title: Evolutionary trends of the COVID-19 epidemic and effectiveness of government interventions in Nigeria: A data-driven analysis.

text: BACKGROUND: Nigeria became the first sub Saharan African country to record a case of COVID-19 after an imported case from Italy was confirmed on February 27, 2020. Moving averages and the Epidemic Evaluation Indices (EEI) are two important but complementary methods useful in monitoring epidemic trends, they can also serve as a useful guide for policy makers and inform the timing of decisions on preventive measures. The objectives of this paper are to graphically depict the trends of new COVID-19 cases nationally and in two key States (Lagos and Kano) and the Federal Capital Territory (FCT) using the moving averages and the EEI. In addition, we examined the effects of government’s public health interventions on the spread of COVID-19 and appraise the progress made so far in addressing the challenges of COVID-19 in Nigeria. METHODS: We used data on new cases of COVID-19 from public sources released by the Nigeria Center for Disease Control (NCDC) from the 27(th) February 2020, when the first case was recorded, to 11(th) May, 2020, one week after the lockdowns in Lagos and the FCT were lifted. We computed moving averages of various orders, the log transformations of the moving averages and then the EEIs of new COVID-19 cases for Nigeria as a whole, and then for two of the most affected states i.e. Lagos and Kano, as well as the Federal Capital Territory (FCT). Then, we plotted graphs to depict these indices and show the epidemic trends for COVID-19 in each scenario. RESULTS: Nationally, the number of new cases of COVID-19 showed an initial gradual rise from the first reported case on the 27(th) February 2020. However, by the second week in April, these numbers began to show a relatively sharper increase and this trend has continued till date. Similar trends were observed in Lagos state and the FCT. The rate of growth of the logarithm-transformed moving average in the period leading to, and including the lockdowns reduced by a factor of 0.65. This suggests that the policies put in place by the government including the lockdown measures in Lagos and the FCT may have had a positive effect on the development of new cases of COVID-19 in Nigeria. Nationally and in Lagos, the EEIs of the COVID-19 cases started off on very high notes, however, the effects of the lockdown gradually became evident by the end of April and early May 2020, as the EEIs headed closer to 1.0. In all case scenarios, the EEIs are still above 1.0. CONCLUSIONS AND RECOMMENDATIONS: The number of new cases of COVID-19 has been on a steady rise since the first reported case. In Nigeria especially across the two states and the FCT, public health interventions including the lockdown measures appear to have played a role in reducing the rate of increase of new infections. The EEIs are still above 1.0, suggesting that despite the progress that appears to have been made, the epidemic is still evolving and Nigeria has not yet reached her peak for COVID-19 cases. We recommend that aggressive public health interventions and restrictions against mass gatherings should be sustained.


title: Can activation of NRF2 be a strategy against COVID-19?

text: Acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 is largely the result of a dysregulated host response, followed by damage to alveolar cells and lung fibrosis. Exacerbated pro-inflammatory cytokines release (cytokine storm) and loss of T-lymphocytes (leucopenia) characterize the most aggressive presentation. Here we propose that a multi-faceted anti-inflammatory strategy based on pharmacological activation of nuclear factor erythroid 2 p45-related factor 2 (NRF2), can be deployed against the virus. The strategy provides robust cytoprotection by restoring the redox and protein homeostasis, promoting resolution of inflammation, and facilitating repair. NRF2 activators such as sulforaphane and bardoxolone methyl are already in clinical trials. The safety and efficacy information of these modulators in humans, together with their well-documented cytoprotective and anti-inflammatory effects in preclinical models, highlight the potential of this armamentarium for deployment to the battlefield against COVID-19.


COVID-19 Outbreak in International Airport – Where the Incidence Case Occurs?


title: Current concepts in the prevention of pathogen transmission via blood/plasma-derived products for bleeding disorders()

text: The pathogen safety of blood/plasma-derived products has historically been a subject of significant concern to the medical community. Measures such as donor selection and blood screening have contributed to increase the safety of these products, but pathogen transmission does still occur. Reasons for this include lack of sensitivity/specificity of current screening methods, lack of reliable screening tests for some pathogens (e.g. prions) and the fact that many potentially harmful infectious agents are not routinely screened for. Methods for the purification/inactivation of blood/plasma-derived products have been developed in order to further reduce the residual risk, but low concentrations of pathogens do not necessarily imply a low level of risk for the patient and so the overall challenge of minimising risk remains. This review aims to discuss the variable level of pathogenic risk and describes the current screening methods used to prevent/detect the presence of pathogens in blood/plasma-derived products.


Covid-19 and thrombosis: beyond a casual association


title: Influenza D Virus of New Phylogenetic Lineage, Japan

text: Influenza D virus (IDV) can potentially cause respiratory diseases in livestock. We isolated a new IDV strain from diseased cattle in Japan; this strain is phylogenetically and antigenically distinguished from the previously described IDVs.


title: Appraisal of recommended respiratory infection control practices in primary care and emergency department settings

text: BACKGROUND: The severe acute respiratory syndrome (SARS) epidemic and concern about pandemic influenza prompted the Centers for Disease Control and Prevention (CDC) to develop guidelines to prevent the transmission of all respiratory infections in health care settings during first contact with a potentially infected person. The extent to which health care workers and institutions use these CDC recommended practices is uncertain. METHODS: The study examined health care worker adherence to CDC recommended respiratory infection control practices in primary care clinics and emergency departments of 5 medical centers in King County, Washington, using a self-administered questionnaire. All clinical, allied, and administrative health care workers in study settings were invited to participate: 653 (53%) responded, and 630 were included. RESULTS: The survey revealed important shortcomings in overall personal and institutional use of CDC recommended practices, including deficiencies in posted alerts, patient masking and separation, hand hygiene, personal protective equipment, staff training, and written procedures. Use of recommended measures was generally higher among nursing staff than medical practitioners. CONCLUSION: This study found significant gaps in adherence to CDC recommendations for the control of respiratory infections in ambulatory care clinical settings. Practical strategies are needed to identify and reduce barriers to implementation of recommended practices for control of respiratory infections.


title: Chronic treatment with hydroxychloroquine and SARS‐CoV‐2 infection

text: BACKGROUND: Hydroxychloroquine sulphate (HCQ) is being scrutinized for repositioning in the treatment and prevention of SARS‐Cov‐2 infection. This antimalarial drug is also chronically used to treat patients with autoimmune diseases. METHODS: By analysing the Portuguese anonymized data on private and public based medical prescriptions we have identified all cases chronically receiving HCQ for the management of diseases such as systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases. Additionally, we have detected all laboratory confirmed cases of SARS‐CoV‐2 infection and all laboratory confirmed negative cases in the Portuguese population (mandatorily registered in a centrally managed database). Cross linking the two sets of data has allowed us to compare the proportion of HCQ chronic treatment (at least 2 grams per month) in laboratory confirmed cases of SARS‐CoV‐2 infection with laboratory confirmed negative cases. RESULTS: Out of 26,815 SARS‐CoV‐2 positive patients, 77 (0.29%) were chronically treated with HCQ, while 1,215 (0.36%) out of 333,489 negative patients were receiving it chronically (P=0.04). After adjustment for age, sex, and chronic treatment with corticosteroids and/or immunosuppressants, the odds ratio of SARS‐CoV‐2 infection for chronic treatment with HCQ has been 0.51 (0.37‐0.70). CONCLUSIONS: Our data suggest that chronic treatment with HCQ confer protection against SARS‐CoV‐2 infection. This article is protected by copyright. All rights reserved.


title: Vacuolating encephalitis in mice infected by human coronavirus OC43

text: Abstract Involvement of viruses in human neurodegenerative diseases and the underlying pathologic mechanisms remain generally unclear. Human respiratory coronaviruses (HCoV) can infect neural cells, persist in human brain, and activate myelin-reactive T cells. As a means of understanding the human infection, we characterized in vivo the neurotropic and neuroinvasive properties of HCoV-OC43 through the development of an experimental animal model. Virus inoculation of 21-day postnatal C57BL/6 and BALB/c mice led to a generalized infection of the whole CNS, demonstrating HCoV-OC43 neuroinvasiveness and neurovirulence. This acute infection targeted neurons, which underwent vacuolation and degeneration while infected regions presented strong microglial reactivity and inflammatory reactions. Damage to the CNS was not immunologically mediated and microglial reactivity was instead a consequence of direct virus-mediated neuronal injury. Although this acute encephalitis appears generally similar to that induced by murine coronaviruses, an important difference rests in the prominent spongiform-like degeneration that could trigger neuropathology in surviving animals.


docid: nnebnagr

title: Cullin E3 Ligases and Their Rewiring by Viral Factors

text: The ability of viruses to subvert host pathways is central in disease pathogenesis. Over the past decade, a critical role for the Ubiquitin Proteasome System (UPS) in counteracting host immune factors during viral infection has emerged. This counteraction is commonly achieved by the expression of viral proteins capable of sequestering host ubiquitin E3 ligases and their regulators. In particular, many viruses hijack members of the Cullin-RING E3 Ligase (CRL) family. Viruses interact in many ways with CRLs in order to impact their ligase activity; one key recurring interaction involves re-directing CRL complexes to degrade host targets that are otherwise not degraded within host cells. Removal of host immune factors by this mechanism creates a more amenable cellular environment for viral propagation. To date, a small number of target host factors have been identified, many of which are degraded via a CRL-proteasome pathway. Substantial effort within the field is ongoing to uncover the identities of further host proteins targeted in this fashion and the underlying mechanisms driving their turnover by the UPS. Elucidation of these targets and mechanisms will provide appealing anti-viral therapeutic opportunities. This review is focused on the many methods used by viruses to perturb host CRLs, focusing on substrate sequestration and viral regulation of E3 activity.


title: Gauge field, strings, solitons, anomalies and the speed of life

text: It's been said that"mathematics is biology's next microscope, only better; biology is mathematics' next physics, only better". Here we aim for something even better. We try to combine mathematical physics and biology into a picoscope of life. For this we merge techniques which have been introduced and developed in modern mathematical physics, largely by Ludvig Faddeev to describe objects such as solitons and Higgs and to explain phenomena such as anomalies in gauge fields. We propose a synthesis that can help to resolve the protein folding problem, one of the most important conundrums in all of science. We apply the concept of gauge invariance to scrutinize the extrinsic geometry of strings in three dimensional space. We evoke general principles of symmetry in combination with Wilsonian universality and derive an essentially unique Landau-Ginzburg energy that describes the dynamics of a generic string-like configuration in the far infrared. We observe that the energy supports topological solitons, that pertain to an anomaly in the manner how a string is framed around its inflection points. We explain how the solitons operate as modular building blocks from which folded proteins are composed. We describe crystallographic protein structures by multi-solitons with experimental precision, and investigate the non-equilibrium dynamics of proteins under varying temperature. We simulate the folding process of a protein at in vivo speed and with close to pico-scale accuracy using a standard laptop computer: With pico-biology as mathematical physics' next pursuit, things can only get better.


title: Combating COVID-19 with Mesenchymal Stem Cell therapy

text: The COVID-19 disease is caused by a positive stranded RNA virus called SARS-CoV-2. The virus mainly targets the pulmonary epithelial cells as it’s initial site of infection by letting its surface spike protein interact and bind to the host ACE2 receptor. The internalization and gradual replication of the virus results in an exaggerated immune response triggering release of many pro-inflammatory cytokines and chemokines. This immune storm is responsible for multiple health hazards in the host ultimately leading to multiple organ failure. Mesenchymal stem cell therapy offers a promising approach towards mitigating the delirious effects of the infection in the COVID-19 patients. This therapy has shown to reduce the expression of pro-inflammatory cytokines as well as repair of damaged tissues in COVID-19 patients. This review has been organized to put forward the positive aruments and implications in support of mesenchymal stem cell therapy as a necessary approach for treating COVID-19 patients.


title: IFITM3 directly engages and shuttles incoming virus particles to lysosomes

text: Interferon-induced transmembrane proteins (IFITMs) (1, 2 and 3) have emerged as important innate immune effectors that prevent diverse virus infections in vertebrates. However, the cellular mechanisms and live cell imaging of these small membrane proteins have been challenging to evaluate during viral entry of mammalian cells. Using CRISPR-Cas9-mediated IFITM-mutant cell lines, we demonstrate that human IFITM1, 2 and 3 act cooperatively and function in dose-dependent fashion in interferon-stimulated cells. Through site-specific fluorophore tagging and live cell imaging studies, we show IFITM3 is on endocytic vesicles that fuse with incoming virus particles and enhances the trafficking of this pathogenic cargo to lysosomes. IFITM3 trafficking is specific to restricted viruses, requires S-palmitoylation and is abrogated with loss-of-function mutants. The site-specific protein labeling and live cell imaging approaches described here should facilitate the functional analysis of host factors involved in pathogen restriction as well as their mechanisms of regulation.


title: Survival of mechanically ventilated patients admitted to intensive care units: Results from a tertiary care center between 2016-2018

text: OBJECTIVES: To estimate the survival of adult and pediatric patients receiving mechanical ventilation and determine the associated risk factors METHODS: A retrospective cohort study was carried out in the intensive care unit (ICU) at King Abdulaziz Medical City (KAMC) and King Abdullah Children’s Specialist Hospital (KACSH), Riyadh, Saudi Arabia. The analysis includes data from medical records of all patients admitted to ICUs who received mechanical ventilation between 2016-2018. For each patient, potential risk factors were collected. The main outcome of this study was the mortality during the stay in ICU after receiving mechanical ventilation RESULTS: A total of 262 adults and 175 pediatric patients were admitted to ICUs and received mechanical ventilation during the study period. For adult patients, the overall mortality was 37%, with a median survival time of 11 days (interquartile range [IQR] 6-20 days). The main risk factors independently associated with the increased mortality rate were being aged 51-60 (odds ratio [OR] 2.6, 95% confidence interval [CI] 6.7-1.0) and factors related to ICU admission. For the pediatric population, the mortality rate was 17%, with a median survival time of 16 days (IQR 7-37 days). Prematurity with respiratory problems was the main recorded cause of initiation of mechanical ventilation (50% of patients). Neonates who had mechanical ventilation within one month of their birth and were born extremely preterm had a high mortality rate after the initiation of mechanical ventilation. CONCLUSION: Both patient age and the causes of the initiation of mechanical ventilation were influencing the survival of patients who required mechanical ventilation.


title: Covid‐19 in solid organ transplant recipients: A single center experience

text: BACKGROUND: Solid organ transplant (SOT) recipients may be at risk for severe COVID‐19. Data on the clinical course of COVID‐19 in immunosuppressed patients are limited and the effective treatment strategy for these patients is unknown. METHODS: We describe our institutional experience with COVID‐19 in SOT. Demographic, clinical and treatment data were extracted from the electronic patient files. RESULTS: A total of 23 SOT transplant recipients suffering from COVID‐19 were identified (n = 3 heart; n =15 kidney; n = 1 kidney‐after‐heart; n = 3 lung and n = 1 liver transplant recipient). The presenting symptoms were similar to non‐immunocompromised patients Eighty‐three percent (19/23) of the patients required hospitalization but only two of these were transferred to the intensive care unit. Five patients died from COVID‐19; all had high Clinical Frailty scores. In four of these patients, mechanical ventilation was deemed futile. In 57% of patients, the immunosuppressive therapy was not changed and only 3 patients were treated with chloroquine. Most patients recovered without experimental anti‐viral therapy. CONCLUSIONS: Modification of the immunosuppressive regimen alone could be a therapeutic option for SOT recipients suffering from moderate to severe COVID‐19. Pre‐existent frailty is associated with death from COVID‐19.


title: The Future of Emergency Medicine Public Health Research

text: This chapter addresses past successes and challenges and then elaborates on the potential for further advances in three areas that bridge emergency medicine and the broader public health and health services research agenda: (1) monitoring health care access; (2) surveillance of diseases, injuries, and health risks; and (3) delivering clinical preventive services. This article also suggests ways to advance policy-relevant research on systems of health and social welfare that impact the health of the public.


title: Nurses' participation in the Holocaust: A call to nursing educators

text: This year marks the 75th anniversary of the liberation of Auschwitz. The number of people able to provide first-person accounts of the atrocities of the Holocaust is dwindling in numbers. Prior to the mass extermination of Jews at Auschwitz and other extermination camps, nurses actively participated in the execution of tens of thousands of mentally, physically, and emotionally ill German citizens. Nursing educators must ensure that nursing students not only know about the Holocaust, but that they know that ordinary nurses were directly involved in the identification of vulnerable humans to be killed, and actually murdered them. Social, economic, and political pressures existed enabling the Nazi regime to involve nurses in this way. Similarly, social, economic, and political pressures today have the potential to encourage nurses to act in ways that violate personal or professional values. This paper provides four learning objectives that can be incorporated into existing nursing curricula to ensure that nurses do not forget how and why nurses in Germany came to murder more than 10,000 people in their care. With the passage of time comes the risk that the legacy of the Holocaust will be forgotten, nursing educators must participate in preventing that from happening.


title: Progress towards Health for All: Time to End Discrimination and Marginalization

text: Although it has been more than 40 years since "health for all" was presented as a focus in the Alma Ata declaration [...].


title: Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is continuously spreading and causing severe and fatal acute respiratory disease in humans. Prophylactic and therapeutic strategies are therefore urgently needed to control MERS-CoV infection. Here, we generated a humanized monoclonal antibody (mAb), designated hMS-1, which targeted the MERS-CoV receptor-binding domain (RBD) with high affinity. hMS-1 significantly blocked MERS-CoV RBD binding to its viral receptor, human dipeptidyl peptidase 4 (hDPP4), potently neutralized infection by a prototype MERS-CoV, and effectively cross-neutralized evolved MERS-CoV isolates through recognizing highly conserved RBD epitopes. Notably, single-dose treatment with hMS-1 completely protected hDPP4 transgenic (hDPP4-Tg) mice from lethal infection with MERS-CoV. Taken together, our data suggest that hMS-1 might be developed as an effective immunotherapeutic agent to treat patients infected with MERS-CoV, particularly in emergent cases.


title: Lesser Mealworm (Coleoptera: Tenebrionidae) Emergence After Mechanical Incorporation of Poultry Litter into Field Soils

text: Lesser mealworm, Alphitobius diaperinus (Panzer), emergence from North Carolina field soils was evaluated in a controlled experiment simulating land application of turkey litter and again in field studies. Adult lesser mealworms were buried in central North Carolina Cecil red clay at depths of 0, 8, 15, 23, and 30 cm and the beetles emerging from the soil counted 1, 3, 7, 10, 13, 17, 21, 24, and 28 d after burial. Beetles emerged from all depths and differences among depths were not significant. Beetles survived at least 28 d buried in the soil at depths ≤30 cm. In seasonal field studies, lesser mealworm emergence from clay soil with poultry litter incorporated by disk, mulch and plow was compared with emergence from plots with no incorporation. Incorporation significantly reduced beetle emergence when poultry litter containing large numbers of beetles was applied to clay field soils during the summer (F = 3.45; df = 3, 143; P = 0.018). Although mechanical incorporation of poultry litter reduced beetle emergence relative to the control, greatest reductions were seen in plowed treatments. Beetle activity was reduced after land application of litter during colder months. Generally, lesser mealworm emergence decreased with time and few beetles emerged from the soil 28 d after litter was applied. Similarly, mechanical incorporation of poultry litter into sandy soils reduced beetle emergence (F = 4.06; df = 3, 143; P < 0.008). In sandy soils typical of eastern North Carolina, disk and plow treatments significantly reduced beetle emergence compared with control.


title: Immunotherapy of SARS based on combinations of neutralizing human monoclonal antibodies

text: Evaluation of: Coughlin MM, Babcook J, Prabhakar BS: Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms. Virology 394(1), 39–46 (2009). This work discusses passive immunotherapy based on neutralizing human monoclonal antibodies (mAbs) with different mechanisms of action. The authors have demonstrated that combining such mAbs, which target distinct epitopes, may greatly increase inhibition of virus infection and suppress the generation of neutralization escape mutants. The inhibition of human mAbs to SARS-coronavirus (CoV) may also act through different mechanisms of action, depending on their target epitopes or regions. Therefore, this approach could provide fast and effective prophylaxis and treatment of SARS-CoV infection during a SARS outbreak. Specifically, Coughlin et al. have indicated that most of the tested anti-S1 mAbs recognized epitopes within the receptor-binding domain and blocked virus attachment to its cellular receptor. These findings could provide a further step in understanding the mechanism of these mAbs in the prevention of SARS-CoV infection, as well as an insight into the design and development of novel therapeutic treatments.


Collaborative Delirium Prevention in the Age of COVID‐19


title: Feasibility of a 5G-based robot-assisted remote ultrasound system for cardiopulmonary assessment of COVID-19 patients

text: Abstract Background Traditional methods for cardiopulmonary assessment of Coronavirus Disease 2019 (COVID-19) patients pose risks to, both, patients and examiners. This necessitates a remote examination of such patients without sacrificing information quality. Research Question Assess the feasibility of a 5G-based robot-assisted remote ultrasound system in examining COVID-19 patients and establish an examination protocol for telerobotic ultrasound scanning. Study Design and Methods Twenty-three COVID-19 patients were included and divided into two groups. Twelve were non-severe cases, and 11 were severe cases. All patients underwent a 5G-based robot-assisted remote ultrasound system examination of the lungs and heart following an established protocol. Distribution characteristics and morphology of the lung and surrounding tissue lesions, left ventricular ejection fraction (LVEF), ventricular area ratio, pericardial effusion, and examination-related complications were recorded. Bilateral lung lesions were evaluated by lung ultrasound score (LUS). Results The remote ultrasound system successfully and safely performed cardiopulmonary examinations of all patients. Peripheral lung lesions were clearly evaluated. Severe cases had significantly more diseased regions [median (interquartile range), 6.0 (2.0-11.0) vs. 1.0 (0.0-2.8)] and higher LUSs [12.0 (4.0-24.0) vs. 2.0 (0.0-4.0)] than non-severe cases (both, P < 0.05 ). One non-severe case (8.3%, 95%CI, 1.5% to 35.4%) and three severe cases (27.3%, 95%CI, 9.7% to 56.6%) were complicated by pleural effusions. Four severe cases (36.4%, 95%CI, 15.2% to 64.6%) were complicated by pericardial effusions (vs 0% of non-severe cases, P < 0.05). No patients had significant examination-related complications. Interpretation 5G-based robot-assisted remote ultrasound system is feasible, and effectively obtains ultrasound characteristics for cardiopulmonary assessment of COVID-19 patients. By following established protocols and considering medical history, clinical manifestations, and laboratory markers, it might help to evaluate the severity of COVID-19 remotely.


title: Development of Autonomous Advanced Disinfection Tunnel to Tackle External Surface Disinfection of COVID-19 Virus in Public Places

text: This paper describes a robust autonomous disinfection tunnel to disinfect external surfaces of COVID-19 virus such as clothes and open body sections in public places such as airports, office complexes, schools, and malls. To make the tunnel effective and highly efficient, it has been provided with two chambers with three disinfection processes. Due to the multiple processes, the possibility of neutralizing the virus is quite high and higher than other solutions available at this point for this purpose. Chamber 1 sprays the solution of a disinfectant on the person. This solution can be either a dilute solution of approved chemical or any Ayurvedic/herbal disinfectant. Once the person enters chamber 2, he/she is exposed to hot air at 70 °C along with far-ultraviolet C rays (207–222 nm). Both chambers function autonomously by detecting a person in a chamber using ultrasonic sensors. The proposed tunnel is developed under industry–academia collaboration jointly by Technopark@iitk and ALIMCO under the ambit of the Ministry of Human Resources Development and the Ministry of Social Justice and Empowerment, respectively. The tunnel is referred to as the ‘Techno Advanced Disinfection Tunnel’ (TADT).


title: Evaluation of clinical applicability of reverse transcription-loop-mediated isothermal amplification assay for detection and subtyping of Influenza A viruses

text: Abstract Background Influenza A viruses (IAVs) have always remain a serious concern for the global economy and public health. A rapid, specific and sensitive detection method is always needed to control the influenza in its early stages by timely intervention of therapy and early clinical management. Objectives To develop RT-LAMP assays for detection of influenza A viruses, their further subtyping into seasonal (H1N1, H3N2) and novel pandemic H1N1 viruses and to evaluate clinical applicability of optimized RT-LAMP assays on patients’ samples. Study design In this study, we optimized RT-LAMP assay to detect IAVs by using primers against matrix gene and subtyping of IAVs was done by using primers against hemagglutinin gene. Optimized RT-LAMP assays were applied on clinical samples from patients having influenza like illness and results were compared with conventional one-step RT-PCR and real-time RT-PCR. Results RT-LAMP assays successfully detected and differentiated IAVs into H1N1, H3N2 and pdm09/H1N1 subtypes. One hundred and sixty seven clinical swab samples from influenza suspected patients were taken and tested with RT-LAMP assay, detecting 30 (17.9%) samples positive for Influenza A virus. Out of 30 samples, 21, 7 and 2 were found positive for pdm09/H1N1, H3N2 and seasonal H1 respectively. Conventional one-step RT-PCR detected a total of 27 (16.2%) samples for influenza A and further subtyping showed 20 and 7 samples positive for pdm09/H1N1 and H3N2 virus respectively whereas none was found positive for seasonal H1N1. RT-LAMP assay demonstrated higher sensitivity (93.8%) than conventional RT-PCR (84.4%) for influenza A viruses detection in clinical samples. Conclusions RT-LAMP assay is rapid, sensitive, specific and cost effective method for detection of influenza A viruses than conventional one-step RT-PCR and it can serve as a good alternate for diagnosis and surveillance studies during influenza outbreaks in resource-limited setups of developing countries.


Ventilatory support recommendations in children with Sars-CoV-2


title: Metagenomic analysis of viromes of dromedary camel fecal samples reveals large number and high diversity of circoviruses and picobirnaviruses

text: Abstract The recent discovery of Middle East Respiratory Coronavirus and another novel dromedary camel coronavirus UAE-HKU23 in dromedaries has boosted interest in search of novel viruses in dromedaries. In this study, fecal samples of 203 dromedaries in Dubai were pooled and deep sequenced. Among the 7330 assembled viral contigs, 1970 were assigned to mammalian viruses. The largest groups of these contigs matched to Picobirnaviridae, Circoviridae, Picornaviridae, Parvoviridae, Astroviridae and Hepeviridae. Many of these viral families were previously unknown to dromedaries. In addition to the high abundance of contigs from Circoviridae (n=598 with 14 complete genomes) and Picobirnaviridae (n=1236), a high diversity of contigs from these two families was found, with the 14 Circoviridae complete genomes forming at least five clusters and contigs from both genogroup I and genogroup II potentially novel picobirnaviruses. Further studies comparing the incidence of these viral families in healthy and sick dromedaries will reveal their pathogenic potential.


Sedation for critically ill patients with COVID-19: which specificities? One size does not fit all


title: Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19

text: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with Corona Virus Disease 2019 (COVID-19), we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. Food and Drug Administration (FDA) approved drug library, we identified an anticoagulation agent dipyridamole (DIP) in silico, which suppressed SARS-CoV-2 replication in vitro. In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers (P<0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.


Risk of transmission of severe acute respiratory syndrome to household contacts by infected health care workers and patients


A Case of COVID-19 Presenting after Coronary Artery Bypass Grafting


title: Viral and Developmental Cell Fusion Mechanisms: Conservation and Divergence

text: Membrane fusion is a fundamental requirement in numerous developmental, physiological, and pathological processes in eukaryotes. So far, only a limited number of viral and cellular fusogens, proteins that fuse membranes, have been isolated and characterized. Despite the diversity in structures and functions of known fusogens, some common principles of action apply to all fusion reactions. These can serve as guidelines in the search for new fusogens, and may allow the formulation of a cross-species, unified theory to explain divergent and convergent evolutionary principles of membrane fusion.


The Importance of Video Visits in the Time of COVID‐19


title: To recover faster from Covid-19, open up: Managerial implications from an open innovation perspective

text: Abstract Covid-19 has severely tested our public health systems. Recovering from Covid-19 will soon test our economic systems. Innovation will have an important role to play in recovering from the aftermath of the coronavirus. This article discusses both how to manage innovation as part of that recovery, and also derives some lessons from how we have responded to the virus so far, and what those lessons imply for managing innovation during the recovery.


title: New advances in CNS immunity against viral infection

text: The central nervous system (CNS) is an immunologically specialized organ where restrictive barrier structures protect the parenchyma from inflammation and infection. This protection is important in preventing damage to non-renewable resident cell populations, such as neurons, responsible for functions ranging from executive to autonomic. Despite these barriers, the CNS can be infected through several entry portals, giving rise to meningitis and encephalitis. Following infection, resident cells recruit peripherally derived immune cells to sites of viral infection. In this review, we discuss recent advances in immune recruitment and entry at barrier structures as well as current immunotherapeutic strategies for the treatment of persistent viral infections.


docid: bcegtaep

title: Detection and characterization of bovine torovirus from the respiratory tract in Japanese cattle

text: Abstract Bovine torovirus (BToV), a member of the Coronaviridae family, is a causative agent of diarrhea in cattle, but it may also possess tropism for the respiratory tract. However, no surveys concerning with the relation between respiratory symptoms and the detection of BToV have been conducted in wide range. Among 311 nasal samples, BToV gene products were detected in seven samples (rBToV-1 to -7) derived only from calves with respiratory symptoms, suggesting that BToV may be a predisposing factor and/or causative agent for bovine respiratory disease. Regarding the degree of similarity between the spike and hemagglutinin-esterase coding regions, the rBToVs showed over 90.8% similarity with one another and 73.5–99.0% similarity with fecal tract-derived BToVs. rBToV-1, -2, and -3 were identical despite their being collected during different seasons; in comparison, rBToV-4 and -5 were distinct despite the fact that they were collected from the same herd, suggesting the existence of diversity among domestic rBToVs. One animal with a BToV-positive nasal sample also shed the virus in its feces, suggesting dual tropisms for BToV.


docid: lwcesfgx

title: Knowledge, attitudes, beliefs, and practices pertaining to camel-to-human disease risks among persons at camel farms, abattoirs, and meat markets in Jordan


Continues Renal Replacement Therapy (CRRT) With Disposable Hemoperfusion Cartridge: A Promising Option for Severe COVID-19


title: Prostate Cancer Radiotherapy Recommendations in Response to COVID-19

text: Abstract Purpose During a global pandemic the benefit of routine visits and treatment of cancer patients must be weighed against the risks to patients, staff, and society. Prostate cancer is one of the most common cancers Radiation Oncology departments treat, and efficient resource utilization is essential in the setting of a pandemic. Herein, we aim to establish recommendations and a framework by which to evaluate prostate radiotherapy management decisions. Patients and Methods Radiation Oncologists from the United States and United Kingdom rapidly conducted a systematic review and agreed upon recommendations to safely manage prostate cancer patients during the COVID-19 pandemic. A RADS framework was created: Remote visits, and Avoidance, Deferment, and Shortening of radiotherapy was applied to determine appropriate approaches. Results Recommendations are provided by National Comprehensive Cancer Network (NCCN) risk group, including clinical node positive, post-prostatectomy, oligometastatic, and low volume M1 disease. Across all prostate cancer stages, telemedicine consultations and return visits were recommended when resources/staff available. Delays in consultations and return visits was deemed safe based on stage of disease between 1-6 months. Treatment can be avoided or delayed until safe for very low, low, and favorable intermediate-risk disease. Unfavorable intermediate-risk, high-risk, clinical node positive, recurrence post-surgery, oligometastatic, and low-volume M1 disease can receive neoadjuvant hormone therapy for 4-6 months as necessary. Ultrahypofractionation was preferred for localized, oligometastatic, and low volume M1, and moderate hypofractionation was preferred for post-prostatectomy and clinical node positive disease. Salvage was preferred to adjuvant radiation. Conclusion Resources can be reduced for all identified stages of prostate cancer. The RADS (Remote visits, and Avoidance, Deferment, and Shortening of radiotherapy) framework can be applied to other disease sites to help with decision making in a global pandemic.


The importance of vaginal natural orifice surgeries in the era of COVID-19 pandemic


title: A mRNA PCR for the diagnosis of feline infectious peritonitis

text: Abstract A reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of feline coronavirus (FCoV) messenger RNA in peripheral blood mononuclear cells (PBMCs) is described. The assay is evaluated as a diagnostic test for feline infectious peritonitis (FIP). It is based on a well-documented key event in the development of FIP: the replication of virulent FCoV mutants in monocytes/macrophages. To detect most feline coronavirus field strains, the test was designed to amplify subgenomic mRNA of the highly conserved M gene. The test was applied to 1075 feline blood samples (424 from healthy, 651 from sick cats suspected of FIP) and returned 46% of the diseased cats as positive for feline coronavirus mRNA in their peripheral blood cells; of the healthy cats, 5% tested positive. Of a group of 81 animals in which FIP had been confirmed by post-mortem examination, 75 (93%) tested positive, whereas 17 cats with different pathologies (non-FIP cases) all tested negative. In view of the low rate of false-positive results (high specificity) the mRNA RT-PCR may be a valuable addition to the diagnostic arsenal for FIP.


title: Microplastics in waters and soils: Occurrence, analytical methods and ecotoxicological effects

text: Microplastics (MPs) are ubiquitous in the environment and more abundant in the marine environment. Consequently, increasing focus has been put on MPs in oceans and seas, while little importance has been attached to their presence in freshwaters and soils. Therefore, this paper aimed to provide a comprehensive review of the occurrence, analysis and ecotoxicology of MPs. The abundance and distribution of MPs in several typical freshwater systems of China were summarized. It suggested that the surface water of Poyang Lake contained the highest concentration of 34 items/L MPs among all the 8 freshwater systems, and the content of MPs in sediments were higher than that of the surface water. Net-based zooplankton sampling methods are the most frequently utilized sampling methods for MPs, and density separation, elutriation and digestion are three major pretreatment methods. Fourier transform infrared spectroscopy, Raman spectroscopy and pyrolysis-gas chromatography coupled to mass spectrometry are often used to identify the polymer types of MPs. Besides, MPs might damage the digestive tract of various organisms and negatively inhibit their growth, feeding and reproduction. The ways of human exposure to MPs are by ingestion, inhalation and dermal exposure, digestive and respiratory system might be adversely influenced. However, potential health risks of MPs to humans are remained insufficiently researched. Overall, by showing the presence of MPs in freshwaters and soils as well as possible ecotoxicological effects on the environment and humans, this paper provided a framework for future research in this field.


Optometry in times of pandemic: Spanish flu (1919) versus COVID‐19 (2020)


title: Anti-influenza A virus effects of fructan from Welsh onion (Allium fistulosum L.)

text: Abstract A fructan that acts as an anti-influenza A virus substance was isolated from hot water extract of the green leafy part of a Welsh onion (Allium fistulosum L.). The structure of the fructan was characterised and elucidated by chemical and spectroscopic analyses. The fructan was composed of terminal (21.0%) and 2,1-linked β-d-Fruf residues (65.3%) with 1,6-linked β-d-Glcp residues (13.7%). The molecular weight of the polysaccharide and polydispersity was estimated to be 1.5×103 and 1.18, respectively. Although the fructan did not show anti-influenza A virus activity in vitro, it demonstrated an inhibitory effect on virus replication in vivo when it was orally administered to mice. In addition, the polysaccharide enhanced the production of neutralising antibodies against influenza A virus. Therefore, the antiviral mechanism of the polysaccharide seemed to be dependent on the host immune system, i.e., enhancement of the host immune function was achieved by the administration of the polysaccharide. From our observations, the fructan from Welsh onions is suggested to be one of the active principles which exert an anti-influenza virus effect.


title: Host Shutoff in Influenza A Virus: Many Means to an End

text: Influenza A virus carries few of its own proteins, but uses them effectively to take control of the infected cells and avoid immune responses. Over the years, host shutoff, the widespread down-regulation of host gene expression, has emerged as a key process that contributes to cellular takeover in infected cells. Interestingly, multiple mechanisms of host shutoff have been described in influenza A virus, involving changes in translation, RNA synthesis and stability. Several viral proteins, notably the non-structural protein NS1, the RNA-dependent RNA polymerase and the endoribonuclease PA-X have been implicated in host shutoff. This multitude of host shutoff mechanisms indicates that host shutoff is an important component of the influenza A virus replication cycle. Here we review the various mechanisms of host shutoff in influenza A virus and the evidence that they contribute to immune evasion and/or viral replication. We also discuss what the purpose of having multiple mechanisms may be.


Early preemptive immunomodulators (corticosteroids) for severe pneumonia patients infected with SARS-CoV-2


title: The behaviour of recent isolates of human respiratory coronavirus in vitro and in volunteers: Evidence of heterogeneity among 229E‐related strains

text: Strains of human coronavirus (HCV) isolated between 1974 and 1976 have been studied in vitro and in volunteers. All strains caused colds in volunteers, and those cultivable in tissue culture (TC) produced significantly more coryza and less sore throat than strains growing only in organ culture (OC). The TC strains were serologically related to 229E, but these isolates produced colds with a frequency and severity that contrasted with the effects of 229E itself. Tests on volunteers' preinfection sera showed that the prevalence of antibody to 229E had increased during the period 1961–1979 and that during 1977–1979 only 11% of subjects had no neutralising antibody against 229E. Susceptibility to the 229E‐related isolates PR and TO was associated with low preinfection serum neutralising antibody against the homologous virus, and paired sera frequently showed fourfold or greater antibody rises, most commonly against the homologous strain. Volunteers infected with TO were immune when reinoculated with the same strain approximately 1 year later, but other similar volunteers were at least partly susceptible to infection with a heterologous 229E‐related virus after similar time intervals. Although the strains of HCV that were grown in tissue culture were all related to the prototype 229E, they appeared not to be identical with it, and this heterogeneity is probably a significant factor in the epidemiology of HCV infections.


COVID–19, Journal de bord–18/02/2020–Questions à François Bricaire


title: Determination and analysis of complete coding sequence regions of new discovered human bocavirus types 2 and 3

text: In this study, two human bocaviruses (HBoV), HBoV2 and HBoV3, that were detected previously in enteric samples were characterized genetically. Nearly complete genome sequences of three HBoV2 variants and one HBoV3 variant originating from Thailand and the UK were compared to published HBoV sequences. HBoV2 showed divergence from HBoV1 throughout the genome, while the HBoV3 sequence grouped phylogenetically with HBoV1 in the non-structural region and with HBoV2 sequences in the structural gene, consistent with its proposed recombinant origin. Compared to HBoV1 and HBoV3, HBoV2 shows substantially greater intra-species diversity, consistent with a longer period of human circulation.


Kawasaki disease coincident with influenza A H1N1/09 infection


docid: jbjfqiqw

title: Comparison of respiratory virus shedding by conventional and molecular testing methods in patients with haematological malignancy

text: Respiratory viruses (RV) are a leading cause of infection-related morbidity and mortality for patients undergoing treatment for cancer. This analysis compared duration of RV shedding as detected by culture and PCR among patients in a high-risk oncology setting (adult patients with haematological malignancy and/or stem cell transplant and all paediatric oncology patients) and determined risk factors for extended shedding. RV infections due to influenza virus, parainfluenza virus (PIV), human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) from two study periods—January 2009–September 2011 (culture-based testing) and September 2011–April 2013 (PCR-based testing)—were reviewed retrospectively. Data were collected from patients in whom re-testing for viral clearance was carried out within 5–30 days after the most recent test. During the study period 456 patients were diagnosed with RV infection, 265 by PCR and 191 by culture. The median range for duration of shedding (days) by culture and PCR, respectively, were as follows—influenza virus: 13 days (5–38 days) versus 14 days (5–58 days), p 0.5; RSV: 11 days (5–35 days) versus 16 days (5–50 days), p 0.001; PIV: 9 days (5–41 days) versus 17 days (5–45 days), p ≤0.0001; HMPV 10.5 days (5–29 days) versus 14 days (5–42 days), p 0.2. In multivariable analysis, age and underlying disease or transplant were not independently associated with extended shedding regardless of testing method. In high-risk oncology settings for respiratory illness due to RSV and PIV, the virus is detectable by PCR for a longer period of time than by culture and extended shedding is observed.


docid: vgfdfuza

title: Combating Antimicrobial Resistance in Singapore: A Qualitative Study Exploring the Policy Context, Challenges, Facilitators, and Proposed Strategies

text: Antimicrobial resistance (AMR) is a global public health threat that warrants urgent attention. However, the multifaceted nature of AMR often complicates the development and implementation of comprehensive policies. In this study, we describe the policy context and explore experts’ perspectives on the challenges, facilitators, and strategies for combating AMR in Singapore. We conducted semi-structured interviews with 21 participants. Interviews were transcribed verbatim and were analyzed thematically, adopting an interpretative approach. Participants reported that the Ministry of Health (MOH) has effectively funded AMR control programs and research in all public hospitals. In addition, a preexisting One Health platform, among MOH, Agri-Food & Veterinary Authority (restructured to form the Singapore Food Agency and the Animal & Veterinary Service under NParks in April 2019), National Environment Agency, and Singapore’s National Water Agency, was perceived to have facilitated the coordination and formulation of Singapore’s AMR strategies. Nonetheless, participants highlighted that the success of AMR strategies is compounded by various challenges such as surveillance in private clinics, resource constraints at community-level health facilities, sub-optimal public awareness, patchy regulation on antimicrobial use in animals, and environmental contamination. This study shows that the process of planning and executing AMR policies is complicated even in a well-resourced country such as Singapore. It has also highlighted the increasing need to address the social, political, cultural, and behavioral aspects influencing AMR. Ultimately, it will be difficult to design policy interventions that cater for the needs of individuals, families, and the community, unless we understand how all these aspects interact and shape the AMR response.


title: A qualitative study of the duty to care in communicable disease outbreaks

text: Abstract Health care providers’ (HCPs’) duty to care during communicable disease outbreaks has resurfaced as an important and contentious topic. This renewed interest follows the re-emergence of communicable diseases, largely thought to have disappeared and therefore irrelevant to modern day practitioners. The 2003 SARS outbreak particularly presented propitious circumstances for reconsidering this issue. This study seeks to characterize the views of individuals on the nature and limits of this duty. The authors employed qualitative methods to gather lay and expert perspectives. Individual interviews were conducted with 67 participants consisting of HCPs, spiritual leaders, regulators, and members of the public from the greater Toronto area. Participants’ views were analyzed and organized according to three main themes, constituting a framework that combines micro-, meso-, and macro-level structures and processes: the scope of obligations of HCPs, the roles of health care institutions, and the broader social context, respectively. Our data suggest that the duty to care must be placed in a wider context to include considerations that transcend individual provider obligations. It thus follows, based on our data, that the duty to care cannot be left to personal choice or an appeal to morality based on an ethic derived entirely from individual obligations. The micro-meso-macro analytical framework that we have developed can guide the articulation of accepted norms of duty to care during epidemics and the development of policy for public health crises. It can also enhance the focus of our current expectations of HCPs’ duty during epidemics. This can be achieved by informing regulatory bodies, collaborating with policy makers and engaging the public.


docid: itdzectu

title: Multiplex polymerase chain reaction testing in pediatric inpatients with febrile seizures


title: Evaluation of Seegene Allplex Respiratory Panel 1 kit for the detection of influenza virus and human respiratory syncytial virus

text: Abstract Background Influenza (FLUV) and human respiratory syncytial (HRSV) viruses are etiological agents of respiratory infections that cause a significant morbidity and mortality worldwide. A rapid and accurate diagnosis of these respiratory viruses is essential for an appropriate patient management. Molecular tests are the best detection option due to their high sensitivity and specificity. Seegene’s Allplex™ Respiratory Panel 1 (Allplex RP1) is a real-time one-step RT-PCR assay for the simultaneous detection of FLUAV, FLUBV, HRSV-A and HRSV-B. In addition, it allows the determination of FLUAV subtype (H1, H3 and H1pdm09). Objectives This study aims to evaluate Allplex RP1 as a rapid molecular test for the detection of FLUAV, FLUBV, HRSV-A and HRSV-B viruses. Study design The Allplex RP1 assay will be compared with other two commercial molecular assays, Prodesse ProFlu+ and ProFAST+ (Hologic, Madison, WI, USA), and GeneXpert Flu/RSV XC (Cepheid, USA). Results Allplex RP1, ProFlu+ and GeneXpert tests showed 95%, 91% and 96% of accuracy; and 94%, 88% and 95% of sensitivity, respectively. Moreover, Allplex RP1 showed a FLUAV subtype sensitivity of 91% and 88% for FLUAV-H1pdm09 and FLUAV-H3 respectively, and ProFAST+ assay showed sensitivities of 100% for both targets. The three assays showed a 100% of specificity and PPV, while the NPV were 84%, 73% and 86% for Allplex RP1, Prodesse and GeneXpert, respectively. Conclusions In this study, Seegene’s Allplex RP1 assay showed to be highly sensitive, specific, and suitable for detection of FLUV and HRSV, including FLUAV subtyping. In addition, it is also a hands-on-time saving assay due to the automated nucleic acid extraction and PCR setup.


Men, Suicide, and Covid-19: Critical Masculinity Analyses and Interventions


title: Factors impacting compliance with standard precautions in nursing, China

text: Summary Objectives To evaluate registered nurse compliance with standard precautions and to analyze the factors that affect compliance. Methods Study data were collected over a 3-month period from June to September 2007. The survey research method was used. A total of 1500 randomly sampled registered nurses from 18 hospitals in Hunan, China completed self-report questionnaires. Results Of the 1500 nurses included in the study, 1444 returned valid self-report questionnaires. Compliance with standard precautions was found to be low in the surveyed nurses. With a maximum possible score of 80, the quartile range of the overall score for compliance for all nurses was 48.29 (upper quartile score 76.36, lower quartile score 28.07), which was occupied by 64.7% of the participants. The factors most affecting compliance were: standard precautions training (odds ratio (OR) 2.17, 95% confidence interval (CI) 1.85–2.55) and knowledge (OR 1.94, 95% CI 1.01–3.41), followed by hospital grade (OR 1.61, 95% CI 1.79–1.86), presence of sharps disposal box in the department (OR 1.43, 95% CI 1.10–3.41), general self-efficacy (OR 1.29, 95% CI 1.04–1.59), exposure experience (OR 0.69, 95% CI 0.56–0.85), and department in which the nurse worked (OR 1.24, 95% CI 1.05–1.46). Conclusions The relevant authorities and hospital infection control department should pay more attention to nurse compliance with standard precautions. Standard precautions training should be strengthened and sufficient practical personal protection equipment provided in order to reduce hospital infections and protect the health of patients and medical staff.


title: Respiratory Syncytial Virus and Other Respiratory Viral Infections in Older Adults With Moderate to Severe Influenza-like Illness

text: Background. Few studies have prospectively assessed viral etiologies of acute respiratory infections in community-based elderly individuals. We assessed viral respiratory pathogens in individuals ≥65 years with influenza-like illness (ILI). Methods. Multiplex reverse-transcriptase polymerase chain reaction identified viral pathogens in nasal/throat swabs from 556 episodes of moderate-to-severe ILI, defined as ILI with pneumonia, hospitalization, or maximum daily influenza symptom severity score (ISS) >2. Cases were selected from a randomized trial of an adjuvanted vs nonadjuvanted influenza vaccine conducted in elderly adults from 15 countries. Results. Respiratory syncytial virus (RSV) was detected in 7.4% (41/556) moderate-to-severe ILI episodes in elderly adults. Most (39/41) were single infections. There was a significant association between country and RSV detection (P = .004). RSV prevalence was 7.1% (2/28) in ILI with pneumonia, 12.5% (8/64) in ILI with hospitalization, and 6.7% (32/480) in ILI with maximum ISS > 2. Any virus was detected in 320/556 (57.6%) ILI episodes: influenza A (104/556, 18.7%), rhinovirus/enterovirus (82/556, 14.7%), coronavirus and human metapneumovirus (each 32/556, 5.6%). Conclusions. This first global study providing data on RSV disease in ≥65 year-olds confirms that RSV is an important respiratory pathogen in the elderly. Preventative measures such as vaccination could decrease severe respiratory illnesses and complications in the elderly.


title: Susceptibility to SARS coronavirus S protein-driven infection correlates with expression of angiotensin converting enzyme 2 and infection can be blocked by soluble receptor

text: Abstract The angiotensin converting enzyme 2 (ACE2) has been identified as a receptor for the severe acute respiratory syndrome associated coronavirus (SARS-CoV). Here we show that ACE2 expression on cell lines correlates with susceptibility to SARS-CoV S-driven infection, suggesting that ACE2 is a major receptor for SARS-CoV. The soluble ectodomain of ACE2 specifically abrogated S-mediated infection and might therefore be exploited for the generation of inhibitors. Deletion of a major portion of the cytoplasmic domain of ACE2 had no effect on S-driven infection, indicating that this domain is not important for receptor function. Our results point to a central role of ACE2 in SARS-CoV infection and suggest a minor contribution of the cytoplasmic domain to receptor function.


title: Dendritic cells: microbial clearance via autophagy and potential immunobiological consequences for periodontal disease

text: Dendritic cells are potent antigen-capture and -presenting cells that play a key role in the initiation and regulation of the adaptive immune response. This process of immune homeostasis, as maintained by dendritic cells, is susceptible to dysregulation by certain pathogens during chronic infections. Such dysregulation may lead to disease perpetuation with potentially severe systemic consequences. Here we discuss in detail how intracellular pathogens exploit dendritic cells and evade degradation by altering or evading autophagy. This novel mechanism explains in part the chronic, persistent nature observed in several immuno-inflammatory diseases, including periodontal disease. Also, here we propose a hypothetical model on the plausible role of autophagy in the context of periodontal disease. Promotion of autophagy may open new therapeutic strategies in the search for a “cure” for periodontal disease in humans.


title: SARS2-CoV-2 and Stroke in a New York Healthcare System

text: BACKGROUND AND PURPOSE: With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke. However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19. METHODS: We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic. We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls). In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls). RESULTS: During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke. Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P=0.003) and historical controls (25.0%, P<0.001). When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels. When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate. Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls. CONCLUSIONS: We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19. Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased. Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19.


title: Personal protective equipment induced facial dermatoses in healthcare workers managing Coronavirus disease 2019

text: During the COVID-19 pandemic, frontline healthcare workers (HCW) are working tirelessly for long hours to provide patient care. Although COVID is not dermatotropic, prolonged contact with personal protective equipment (PPE i.e. goggles, face-shield/visor, N 95 respirator, double layered gloves, coverall/gowns, head cover and shoe cover) may cause various dermatoses. Several dermatoses have been reported due to PPE, such as pressure injury, contact dermatitis, pressure urticaria, and exacerbation of pre-existing skin diseases, including seborrheic dermatitis and acne.


title: Novel genotype of infectious bronchitis virus isolated in China

text: Abstract Recombination events are known to contribute to the emergence of novel infectious bronchitis virus (IBV) genotypes. In this study, we carried out detailed phylogenetic analysis and sequence comparisons based on 74 complete nucleotide sequences of the IBV S1 gene, including strain I0636/16 and 73 representative sequences from each genotype and lineage. The results showed that strain I0636/16 represented a novel genotype, designated as lineage 1 within genotype VII (GVII-1). Further comparative genomic analysis revealed at least two recombination sites that replaced the spike gene in a lineage 18 within genotype I (GI-18)-like virus with an as-yet-unidentified sequence, likely derived from another IBV strain, resulting a novel serotype with a lower affinity to the respiratory tract in chickens. To the best of our knowledge, this provides the first evidence for recombination leading to replacement of the complete spike gene and the emergence of a novel genotype/serotype with a lower affinity to the respiratory tract in chickens comparing to one of its parental virus ck/CH/LGX/111119. These results emphasize the importance of limiting exposure to novel IBVs that may serve as a source of genetic material for emerging viruses, as well as the importance of IBV surveillance in chicken flocks.


title: Evidence for Cross-Protection Against Subsequent Febrile Respiratory Illness Episodes From Prior Infections by Different Viruses Among Singapore Military Recruits 2009–2014

text: BACKGROUND: Few studies have evaluated the relative cross-protection conferred by infection with different groups of viruses through studies of sequential infections in humans. We investigated the presence of short-lived relative cross-protection conferred by specific prior viral infections against subsequent febrile respiratory illness (FRI). METHODS: Men enlisted in basic military training between December 2009 and December 2014 were recruited, with the first FRI as the study entry point. ResPlex II assays and real-time polymerase chain reaction assays were used to detect viral pathogens in nasal wash samples, and survival analyses were performed to determine whether infection with particular viruses conferred short-lived relative cross-protection against FRI. RESULTS: Prior infection with adenovirus (hazard ratio [HR], 0.24; 95% confidence interval [CI], .14–.44) or influenza virus (HR, 0.52; 95% CI, .38–.73) conferred relative protection against subsequent FRI episode. Results were statistically significant even after adjustment for the interval between enlistment and FRI (P < .001). Adenovirus-positive participants with FRI episodes tended to be protected against subsequent infection with adenovirus, coronavirus, enterovirus/rhinovirus, and influenza virus (P = .062–.093), while men with influenza virus–positive FRI episodes tended be protected against subsequent infection with adenovirus (P = .044) and influenza virus (P = .081). CONCLUSION: Prior adenovirus or influenza virus infection conferred cross-protection against subsequent FRI episodes relative to prior infection due to other circulating viruses.


What’s the way out? Potential exit strategies from the COVID-19 lockdown


title: Community-acquired pneumonia

text: Summary This seminar reviews important features and management issues of community-acquired pneumonia (CAP) that are especially relevant to immunocompetent adults in light of new information about cause, clinical course, diagnostic testing, treatment, and prevention. Streptococcus pneumoniae remains the most important pathogen; however, emerging resistance of this organism to antimicrobial agents has affected empirical treatment of CAP. Atypical pathogens have been quite commonly identified in several prospective studies. The clinical significance of these pathogens (with the exception of Legionella spp) is not clear, partly because of the lack of rapid, standardised tests. Diagnostic evaluation of CAP is important for appropriate assessment of severity of illness and for establishment of the causative agent in the disease. Until better rapid diagnostic methods are developed, most patients will be treated empirically. Antimicrobials continue to be the mainstay of treatment, and decisions about specific agents are guided by several considerations that include spectrum of activity, and pharmacokinetic and pharmacodynamic principles. Several factors have been shown to be associated with a beneficial clinical outcome in patients with CAP. These factors include administration of antimicrobials in a timely manner, choice of antibiotic therapy, and the use of a critical pneumonia pathway. The appropriate use of vaccines against pneumococcal disease and influenza should be encouraged. Several guidelines for management of CAP have recently been published, the recommendations of which are reviewed.


title: Serial interval of novel coronavirus (COVID-19) infections

text: Abstract Objective To estimate the serial interval of novel coronavirus (COVID-19) from information on 28 infector-infectee pairs. Methods We collected dates of illness onset for primary cases (infectors) and secondary cases (infectees) from published research articles and case investigation reports. We subjectively ranked the credibility of the data and performed analyses on both the full dataset (n = 28) and a subset of pairs with highest certainty in reporting (n = 18). In addition, we adjust for right truncation of the data as the epidemic is still in its growth phase. Results Accounting for right truncation and analyzing all pairs, we estimated the median serial interval at 4.0 days (95% credible interval [CrI]: 3.1, 4.9). Limiting our data to only the most certain pairs, the median serial interval was estimated at 4.6 days (95% CrI: 3.5, 5.9). Conclusions The serial interval of COVID-19 is close to or shorter than its median incubation period. This suggests that a substantial proportion of secondary transmission may occur prior to illness onset. The COVID-19 serial interval is also shorter than the serial interval of severe acute respiratory syndrome (SARS), indicating that calculations made using the SARS serial interval may introduce bias.


title: Interferon, Mx, and viral countermeasures

text: Abstract The interferon system provides a powerful and universal intracellular defense mechanism against viruses. Knockout mice defective in IFN signaling quickly succumb to all kinds of viral infections. Likewise, humans with genetic defects in interferon signaling die of viral disease at an early age. Among the known interferon-induced antiviral mechanisms, the Mx pathway is one of the most powerful. Mx proteins belong to the dynamin superfamily of large GTPases and have direct antiviral activity. They inhibit a wide range of viruses by blocking an early stage of the viral replication cycle. Likewise, the protein kinase R (PKR), and the 2–5 OAS/RNaseL system represent major antiviral pathways and have been extensively studied. Viruses, in turn, have evolved multiple strategies to escape the IFN system. They try to go undetected, suppress IFN synthesis, bind and neutralize secreted IFN molecules, block IFN signaling, or inhibit the action of IFN-induced antiviral proteins. Here, we summarize recent findings about the astonishing interplay of viruses with the IFN response pathway.


docid: zbjaslsa

title: A High-Throughput Yeast Two-Hybrid Protocol to Determine Virus-Host Protein Interactions

text: The yeast two-hybrid (Y2H) system is a powerful method to identify and analyze binary protein interactions. In the field of virology, the Y2H system has significantly increased our knowledge of structure and function of viral proteins by systematically assessing intraviral protein interactions. Several comprehensive approaches to determine virus-host interactions have provided insight into viral strategies to manipulate the host for efficient replication and to escape host-derived countermeasures. To expand our knowledge of intraviral and virus-host protein interactions, we here present a Y2H protocol that is well suited for high-throughput screening. Yeast mating followed by liquid handling in a 96-well format as well as fluorescent readout of the reporter system provides a highly standardized and fully automated screening situation. The protocol can either be applied to screen complex host cDNA libraries or protein pairs arrayed for cross-testing. The ease of use, the cost-effectiveness as well as the robotic handling allows for extensive and multiple rounds of screening providing high coverage of protein-protein interactions. Thus, this protocol represents an improved “deep” screening method for high-throughput Y2H assays.


Weaker together or weaker apart? Great power relations after the coronavirus


title: Analysis of the Microbiota of the Physiotherapist's Environment

text: ABSTRACT. Objetive To analyse the microbiota of the physiotherapist´s work environment to understand the existing potential risks in order to adopt appropriate preventive measures. Design Cross-sectional descriptive observational study. Setting Physiotherapist´s working environment. Participants 19 physiotherapy and rehabilitation centres. Intervention A microbiological sampling was carried out in the physiotherapy centers. The samples were studied using the usual culture and analysis methodology for characterization and isolation of a range of bacteria. Main outcome measures Absolute and relative frequency of microorganism isolation. Results In the analysis, pathogens normally responsible for nosocomial infections were detected, especially on instruments and equipment used by the physiotherapist like sponge electrodes, and were significantly more contaminated than the rest of the places studied (p<0.01). Conclusion This situation confirms the absence of measures and protocols for the prevention and control of such infections in the physiotherapist's environment, which is why they must be considered in order to protect both physiotherapy professionals and patients.


A case with psychotic disorder as a clinical presentation of COVID‐19


title: Targeting CCL5 in inflammation

text: Introduction: Chemokines play important roles in inflammation and in immune responses. This article will discuss the current literature on the C–C chemokine ligand 5 (CCL5), and whether it is a therapeutic target in the context of various allergic, autoimmune or infectious diseases. Areas covered: Small-molecule inhibitors, chemokine and chemokine receptor-deficient mice, antibodies and modified chemokines are the current tools available for CCL5 research, and there are several ongoing clinical trials targeting the CCL5 receptors, CCR1, CCR3 and CCR5. There are fewer studies specifically targeting the chemokine itself and clinical studies with anti-CCL5 antibodies are still to be carried out. Expert opinion: Although clinical trials are strongly biased toward HIV treatment and prevention with blockers of CCR5, the therapeutic potential for CCL5 and its receptors in other diseases is relevant. Overall, it is not likely that specific targeting of CCL5 will result in new adjunct strategies for the treatment of infectious diseases with a major inflammatory component. However, targeting CCL5 could result in novel therapies for chronic inflammatory diseases, where it may decrease inflammatory responses and fibrosis, and certain solid tumors, where it may have a role in angiogenesis.


title: Antiviral responses against chicken respiratory infections: Focus on avian influenza virus and infectious bronchitis virus

text: Abstract Some of the respiratory viral infections in chickens pose a significant threat to the poultry industry and public health. In response to viral infections, host innate responses provide the first line of defense against viruses, which often act even before the establishment of the infection. Host cells sense the presence of viral components through germinal encoded pattern recognition receptors (PRRs). The engagement of PRRs with pathogen-associated molecular patterns leads to the induction of pro-inflammatory and interferon productions. Induced antiviral responses play a critical role in the outcome of the infections. In order to improve current strategies for control of viral infections or to advance new strategies aimed against viral infections, a deep understanding of host-virus interaction and induction of antiviral responses is required. In this review, we summarized recent progress in understanding innate antiviral responses in chickens with a focus on the avian influenza virus and infectious bronchitis virus.


title: Effects of temperature variation and humidity on the death of COVID-19 in Wuhan, China

text: Abstract Meteorological parameters are the important factors influencing the infectious diseases such as severe acute respiratory syndrome (SARS) and influenza. This study aims to explore the association between Corona Virus Disease 2019 (COVID-19) deaths and weather parameters. In this study, we collected the daily death numbers of COVID-19, meteorological parameters and air pollutant data from 20 January 2020 to 29 February 2020 in Wuhan, China. Generalized additive model was applied to explore the effect of temperature, humidity and diurnal temperature range on the daily death counts of COVID-19. There were 2299 COVID-19 death counts in Wuhan during the study period. A positive association with COVID-19 daily death counts was observed for diurnal temperature range (r = 0.44), but negative association for relative humidity (r = −0.32). In addition, one unit increase in diurnal temperature range was only associated with a 2.92% (95% CI: 0.61%, 5.28%) increase in COVID-19 deaths in lag 3. However, both 1 unit increase of temperature and absolute humidity were related to the decreased COVID-19 death in lag 3 and lag 5, with the greatest decrease both in lag 3 [−7.50% (95% CI: −10.99%, −3.88%) and −11.41% (95% CI: −19.68%, −2.29%)]. In summary, this study suggests the temperature variation and humidity may also be important factors affecting the COVID-19 mortality.


title: Journey of cystatins from being mere thiol protease inhibitors to at heart of many pathological conditions

text: Abstract Cystatins are thiol proteinase inhibitors (TPI), present ubiquitously in animals, plants and micro-organisms. These are not merely inhibitors rather they are at heart of many pathological conditions ranging from diabetes to renal failure. These are essential for maintenance of protein balance of the cell; once this balance gets disturbed, it may lead to cell death. Thus, cystatins cannot be merely regarded as TPI’s as these have been found to play a pivotal role in tumorigenesis and neurodegenerative diseases. Many studies have reported the variation in cystatin level in incidences of different types of cancer; highlighting an important role played by these inhibitors in cancer development and progression. Cystatin C is increasingly replacing creatinine as a biomarker of glomerular filtration rate (GFR) thereby highlighting the importance of this important inhibitor. Some recent studies have also reported the interaction pattern of various anti-cancer drugs with cystatins in a bid to find how these drugs affect this important inhibitors and whether these drugs have any side effect on cystatins. Thus, in this growing disease era it can be said that cystatins are no more just inhibitors blocking the activity of thiol proteases rather they play a pivotal role in variety of pathological conditions.


title: Pathophysiology of acute fibrinous and organizing pneumonia – Clinical and morphological spectra

text: Abstract Acute Fibrinous and Organizing Pneumonitis (AFOP) is a disease with histopathological pattern characterized by the presence of intra-alveolar fibrin in the form of fibrin “balls” and organizing pneumonia represented by inflammatory myofibroblastic polyps. Symptoms of this rare interstitial pulmonary disease can be either acute or sub-acute and it can rapidly progress to death. Diagnosis should be considered in the Intensive Care Unit (ICU) if patients’ symptomatology and radiology correlates with non-responding or progressive pneumonia and when morphology, on biopsies, encompasses criteria of diffuse alveolar damage (DAD) and organizing pneumonia (OP) balancing in between. Three clinical cases of patients presenting severe lung disease requiring mechanical ventilation and prolonged intensive care fitted on the variable spectra of AFOP histopathology and had poor outcome: a 23 year-old women had AFOP in the context of antiphospholipid syndrome pulmonary compromise; a 35 year-old man developed a letal intensive care pneumonia with AFOP pattern registered in post-mortem biopsy; and a 79 year-old man died 21 days after intensive care unit treatment of a sub-pleural organizing pneumonia with intra-alveolar fibrin, seen in post-mortem biopsy. The predominance of acute fibrin alveolar deposition pattern is helpful in raising AFOP differential diagnosis while organizing pneumonia pattern establishes a wider range of diagnosis that can go till solitary pulmonary nodule, remaining indefinite to suggest diagnosis. The performance time of biopsy in a larger number of clinical cases may be helpful in establishing the evolutionary morphological pattern, taking in mind the poor outcome of the disease, deserving rapid diagnosis to define treatment.


title: COVID-19 and ART: the view of the Italian Society of Fertility and Sterility and Reproductive Medicine

text: Abstract The COVID-19 pandemic is an unprecedented global situation. As ART specialists we should be cautious, carefully monitoring the situation whilst contributing by sharing novel evidence to counsel our patients, both pregnant women and would-be mothers. Time to egg collection and drop-out rates are parameters critical to scheduling treatments once the curve of infections has peaked and plateaued in each country. In order to reduce both parameters, infertile patients now require even more support from their IVF team: urgent oocyte collection for oncologic patients must be guaranteed, and oocyte retrievals for women of advanced maternal age and/or reduced ovarian reserve cannot be postponed indefinitely. This document represents the position of the Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR) in outlining ART priorities during and after this emergency.


title: Cytokine and Chemokine Profiles in Lung Tissues from Fatal Cases of 2009 Pandemic Influenza A (H1N1) Role of the Host Immune Response in Pathogenesis

text: Pathological studies on fatal cases caused by 2009 pandemic influenza H1N1 virus (2009 pH1N1) reported extensive diffuse alveolar damage and virus infection predominantly in the lung parenchyma. However, the host immune response after severe 2009 pH1N1 infection is poorly understood. Herein, we investigated viral load, the immune response, and apoptosis in lung tissues from 50 fatal cases with 2009 pH1N1 virus infection. The results suggested that 7 of the 27 cytokines/chemokines showed remarkably high expression, including IL-1 receptor antagonist protein, IL-6, tumor necrosis factor-α, IL-8, monocyte chemoattractant protein-1, macrophage inflammatory protein 1-β, and interferon-inducible protein-10 in lung tissues of 2009 pH1N1 fatal cases. Viral load, which showed the highest level on day 7 of illness onset and persisted until day 17 of illness, was positively correlated with mRNA levels of IL-1 receptor antagonist protein, monocyte chemoattractant protein-1, macrophage inflammatory protein 1-β, interferon-inducible protein-10, and regulated on activation normal T-cell expressed and secreted. Apoptosis was evident in lung tissues stained by the TUNEL assay. Decreased Fas and elevated FasL mRNA levels were present in lung tissues, and cleaved caspase-3 was frequently seen in pneumocytes, submucosal glands, and lymphoid tissues. The pathogenesis of the 2009 pH1N1 virus infection is associated with viral replication and production of proinflammatory mediators. FasL and caspase-3 are involved in the pathway of 2009 pH1N1 virus-induced apoptosis in lung tissues, and the disequilibrium between the Fas and FasL level in lung tissues could contribute to delayed clearance of the virus and subsequent pathological damages.


Italian pulmonologist units and COVID-19 outbreak: “mind the gap”!


title: Intérêt de l’identification en routine des agents pathogènes respiratoires chez les enfants hospitalisés pour une exacerbation d’asthme

text: Résumé Introduction Chez l’enfant les exacerbations d’asthme sont le plus souvent déclenchées par une infection respiratoire. L’objectif de cette étude était d’évaluer l’intérêt de l’identification des pathogènes respiratoires chez les enfants hospitalisés pour une exacerbation d’asthme. Patients et méthodes Il s’agit d’une étude rétrospective incluant tout enfant hospitalisé pour une exacerbation d’asthme dans notre unité entre janvier 2010 et décembre 2011 et analysant la prescription des examens microbiologiques, leurs indications, leur rendement, leur impact sur la prise en charge médicale et leur coût. Résultats Cent quatre-vingt-dix-sept enfants ont été inclus. Une recherche d’agent pathogène respiratoire avait été réalisée chez 157 enfants (79,7 %), surtout en cas d’infection oto-rhino-laryngologique (ORL), d’hypoxémie ou de pneumonie. Un virus avait été identifié chez 30 (23,8 %) des 126 enfants prélevés. Les analyses bactériologiques avaient eu un rendement faible puisque seulement 3,2 % des analyses par amplification génique (PCR) pour Mycoplasma pneumoniae avaient été positives (n =4/125). Aucune autre bactérie n’avait été identifiée. Aucun lien n’a pu être établi entre les résultats microbiologiques et la gravité de l’exacerbation. La prise en charge thérapeutique avait été peu modifiée par ces résultats. Le coût global avait été de plus de 40 400euros pour les 2ans d’étude. Conclusion D’après nos résultats la recherche de pathogènes respiratoires au cours des exacerbations d’asthme a un intérêt modéré en dehors de l’aspect épidémiologique. L’impact du rhinovirus, du coronavirus, du bocavirus et de l’entérovirus, non recherchés en routine hospitalière, reste cependant à préciser. Summary Background Asthma is the most common chronic disease in childhood. With its high economic burden, it is considered a disease of major public health importance by the World Health Organization. The link between respiratory tract infections and acute exacerbation has been recognized for a long time. The aim of this retrospective study in routine care was to evaluate our practices concerning microbiological prescriptions in children hospitalized for asthma exacerbation. Study design All children aged from 2 to 15years hospitalized for asthma exacerbation between January 2010 and December 2011 in our unit were included in the study. Microbiological prescriptions, their indications, their results, and their cost were studied. Results One hundred ninety-seven children were included in the study. A potential causative agent was sought in 79.7% of the children (n =157) by immunofluorescence assay (IFA) and/or polymerase chain reaction (PCR). The main indications were upper airway infections, hypoxemia, and pneumonia. Viruses were detected in 23.8% of them (30/126). Mycoplasma pneumoniae was detected by PCR in only 3.2% of these patients (4/125). No other bacterial agent was identified. There was no correlation between the severity of asthma exacerbation and the microbiological diagnosis of infection. The results did not influence the therapy given. These prescriptions represented a substantial cost for each child. Conclusion These analyses do not seem to have a real advantage for the patient except for epidemiology. It would be important to conduct a new study analyzing the role of rhinovirus, and of other viruses such as coronavirus, bocavirus, and enterovirus, not routinely investigated in our hospital, and to question the value of these costly microbiological tests.


title: Sequestration of RNA by grass carp Ctenopharyngodon idella TIA1 is associated with its positive role in facilitating grass carp reovirus infection

text: Abstract Previous report demonstrated that grass carp reovirus (GCRV) infection resulted in unlinking cellular stress granule formation from aggregation of grass carp Ctenopharyngodon idella TIA1 (CiTIA1). Here, we provided evidence to show that CiTIA1 bound to synthesized ssRNA and dsRNA in vitro. Both GST-pull down assay and RNA immunoprecipitation analysis confirmed the association between GCRV-specific RNA and GST-tagged CiTIA1 in C. idella kidney (CIK) cells. Furthermore, CiTIA1 was shown to protect dsRNA of virus-origin from degradation in CIK cells through Northern blot analysis. Finally, transient overexpression of CiTIA1 enhanced the replication efficiency of GCRV in CIK cells. Taken together, our results suggested that cellular CiTIA1 might facilitate GCRV replication through sequestrating and protecting viral RNA from degradation.


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title: Maintenance of Skill Proficiency for Emergency Skills With and Without Adjuncts Despite the Use of Level C Personal Protective Equipment

text: Objective To determine the impact of Level C personal protective equipment (PPE) on the time to perform intravenous (IV) cannulation and endotracheal intubation, both with and without the use of adjuncts. Methods This prospective, case-control study of emergency medicine resident physicians was designed to assess the time taken by each subject to perform endotracheal intubation using both direct laryngoscopy (DL) and video laryngoscopy (VL), as well as peripheral IV cannulation both with and without ultrasound guidance and with and without PPE. Results While median times were higher using VL as compared to DL, there was no significant difference between intubation with either DL or VL in subjects with and without Level C PPE. Similarly, no significant difference in time was found for intravenous cannulation in the PPE and no-PPE groups, both with and without ultrasound guidance. Conclusions Existing skill proficiency was maintained despite wearing PPE and there was no advantage with the addition of adjuncts such as video-assisted laryngoscopy and ultrasound-guided intravenous cannulation. A safe and cost-effective strategy might be to conduct basic, just-in-time PPE training to enhance familiarity with donning, doffing, and mobility, and couple this with the use of personnel who have maximal proficiency in the relevant emergency skill, instead of more expensive, continuous, skills-focused PPE training.


title: Monitoring of viable airborne SARS virus in ambient air

text: Abstract Due to recent SARS related issues (Science 300 (5624) 1394; Nature 423 (2003) 240; Science 300 (5627) 1966), the development of reliable airborne virus monitoring procedures has become galvanized by an exceptional sense of urgency and is presently in a high demand (In: Cox, C.S., Wathers, C.M. (Eds.), Bioaerosols Handbook, Lewis Publishers, Boca Raton, FL, 1995, pp. 247–267). Based on engineering control method (Aerosol Science and Technology 31 (1999) 249; 35 (2001) 852), which was previously applied to the removal of particles from gas carriers, a new personal bioaerosol sampler has been developed. Contaminated air is bubbled through porous medium submerged into liquid and subsequently split into multitude of very small bubbles. The particulates are scavenged by these bubbles, and, thus, effectively removed. The current study explores its feasibility for monitoring of viable airborne SARS virus. It was found that the natural decay of such virus in the collection fluid was around 0.75 and 1.76lg during 2 and 4h of continuous operation, respectively. Theoretical microbial recovery rates of higher than 55 and 19% were calculated for 1 and 2h of operation, respectively. Thus, the new sampling method of direct non-violent collection of viable airborne SARS virus into the appropriate liquid environment was found suitable for monitoring of such stress sensitive virus.


title: Acute symptomatic hyponatremia in setting of SIADH as an isolated presentation of COVID-19

text: The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is one of the most common causes of hyponatremia in hospitalized patients. Wide spectrum of etiologies associated with hyponatremia pose significant challenges in detecting and treating this disorder. Several infectious causes of SIADH have been reported; however, hyponatremia associated with SIADH and Coronavirus disease 2019 (COVID-19) was only recently mentioned in a few case reports. We discuss a unique presentation of COVID-19, in which the patient presented with acute severe symptomatic hyponatremia thought to be the initial and isolated presentation of SARS-CoV-2 infection.


Addressing the Gap in International Norms for Biosafety


Corrigendum to ‘Phagocytic cells contribute to the antibody-mediated elimination of pulmonary-infected SARS coronavirus’ [Virology (2014) 157–168]


title: Biodistribution and residence time of adenovector serotype 5 in normal and immunodeficient mice and rats detected with bioluminescent imaging

text: As concerns increase about adenovirus type 5 (Ad5) being a safe gene transfer vector, it is important to evaluate its distribution, residence time, and possible toxicity in immunodeficient populations. To characterize the potential risk associated with different Ad5 vector delivery modes, we used immunocompetent and immunodeficient Rag2 (−/−) animals to establish mouse and rat models that could be monitored with bioluminescent imaging following intramuscular or intravascular infection with an engineered replication-incompetent Ad5 virus carrying the firefly luciferase gene (Ad5-Fluc). The Ad5 vector was less well-tolerated by Rag2 (−/−) animals than by wildtype ones, with delayed residence time, wider virus dissemination, less weight gain, and relatively severe pathological changes. In intravascularly Ad5-Fluc-infected Rag2 (−/−) mice, systemic virus dissemination extended from the abdomen to the limbs and head on day 9 post-infection. Additionally, significant increases in plasma TNF-α and IFN-γ, which may be important factors in the heightened immunopathology in the liver and brain, were detected in the Rag2 (−/−) mice 30 days after intravascular delivery. The Ad5 vector was better tolerated after intramuscular delivery than after intravascular delivery. Ad5-Fluc/Rag2 (−/−) mice and rats can be used as reliable models of an immunodeficient population in which to evaluate the safety of Ad5-vectored vaccines or gene therapy products.


title: Mechanism of Nucleic Acid Unwinding by SARS-CoV Helicase

text: The non-structural protein 13 (nsp13) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is a helicase that separates double-stranded RNA (dsRNA) or DNA (dsDNA) with a 5′→3′ polarity, using the energy of nucleotide hydrolysis. We determined the minimal mechanism of helicase function by nsp13. We showed a clear unwinding lag with increasing length of the double-stranded region of the nucleic acid, suggesting the presence of intermediates in the unwinding process. To elucidate the nature of the intermediates we carried out transient kinetic analysis of the nsp13 helicase activity. We demonstrated that the enzyme unwinds nucleic acid in discrete steps of 9.3 base-pairs (bp) each, with a catalytic rate of 30 steps per second. Therefore the net unwinding rate is ∼280 base-pairs per second. We also showed that nsp12, the SARS-CoV RNA-dependent RNA polymerase (RdRp), enhances (2-fold) the catalytic efficiency of nsp13 by increasing the step size of nucleic acid (RNA/RNA or DNA/DNA) unwinding. This effect is specific for SARS-CoV nsp12, as no change in nsp13 activity was observed when foot-and-mouth-disease virus RdRp was used in place of nsp12. Our data provide experimental evidence that nsp13 and nsp12 can function in a concerted manner to improve the efficiency of viral replication and enhance our understanding of nsp13 function during SARS-CoV RNA synthesis.


title: The Effect of Contact Investigations and Public Health Interventions in the Control and Prevention of Measles Transmission: A Simulation Study

text: BACKGROUND: Measles cases continue to occur despite its elimination status in the United States. To control transmission, public health officials confirm the measles diagnosis, identify close contacts of infectious cases, deliver public health interventions (i.e., post-exposure prophylaxis) among those who are eligible, and follow-up with the close contacts to determine overall health outcomes. A stochastic network simulation of measles contact tracing was conducted using existing agent-based modeling software and a synthetic population with high levels of immunity in order to estimate the impact of different interventions in controlling measles transmission. METHODS AND FINDINGS: The synthetic population was created to simulate California`s population in terms of population demographics, household, workplace, school, and neighborhood characteristics using California Department of Finance 2010 census data. Parameters for the model were obtained from a review of the literature, California measles case surveillance data, and expert opinion. Eight different scenarios defined by the use of three different public health interventions were evaluated: (a) post-exposure measles, mumps, and rubella (MMR) vaccine, (b) post-exposure immune globulin (IG), and (c) voluntary isolation and home quarantine in the presence or absence of public health response delays. Voluntary isolation and home quarantine coupled with one or two other interventions had the greatest reduction in the number of secondary cases infected by the index case and the probability of escape situations (i.e., the outbreak continues after 90 days). CONCLUSIONS: Interrupting contact patterns via voluntary isolation and home quarantine are particularly important in reducing the number of secondary cases infected by the index case and the probability of uncontrolled outbreaks.