title: Drive-Through Screening Center for COVID-19: A Safe and Efficient Screening System Against Massive Community Outbreak Kwon KT, Ko JH, Shin H, et al. J Korean Med Sci. Published online March 16, 2020. doi: https://doi.org/10.3346/jkms.2020.35.e123.

text: The current Coronavirus Disease 2019 (COVID-19) pandemic has necessitated the testing of significant numbers of patients. Modeled after those used during a previous bioterrorism disaster and influenza pandemic, the authors present a descriptive report of their drive-through screening center and processes. The authors recommend use of a large parking lot geographically removed from large population centers. Additionally, they recommend either a tent or temporary building to be used for work space and shelter from weather. They utilized a four-step process: Entrance → Registration → Examination → Specimen collection → Instructions → Exit. Patients do not leave their cars during this process. To minimize contact and preserve personal protective equipment (PPE), communication is performed either by mobile phone or electronic medical record whenever possible. Temperature is obtained with a contactless thermometer. If the physician strongly suspects COVID-19 during the examination step, the patient is transported to a designated hospital after specimen collection. Test specimens were collected with the car window opened the minimum amount necessary and car ventilation mode on internal circulation. Patients are provided with information about obtaining test results, home quarantine, and anticipatory guidance. Healthcare workers (HCWs) who had direct contact with patients wore the following PPE: N95 respirator, eye shield/face shield/goggles, hooded coverall/gown, and inner and outer gloves. To decrease viral spread and minimize the possibility of specimen contamination, HCWs wore two gowns and two pairs of gloves for patients who required testing; the external gloves/gown were removed and hands disinfected after each patient contact. The authors reported that this process took approximately ten minutes per test, allowing them to screen 100 people per day with a staff of 4-8 HCWs. This is estimated to be 1/3 the amount of time that a typical screening process would take. The authors recommended rotating staff every 1-2 hours if possible, and to ensure that no HCW wore an N95 respirator for longer than four consecutive hours. They also noted the need to be cognizant of relevant environmental issues, such as hot/cold weather, etc., and to adapt the working environment accordingly. Lastly, there must be adequate communication with the public regarding the limitations of the screening center to minimize the number of people who may attempt to use this resource inappropriately. They recommend considering a similar process for other uses such as medication distribution or vaccine administration. Comment: While not a typical research manuscript we would select for Abstracts, this article describes a non-novel approach to a novel viral pandemic. The drive-through screening process has a number of advantages as outlined above, especially as centers begin seeing higher numbers of potential COVID-19 patients. It is important to consider and plan for the unintended consequences of such a program, including how HCWs will handle unexpectedly ill patients and patients arriving by alternative transportation (bike, walking, public transportation). Healthcare leaders considering a drive-through screening option should also consider the heightened emotions and fear that are present during epidemic/pandemic conditions and plan for security accordingly.


title: Validation of Syndromic Surveillance for Respiratory Pathogen Activity

text: Syndromic surveillance is increasingly used to signal unusual illness events. To validate data-source selection, we retrospectively investigated the extent to which 6 respiratory syndromes (based on different medical registries) reflected respiratory pathogen activity. These syndromes showed higher levels in winter, which corresponded with higher laboratory counts of Streptococcus pneumoniae, respiratory syncytial virus, and influenza virus. Multiple linear regression models indicated that most syndrome variations (up to 86%) can be explained by counts of respiratory pathogens. Absenteeism and pharmacy syndromes might reflect nonrespiratory conditions as well. We also observed systematic syndrome elevations in the fall, which were unexplained by pathogen counts but likely reflected rhinovirus activity. Earliest syndrome elevations were observed in absenteeism data, followed by hospital data (+1 week), pharmacy/general practitioner consultations (+2 weeks), and deaths/laboratory submissions (test requests) (+3 weeks). We conclude that these syndromes can be used for respiratory syndromic surveillance, since they reflect patterns in respiratory pathogen activity.


New vaccine coalition targets epidemics


Characteristics of critically ill patients infected with COVID-19 in Abu Dhabi, United Arab Emirates


title: Viral nucleic acid analysis with PCR in lacrimal tissue and nasal swab samples of primary acquired nasolacrimal duct obstruction cases

text: PURPOSE: To evaluate the role of viral infections in the pathogenesis of primary acquired nasolacrimal duct obstruction. METHODS: The study included 48 patients diagnosed with primary acquired nasolacrimal duct obstruction undergoing dacryocystorhinostomy surgery. Prior to dacryocystorhinostomy surgery, nasal swab sample was taken from the inferior meatus at the same side. During dacryocystorhinostomy, tissue biopsy sample (2 × 2 mm) was taken from the junction area of the lacrimal sac and nasolacrimal duct. Following nucleic acid extraction, polymerase chain reaction was performed. RESULTS: The patients consisted of 9 (18.8%) men and 39 (81.2%) women with a mean age of 51.0 ± 14.3 years. Qualitative polymerase chain reaction showed viral genome in the nasal swabs of 10 (20.8%) patients, including coronavirus 229E (three cases), coronavirus HKU1 (two cases), respiratory syncytial virus (two cases), coronavirus OC43 (one case), coronavirus NL63 (one case), and adenovirus (one case). In the dacryocystorhinostomy samples, viral genomes were detected in four (8.3%) cases, including respiratory syncytial virus (two cases), coronavirus HKU1 (one case), and adenovirus (one case). There was a statistically significant agreement between nasal mucosal swab and dacryocystorhinostomy biopsy samples in terms of respiratory syncytial virus positivity (kappa = 1.000, p = 0.001). CONCLUSION: Although the viral genome was detected in the samples, a direct relationship between viruses and pathogenesis of primary acquired nasolacrimal duct obstruction could not be revealed because of the low number of positive results. However, considering the profibrotic characteristics of specific viruses such as respiratory syncytial virus and adenovirus, viral infections may be one of the many predisposing factors of primary acquired nasolacrimal duct obstruction.


title: Influenza Virus-Induced Robust Expression of SOCS3 Contributes to Excessive Production of IL-6

text: Influenza A virus (IAV) remains a major public health threat in the world, as indicated by the severe pneumonia caused by its infection annually. Interleukin-6 (IL-6) involved excessive inflammatory response to IAV infection profoundly contributes to the virus pathogenesis. However, the precise mechanisms underlying such a response are poorly understood. Here we found from both in vivo and in vitro studies that IAV not only induced a surge of IL-6 release, but also greatly upregulated expression of suppressor of cytokine signaling-3 (SOCS3), the potent suppressor of IL-6-associated signal transducer and activator of transcription 3 (STAT3) signaling. Interestingly, there existed a cytokine-independent mechanism of the robust induction of SOCS3 by IAV at early stages of the infection. Furthermore, we employed SOCS3-knockdown transgenic mice (TG), and surprisingly observed from virus challenge experiments using these mice that disruption of SOCS3 expression provided significant protection against IAV infection, as evidenced by attenuated acute lung injury, a higher survival rate of infected animals and lower viral load in infected tissues as compared with those of wild-type littermates under the same condition. The activity of nuclear factor-kappa B (NFκB) and the expression of its target gene IL-6 were suppressed in SOCS3-knockdown A549 cells and the TG mice after infection with IAV. Moreover, we defined that enhanced STAT3 activity caused by SOCS3 silencing was important for the regulation of NFκB and IL-6. These findings establish a critical role for IL-6-STAT3-SOCS3 axis in the pathogenesis of IAV and suggest that influenza virus may have evolved a strategy to circumvent IL-6/STAT3-mediated immune response through upregulating SOCS3.


title: Ingepakt aan het werk

text: WUHAN, CHINA - Verpleegkundigen in Wuhan hebben het niet gemakkelijk sinds de uitbraak van het nieuwe coronavirus. Deze icverpleegkundigen doen hun werk in hermetisch afgesloten pakken. Toch zijn er in China zeker 6 zorgverleners overleden en zouden er ruim 1700 artsen en verpleegkundigen besmet zijn.


title: Innate Immune Evasion Strategies of DNA and RNA viruses

text: Upon infection, both DNA and RNA viruses can be sensed by pattern recognition receptors (PRRs) in the cytoplasm or the nucleus to activate antiviral innate immunity. Sensing of viral products leads to the activation of a signaling cascade that ultimately results in transcriptional activation of Type I and III interferons, as well as other antiviral genes that mediate viral clearance and inhibit viral spread. Therefore, in order for viruses to replicate and spread efficiently, they must inhibit the host signaling pathways that induce the innate antiviral immune response. In this review, we will highlight recent advances the understanding of the mechanisms by which viruses evade PRR detection, intermediate signaling molecule activation, transcription factor activation, and the actions of antiviral proteins.


title: Epidemiology and etiology of influenza-like-illness in households in Vietnam; it’s not all about the kids!

text: BACKGROUND: Household studies provide opportunities to understand influenza-like-illness (ILI) transmission, but data from (sub)tropical developing countries are scarce. OBJECTIVE: To determine the viral etiology and epidemiology of ILI in households. STUDY DESIGN: ILI was detected by active case finding amongst a cohort of 263 northern Vietnam households between 2008 and 2013. Health workers collected nose and throat swabs for virus detection by multiplex real-time RT-PCR. RESULTS: ILI was detected at least once in 219 (23.7%) of 945 household members. 271 (62.3%) of 435 nose/throat swabs were positive for at least one of the 15 viruses tested. Six viruses predominated amongst positive swabs: Rhinovirus (28%), Influenza virus (17%), Coronavirus (8%), Enterovirus (5%), Respiratory syncytial virus (3%), Metapneumovirus virus (2.5%) and Parainfluenza virus 3 (1.8%). There was no clear seasonality, but 78% of episodes occurred in Winter/Spring for Influenza compared to 32% for Rhinovirus. Participants, on average, suffered 0.49 ILI, and 0.29 virus-positive ILI episodes, with no significant effects of gender, age, or household size. In contrast to US and Australian community studies, the frequency of ILI decreased as the number of household members aged below 5 years increased (p = 0.006). CONCLUSION: The findings indicate the need for tailored ILI control strategies, and for better understanding of how local childcare practices and seasonality may influence transmission and the role of children.


title: Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus

text: Summary Objectives Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged to cause fatal infections in patients in the Middle East and traveler-associated secondary cases in Europe and Africa. Person-to-person transmission is evident in outbreaks involving household and hospital contacts. Effective antivirals are urgently needed. Methods We used small compound-based forward chemical genetics to screen a chemical library of 1280 known drugs against influenza A virus in Biosafety Level-2 laboratory. We then assessed the anti-MERS-CoV activities of the identified compounds and of interferons, nelfinavir, and lopinavir because of their reported anti-coronavirus activities in terms of cytopathic effect inhibition, viral yield reduction, and plaque reduction assays in Biosafety Level-3 laboratory. Results Ten compounds were identified as primary hits in high-throughput screening. Only mycophenolic acid exhibited low EC50 and high selectivity index. Additionally, ribavirin and interferons also exhibited in-vitro anti-MERS-CoV activity. The serum concentrations achievable at therapeutic doses of mycophenolic acid and interferon-β1b were 60–300 and 3–4 times higher than the concentrations at which in-vitro anti-MERS-CoV activities were demonstrated, whereas that of ribavirin was ∼2 times lower. Combination of mycophenolic acid and interferon-β1b lowered the EC50 of each drug by 1–3 times. Conclusions Interferon-β1b with mycophenolic acid should be considered in treatment trials of MERS.


COVID‐19 outbreak and the practice of surgery: do we need to change?


title: A novel strain of porcine deltacoronavirus in Vietnam

text: Two porcine deltacoronavirus (PDCoV) strains (Binh21 and HaNoi6) were isolated from two pig farms in North Vietnam. Phylogenetic analysis of the complete genomes and the Spike and Membrane genes revealed that the two Vietnam PDCoVs belong to the same lineage as PDCoVs from Thailand and Laos; however, the N genes belonged to the same lineage as PDCoVs from the USA, Korea, China, and Hong Kong. The recombination detection program subsequently identified the major parent (S5011 strain) and minor parent (HKU15-44 strain) of the two Vietnam PDCoV strains (p < 0.01).


title: Development of a multiplex RT-PCR for simultaneous diagnosis of human metapneumovirus (HMPV) and human respiratory syncytial virus (HRSV) from clinical specimens

text: Human metapneumovirus (HMPV) and human respiratory syncytial virus (HRSV) are ubiquitous respiratory viral pathogens. They belong to the family Paramyxoviridae (subfamily Pneumovirinae) and is responsible for acute respiratory tract infections in children, elderly and immunocompromised patients. We designed and tested a multiplex reverse transcriptase polymerase chain reaction (mRT-PCR) as a cost-effective alternative to real-time PCR and cell culture based detection for HMPV and HRSV. The newly developed PCR was used to screen nasal/throat swab samples from 356 patients with suspected acute respiratory infection attending the Government Medical College, Thiruvananthapuram, Kerala, India. The method was compared with a commercially available kit employing real time PCR, for its sensitivity and specificity. 53 (14.9 %) samples were positive for at least one tested pathogen by mRT-PCR. All except one among the positive samples showed similar pathogen profile when tested using real time PCR. 8 (15.1 %) among these 53 were positive for HRSVA, 33 (62.3 %) positive for HRSVB and 12 (22.6 %) were positive for HMPV. 17 (32.7 %) samples showed co-infections in them. Sensitivity and specificity of the mRT-PCR was comparable to that of the commercial kit. Our findings indicate that this newly developed mRT-PCR can be used as a cost-effective alternative for laboratory diagnosis of HMPV/HRSV infection and will significantly reduce diagnostic costs for these viruses in clinical settings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13337-016-0348-2) contains supplementary material, which is available to authorized users.


Patients flee, drawing attention to quarantine dilemma


title: Intranasally administered peptidic viral fusion inhibitor protected hDPP4 transgenic mice from MERS-CoV infection

text: Abstract Background Middle East respiratory syndrome coronavirus (MERS-CoV), a new coronavirus that emerged in 2012, causes severe and fatal acute respiratory illness in man. Its high mortality (roughly 38%) has raised public fear worldwide, calling for the development of effective and safe therapeutics to combat MERS-CoV infection. On the basis of our previous work in development of peptide fusion inhibitors against HIV and SARS-CoV, and the crystal structure of the six-helix-bundle core of the MERS-CoV spike protein, we identified a peptide derived from the MERS-CoV S protein S2 subunit HR2 domain (HR2P) with a potent inhibitory activity against S-protein-mediated cell–cell fusion. Here, we tested an HR2P analogue with improved pharmaceutical properties, HR2P-M2, for its inhibitory activity against MERS-CoV infection in vitro and in vivo (appendix). Methods We assessed the anti-MERS-CoV activities of HR2P-M2 in vitro with pseudotyped MERS-CoVs in cell culture and in vivo with live MERS-CoVs in hDPP4-transgenic mice. The activities of HR2P-M2 to form six-helix bundles with HR1 peptides and to block fusion core formation between HR1 and HR2 peptides were studied using methods such as circular dichroism, N-PAGE, and FN-PAGE. Findings HR2P-M2 was highly effective in blockade of cell–cell fusion mediated by MERS-CoV S proteins and inhibition of infection by MERS pseudoviruses expressing MERS-CoV S protein with or without mutation in the HR1 region, with IC50 (the concentration causing 50% inhibition) less than 0·7 μM. HR2P-M2 bound to the HR1 peptide to form stable six-helix bundles and blocked fusion core formation between the HR1 and HR2 peptides. Intranasal administration of HR2P-M2 before viral challenge fully protected hDPP4-transgenic mice (n=5) from MERS-CoV infection, whereas all the untreated mice (n=5) died 8 days after viral challenge. Interpretation Our findings suggest that the HR2P-M2 peptide merits further development as an effective and safe anti-MERS-CoV drug, alone or in combination with other antiviral drugs, to treat MERS-CoV-infected patients and to prevent the disease in high-risk populations, including health-care workers and family members of patients. Funding This work was supported by grants from the National Science Fund of China (81173098 and 81361120378 to SJ, 81373456 to LL), the National 973 Program of China (2012CB519001 to SJ), and the US National Biocontainment Laboratories Operations Support (5UC7AI094660-05 to C-TKT). The funders had no role in interpretation of the findings and writing of this abstract.


title: Caspofungin for primary antifungal prophylaxis after T‐cell–replete haploidentical stem cell transplantation with post‐transplant cyclophosphamide

text: OBJECTIVES: T‐cell–replete haploidentical stem cell transplantation (Haplo‐SCT) with post‐transplant cyclophosphamide (PT‐Cy) is at high risk of invasive fungal infections (IFI), and anti‐mold–active drug is required for primary antifungal prophylaxis (PAP) according to international guidelines. No data are available on the efficacy of caspofungin as PAP in this setting. METHODS: Here, we report our retrospective experience with 103 consecutive patients treated with caspofungin as PAP after Haplo‐SCT. Caspofungin was administered only during the pre‐engraftment phase. RESULTS: Hundred‐day cumulative incidence of proven‐probable IFI (PP‐IFI) was 8.7% and median day of onset was 19 post‐SCT. No patient died of PP‐IFI, and overall survival (OS) and non‐relapse mortality (NRM) hazard ratio (HR) for patients experiencing IFI were 1.02 (P = 0.9) and 0.7 (P = 0.7), respectively. Three‐year overall survival (OS) and 1‐year non‐relapse mortality (NRM) were 55% and 19%, respectively. By univariate analysis, duration of neutropenic phase and partial remission pre‐transplant disease status were associated with increased incidence of IFI, but were not confirmed by multivariate analysis. CONCLUSION: In summary, PAP with caspofungin is an effective strategy for preventing IFI in the context of Haplo‐SCT with PT‐Cy. Further efforts are required in order to identify more potent strategies able to avoid the occurrence of breakthrough infections.


Response to “COVID-19 in persons with haematological cancers”


title: Real-time forecasts of the COVID-19 epidemic in China from February 5th to February 24th, 2020

text: The initial cluster of severe pneumonia cases that triggered the COVID-19 epidemic was identified in Wuhan, China in December 2019. While early cases of the disease were linked to a wet market, human-to-human transmission has driven the rapid spread of the virus throughout China. The Chinese government has implemented containment strategies of city-wide lockdowns, screening at airports and train stations, and isolation of suspected patients; however, the cumulative case count keeps growing every day. The ongoing outbreak presents a challenge for modelers, as limited data are available on the early growth trajectory, and the epidemiological characteristics of the novel coronavirus are yet to be fully elucidated. We use phenomenological models that have been validated during previous outbreaks to generate and assess short-term forecasts of the cumulative number of confirmed reported cases in Hubei province, the epicenter of the epidemic, and for the overall trajectory in China, excluding the province of Hubei. We collect daily reported cumulative confirmed cases for the 2019-nCoV outbreak for each Chinese province from the National Health Commission of China. Here, we provide 5, 10, and 15 day forecasts for five consecutive days, February 5th through February 9th, with quantified uncertainty based on a generalized logistic growth model, the Richards growth model, and a sub-epidemic wave model. Our most recent forecasts reported here, based on data up until February 9, 2020, largely agree across the three models presented and suggest an average range of 7409–7496 additional confirmed cases in Hubei and 1128–1929 additional cases in other provinces within the next five days. Models also predict an average total cumulative case count between 37,415 and 38,028 in Hubei and 11,588–13,499 in other provinces by February 24, 2020. Mean estimates and uncertainty bounds for both Hubei and other provinces have remained relatively stable in the last three reporting dates (February 7th – 9th). We also observe that each of the models predicts that the epidemic has reached saturation in both Hubei and other provinces. Our findings suggest that the containment strategies implemented in China are successfully reducing transmission and that the epidemic growth has slowed in recent days.


title: Bat‐borne viruses in Africa: a critical review

text: In Africa, bat‐borne zoonoses emerged in the past few decades resulting in large outbreaks or just sporadic spillovers. In addition, hundreds of more viruses are described without any information on zoonotic potential. We discuss important characteristics of bats including bat biology, evolution, distribution and ecology that not only make them unique among most mammals but also contribute to their potential as viral reservoirs. The detection of a virus in bats does not imply that spillover will occur and several biological, ecological and anthropogenic factors play a role in such an event. We summarize and critically analyse the current knowledge on African bats as reservoirs for corona‐, filo‐, paramyxo‐ and lyssaviruses. We highlight that important information on epidemiology, bat biology and ecology is often not available to make informed decisions on zoonotic spillover potential. Even if knowledge gaps exist, it is still important to recognize the role of bats in zoonotic disease outbreaks and implement mitigation strategies to prevent exposure to infectious agents including working safely with bats. Equally important is the crucial role of bats in various ecosystem services. This necessitates a multidisciplinary One Health approach to close knowledge gaps and ensure the development of responsible mitigation strategies to not only minimize risk of infection but also ensure conservation of the species.


Is one- or two-meters social distancing enough for COVID-19?


title: In Silico Exploration of the Molecular Mechanism of Clinically Oriented Drugs for Possibly Inhibiting SARS-CoV-2’s Main Protease

text: [Image: see text] Currently, the new coronavirus disease 2019 (COVID-19) is a global pandemic without any well-calibrated treatment. To inactivate the SARS-CoV-2 virus that causes COVID-19, the main protease (Mpro) that performs key biological functions in the virus has been the focus of extensive studies. With the fast-response experimental efforts, the crystal structures of Mpro of the SARS-CoV-2 virus have just become available recently. Herein, we theoretically investigated the mechanism of binding between the Mpro’s pocket and various marketed drug molecules being tested in clinics to fight COVID-19 that show promising outcomes. By combining the existing experimental results with our computational ones, we revealed an important ligand binding mechanism of the Mpro, demonstrating that the binding stability of a ligand inside the Mpro pocket can be significantly improved if part of the ligand occupies its so-called “anchor” site. Along with the highly potent drugs and/or molecules (such as nelfinavir) revealed in this study, the newly discovered binding mechanism paves the way for further optimizations and designs of Mpro’s inhibitors with a high binding affinity.


Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients


Human SARS‐coronavirus RNA‐dependent RNA polymerase: Activity determinants and nucleoside analogue inhibitors


Re-emerging Middle East respiratory syndrome coronavirus: The hibernating bat hypothesis


title: Neumonía aguda extrahospitalaria

text: La neumonía aguda extrahospitalaria sigue estando asociada a una elevada morbimortalidad. Durante estos últimos años, y gracias al desarrollo de técnicas de biología molecular, se han realizado importantes progresos en los métodos diagnósticos. Estas técnicas permiten mejorar la detección de bacterias atípicas y de virus respiratorios estacionales. Han permitido asimismo subrayar el lugar de los virus respiratorios en su aparición. El protocolo terapéutico se basa siempre en la instauración precoz de una antibioticoterapia que casi siempre es empírica. Las recomendaciones europeas para el tratamiento de las neumonías extrahospitalarias han sido puestas al día en 2011, como también lo han sido recientemente las pautas vacunales frente al neumococo. En este artículo, se resumen las etiologías de las neumonías, su diagnóstico, las escalas que permiten evaluar su gravedad y orientar el tratamiento del paciente, los datos sobre la sensibilidad a los antibióticos y las recomendaciones terapéuticas resultantes, así como las estrategias de prevención.


title: Neutralizing Antibodies Responses to SARS-CoV-2 in COVID-19 Inpatients and Convalescent Patients

text: BACKGROUND: COVID-19 is a pandemic with no specific antiviral treatments or vaccines. The urgent needs for exploring the neutralizing antibodies from patients with different clinical characteristics are emerging. METHODS: A total of 117 blood samples were collected from 70 COVID-19 inpatients and convalescent patients. Antibodies were determined with a modified cytopathogenic neutralization assay (NA) based on live SARS-CoV-2 and enzyme linked immunosorbent assay (ELISA). The dynamics of neutralizing antibody levels at different time points with different clinical characteristics were analyzed. RESULTS: The seropositivity rate reached up to 100.0% within 20 days since onset, and remained 100.0% till day 41-53. The total GMT was 1:163.7 (95% CI, 128.5 to 208.6) by NA and 1:12441.7 (95% CI, 9754.5 to 15869.2) by ELISA. The antibody level by NA and ELISA peaked on day 31-40 since onset, and then decreased slightly. In multivariate GEE analysis, patients at age of 31-45, 46-60, and 61-84 had a higher neutralizing antibody level than those at age of 16-30 (β=1.0470, P=0.0125; β=1.0613, P=0.0307; β=1.3713, P=0.0020). Patients with a worse clinical classification had a higher neutralizing antibody titer (β=0.4639, P=0.0227). CONCLUSIONS: The neutralizing antibodies were detected even at the early stage of disease, and a significant response showed in convalescent patients.


title: Conditions that generally bring about bank bailouts, bail-ins, and other resolution methods

text: This chapter discusses the conditions that typically bring about bailouts, bail-ins, and other types of bank resolution. Bailouts and bail-ins are usually triggered by financial crises, but may also occur during normal times in response to the distress of too-big-to-fail (TBTF), too-important-to-fail (TITF), or too-many-to-fail (TMTF) banks.


title: Mutations in the coat protein-binding cis-acting RNA motifs debilitate RNA recombination of Brome mosaic virus

text: Abstract We have previously described the efficient homologous recombination system between 5′ subgenomic RNA3a (sgRNA3a) and genomic RNA3 of Brome mosaic virus (BMV) in barley protoplasts (Sztuba-Solińska et al., 2011a). Here, we demonstrated that sequence alterations in the coat protein (CP)-binding cis-acting RNA motifs, the Bbox region (in the intercistronic RNA3 sequence) and the RNA3 packaging element (PE, in the movement protein ORF), reduced crossover frequencies in protoplasts. Additionally, the modification of Bbox-like element in the 5′ UTR region strongly debilitated crossovers. Along the lines of these observations, RNA3 mutants not expressing CP or expressing mutated CPs also reduced recombination. A series of reciprocal transfections demonstrated a functional crosstalk between the Bbox and PE elements. Altogether, our data imply the role of CP in sgRNA3a-directed recombination by either facilitating the interaction of the RNA substrates and/or by creating roadblocks for the viral replicase.


title: Rhinovirus-induced Rapidly Progressing Acute Respiratory Distress Syndrome in an Immunocompetent Host

text: A previously healthy, 59-year-old female presented with respiratory distress and dry cough for one week. Outpatient radiographic findings were suspicious for basilar pneumonia. Empiric broad-spectrum antibiotics were started; however, she continued to deteriorate rapidly over the next 48 hours, with chest X-ray showing diffuse bilateral multifocal airspace opacities consistent with acute respiratory distress syndrome. The ratio of partial pressure arterial oxygen to fraction of inspired oxygen was 225. She required a high-flow nasal cannula with a subsequent upgrade to the intensive care unit (ICU) for increasing respiratory compromise. Polymerase chain reaction (PCR) of the nasopharyngeal aspirate confirmed human rhinovirus (hRV). High-dose intravenous steroids were started as adjuvant therapy due to the rapid decline, presumably due to a dysregulated host immune response. After 10 days in the ICU, she was discharged with tiotropium and steroid taper. Historically thought to be limited to pandemic viruses, improved detection of hRV has led to its implication in serious respiratory disorders extending beyond the oropharynx in immunocompetent hosts. We report a rare case of hRV-induced severe acute respiratory distress syndrome (ARDS) in an immunocompetent host. This case highlights the need for the early identification of viral culprits, which can minimize the use of invasive diagnostic testing and antibiotic usage.


title: Phylogenetic characterization of rhinoviruses from infants in Sarlahi, Nepal

text: PROBLEM: Rhinoviruses (RVs), the most common causes of acute respiratory infections in young children and infants, are highly diverse genetically. OBJECTIVE: To characterize the RV types detected with respiratory illness episodes in infants in Nepal. STUDY METHODS: Infants born to women enrolled in a randomized trial of maternal influenza immunization in rural, southern Nepal were followed with household‐based weekly surveillance until 180 days of age. Infants with respiratory symptoms had nasal swabs tested for twelve respiratory viruses. A subset with RV alone was selected for sequencing of the VP4/2 gene to identify RV types. RESULTS: Among 547 RV‐only positive illnesses detected from December 2012 to April 2014, 285 samples (52%) were sequenced. RV‐A, B, and C species were detected in 193 (68%), 18 (6%), and 74 (26%) specimens, respectively. A total of 94 unique types were identified from the sequenced samples, including 52 RV‐A, 11 RV‐B, and 31 RV‐C. Multiple species and types circulated simultaneously throughout the study period. No seasonality was observed. The median ages at illness onset were 88, 104, and 88 days for RV‐A, B, and C, respectively. The median polymerase chain reaction cycle threshold values did not differ between RV species. No differences between RV species were observed for reported respiratory symptoms, including pneumonia, or for medical care‐seeking. CONCLUSIONS: Among very young, symptomatic infants in rural Nepal, all three species and many types of RV were identified; RV‐A was detected most frequently. There was no association between RV species and disease severity.


title: Systematic Identification of Spontaneous Preterm Birth-Associated RNA Transcripts in Maternal Plasma

text: BACKGROUND: Spontaneous preterm birth (SPB, before 37 gestational weeks) is a major cause of perinatal mortality and morbidity, but its pathogenesis remains unclear. Studies on SPB have been hampered by the limited availability of markers for SPB in predelivery clinical samples that can be easily compared with gestational age-matched normal controls. We hypothesize that SPB involves aberrant placental RNA expression, and that such RNA transcripts can be detected in predelivery maternal plasma samples, which can be compared with gestational age-matched controls. PRINCIPAL FINDINGS: Using gene expression microarray to profile essentially all human genes, we observed that 426 probe signals were changed by >2.9-fold in the SPB placentas, compared with the spontaneous term birth (STB) placentas. Among the genes represented by those probes, we observed an over-representation of functions in RNA stabilization, extracellular matrix binding, and acute inflammatory response. Using RT-quantitative PCR, we observed differences in the RNA concentrations of certain genes only between the SPB and STB placentas, but not between the STB and term elective cesarean delivery placentas. Notably, 36 RNA transcripts were observed at placental microarray signals higher than a threshold, which indicated the possibility of their detection in maternal plasma. Among them, the IL1RL1 mRNA was tested in plasma samples taken from 37 women. It was detected in 6 of 10 (60%) plasma samples collected during the presentation of preterm labor (≤32.9 weeks) in women eventually giving SPB, but was detected in only 1 of 27 (4%) samples collected during matched gestational weeks from women with no preterm labor (Fisher exact test, p = 0.00056). CONCLUSION: We have identified 36 SPB-associated RNA transcripts, which are possibly detectable in maternal plasma. We have illustrated that the IL1RL1 mRNA was more frequently detected in predelivery maternal plasma samples collected from women resulting in SPB than the gestational-age matched controls.


Severe Pneumonia and Human Bocavirus in Adult


title: Emerging infectious disease: trends in the literature on SARS and H7N9 influenza

text: Severe acute respiratory syndrome (SARS) and human infection H7N9 influenza are emerging infectious diseases having a relatively high mortality. Epidemics of each began in China. By searching through Science Citation Index, this study analyzed the article literature on SARS and H7N9 influenza, particularly papers in the leading journals The Lancet, New England Journal of Medicine (NEJM), Nature and Science. The results show that the quantity and quality of SARS and H7N9 influenza literature from mainland China changed distinctly over the course of 10 years. Researchers from mainland China published 12 article literature in the The Lancet, NEJM, Nature and Science about H7N9 influenza, whereas mainland China had only 2 article literature about SARS in the same journals. The literature reflects China’s growing strength in the science and technology of emerging infectious disease.


title: Psychopathologie de crise : chronique des tensions ordinaires en situation sanitaire extraordinaire. Phase 1 : la réorganisation anxieuse

text: Résumé Les premiers mois de l’année 2020 sont marqués en France par une situation de crise sanitaire exceptionnelle. Dans l’urgence, l’ensemble des acteurs du soin sont appelés à se mobiliser afin de faire face à la crise. Entre l’angoisse liée à la contamination, les incertitudes concernant la menace, le réaménagement de l’outil de travail, la formation de nouvelles équipes et les modifications de la vie personnelle, les équipes hospitalières sont soumises à un effort d’adaptation majeur. Psychiatre exerçant au sein d’un hôpital d’instruction des armées (HIA) réorganisé pour faire face à la crise, nous avons interrompu la majeure partie de notre activité programmée pour nous rapprocher des services susceptibles d’accueillir des patients Covid afin de leur proposer un soutien psychologique. L’objet de ce propos est, après avoir fait l’inventaire des différents facteurs de stress que nous avons observés, de décrire les manifestations psychopathologiques individuelles et collectives constatées lors de cette période si particulière de préparation à la crise. Entre le normal et le pathologique, la mise en mot de cette psychopathologie ordinaire de l’exception nous paraît en effet être un préalable indispensable au maintien d’une distance nécessaire pour être thérapeutique et participer efficacement à la mise en place d’un dispositif de soutien psychologique adapté. Abstract Introduction: Humanity is facing a global pandemic at the start of 2020. The health systems of each country are reorganizing to cope with an influx of patients. This crisis reorganization is the source of psychological tension that can lead to symptomatic manifestations in many caregivers. This situation is similar in many points to that encountered by soldiers on external operations (loss of usual bearings, feeling of threat, focusing of attention on the crisis, deterioration of living conditions with limitation of the possibility of taking breaks). The aim of this work is to describe at the hospital level the changes in the professional and personal environment linked to the crisis likely to cause stress and then to describe the clinical manifestations observed both on an individual and collective level. Analysis of the situation: In this chapter, after having described the reorganization of the hospital in which we operate, we try to identify various factors likely to have psychological repercussions such as: the perceived urgency of the situation, the achievement of privacy, the reorganization of the work tool and the exercise of unusual tasks in newly formed teams, but also the fear of lack, the anxiety linked to contamination, the uncertainties linked to the threat. Clinical Description: In this chapter, we describe the clinical manifestations observed in the caregivers of the hospital in reaction to the crisis. Rather than decompensations, they are mainly anxious manifestations characterized by an increase in somatic concerns, an accentuation of verification rituals, an increase in snacking and the consumption of certain psychoactive substances (coffee, tobacco) and for certain people a character stiffening. On a collective level, it was mainly the misuse of social networks reflecting the group's anxieties (search for meaning and responsibility, need for certainty) that was observed. Conclusion: We then conclude with a description of the approach that led to the establishment of a support system by offering a graduated response, re-assessable over time, compatible with the maintenance of usual activity while maintaining a therapeutic distance.


title: IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry

text: To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats.


title: Identification of a novel nidovirus as a potential cause of large scale mortalities in the endangered Bellinger River snapping turtle (Myuchelys georgesi)

text: In mid-February 2015, a large number of deaths were observed in the sole extant population of an endangered species of freshwater snapping turtle, Myuchelys georgesi, in a coastal river in New South Wales, Australia. Mortalities continued for approximately 7 weeks and affected mostly adult animals. More than 400 dead or dying animals were observed and population surveys conducted after the outbreak had ceased indicated that only a very small proportion of the population had survived, severely threatening the viability of the wild population. At necropsy, animals were in poor body condition, had bilateral swollen eyelids and some animals had tan foci on the skin of the ventral thighs. Histological examination revealed peri-orbital, splenic and nephric inflammation and necrosis. A virus was isolated in cell culture from a range of tissues. Nucleic acid sequencing of the virus isolate has identified the entire genome and indicates that this is a novel nidovirus that has a low level of nucleotide similarity to recognised nidoviruses. Its closest relatives are nidoviruses that have recently been described in pythons and lizards, usually in association with respiratory disease. In contrast, in the affected turtles, the most significant pathological changes were in the kidneys. Real time PCR assays developed to detect this virus demonstrated very high virus loads in affected tissues. In situ hybridisation studies confirmed the presence of viral nucleic acid in tissues in association with pathological changes. Collectively these data suggest that this virus is the likely cause of the mortalities that now threaten the survival of this species. Bellinger River Virus is the name proposed for this new virus.


title: Empiric Antibiotic Therapy in the Treatment of Community-acquired Pneumonia in a General Hospital in Saudi Arabia

text: BACKGROUND: Guideline-based empiric antimicrobial therapy is recommended for the treatment of community-acquired pneumonia (CAP). In this study, we evaluate the pattern of empiric antibiotics of CAP patients. MATERIALS AND METHODS: Patients with CAP were retrieved from the health information unit using the International Classification of Diseases, Ninth Revision. The electronic pharmacy database was used to retrieve prescribed antibiotics and the duration of therapy for each antibiotic. RESULTS: A total of 1672 adult patients were included in the study and 868 (52%) were male. Of all the patients, 47 (2.8%) were admitted to the intensive care unit (ICU). The most frequently used antibiotics were levofloxacin (68.12%), ceftriaxone (37.7%), imipenem-cilastatin (32.5%), and azithromycin (20.6%). The mean days of therapy of each of these antibiotics were 3.2, 2.8, 4.4, and 2.9, respectively. A combination therapy of levofloxacin and imipenem-cilastatin was prescribed for 355 (21.8%) of non-ICU patients versus 20 (60.6%) of ICU patients (P = 0.0007). Imipenem-cilastatin was prescribed for 518 (31.8%) of non-ICU patients versus 25 (56.8%) of ICU patients (P = 0.0009). Levofloxacin was prescribed for 1106 (68%) of non-ICU patients versus 33 (75%) of ICU patients (P = 0.412). Ceftriaxone use decreased significantly from 40.9% in 2013 to 25.9% in 2016 (P = 0.034). In addition, levofloxacin use increased from 63.7% to 75% (P = 0.63). CONCLUSION: The most commonly used antibiotics were levofloxacin, ceftriaxone, imipenem-cilastatin, and azithromycin. The data call for further refinement and prospective audit of antibiotic use in CAP, especially in non-ICU settings.


title: Herpesviral Fcγ receptors: culprits attenuating antiviral IgG?

text: Abstract Production of IgG in response to virus infection is central to antiviral immune effector functions and a hallmark of B cell memory. Antiviral antibodies (Abs) recognising viral glycoproteins or protein antigen displayed on the surface of virions or virus-infected cells are crucial in rendering the virus noninfectious and in eliminating viruses or infected cells, either acting alone or in conjunction with complement. In many instances, passive transfer of Abs is sufficient to protect from viral infection. Herpesviruses (HV) are equipped with a large array of immunomodulatory functions which increase the efficiency of infection by dampening the antiviral immunity. Members of the α- and β-subfamily of the Herpesviridae are distinct in encoding transmembrane glycoproteins which selectively bind IgG via its Fc domain. The Fc-binding proteins constitute viral Fcγ receptors (vFcγRs) which are expressed on the cell surface of infected cells. Moreover, vFcγRs are abundantly incorporated into the envelope of virions. Despite their molecular and structural heterogeneity, the vFcγRs generally interfere with IgG-mediated effector functions like antibody (Ab)-dependent cellular cytolysis, complement activation and neutralisation of infectivity of virions. vFcγRs may thus contribute to the limited therapeutic potency of antiherpesviral IgG in clinical settings. A detailed molecular understanding of vFcγRs opens up the possibility to design recombinant IgG molecules resisting vFcγRs. Engineering IgG with a better antiviral efficiency represents a new therapeutic option against herpesviral diseases.


title: 5 Operating environment

text: Abstract The operating environment of an airport is affecting its financial performance. This will be worked out for different regions and size brackets, based on empirical airport data provided by ACI’s economic surveys. This chapter will also investigate influencing factors such as major traffic flows and their consequences for airport demand as well as site-specific circumstances, including aviation policy. Due to their importance for the economic development of a region, airports have frequently been subject to political activities. This chapter’s feature is on potential effects of aviation policy on regional airports. It is focusing on the European Commission’s 2014 guidelines on state aid and their amendment as of May 2017.


title: Control Measures for Human Respiratory Viral Infection

text: New viral respiratory pathogens are emerging with increasing frequency and have potentially devastating impacts on the population worldwide. Recent examples of newly emerged threats include severe acute respiratory syndrome coronavirus, the 2009 H1N1 influenza pandemic, and Middle East respiratory syndrome coronavirus. Experiences with these pathogens have shown up major deficiencies in how we deal globally with emerging pathogens and taught us salient lessons in what needs to be addressed for future pandemics. This article reviews the lessons learnt from past experience and current knowledge on the range of measures required to limit the impact of emerging respiratory infections from public health responses down to individual patient management. Key areas of interest are surveillance programs, political limitations on our ability to respond quickly enough to emerging threats, media management, public information dissemination, infection control, prophylaxis, and individual patient management. Respiratory physicians have a crucial role to play in many of these areas and need to be aware of how to respond as new viral pathogens emerge.


title: Transfer of Anti-Rotavirus Antibodies during Pregnancy and in Milk Following Maternal Vaccination with a Herpes Simplex Virus Type-1 Amplicon Vector

text: Rotaviruses (RVs) are important enteric pathogens of newborn humans and animals, causing diarrhea and in rare cases death, especially in very young individuals. Rotavirus vaccines presently used are modified live vaccines that lack complete biological safety. Previous work from our laboratory suggested that vaccines based on in situ produced, non-infectious rotavirus-like particles (RVLPs) are efficient while being entirely safe. However, using either vaccine, active mucosal immunization cannot induce protective immunity in newborns due to their immature immune system. We therefore hypothesized that offspring from vaccinated dams are passively immunized either by transfer of maternal antibodies during pregnancy or by taking up antibodies from milk. Using a codon optimized polycistronic gene expression cassette packaged into herpesvirus particles, the simultaneous expression of the RV capsid genes led to the intracellular formation of RVLPs in various cell lines. Vaccinated dams developed a strong RV specific IgG antibody response determined in sera and milk of both mother and pups. Moreover, sera of naïve pups nursed by vaccinated dams also had RV specific antibodies suggesting a lactogenic transfer of antibodies. Although full protection of pups was not achieved in this mouse model, our observations are important for the development of improved vaccines against RV in humans as well as in various animal species.


COVID-19-associated pulmonary aspergillosis: adding insult to injury


title: How We Do It: Lessons on Outbreak Preparedness from the Cleveland Clinic

text: Abstract Disasters, including infectious disease outbreaks, are inevitable. Hospitals need to plan in advance to ensure that their systems can adapt to a rapidly changing environment if necessary. This review provides an overview of ten general principles that hospitals and healthcare systems should consider when developing disaster plans. The principles are consistent with an “all-hazards” approach to disaster mitigation. This approach is adapted to planning for a multiplicity of threats, but emphasizes highly relevant scenarios, such as the COVID-19 pandemic. We also describe specific ways these principles helped prepare our hospital for this pandemic. Key points include acting quickly, identifying and engaging key stakeholders early, providing accurate information, prioritizing employee safety and mental health, promoting a fully integrated clinical response, developing surge plans, preparing for ethical dilemmas, and having a cogent exit strategy for post disaster recovery.


title: Economic Assessment of FMDv Releases from the National Bio and Agro Defense Facility

text: This study evaluates the economic consequences of hypothetical foot-and-mouth disease releases from the future National Bio and Agro Defense Facility in Manhattan, Kansas. Using an economic framework that estimates the impacts to agricultural firms and consumers, quantifies costs to non-agricultural activities in the epidemiologically impacted region, and assesses costs of response to the government, we find the distribution of economic impacts to be very significant. Furthermore, agricultural firms and consumers bear most of the impacts followed by the government and the regional non-agricultural firms.


COVID‐19


Guillain–Barré Syndrome Associated with SARS-CoV-2


title: Therapeutic and Prophylactic Potential of Small Interfering RNAs against Severe Acute Respiratory Syndrome: Progress to Date

text: Severe acute respiratory syndrome (SARS), caused by the novel coronavirus SARS-CoV, produced a scare when it appeared in 2003 in China and later quickly spread to other countries around the world. Although it has since disappeared, its threat to human health remains. Therefore, studies on the prevention and treatment of SARS are important for dealing with epidemics of this and other infectious diseases. The most promising newly developed technology for intervention in SARS may be RNA interference, an endogenous cellular process for the inhibition of gene expression mediated by sequence-specific double-stranded RNAs. Numerous studies have reported the therapeutic potential of RNA interference for the treatment of various human diseases ranging from cancers to infectious diseases such as HIV and hepatitis. To date, most studies on inhibition of SARS-CoV replication using small interfering RNAs (siRNAs) have been conducted in cell lines in vitro. One study using siRNAs to inhibit SARS-CoV infection in Rhesus macaques demonstrated that siRNAs were effective both prophylactically and therapeutically with no adverse effects in the animals. Challenges remaining for the application of siRNA in vivo for SARS prevention and treatment include the specificity of the siRNAs and the efficiency of delivery. However, with improvements in siRNA design and delivery methods, RNA interference has the potential to become another major weapon for combating dangerous infections due to viruses such as SARS-CoV.


title: Inoculation of Goats, Sheep, and Horses with MERS-CoV Does Not Result in Productive Viral Shedding

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) was first recognized in 2012 and can cause severe disease in infected humans. Dromedary camels are the reservoir for the virus, although, other than nasal discharge, these animals do not display any overt clinical disease. Data from in vitro experiments suggest that other livestock such as sheep, goats, and horses might also contribute to viral transmission, although field data has not identified any seropositive animals. In order to understand if these animals could be infected, we challenged young goats and horses and adult sheep with MERS-CoV by intranasal inoculation. Minimal or no virus shedding was detected in all of the animals. During the four weeks following inoculation, neutralizing antibodies were detected in the young goats, but not in sheep or horses.


title: Right ventricular aneurysm and atrial septal defect in a cat

text: Abstract This case report shows the development of a right ventricular aneurysm in a cat with a large atrial septal defect. Despite this complex cardiac pathology, the cat lived normally for more than 4 years and developed fatal congestive heart failure.


title: Association between Use of Oral Anti-Diabetic Drugs and the Risk of Sepsis: A Nested Case-Control Study

text: Although oral antidiabetic drugs (OADs) have been associated with immunomodulation in preclinical studies, little is still known about the association between the use of OADs and the risk of sepsis. Using a cohort of patients, extracted from Taiwan’s National Health Insurance Research Database, with type 2 diabetes who were newly diagnosed between 2010 and 2012 and treated with OADs, we conducted a nested case-control study involving 43,015 cases (patients who were first hospitalized for sepsis) and 43,015 matched controls. Compared with non-use, metformin use was associated with a decreased risk of developing sepsis (adjusted odds ratio [OR] 0.80, 95% confidence interval [CI] 0.77–0.83, P < 0.001), but meglitinide (adjusted OR 1.32, 95% CI 1.25–1.40, P < 0.001) use was associated with the increased risk of developing sepsis. The risk for development of sepsis was also lower among current (adjusted OR 0.87, 95% CI 0.78–0.96) and recent (adjusted OR 0.83, 95% CI 0.73–0.94) thiazolidinedione users. Current or recent sulfonylurea use and dipeptidyl peptidase-4 inhibitor use were not significantly associated with the development of sepsis. Our results highlight the need to consider the potential pleiotropic effect of OADs against sepsis in addition to the lowering of blood glucose.


title: Understanding evolution of SARS‐CoV‐2: a perspective from analysis of genetic diversity of RdRp gene

text: BACKGROUND & OBJECTIVES: COVID‐19 emerged as the first example of “Disease X”, a hypothetical disease of humans caused by an unknown infectious agent that was named as novel coronavirus and subsequently designated as SARS‐CoV‐2. The origin of the outbreak at the animal market in Wuhan, China implies it as a case of zoonotic spillover. The study was designed to understand evolution of Betacoronaviruses and in particular diversification of SARS‐CoV‐2 using RdRp gene, a stable genetic marker. METHODS: Phylogenetic and population stratification analyses were carried out using Maximum likelihood and Bayesian methods, respectively. RESULTS: Molecular phylogeny using RdRp, showed that SARS‐CoV‐2 isolates cluster together. Bat‐CoV isolate RaTG13 and Pangolin‐CoVs are observed to branch off prior to SARS‐CoV‐2 cluster. While SARS‐CoV form a single cluster, Bat‐CoVs form multiple clusters. Population‐based analyses revealed that both SARS‐CoV‐2 and SARS‐CoV form separate clusters with no admixture. Bat‐CoVs were found to have single and mixed ancestry and clustered as four sub‐populations. CONCLUSIONS: Population‐based analyses of Betacoronaviruses using RdRp, revealed that SARS‐CoV‐2 is a homogeneous population. SARS‐CoV‐2 appears to have evolved from Bat‐CoV isolate RaTG13, which diversified from a common ancestor from which Pangolin‐CoVs have also evolved. The admixed Bat‐CoV sub‐populations indicate that bats serve as reservoirs harboring virus ensembles that are responsible for zoonotic spillovers such as SARS‐CoV and SARS‐CoV‐2. The extent of admixed isolates of Bat‐CoVs observed in population diversification studies underline the need for periodic surveillance of bats and other animal reservoirs for potential spillovers as a measure towards preparedness for emergence of zoonosis. This article is protected by copyright. All rights reserved.


title: A tissue level atlas of the healthy human virome

text: BACKGROUND: Human-resident microbes can influence both health and disease. Investigating the microbiome using next-generation sequencing technology has revealed examples of mutualism and conflict between microbes and humans. Comparing to bacteria, the viral component of the microbiome (i.e., the “virome”) is understudied. Somatic tissues of healthy individuals are usually inaccessible for the virome sampling; therefore, there is limited understanding of the presence and distribution of viruses in tissues in healthy individuals and how virus infection associates with human gene expression and perturbs immunological homeostasis. RESULTS: To characterize the human virome in a tissue-specific manner, here we performed meta-transcriptomic analysis using the RNA-sequencing dataset from the Genotype-Tissue Expression (GTEx) Project. We analyzed the 8991 RNA-sequencing data obtained from 51 somatic tissues from 547 individuals and successfully detected 39 viral species in at least one tissue. We then investigated associations between virus infection and human gene expression and human disease onset. We detected some expected relationships; for instance, hepatitis C virus infection in the liver was strongly associated with interferon-stimulated gene upregulation and pathological findings of chronic hepatitis. The presence of herpes simplex virus type 1 in one subject’s brain strongly associated with immune gene expression. While torque teno virus was detected in a broad range of human tissues, it was not associated with interferon responses. Being notable in light of its association with lymphoproliferative disorders, Epstein-Barr virus infection in the spleen and blood was associated with an increase in plasma cells in healthy subjects. Human herpesvirus 7 was often detected in the stomach; intriguingly, it associated with the proportion of human leukocytes in the stomach as well as digestive gene expression. Moreover, virus infections in the local tissues associated with systemic immune responses in circulating blood. CONCLUSIONS: To our knowledge, this study is the first comprehensive investigation of the human virome in a variety of tissues in healthy individuals through meta-transcriptomic analysis. Further investigation of the associations described here, and application of this analytical pipeline to additional datasets, will be useful to reveal the impact of viral infections on human health.


Outbreak of COVID-19 in Thailand: Time Serial Analysis on Imported and Local Transmission Cases


title: The adverse effect of COVID pandemic on the care of patients with kidney diseases in India

text: INTRODUCTION: The Coronavirus disease-19 (COVID-19) pandemic has affected the care of patients with non-communicable diseases, including those suffering from kidney-related ailments. Many parts of the world, including India, adopted lockdown to curb community transmission of disease. The lockdown affected transportation, access to healthcare facilities, availability of medicines, and consumables as well as out and inpatient services. We aimed to analyze the effect of lockdown imposed due to COVID-19 pandemic on the care of patients with kidney diseases in India. METHODS: We surveyed 19 major hospitals (8 in public and 11 in private sector) to determine the effect of lockdown on the care of patients with kidney disease, including those on dialysis after the first 3 weeks of lockdown. RESULTS: The total number of dialysis patients in these centres came down from 2517 to 2404. About 710(28.2%) of patients missed one or more dialysis sessions, 69 (2.74%) required emergency dialysis sessions, 104 (4.13%) stopped reporting for dialysis, and 9 (0.36%) were confirmed to have died. Outpatient attendance in the surveyed hospital came down by 92.3%, and inpatient service reduced by 61%. Tele-consultation was started but accessed by only a small number of patients. CONCLUSION: Lack of preparedness before lockdown resulted in an interruption in health care services and posed an immediate adverse effect on the outcome of dialysis and kidney disease patients in India. The long-term impact on the health of patients with less severe forms of kidney disease remains unknown.


title: Geographic Distribution of MERS Coronavirus among Dromedary Camels, Africa

text: We found serologic evidence for the circulation of Middle East respiratory syndrome coronavirus among dromedary camels in Nigeria, Tunisia, and Ethiopia. Circulation of the virus among dromedaries across broad areas of Africa may indicate that this disease is currently underdiagnosed in humans outside the Arabian Peninsula.


title: Crohn's disease and multiple sclerosis: A single case report

text: A case of the association of multiple sclerosis and Crohn's disease in a 47 year old patient is reported. A possible relationship between these two diseases has been widely documented, both sporadically and at a familial level. Albeit in the absence of precise experimental data, it is legitimate to presume that the two diseases share common pathogenetic traits


title: Glycosylator: a Python framework for the rapid modeling of glycans

text: BACKGROUND: Carbohydrates are a class of large and diverse biomolecules, ranging from a simple monosaccharide to large multi-branching glycan structures. The covalent linkage of a carbohydrate to the nitrogen atom of an asparagine, a process referred to as N-linked glycosylation, plays an important role in the physiology of many living organisms. Most software for glycan modeling on a personal desktop computer requires knowledge of molecular dynamics to interface with specialized programs such as CHARMM or AMBER. There are a number of popular web-based tools that are available for modeling glycans (e.g., GLYCAM-WEB (http://https://dev.glycam.org/gp/) or Glycosciences.db (http://www.glycosciences.de/)). However, these web-based tools are generally limited to a few canonical glycan conformations and do not allow the user to incorporate glycan modeling into their protein structure modeling workflow. RESULTS: Here, we present Glycosylator, a Python framework for the identification, modeling and modification of glycans in protein structure that can be used directly in a Python script through its application programming interface (API) or through its graphical user interface (GUI). The GUI provides a straightforward two-dimensional (2D) rendering of a glycoprotein that allows for a quick visual inspection of the glycosylation state of all the sequons on a protein structure. Modeled glycans can be further refined by a genetic algorithm for removing clashes and sampling alternative conformations. Glycosylator can also identify specific three-dimensional (3D) glycans on a protein structure using a library of predefined templates. CONCLUSIONS: Glycosylator was used to generate models of glycosylated protein without steric clashes. Since the molecular topology is based on the CHARMM force field, new complex sugar moieties can be generated without modifying the internals of the code. Glycosylator provides more functionality for analyzing and modeling glycans than any other available software or webserver at present. Glycosylator will be a valuable tool for the glycoinformatics and biomolecular modeling communities.


title: Immunosenescence and age-related viral diseases

text: Immunosenescence is described as a decline in the normal functioning of the immune system associated with physiologic ageing. Immunosenescence contributes to reduced efficacy to vaccination and increased susceptibility to infectious diseases in the elderly. Extensive studies of laboratory animal models of ageing or donor lymphocyte analysis have identified changes in immunity caused by the ageing process. Most of these studies have identified phenotypic and functional changes in innate and adaptive immunity. However, it is unclear which of these defects are critical for impaired immune defense against infection. This review describes the changes that occur in innate and adaptive immunity with ageing and some age-related viral diseases where defects in a key component of immunity contribute to the high mortality rate in mouse models of ageing.


title: Detection of porcine epidemic diarrhea virus (PEDV) IgG and IgA in muscle tissue exudate (“meat juice”) specimens

text: The diagnostic performance of porcine epidemic diarrhea virus (PEDV) IgG and IgA ELISAs was evaluated using paired serum and meat juice samples collected from PEDV-negative (n = 50) and PEDV-inoculated pigs (n = 87). Serum samples were tested by PEDV (IgG, IgA) ELISAs using a procedure performed routinely at the Iowa State University-Veterinary Diagnostic Laboratory (ISU-VDL). Serum samples were tested using PEDV serum IgG and IgA ELISA procedures as routinely performed at the Iowa State University-Veterinary Diagnostic Laboratory (ISU-VDL). Serum samples were diluted 1:50 and conjugate concentrations were 1/20,000 for IgG and 1/3000 for IgA. Meat juice samples were tested using the serum PEDV IgG and IgA ELISAs, with modifications, i.e., meat juice samples were diluted 1:25 and conjugate concentrations were 1/40,000 for IgG and 1/10,000 for IgA. Receiver operator characteristic (ROC) curve analyses were used to estimate diagnostic sensitivities and specificities over a range of sample-to-positive (S/P) cutoffs. Consistent with previous reports, this study showed that the PEDV IgG and IgA meat juice ELISAs provided excellent diagnostic performance and suggest that meat juice recovered from samples collected at slaughter could be used in routine PEDV surveillance.


title: Isolation of porcine epidemic diarrhea virus in porcine cell cultures and experimental infection of pigs of different ages

text: Abstract This paper describes the isolation of porcine epidemic diarrhea (PED) virus in Vero and porcine cell cultures, and the influence of age on disease in experimental infection. PED virus was isolated from the small intestine of piglets inoculated with PED samples and cultured in Vero, porcine bladder and kidney cells propagated in collagen-coated tissue culture plates in maintenance medium (MM) containing trypsin. In porcine bladder and kidney cell cultures inoculated with isolated PED virus, cytopathic effects (CPE) including cell fusion were detected. Specific brilliant fluorescence was observed in the cytoplasm of these cells. Two- and 7-day old, and 2-, 4-, 8- and 12-week old specific pathogen-free (SPF) pigs were orally inoculated with PED virus isolated from an outbreak. All 2- and 7-day old pigs inoculated developed severe watery diarrhea from post-inoculation day (PID) 1 and died between PID 3 and 4. Although three of five 2-week old pigs developed diarrhea on PID 1–4, they eventually recovered. In the 4-week old group, three of five pigs had mild diarrhea for 1–2 days. None of the 8- and 12-week old pigs showed any clinical signs. Antibodies against PED virus were detected in all surviving pigs by virus neutralization (VN) test and immunofluorescence assay (IFA). Therefore, there is an age-dependent resistance to pathogenic PED virus infection in pigs.


title: Curative anticoagulation prevents endothelial lesion in COVID‐19 patients

text: BACKGROUND: Coronavirus disease‐2019 (COVID‐19) has been associated with cardiovascular complications and coagulation disorders. OBJECTIVES: To explore the coagulopathy and endothelial dysfunction in COVID‐19 patients. METHODS: Study analyzed clinical and biological profiles of patients with suspected COVID‐19 infection at admission, including hemostasis tests and quantification of circulating endothelial cells (CECs). RESULTS: Among 96 consecutive COVID‐19‐suspected patients fulfilling criteria for hospitalization, 66 were tested positive for SARS‐CoV‐2. COVID‐19 positive patients were more likely to present with fever (p=0.02), cough (p=0.03) and pneumonia at CT‐scan (p=0.002) at admission. Prevalence of D‐dimer >500 ng/mL was higher in COVID‐19 positive patients (74.2% vs. 43.3%; p=0.007). No sign of disseminated intravascular coagulation were identified. Adding D‐dimers >500 ng/mL to gender and pneumonia at CT scan in ROC curve analysis significantly increased AUC for COVID‐19 diagnosis. COVID‐19 positive patients had significantly more CECs at admission (p=0.008) than COVID‐19 negative ones. COVID‐19 positive patients treated with curative anticoagulant prior to admission had less CECs (p=0.02) than those without. Interestingly, patients treated with curative anticoagulation and ACEi or ARBs had even lesser CECs (p=0.007). CONCLUSION: Curative anticoagulation could prevent COVID‐19‐associated coagulopathy and endothelial lesion.


title: Diversity of Dromedary Camel Coronavirus HKU23 in African Camels Revealed Multiple Recombination Events among Closely Related Betacoronaviruses of the Subgenus Embecovirus

text: Genetic recombination has frequently been observed in coronaviruses. Here, we sequenced multiple complete genomes of dromedary camel coronavirus HKU23 (DcCoV-HKU23) from Nigeria, Morocco, and Ethiopia and identified several genomic positions indicative of cross-species virus recombination events among other betacoronaviruses of the subgenus Embecovirus (clade A beta-CoVs). Recombinant fragments of a rabbit coronavirus (RbCoV-HKU14) were identified at the hemagglutinin esterase gene position. Homolog fragments of a rodent CoV were also observed at 8.9-kDa open reading frame 4a at the 3′ end of the spike gene. The patterns of recombination differed geographically across the African region, highlighting a mosaic structure of DcCoV-HKU23 genomes circulating in dromedaries. Our results highlighted active recombination of coronaviruses circulating in dromedaries and are also relevant to the emergence and evolution of other betacoronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV). IMPORTANCE Genetic recombination is often demonstrated in coronaviruses and can result in host range expansion or alteration in tissue tropism. Here, we showed interspecies events of recombination of an endemic dromedary camel coronavirus, HKU23, with other clade A betacoronaviruses. Our results supported the possibility that the zoonotic pathogen MERS-CoV, which also cocirculates in the same camel species, may have undergone similar recombination events facilitating its emergence or may do so in its future evolution.


title: Chapter 19 Current and New Approaches for Mucosal Vaccine Delivery

text: Abstract Mucosal surfaces are the interface between the host’s internal milieu and the external environment, and they have dual functions, serving as physical barriers to foreign antigens and as accepting sites for vital materials. Mucosal vaccines are more favored to prevent mucosal infections from the portal of entry. Although mucosal vaccination has many advantages, licensed mucosal vaccines are scarce. The most widely studied mucosal routes are oral and intranasal. Licensed oral and intranasal vaccines are composed mostly of whole cell killed or live attenuated microorganisms serving as both delivery systems and built-in adjuvants. Future mucosal vaccines should be made with more purified antigen components, which will be relatively less immunogenic. To induce robust protective immune responses against well-purified vaccine antigens, an effective mucosal delivery system is an essential requisite. Recent developments in biomaterials and nanotechnology have enabled many innovative mucosal vaccine trials. For oral vaccination, the vaccine delivery system should be able to stably carry antigens and adjuvants and resist harsh physicochemical conditions in the stomach and intestinal tract. Besides many nano/microcarrier tools generated by using natural and chemical materials, the development of oral vaccine delivery systems using food materials should be more robustly researched to expand vaccine coverage of gastrointestinal infections in developing countries. For intranasal vaccination, the vaccine delivery system should survive the very active mucociliary clearance mechanisms and prove safety because of the anatomical location of nasal cavity separated by a thin barrier. Future mucosal vaccine carriers, regardless of administration routes, should have certain common characteristics. They should maintain stability in given environments, be mucoadhesive, and have the ability to target specific tissues and cells.


Caring for elderly adults with cognitive impairment in containment


title: Analysis of CDC social control measures using an agent-based simulation of an influenza epidemic in a city

text: BACKGROUND: The transmission of infectious disease amongst the human population is a complex process which requires advanced, often individual-based, models to capture the space-time details observed in reality. METHODS: An Individual Space-Time Activity-based Model (ISTAM) was applied to simulate the effectiveness of non-pharmaceutical control measures including: (1) refraining from social activities, (2) school closure and (3) household quarantine, for a hypothetical influenza outbreak in an urban area. RESULTS: Amongst the set of control measures tested, refraining from social activities with various compliance levels was relatively ineffective. Household quarantine was very effective, especially for the peak number of cases and total number of cases, with large differences between compliance levels. Household quarantine resulted in a decrease in the peak number of cases from more than 300 to around 158 for a 100% compliance level, a decrease of about 48.7%. The delay in the outbreak peak was about 3 to 17 days. The total number of cases decreased to a range of 3635-5403, that is, 63.7%-94.7% of the baseline value. When coupling control measures, household quarantine together with school closure was the most effective strategy. The resulting space-time distribution of infection in different classes of activity bundles (AB) suggests that the epidemic outbreak is strengthened amongst children and then spread to adults. By sensitivity analysis, this study demonstrated that earlier implementation of control measures leads to greater efficacy. Also, for infectious diseases with larger basic reproduction number, the effectiveness of non-pharmaceutical measures was shown to be limited. CONCLUSIONS: Simulated results showed that household quarantine was the most effective control measure, while school closure and household quarantine implemented together achieved the greatest benefit. Agent-based models should be applied in the future to evaluate the efficacy of control measures for a range of disease outbreaks in a range of settings given sufficient information about the given case and knowledge about the transmission processes at a fine scale.


SARS-CoV-2: Herausforderung für alle


title: Estimating Sensitivity of Laboratory Testing for Influenza in Canada through Modelling

text: BACKGROUND: The weekly proportion of laboratory tests that are positive for influenza is used in public health surveillance systems to identify periods of influenza activity. We aimed to estimate the sensitivity of influenza testing in Canada based on results of a national respiratory virus surveillance system. METHODS AND FINDINGS: The weekly number of influenza-negative tests from 1999 to 2006 was modelled as a function of laboratory-confirmed positive tests for influenza, respiratory syncytial virus (RSV), adenovirus and parainfluenza viruses, seasonality, and trend using Poisson regression. Sensitivity was calculated as the number of influenza positive tests divided by the number of influenza positive tests plus the model-estimated number of false negative tests. The sensitivity of influenza testing was estimated to be 33% (95%CI 32–34%), varying from 30–40% depending on the season and region. CONCLUSIONS: The estimated sensitivity of influenza tests reported to this national laboratory surveillance system is considerably less than reported test characteristics for most laboratory tests. A number of factors may explain this difference, including sample quality and specimen procurement issues as well as test characteristics. Improved diagnosis would permit better estimation of the burden of influenza.


title: Factors associated with motivation and hesitation to work among health professionals during a public crisis: a cross sectional study of hospital workers in Japan during the pandemic (H1N1) 2009

text: BACKGROUND: The professionalism of hospital workers in Japan was challenged by the pandemic (H1N1) 2009. To maintain hospital function under critical situations such as a pandemic, it is important to understand the factors that increase and decrease the willingness to work. Previous hospital-based studies have examined this question using hypothetical events, but so far it has not been examined in an actual pandemic. Here, we surveyed the factors that influenced the motivation and hesitation of hospital workers to work in Japan soon after the pandemic (H1N1) 2009. METHODS: Self-administered anonymous questionnaires about demographic character and stress factors were distributed to all 3635 employees at three core hospitals in Kobe city, Japan and were collected from June to July, 2009, about one month after the pandemic (H1N1) in Japan. RESULTS: Of a total of 3635 questionnaires distributed, 1693 (46.7%) valid questionnaires were received. 28.4% (N = 481) of workers had strong motivation and 14.7% (N = 249) had strong hesitation to work. Demographic characters and stress-related questions were categorised into four types according to the odds ratios (OR) of motivation and hesitation to work: some factors increased motivation and lowered hesitation; others increased motivation only; others increased hesitation only and others increased both motivation and hesitation. The strong feeling of being supported by the national and local governments (Multivariate OR: motivation; 3.5; CI 2.2-5.4, hesitation; 0.2; CI 0.1-0.6) and being protected by hospital (Multivariate OR: motivation; 2.8; CI 2.2-3.7, hesitation; 0.5; CI 0.3-0.7) were related to higher motivation and lower hesitation. Here, protection included taking precautions to prevent illness among workers and their families, providing for the care of those who do become ill, reducing malpractice threats, and financial support for families of workers who die on duty. But 94.1% of the respondents answered protection by the national and local government was weak and 79.7% answered protection by the hospital was weak. CONCLUSIONS: Some factors have conflicting effects because they increase both motivation and hesitation. Giving workers the feeling that they are being protected by the national and local government and hospital is especially valuable because it increases their motivation and lowers their hesitation to work.


title: Glycan arrays: biological and medical applications

text: Carbohydrates and their conjugates are involved in various biological events, including viral and bacterial infection, the immune response, differentiation and development, and the progression of tumor cell metastasis. Glycan arrays are a new technology that has enabled the high-sensitivity and rapid analysis carbohydrate–protein interaction and contribute to significant advances in glycomics. Glycan arrays use a minute amount of materials and can be used for high-throughput profiling and quantitative analysis and provide information for the development of carbohydrate-based vaccines and new drug discovery.


The Coronavirus Pandemic: The Most Disruptive Force to Affect My Life and Practice During the Coronavirus Pandemic


title: Pro/Con debate: Are barrier precautions cost-effective in improving patient outcomes in the intensive care unit?

text: You are responsible for a large medical surgical ICU. Your hospital administration has been very focused on reducing rates of hospital-acquired infections particularly in the wake of increasing public attention. However, it is time for budget preparation and your financial officer is concerned about the escalating costs associated with patient isolation and barrier precautions/personal protective equipment. Having become aware of the high costs associated with these interventions, you start to wonder about the wisdom of spending so much in this area. Your hospital administration wants your direction on next year's expenditures. You are debating whether the expense is worthwhile and advise your hospital administration accordingly.


title: Epidemiological shift and geographical heterogeneity in the burden of leptospirosis in China

text: BACKGROUND: Leptospirosis morbidity and mortality rates in China have decreased since the 2000s. Further analyses of the spatiotemporal and demographic changes occurring in the last decade and its implication on estimates of disease burden are required to inform intervention strategies. In this study, we quantified the epidemiological shift and geographical heterogeneity in the burden of leptospirosis during 2005–2015 in China. METHODS: We used reported leptospirosis case data from 1st January 2005 to 31st of December 2015 that routinely collected by the China Information System for Disease Control and Prevention (CISDCP) to analyze the epidemiological trend and estimate the burden in terms of disability-adjusted life-years (DALYs) over space, time, and demographical groups. RESULTS: A total of 7763 cases were reported during 2005–2015. Of which, 2403 (31%) cases were the laboratory-confirmed case. Since 2005, the notified incidence rate was gradually decreased (P < 0.05) and it was relatively stable during 2011–2015 (P > 0.05). During 2005–2015, we estimated a total of 10 313 DALYs were lost due to leptospirosis comprising a total of 1804 years-lived with disability (YLDs) and 8509 years-life lost (YLLs). Males had the highest burden of disease (7149 DALYs) compared to females (3164 DALYs). The highest burden estimate was attributed to younger individuals aged 10–19 years who lived in southern provinces of China. During 2005–2015, this age group contributed to approximately 3078 DALYs corresponding to 30% of the total DALYs lost in China. Yet, our analysis indicated a declining trend in burden estimates (P < 0.001) since 2005 and remained relatively low during 2011–2015. Low burden estimates have been identified in the endemic regions where infections principally distributed. Most of the changes in DALY estimates were driven by changes in YLLs. CONCLUSIONS: In the last 11-years, the burden estimates of leptospirosis have shown a declining trend across the country; however, leptospirosis should not be neglected as it remains an important zoonotic disease and potentially affecting the young and productive population in economically less-developed provinces in southern of China. In addition, while in the last five years the incidence has been reported at very low-level, this might not reflect the true incidence of leptospirosis. Strengthened surveillance in the endemic regions is, hence, substantially required to capture the actual prevalence to better control leptospirosis in China. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-018-0435-2) contains supplementary material, which is available to authorized users.


title: COVID‐19 diagnosis and management: a comprehensive review

text: Severe acute respiratory syndrome coronavirus (SARS‐CoV)‐2, a novel coronavirus from the same family as SARS‐CoV and Middle East respiratory syndrome coronavirus, has spread worldwide leading the World Health Organization to declare a pandemic. The disease caused by SARS‐CoV‐2, coronavirus disease 2019 (COVID‐19), presents flu‐like symptoms which can become serious in high‐risk individuals. Here, we provide an overview of the known clinical features and treatment options for COVID‐19. We carried out a systematic literature search using the main online databases (PubMed, Google Scholar, MEDLINE, UpToDate, Embase and Web of Science) with the following keywords: ‘COVID‐19’, ‘2019‐nCoV’, ‘coronavirus’ and ‘SARS‐CoV‐2’. We included publications from 1 January 2019 to 3 April 2020 which focused on clinical features and treatments. We found that infection is transmitted from human to human and through contact with contaminated environmental surfaces. Hand hygiene is fundamental to prevent contamination. Wearing personal protective equipment is recommended in specific environments. The main symptoms of COVID‐19 are fever, cough, fatigue, slight dyspnoea, sore throat, headache, conjunctivitis and gastrointestinal issues. Real‐time PCR is used as a diagnostic tool using nasal swab, tracheal aspirate or bronchoalveolar lavage samples. Computed tomography findings are important for both diagnosis and follow‐up. To date, there is no evidence of any effective treatment for COVID‐19. The main therapies being used to treat the disease are antiviral drugs, chloroquine/hydroxychloroquine and respiratory therapy. In conclusion, although many therapies have been proposed, quarantine is the only intervention that appears to be effective in decreasing the contagion rate. Specifically designed randomized clinical trials are needed to determine the most appropriate evidence‐based treatment modality.


Pentoxifylline and complicated COVID-19: a pathophysiologically based treatment proposal


title: Biosensors in clinical chemistry — 2011 update

text: Abstract Research activity and applications of biosensors for measurement of analytes of clinical interest over the last eight years are reviewed. Nanotechnology has been applied to improve performance of biosensors using electrochemical, optical, mechanical and physical modes of transduction, and to allow arrays of biosensors to be constructed for parallel sensing. Biosensors have been proposed for measurement of cancer biomarkers, cardiac biomarkers as well as biomarkers for autoimmune disease, infectious disease and for DNA analysis. Novel applications of biosensors include measurements in alternate sample types, such as saliva. Biosensors based on immobilized whole cells have found new applications, for example to detect the presence of cancer and to monitor the response of cancer cells to chemotherapeutic agents. The number of research reports describing new biosensors for analytes of clinical interest continues to increase; however, movement of biosensors from the research laboratory to the clinical laboratory has been slow. The greatest impact of biosensors will be felt at point-of-care testing locations without laboratory support. Integration of biosensors into reliable, easy-to-use and rugged instrumentation will be required to assure success of biosensor-based systems at the point-of-care.


title: Novel broad spectrum virucidal molecules against enveloped viruses

text: Viral infections are an important cause of death worldwide. Unfortunately, there is still a lack of antiviral drugs or vaccines for a large number of viruses, and this represents a remarkable challenge particularly for emerging and re-emerging viruses. For this reason, the identification of broad spectrum antiviral compounds provides a valuable opportunity for developing efficient antiviral therapies. Here we report on a class of rhodanine and thiobarbituric derivatives displaying a broad spectrum antiviral activity against seven different enveloped viruses including an HSV-2 acyclovir resistant strain with favorable selectivity indexes. Due to their selective action on enveloped viruses and to their lipid oxidation ability, we hypothesize a mechanism on the viral envelope that affects the fluidity of the lipid bilayer, thus compromising the efficiency of virus-cell fusion and preventing viral entry.


Bacterial Pneumonia in COVID-19 Critically Ill Patients: A Case Series


title: Human factors recognition at virtual meetings and video conferencing: how to get the best performance from yourself and others

text: During the current coronavirus pandemic, social distancing and restrictions on travel have resulted in a dramatic rise in the use of technology (including video conferencing) for remote meetings. From local multidisciplinary team (MDT) meetings to national and international committees, this form of communication has been vital to ensure patient-related and other business can continue, albeit in a sometimes unfamiliar environment. In this article we consider some of the human factors elements of remote meetings and provide suggestions to enhance the experience of team and committee members during this unsettling time. It is possible that this form of communication will continue to flourish after the pandemic is over.


title: Association between ABO blood groups and risk of SARS‐CoV‐2 pneumonia

text: In December, 2019, a cluster of acute respiratory illness caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), occurred in Wuhan, China.1,2 Epidemiological, clinical characteristics, risk factors for mortality of patients infected with SARS-CoV-2, and risk factors in the susceptibility to SARS-CoV-2 included age and chronic disease have been reported.


title: Viral Double-Strand RNA-Binding Proteins Can Enhance Innate Immune Signaling by Toll-Like Receptor 3

text: Toll-like Receptor 3 (TLR3) detects double-stranded (ds) RNAs to activate innate immune responses. While poly(I:C) is an excellent agonist for TLR3 in several cell lines and in human peripheral blood mononuclear cells, viral dsRNAs tend to be poor agonists, leading to the hypothesis that additional factor(s) are likely required to allow TLR3 to respond to viral dsRNAs. TLR3 signaling was examined in a lung epithelial cell line by quantifying cytokine production and in human embryonic kidney cells by quantifying luciferase reporter levels. Recombinant 1b hepatitis C virus polymerase was found to enhance TLR3 signaling in the lung epithelial BEAS-2B cells when added to the media along with either poly(I:C) or viral dsRNAs. The polymerase from the genotype 2a JFH-1 HCV was a poor enhancer of TLR3 signaling until it was mutated to favor a conformation that could bind better to a partially duplexed RNA. The 1b polymerase also co-localizes with TLR3 in endosomes. RNA-binding capsid proteins (CPs) from two positive-strand RNA viruses and the hepadenavirus hepatitis B virus (HBV) were also potent enhancers of TLR3 signaling by poly(I:C) or viral dsRNAs. A truncated version of the HBV CP that lacked an arginine-rich RNA-binding domain was unable to enhance TLR3 signaling. These results demonstrate that several viral RNA-binding proteins can enhance the dsRNA-dependent innate immune response initiated by TLR3.


title: Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats

text: Biological factors that influence the host range and spillover of Ebola virus (EBOV) and other filoviruses remain enigmatic. While filoviruses infect diverse mammalian cell lines, we report that cells from African straw-colored fruit bats (Eidolon helvum) are refractory to EBOV infection. This could be explained by a single amino acid change in the filovirus receptor, NPC1, which greatly reduces the affinity of EBOV-NPC1 interaction. We found signatures of positive selection in bat NPC1 concentrated at the virus-receptor interface, with the strongest signal at the same residue that controls EBOV infection in Eidolon helvum cells. Our work identifies NPC1 as a genetic determinant of filovirus susceptibility in bats, and suggests that some NPC1 variations reflect host adaptations to reduce filovirus replication and virulence. A single viral mutation afforded escape from receptor control, revealing a pathway for compensatory viral evolution and a potential avenue for expansion of filovirus host range in nature. DOI: http://dx.doi.org/10.7554/eLife.11785.001


title: Lassa virus glycoprotein: stopping a moving target

text: The structure of a prefusion arenavirus GPC was enigmatic for many years, owing to the metastable and non-covalent nature of the association between the receptor binding and fusion subunits. Recent engineering efforts to stabilize the glycoprotein of the Old World arenavirus Lassa in a native, yet cleaved state, allowed the first structure of any arenavirus prefusion GPC trimer to be determined. Comparison of this structure with the structures of other arenavirus glycoprotein subunits reveals surprising findings: that the receptor binding subunit, GP1, of Lassa virus is conformationally labile, while the GP1 subunit of New World arenaviruses is not, and that the arenavirus GPC adopts a trimeric state unlike other glycoproteins with similar fusion machinery. Structural analysis, combined with recent biochemical data regarding antibody epitopes and receptor binding requirements, provides a basis for rational vaccine design.


title: Diagnosis of Kawasaki disease

text: Kawasaki disease (KD) is a medium vessel vasculitis with predilection for coronary arteries. Due to lack of a reliable confirmatory laboratory test, the diagnosis of KD is based on a constellation of clinical findings that appear in a typical temporal sequence. These diagnostic criteria have been modified from time to time and the most recent guidelines have been proposed by the American Heart Association (AHA) in 2017. However, several children may have incomplete or atypical forms of KD and the diagnosis can often be difficult, especially in infants and young children. In this review, we have detailed the steps involved in arriving at a diagnosis of KD and also highlight the important role of echocardiography in diagnosis and management of children with KD.


title: Arterivirus RNA-dependent RNA polymerase: Vital enzymatic activity remains elusive

text: Abstract All RNA viruses encode an RNA-dependent RNA polymerase (RdRp), which in arteriviruses is expressed as the C-terminal domain of nonstructural protein 9 (nsp9). Previously, potent primer-dependent RdRp activity has been demonstrated for the homologous polymerase subunit (nsp12) of the distantly related coronaviruses. The only previous study focusing on the in vitro activity of nsp9 of an arterivirus (equine arteritis virus; EAV) reported weak de novo polymerase activity on homopolymeric RNA templates. However, this activity was not retained when Mn2+ ions were omitted from the assay or when biologically relevant templates were supplied, which prompted us to revisit the biochemical properties of this polymerase. Based on the properties of active-site mutants, we conclude that the RNA-synthesizing activities observed in de novo and primer-dependent polymerase and terminal transferase assays cannot be attributed to recombinant EAV nsp9-RdRp. Our results illustrate the potential pitfalls of characterizing polymerases using highly sensitive biochemical assays.