobile phones (MPs) are potential reservoirs of nosocomial bacteria, but few data are available concerning viruses. We aimed to evaluate the presence of virus RNA from epidemic viruses including metapneumovirus, respiratory syncytial virus, influenza viruses, rotavirus (RV) and norovirus on the MPs used by healthcare workers (HCWs) and to relate it to hygiene measures. An anonymous behavioural questionnaire about MP use at hospital was administered to the HCWs of four adult and paediatric departments of a university hospital. After sampling personal (PMP) and/or professional MPs (digital enhanced cordless telephone, DECT), virus RNAs were extracted and amplified by one-step real-time reverse transcription–quantitative PCR. The molecular results were analysed in a masked manner in relation to the behavioural survey. Questionnaires from 114 HCWs (35 senior physicians, 30 residents, 32 nurses, 27 nurses' assistants) working either in adult (n = 58) or paediatric (n = 56) departments were analysed. Medical personnel used their PMP more frequently than paramedical HCWs (33/65 vs. 10/59, p <0.001). MPs were used during care more frequently in adult wards than in paediatric ones (46/58 vs. 27/56, p <0.001). Virus RNA was detected on 42/109 (38.5%) collected MPs, with RV found on 39, respiratory syncytial virus on three and metapneumovirus on one. The presence of virus RNA was significantly associated with MPs from the paediatric HCWs (p <0.001). MPs routinely used in hospital, even during care, can host virus RNA, especially RV. Promotion of frequent hand hygiene before and after MP use, along with frequent cleaning of MPs, should be encouraged.


title: Surgery of the ear and pinna

text: There are several disease processes of the ear and pinna that warrant surgical intervention. This article reviews surgical anatomy and common surgical procedures of the ear and pinna, including aural hematomas, lateral wall resection, vertical ear canal resection, total ear canal ablation and lateral bulla osteotomy, partial pinna resection, and feline inflammatory polyps. The clinical signs, diagnosis, and surgical treatment along with potential complications for each disease process are discussed.


Calm before the storm: understanding the role of JAK inhibitors in COVID-19


title: GTS-21, an α7nAChR agonist, suppressed the production of key inflammatory mediators by PBMCs that are elevated in COPD patients and associated with impaired lung function

text: Abstract Chronic obstructive pulmonary disease (COPD) is a lung inflammatory disease characterized by progressive airflow limitation, chronic respiratory symptoms and frequent exacerbations. There is an unmet need to identify novel therapeutic alternatives beside bronchodilators that prevent disease progression. Levels of both Nitric Oxide (NO) and IL-6 were significantly increased in the plasma of patients in the exacerbation phase (ECOPD, n = 13) when compared to patients in the stable phase (SCOPD, n = 38). Levels of both NO and IL-6 were also found to inversely correlate with impaired lung function (%FEV1 predicted). In addition, there was a strong positive correlation between levels of IL-6 and NO found in the plasma of patients and those spontaneously produced by their peripheral blood mononuclear cells (PBMCs), identifying these cells as a major source of these key inflammatory mediators in COPD. GTS-21, an agonist for the alpha 7 nicotinic receptors (α7nAChR), was found to exert immune-modulatory actions in PBMCs of COPD patients by suppressing the production of IL-6 and NO. This study provides the first evidence supporting the therapeutic potential of α7nAChR agonists in COPD due to their ability to suppress with the production of key inflammatory markers associated with disease severity.


title: Psychological status of surgical staff during the COVID-19 outbreak

text: Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which appeared in early December 2019, had an atypical viral pneumonia outbreak in Wuhan, Hubei, China. And there is a high risk of global proliferation and impact. The sudden increase in confirmed cases has brought tremendous stress and anxiety to frontline surgical staff. The results showed that the anxiety and depression of surgical staff during the outbreak period were significantly higher and mental health problems appeared, so psychological interventions are essential.


title: Cold Agglutinin Autoimmune Hemolytic Anemia Associated with Novel Coronavirus (COVID‐19)

text: Cold agglutinin syndrome (CAS) is a rare disorder associated with infection, autoimmune disorders, and lymphoid malignancies. We are present a case of CAS associated with SARS‐CoV‐2 that causes COVID‐19. A 46‐year‐old female presented with severe anemia and positive SARS‐CoV‐2 RNA PCR. Direct Coombs test was positive to IgG and complement. LDH was elevated and haptoglobin was undetectable. Peripheral smear revealed RBC agglutination, marked polychromasia, and many nucleated RBCs. Unfortunately, as a result of her severe hypoxemia, patient went into pulseless electrical activity before receiving transfusion and subsequently died. We postulate that CAS can be associated with COVID‐19, and ongoing surveillance is required for potential association.


title: Difficulties in using personal protective equipment: Training experiences with the 2015 outbreak of Middle East respiratory syndrome in Korea

text: This study aimed to evaluate practical barriers to personal protective equipment (PPE) use found through health care personnel (HCP) training sessions held during and after the 2015 Middle East respiratory syndrome outbreak in Korea. Difficulties observed were ill-fitting sizes, anxiety, confusion from unstandardized protocols, doubts about PPE quality and effectiveness, and complexity of using several PPE items together. Further research to generate robust evidence and repeated HCP trainings are necessary to ensure HCP and patient safety in future outbreaks.


title: Accurate closed-form solution of the SIR epidemic model

text: Abstract An accurate closed-form solution is obtained to the SIR Epidemic Model through the use of Asymptotic Approximants (Barlow et al., 2017). The solution is created by analytically continuing the divergent power series solution such that it matches the long-time asymptotic behavior of the epidemic model. The utility of the analytical form is demonstrated through its application to the COVID-19 pandemic.


title: Typing of canine parvovirus strains circulating in Brazil between 2008 and 2010

text: Abstract Detection and characterisation of the canine parvovirus (CPV-2) strains that are currently circulating are essential for the understanding of viral evolution and the development of measures to control its spread. In the present study, stool samples from 144 dogs were analysed by polymerase chain reaction (PCR) for CPV-2, and 29.2% (42/144) of them were positive. From the 42 positive strains, 71.4% (30) of the dogs had signs of haemorrhagic gastroenteritis. The sequencing of the 583bp fragment of the VP2 gene from the positive strains identified 78.6% (33/42) of them as type 2c, 19% (8/42) as type 2b and 2.4% (1/42) as type 2a. A phylogenetic analysis of the variants circulating in the canine population of Brazil showed that they are very similar to those found in other countries and type 2c has become the predominant type circulating in Brazil.


title: PLGA–PEI nanoparticles for gene delivery to pulmonary epithelium

text: Abstract Pulmonary gene delivery is thought to play an important role in treating genetically related diseases and may induce immunity towards pathogens entering the body via the airways. In this study we prepared poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles bearing polyethyleneimine (PEI) on their surface and characterized them for their potential in serving as non-viral gene carriers to the pulmonary epithelium. Particles that were synthesized at different PLGA–PEI ratios and loaded with DNA in several PEI–DNA ratios, exhibited narrow size distribution in all formulations, with mean particle sizes ranging between 207 and 231 nm. Zeta potential was strongly positive (above 30 mV) for all the PEI–DNA ratios examined and the loading efficiency exceeded 99% for all formulations. Internalization of the DNA-loaded PLGA–PEI nanoparticles was studied in the human airway submucosal epithelial cell line, Calu-3, and DNA was detected in the endo-lysosomal compartment 6 h after particles were applied. Cytotoxicity of these nanoparticles was dependent on the PEI–DNA ratio and best cell viability was achieved by PEI–DNA ratios 1:1 and 0.5:1. These findings demonstrate that PLGA–PEI nanoparticles are a potential new delivery system to carry genes to the lung epithelium.


title: People with Suspected COVID-19 Symptoms Were More Likely Depressed and Had Lower Health-Related Quality of Life: The Potential Benefit of Health Literacy

text: The coronavirus disease 2019 (COVID-19) epidemic affects people’s health and health-related quality of life (HRQoL), especially in those who have suspected COVID-19 symptoms (S-COVID-19-S). We examined the effect of modifications of health literacy (HL) on depression and HRQoL. A cross-sectional study was conducted from 14 February to 2 March 2020. 3947 participants were recruited from outpatient departments of nine hospitals and health centers across Vietnam. The interviews were conducted using printed questionnaires including participants’ characteristics, clinical parameters, health behaviors, HL, depression, and HRQoL. People with S-COVID-19-S had a higher depression likelihood (OR, 2.88; p < 0.001), lower HRQoL-score (B, −7.92; p < 0.001). In comparison to people without S-COVID-19-S and low HL, those with S-COVID-19-S and low HL had 9.70 times higher depression likelihood (p < 0.001), 20.62 lower HRQoL-score (p < 0.001), for the people without S-COVID-19-S, 1 score increment of HL resulted in 5% lower depression likelihood (p < 0.001) and 0.45 higher HRQoL-score (p < 0.001), while for those people with S-COVID-19-S, 1 score increment of HL resulted in a 4% lower depression likelihood (p = 0.004) and 0.43 higher HRQoL-score (p < 0.001). People with S-COVID-19-S had a higher depression likelihood and lower HRQoL than those without. HL shows a protective effect on depression and HRQoL during the epidemic.


title: The novel glycoproteins of coronaviruses

text: Abstract The two glycoproteins of coronavirus envelopes have different functions in intracellular budding, cytopathic effects and virus infectivity, and have markedly different biochemical properties.


title: Path to Reopening Surgery in the COVID-19 Pandemic: Neurosurgery Experience

text: Abstract Objective To test the efficacy of an innovative COVID-19 preoperative triage protocol as a way to gradually reopen and ramp-up elective surgeries, we studied our experience and results with 103 non-elective neurosurgical surgeries performed at our institution from March 26th to April 22nd. Patients and Methods We reviewed clinical, radiographic, and laboratory data for all patients that underwent surgery within the neurosurgery department from March 26th to April 22nd 2020. We collected demographic information, comorbidities, pre-operative COVID-19 test result, whether COVID-19 respiratory or other symptoms were developed during hospitalization, hospital length of stay, discharge disposition, and result of post-operative COVID-19 test. Results Using a combination of both preoperative outpatient COVID-19 drive-through and inpatient testing to obtain surgical clearance with selected telemedicine evaluations, 103 non-elective neurosurgical procedures were performed on 102 patients. No patients tested positive for SARS-Cov-2 testing obtained 48h prior to surgery. None of the patients developed any COVID-19 symptoms during their hospitalization or were re-admitted to our ED postoperatively for COVID-19 symptoms. Conclusions We describe a multi-faceted preoperative triage protocol for safely performing non-elective neurosurgical cases during the COVID-19 pandemic, which could help other neurosurgical departments and hospitals minimize coronavirus exposure for patients and healthcare workers. We believe this triage strategy could be implemented at other centers to gradually restart a process towards elective surgeries in a safe way.


title: Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies

text: The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the available SARS-CoV-2 sequences (as of 9 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.


title: Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients

text: Abstract Background: The effect of corticosteroid treatment on the viral load of Severe Acute Respiratory Syndrome (SARS) patients is unknown. Objective: To compare the plasma SARS-CoV RNA concentrations in ribavirin-treated patients who received early hydrocortisone therapy with those who received placebo. Study design: Serial plasma SARS-CoV RNA concentrations measured in the setting of a prospective, randomized double-blinded, placebo-controlled trial designed to assess the efficacy of “early” (<7 days of illness) hydrocortisone use in previously healthy SARS patients were analyzed. SARS-CoV RNA was quantified using a one-step real-time RT-PCR assay targeting the nucleocapsid gene. Results: Among 16 non-ICU cases, SARS-CoV RNA was detected in plasma since day 3–4 after fever onset; viral concentration peaked in the first week, which then rapidly declined in the second week of illness. On days 8, 12, 16, and 20, the cumulative proportion of patients with undetectable virus in plasma was 31%, 69%, 92%, and 100%, respectively. Plasma SARS-CoV RNA concentrations in the second and third week of illness were significantly higher in patients who received initial hydrocortisone treatment (n = 9), as compared to those who received placebo (n = 7)(AUC; Mann–Whitney, P = 0.023). The median time for SARS-CoV to become undetectable in plasma was 12 days (11–20 days) versus 8 days (8–15 days), respectively. Conclusion: Our findings suggested “early” corticosteroid treatment was associated with a higher subsequent plasma viral load.


title: Crazy-paving sign in high-resolution computed tomography in parainfluenza virus pneumonia

text: Abstract The crazy-paving sign is the appearance of a smooth linear pattern superimposed on an area of ground-glass opacity on thin-section computed tomography (CT). A 69-year-old woman was admitted to our hospital for treatment of pneumonia. Thoracic CT showed a crazy-paving sign in the right lung field on admission. She received ceftriaxone and clarithromycin, and the symptoms and infiltration shadow promptly disappeared. Serologic testing revealed a greater than 4-fold increase in the IgG titer for parainfluenza virus I. To our knowledge, there is no previous report of the crazy-paving sign in associated with viral pneumonia in a non-immunocompromised host or with parainfluenza pneumonia.


title: Q-03: Épisode de cas groupés de psittacose lié à la préparation de repas de mariage, Lot-et-Garonne, mai 2013

text: Introduction – objectifs Fin mai 2013, un CH du Lot-et-Garonne signale 4 cas d’infections respiratoires aiguës à la plateforme de veille et d’urgences sanitaires d’Aquitaine. Une investigation est menée pour décrire l’épisode, identifier la source de contamination et contribuer aux mesures de contrôle. Dans un contexte de virus émergents, une exposition à coronavirus MERS-CoV et à H7N9 est rapidement écartée au profit d’une suspicion de psittacose. Matériels et méthodes Une enquête descriptive approfondie est réalisée pour confirmer le diagnostic, recueillir les facteurs d’exposition et assurer une recherche active de cas. Les enquêtes vétérinaires et environnementales sont mises en œuvre pour retrouver les potentielles sources de contamination. Résultats Au total, huit cas de psittacose, dont 4 confirmés par PCR par le CNR, ont été recensés. Ces cas ont été identifiés parmi un groupe de 15 femmes, soit un taux d’attaque de 47 %, ayant éviscéré une centaine de poulets lors de préparation de repas de mariage les jours précédents les signes. La présence de Chlamydia psittaci a été confirmée à partir du lot de poulets concerné. Le génotype déterminé à partir des prélèvements humains et vétérinaires était un génotype classiquement détecté chez les canards, espèce aviaire aussi présente sur l’exploitation. Conclusion L’investigation a permis de conclure à un épisode de cas groupés de psittacose par contact étroit avec des poulets infectés. Ce type d’épisode, relativement rare, rappelle la vigilance nécessaire dans un contexte de virus émergents et l’intérêt d’une collaboration réactive des acteurs pour mettre en œuvre rapidement les mesures de contrôle.


title: Retest positive for SARS‐CoV‐2 RNA of “recovered” patients with COVID‐19: Persistence, sampling issues, or re‐infection?

text: “Retest Positive” for severe acute respiratory syndrome‐related coronavirus‐2 (SARS‐CoV‐2) from “recovered” coronavirus disease‐19 (COVID‐19) has been reported and raised several important questions for this novel coronavirus and COVID‐19 disease. In this commentary, we discussed several questions: (a) Can SARS‐CoV‐2 re‐infect the individuals who recovered from COVID‐19? This question is also associated with other questions: whether or not SARS‐CoV‐2 infection induces protective reaction or neutralized antibody? Will SARS‐CoV‐2 vaccines work? (b) Why could some recovered patients with COVID‐19 be re‐tested positive for SARS‐CoV‐2 RNA? (c) Are some recovered pwith atients COVID‐19 with re‐testing positive for SARS‐CoV‐2 RNA infectious? and (d) How should the COVID‐19 patients with retest positive for SARS‐CoV‐2 be managed?