title: A new millennium conundrum: how to use a powerful class of influenza anti-neuraminidase drugs (NAIs) in the community

text: Influenza A and B viruses cause serious medical problems and social disruption every year in particular countries of the world. The virus is notoriously fickle and may attack citizens in say two adjacent countries but not the third. More rarely a global pandemic virus emerges causing millions of deaths worldwide. The SARS outbreak has illuminated weaknesses in planning for sudden outbreaks of disease in a modern society and in particular how panic can grip and cause intense economic disruption. Many communities in the world are neither prepared for a global pandemic nor a very acute epidemic of influenza. The neuraminidase inhibitors (NAIs) are a new class of antiviral drug targeting a viral influenza enzyme, the neuraminidase, which acts both to facilitate virus infection of cells by clearing a passage through otherwise protective respiratory fluids and also by helping release of the virus by cutting the chemical umbilical cord which links up the virus to the infected cell. Extensive laboratory studies of the two molecules zanamivir and oseltamivir have shown that they block all influenza A and B viruses yet tested and would, in theory, even inhibit the 1918 pandemic virus. Both drugs can be used prophylactically to prevent spread of infection in families and communities where 80–90% protection has been documented. The therapeutic effects are also strong in adults and children abbreviating infection, reducing quantities of excreted virus and reducing antibiotic prescriptions. The drugs have to be taken within 48 h of the onset of symptoms. Drug resistance is not a problem at present because although such mutants occur the mutants are compromised and are less virulent than their drug-sensitive parents and they spread less easily. The two drugs could be stockpiled to prepare for an influenza pandemic but, importantly, clinical and scientific experience need to be gained by using these inhibitors in the yearly conflagrations of epidemic influenza, which unchecked do great harm to our communities.


title: Severe acute respiratory syndrome (SARS): a review of the history, epidemiology, prevention, and concerns for the future

text: Abstract During the first part of 2003, the world experienced the first epidemic of the 21st century with the emergence of a new and readily transmissible disease. The disease, severe acute respiratory syndrome (SARS), spread quickly and caused numerous deaths, as well as public panic. This article provides a brief review of the initial history of the epidemiology, as well as of the clinical definition, occurrence in the pediatric population, etiology, prevention, drug studies, and considerations for the future.


title: HUMAN CORONAVIRUS DATA FROM FOUR CLINICAL TRIALS OF MASKS AND RESPIRATORS

text: There are few published data on the protection of masks or respirators against coronavirus infections. This is an important research question to inform the response to the COVID-19 epidemic. The transmission modes of human coronaviruses are similar, thought to be by droplet, contact and sometimes airborne routes. There are several randomised clinical trials of masks and respirators, but most used clinical endpoints or tested only for influenza. In four trials which we conducted, we tested for human coronaviruses, but only composite viral endpoints were reported in the trials. We reviewed and analysed the coronavirus data from four of our trials. Laboratory-confirmed coronavirus infections were identified in our community household trial (1 case), health worker trials (8 cases) and trial of mask use by sick patients (19 cases). No coronavirus infections were transmitted in households to parents who wore P2 or surgical masks, but one child with coronavirus infection transmitted infection to a parent in the control arm. No transmissions to close contacts occurred when worn by sick patients with coronavirus infections. There was a higher risk of coronavirus infection in HCWs who wore a mask compared to a respirator, but the difference was not statistically significant. These are the only available data on coronavirus infections associated with mask or respirator use. More clinical trials are needed to assess the efficacy of respiratory protection against coronavirus infections.


title: Chapter 26 Cerebrospinal Fluid

text: Publisher Summary This chapter discusses the anatomy, functions, and biochemistry of cerebrospinal fluid (CSF). CSF has four major functions: physical support of neural structures, excretion and “sink” action, intracerebral transport, and control of the chemical environment of the central nervous system. CSF provides a “water jacket” of physical support and buoyancy. The CSF is protective because its volume changes reciprocally with changes in the volume of intracranial contents, particularly blood. Thus, the CSF protects the brain from changes in arterial and central venous pressure associated with posture, respiration, and exertion. Acute or chronic pathological changes in intracranial contents can be accommodated, to a point, by changes in the CSF volume. The direct transfer of brain metabolites into the CSF provides excretory function. This capacity is important because the brain lacks a lymphatic system. The lymphatic function of the CSF is also manifested in the removal of large proteins and cells, such as bacteria or blood cells, by bulk CSF absorption. The “sink” action of the CSF arises from the restricted access of water-soluble substances to the CSF and the low concentration of these solutes in the CSF.


Social psychological theory and research on the novel coronavirus disease (COVID‐19) pandemic: Introduction to the rapid response special section


title: Identification of group A rotaviruses from Zambian fruit bats provides evidence for long-distance dispersal events in Africa

text: Abstract Group A rotavirus (RVA) is a major cause of diarrhea in children worldwide. Although RVA infects many animals, little is known about RVA in bats. The present study investigated the genetic diversity of RVA in Zambian bats. We identified RVA from two straw-colored fruit bats (Eidolon helvum) and an Egyptian fruit bat (Rousettus aegyptiacus), and analyzed the genome sequences of these strains. Genome segments of the RVA strains from Zambian E. helvum showed 97%–99% nucleotide sequence identity with those of other RVA strains from E. helvum in Cameroon, which is 2800 km from the sampling locations. These findings suggest that migratory straw-colored fruit bat species, distributed across sub-Saharan Africa, have the potential to disseminate RVA across long distances. By contrast, the RVA strain from Zambian R. aegyptiacus carried highly divergent NSP2 and NSP4 genes, leading us to propose novel genotypes N21 and E27, respectively. Notably, this RVA strain also shared the same genotype for VP6 and NSP3 with the RVA strains from Zambian E. helvum, suggesting interspecies transmission and genetic reassortment may have occurred between these two bat species in the past. Our study has important implications for RVA dispersal in bat populations, and expands our knowledge of the ecology, diversity and evolutionary relationships of RVA.


Cancer survivorship care at the time of the COVID‐19 pandemic


title: Licorice infusion: Chemical profile and effects on the activation and the cell cycle progression of human lymphocytes

text: A licorice infusion (LI) and its major constituents were investigated for their capacity to stimulate the activation and the cell cycle progression of human lymphocytes, measured by the CD69 expression and DNA content, respectively. The chemical profile of LI was determined by high-performance liquid chromatography-diode array detection (HPLC-DAD). Results: Two major components of LI were identified as liquiritin (1) and glycyrrhizin (2); total flavones and flavonols were shown as its minor constituents. The LI (100-800 μg/ml) stimulated the expression of CD69 on lymphocytes in a concentration-independent manner. Values of the activation index (AI) of total lymphocytes treated with LI (100-800 μg/ml) did not differ significantly among them (P < 0.05), but were 50% lower than the AI value exhibited by cells treated with phytohemagglutinin (PHA). The LI showed a similar effect on T cells, but on a lower scale. Compounds 1 and 2 (12-100 μg/ml) did not stimulate the CD69 expression on lymphocytes. The LI, 1 and 2 showed no meaningful effect on cell cycle progression of lymphocytes. The experimental data indicates that LI stimulates the activation of lymphocytes as a result of a proliferation-independent process. This finding suggests that LI could be considered as a potential specific immune stimulator.


Neurosurgical training during the COVID-19 pandemic: a British perspective


title: Variation in DNA-Damage Responses to an Inhalational Carcinogen (1,3-Butadiene) in Relation to Strain-Specific Differences in Chromatin Accessibility and Gene Transcription Profiles in C57BL/6J and CAST/EiJ Mice

text: BACKGROUND: The damaging effects of exposure to environmental toxicants differentially affect genetically distinct individuals, but the mechanisms contributing to these differences are poorly understood. Genetic variation affects the establishment of the gene regulatory landscape and thus gene expression, and we hypothesized that this contributes to the observed heterogeneity in individual responses to exogenous cellular insults. OBJECTIVES: We performed an in vivo study of how genetic variation and chromatin organization may dictate susceptibility to DNA damage, and influence the cellular response to such damage, caused by an environmental toxicant. MATERIALS AND METHODS: We measured DNA damage, messenger RNA (mRNA) and microRNA (miRNA) expression, and genome-wide chromatin accessibility in lung tissue from two genetically divergent inbred mouse strains, C57BL/6J and CAST/EiJ, both in unexposed mice and in mice exposed to a model DNA-damaging chemical, 1,3-butadiene. RESULTS: Our results showed that unexposed CAST/EiJ and C57BL/6J mice have very different chromatin organization and transcription profiles in the lung. Importantly, in unexposed CAST/EiJ mice, which acquired relatively less 1,3-butadiene-induced DNA damage, we observed increased transcription and a more accessible chromatin landscape around genes involved in detoxification pathways. Upon chemical exposure, chromatin was significantly remodeled in the lung of C57BL/6J mice, a strain that acquired higher levels of 1,3-butadiene–induced DNA damage, around the same genes, ultimately resembling the molecular profile of CAST/EiJ. CONCLUSIONS: These results suggest that strain-specific changes in chromatin and transcription in response to chemical exposure lead to a “compensation” for underlying genetic-driven interindividual differences in the baseline chromatin and transcriptional state. This work represents an example of how chemical and environmental exposures can be evaluated to better understand gene-by-environment interactions, and it demonstrates the important role of chromatin response in transcriptomic changes and, potentially, in deleterious effects of exposure. https://doi.org/10.1289/EHP1937


title: Optimizing lung cancer radiation treatment worldwide in COVID-19 outbreak

text: COVID-19 has spread around the planet, sending billions of people into lockdown as health services struggle to cope. By April 2020, there are over a million two hundred thousand confirmed cases and more than sixty-five thousand deaths worldwide Meanwhile in Asia, where the disease began, the spread continues, in China it seems for now to have passed its peak. Italy, Spain, France, and the US have been the countries more affected in terms of deaths. The coronavirus is more dangerous to the elderly and those with certain pre-existing medical conditions which is precisely the profile of lung cancer patients. Essential cancer services should be delivered but all steps should be taken to protect patients and the health workforce from infection with COVID-19. This presents a major challenge to radiotherapy (RT) departments worldwide in curbing the spread of COVID-19 while ensuring the continuity of services. In RT, shortening overall treatment time to reduce the number of patients present in the department is an important consideration. An international panel, including the majority of countries most affected by the COVID-19 pandemic, with expertise in the management of cancer in high-volume comprehensive centres from the largest societies of radiation oncology worldwide have come together to share their experience on COVID-19 preparedness in the context of lung cancer RT to deliver optimal care in such exceptional circumstances, based on the latest evidence. A comprehensive systematic review of the literature through a PubMed search was undertaken. Given that lung cancer is one of the most common and severe pathologies in radiation oncology departments, the following recommendations require particularly urgent consideration. The decision-making paths strongly depend on locally available resources, and a tailored approach should be used to attend lung cancer patients during this pandemic.


title: Podcasting in nursing and midwifery education: An integrative review

text: Podcasting is used in higher education so various digital resources can be shared with students. This review aims to synthesise evidence on podcasting in nursing and midwifery education. PubMed, MEDLINE, CINAHL, Scopus and ERIC databases were searched using key terms. 242 articles were found and screened. Data extraction, quality assessment and data analysis, underpinned by a Social Media Learning Model, were conducted on relevant studies. Twenty-six studies were included in the review. Three themes emerged; 1) learning and other outcomes, 2) antecedents to learning, and 3) learning process. Students seemed to acquire new knowledge and skills by using podcasts and it also appeared to improve clinical confidence. The organisation of podcasting, digital literacy and e-Professionalism, the personal motivation of learners, and flexible access to the technology seemed to impact the delivery of this educational intervention. Mechanisms that appeared to affect the learning process were the speed of exchange, the type of social media user, the timeframe, quality of information, the functionality of podcasts and other learning activities. This review synthesised evidence on podcasting in nursing and midwifery education. The technology was seen as a positive learning tool but more robust research examining its efficacy in improving learning outcomes is needed.


title: Is chronic rhinosinusitis caused by persistent respiratory virus infection?, ,

text: BACKGROUND: Many chronic rhinosinusitis (CRS) patients recall an upper respiratory tract infection as the inciting event of their chronic illness. Viral infections have been shown to cause obstruction of the osteomeatal complex, which is likely to be a critical step in the development of CRS. There is clear overlap between the pathogenesis of CRS and asthma. Infections with respiratory viruses in childhood increase the risk of subsequently developing asthma. Viral infections in established asthmatics are associated with acute exacerbations. We sought to determine whether respiratory viruses could be detected within the sinonasal mucosa of CRS patients using polymerase chain reaction (PCR) techniques. METHODS: Sinus mucosa was sampled from 13 patients with CRS and 2 patients with normal sinuses. PCR was used to look for common respiratory viruses (parainfluenza 1, 2, and 3; respiratory syncytial virus [RSV]; human metapneumovirus [hMPV]; adenovirus [ADV]; rhinovirus; coronavirus; bocavirus [BoV]; cytomegalovirus [CMV]; and influenza A and B). RESULTS: No respiratory viruses were detected in any of the samples. CONCLUSION: Persistence of respiratory viruses within the sinonasal mucosa is unlikely to be a cause of ongoing inflammation in CRS. The possibility remains that a transient viral infection provides the initial inflammatory stimulus. © 2011 ARS‐AAOA, LLC.


title: Novel insights into pasteurellosis in captive pinnipeds

text: Abstract Pasteurella multocida is a heterogeneous bacterium, which has the capacity to cause disease in a wide range of host species and is also recognized as an important zoonotic pathogen. Two sequential deaths in captive fur seals occurred at Sea World, Australia during December 2017. A fibrinosuppurative bronchopneumonia in a Subantarctic fur seal (Arctocephalus tropicalis) resulted in death within 24 h of nonspecific signs of illness, whereas a septic peritonitis in a New Zealand fur seal (Arctocephalus forsteri) resulted in death within 12 h of clinical presentation. The cases happened within three days in two different pool locations, although both had previously been housed in the same area. A total of six Pasteurella multocida isolates were obtained from several internal organs at necropsy in both cases and were subjected to whole genome sequencing and phylogenomic analysis. In-silico typing of the isolates revealed that all belonged to Multi-Locus Sequence Type 7 and carried lipopolysaccharide outer core biosynthesis loci Type 3. Phylogenomic analysis of the isolates confirmed that the isolates were near identical at the core genome level, suggesting acquisition from a common source. The results also revealed the presence of within host and across animal diversity of P. multocida isolates for the first time even in a clearly connected outbreak.


title: Simulation of the spread of infectious diseases in a geographical environment

text: The study of mathematical models for the spread of infectious diseases is an important issue in epidemiology. Given the fact that most existing models cannot comprehensively depict heterogeneities (e.g., the population heterogeneity and the distribution heterogeneity) and complex contagion patterns (which are mostly caused by the human interaction induced by modern transportation) in the real world, a theoretical model of the spread of infectious diseases is proposed. It employs geo-entity based cellular automata to simulate the spread of infectious diseases in a geographical environment. In the model, physical geographical regions are defined as cells. The population within each cell is divided into three classes: Susceptible, Infective, and Recovered, which are further divided into some subclasses by states of individuals. The transition rules, which determine the changes of proportions of those subclasses and reciprocal transformation formulas among them, are provided. Through defining suitable spatial weighting functions, the model is applied to simulate the spread of the infectious diseases with not only local contagion but also global contagion. With some cases of simulation, it has been shown that the results are reasonably consistent with the spread of infectious diseases in the real world. The model is supposed to model dynamics of infectious diseases on complex networks, which is nearly impossible to be achieved with differential equations because of the complexity of the problem. The cases of simulation also demonstrate that efforts of all kinds of interventions can be visualized and explored, and then the model is able to provide decision-making support for prevention and control of infectious diseases.


title: Risk Factors of Fatal Outcome in Hospitalized Subjects With Coronavirus Disease 2019 From a Nationwide Analysis in China

text: BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has become a global health emergency. The cumulative number of new confirmed cases and deaths are still increasing out of China. Independent predicted factors associated with fatal outcomes remain uncertain. RESEARCH QUESTION: The goal of the current study was to investigate the potential risk factors associated with fatal outcomes from COVID-19 through a multivariate Cox regression analysis and a nomogram model. STUDY DESIGN AND METHODS: A retrospective cohort of 1,590 hospitalized patients with COVID-19 throughout China was established. The prognostic effects of variables, including clinical features and laboratory findings, were analyzed by using Kaplan-Meier methods and a Cox proportional hazards model. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. RESULTS: In this nationwide cohort, nonsurvivors included a higher incidence of elderly people and subjects with coexisting chronic illness, dyspnea, and laboratory abnormalities on admission compared with survivors. Multivariate Cox regression analysis showed that age ≥ 75 years (hazard ratio [HR], 7.86; 95% CI, 2.44-25.35), age between 65 and 74 years (HR, 3.43; 95% CI, 1.24-9.5), coronary heart disease (HR, 4.28; 95% CI, 1.14-16.13), cerebrovascular disease (HR, 3.1; 95% CI, 1.07-8.94), dyspnea (HR, 3.96; 95% CI, 1.42-11), procalcitonin level > 0.5 ng/mL (HR, 8.72; 95% CI, 3.42-22.28), and aspartate aminotransferase level > 40 U/L (HR, 2.2; 95% CI, 1.1-6.73) were independent risk factors associated with fatal outcome. A nomogram was established based on the results of multivariate analysis. The internal bootstrap resampling approach suggested the nomogram has sufficient discriminatory power with a C-index of 0.91 (95% CI, 0.85-0.97). The calibration plots also showed good consistency between the prediction and the observation. INTERPRETATION: The proposed nomogram accurately predicted clinical outcomes of patients with COVID-19 based on individual characteristics. Earlier identification, more intensive surveillance, and appropriate therapy should be considered in patients at high risk.


title: Severe Community-Acquired Pneumonia Caused by Human Adenovirus in Immunocompetent Adults: A Multicenter Case Series

text: BACKGROUND: Severe community-acquired pneumonia (CAP) caused by human adenovirus (HAdV), especially HAdV type 55 (HAdV-55) in immunocompetent adults has raised increasing concerns. Clinical knowledge of severe CAP and acute respiratory distress syndrome induced by HAdV-55 is still limited, though the pathogen has been fully characterized by whole-genome sequencing. METHODS: We conducted a multicentre retrospective review of all consecutive patients with severe CAP caused by HAdV in immunocompetent adults admitted to the Emergency Department Intensive Care Unit of two hospitals in Northern China between February 2012 and April 2014. Clinical, laboratory, radiological characteristics, treatments and outcomes of these patients were collected and analyzed. RESULTS: A total of 15 consecutive severe CAP patients with laboratory-confirmed adenovirus infections were included. The median age was 30 years and all cases were identified during the winter and spring seasons. HAdV-55 was the most frequently (11/15) detected HAdV type. Persistent high fever, cough and rapid progression of dyspnea were typically reported in these patients. Significantly increased pneumonia severity index (PSI), respiratory rate, and lower PaO(2)/FiO(2), hypersensitive CRP were reported in non-survivors compared to survivors (P = 0.013, 0.022, 0.019 and 0.026, respectively). The rapid development of bilateral consolidations within 10 days after illness onset were the most common radiographic finding, usually accompanied by adjacent ground glass opacities and pleural effusions. Total mortality was 26.7% in this study. Corticosteroids were prescribed to 14 patients in this report, but the utilization rate between survivors and non-survivors was not significant. CONCLUSIONS: HAdV and the HAdV-55 sub-type play an important role among viral pneumonia pathogens in hospitalized immunocompetent adults in Northern China. HAdV should be tested in severe CAP patients with negative bacterial cultures and a lack of response to antibiotic treatment, even if radiologic imaging and clinical presentation initially suggest bacterial pneumonia.


Reply to Challenges to paediatric services during COVID-19 Pandemic: a London, UK perspective


title: Diagnostic value and dynamic variance of serum antibody in coronavirus disease 2019

text: Abstract Objective To investigate the diagnostic value of serological testing and dynamic variance of serum antibody in coronavirus disease 2019 (COVID-19). Methods This study retrospectively included 43 patients with a laboratory-confirmed infection and 33 patients with a suspected infection, in whom the disease was eventually excluded. The IgM/IgG titer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was measured by chemiluminescence immunoassay analysis. Results Compared to molecular detection, the sensitivities of serum IgM and IgG antibodies to diagnose COVID-19 were 48.1% and 88.9%, and the specificities were 100% and 90.9%, respectively.In the COVID-19 group, the IgM-positive rate increased slightly at first and then decreased over time; in contrast, the IgG-positive rate increased to 100% and was higher than IgM at all times. The IgM-positive rate and titer were not significantly different before and after conversion to virus-negative. The IgG-positive rate was up to 90% and not significantly different before and after conversion to virus-negative. However, the median IgG titer after conversion to virus-negative was double that before, and the difference was significant. Conclusions Viral serological testing is an effective means of diagnosis for SARS-CoV-2 infection. The positive rate and titer variance of IgG are higher than those of IgM in COVID-19.


title: The estimation of SARS incubation distribution from serial interval data using a convolution likelihood

text: The incubation period of SARS is the time between infection of disease and onset of symptoms. Knowledge about the distribution of incubation times is crucial in determining the length of quarantine period and is an important parameter in modelling the spread and control of SARS. As the exact time of infection is unknown for most patients, the incubation time cannot be determined. What is observable is the serial interval which is the time from the onset of symptoms in an index case to the onset of symptoms in a subsequent case infected by the index case. By constructing a convolution likelihood based on the serial interval data, we are able to estimate the incubation distribution which is assumed to be Weibull, and justifications are given to support this choice over other distributions. The method is applied to data provided by the Ministry of Health of Singapore and the results justify the choice of a ten‐day quarantine period. The indirect estimate obtained using the method of convolution likelihood is validated by means of comparison with a direct estimate obtained directly from a subset of patients for whom the incubation time can be ascertained. Despite its name, the proposed indirect estimate is actually more precise than the direct estimate because serial interval data are recorded for almost all patients, whereas exact incubation times can be determined for only a small subset. It is possible to obtain an even more efficient estimate by using the combined data but the improvement is not substantial. Copyright © 2005 John Wiley & Sons, Ltd.


Enterovirus 71 infection: a new threat to global public health?


title: Integrated Disease Surveillance and Response (IDSR) in Malawi: Implementation Gaps and Challenges for Timely Alert

text: The emerging and recent 2014 Ebola Virus Disease (EVD) outbreaks rang the bell to call upon efforts from globe to assist resource-constrained countries to strengthen public health surveillance system for early response. Malawi adopted the Integrated Disease Surveillance and Response (IDSR) strategy to develop its national surveillance system since 2002 and revised its guideline to fulfill the International Health Regulation (IHR) requirements in 2014. This study aimed to understand the state of IDSR implementation and differences between guideline and practice for future disease surveillance system strengthening. This was a mixed-method observational study. Quantitative data were to analyze completeness and timeliness of surveillance system performance from national District Health Information System 2 (DHIS2). Qualitative data were collected through interviews with 29 frontline health service providers from the selected district and key informants of the IDSR system implementation and administration at district and national levels. The current IDSR system showed relatively good completeness (76.4%) but poor timeliness (41.5%) of total expected monthly reports nationwide and zero weekly reports. The challenges of IDSR implementation revealed through qualitative data included lack of supervision, inadequate resources for training and difficulty to implement weekly report due to overwhelming paperwork at frontline health services. The differences between IDSR technical guideline and actual practice were huge. The developing information technology infrastructure in Malawi and emerging mobile health (mHealth) technology can be opportunities for the country to overcome these challenges and improve surveillance system to have better timeliness for the outbreaks and unusual events detection.


title: N-acetyl-l-cystine (NAC) protects against H9N2 swine influenza virus-induced acute lung injury

text: Abstract The antioxidant N-acetyl-l-cysteine (NAC) had been shown to inhibit replication of seasonal human influenza A viruses. Here, the effects of NAC on H9N2 swine influenza virus-induced acute lung injury (ALI) were investigated in mice. BALB/c mice were inoculated intranasally with 107 50% tissue culture infective doses (TCID50) of A/swine/HeBei/012/2008/(H9N2) viruses with or without NAC treatments to induce ALI model. The result showed that pulmonary inflammation, pulmonary edema, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6, IL-1β and CXCL-10 in BALF were attenuated by NAC. Moreover, our data showed that NAC significantly inhibited the levels of TLR4 protein and TLR4 mRNA in the lungs. Pharmacological inhibitors of TLR4 (E5564) exerted similar effects like those determined for NAC in H9N2 swine influenza virus-infected mice. These results suggest that antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic.


COVID-19 in children: an epidemiology study from China


title: Implementing a Novel Remote Physician Treatment Coverage Practice for Adaptive Radiotherapy during the Coronavirus Pandemic

text: BACKGROUND: and Purposes: The COVID-19 pandemic has placed an increased importance on physical distancing to minimize the risk of transmission in radiation oncology departments. The pandemic has also increased the use of hypo-fractionated treatment schedules where MR-guided online adaptive radiotherapy (ART) can aid in dose escalation. This specialized technique requires increased staffing in close proximity, thus requiring novel coverage practices to increase physical distancing while still providing specialty care. MATERIALS AND METHODS: A remote physician ART coverage practice was developed and described using commercially available software products. Our remote physician coverage practice provided control to the physician to contour, and review images and plans. The time from completion of image registration to the beginning of treatment was recorded for 20 fractions before remote physician ART coverage and 14 fractions after implementation of remote physician ART coverage. Visual quality was calculated using cross correlation between the treatment delivery computer screen and the remote physician screen. RESULTS: For the 14 fractions after implementation, the average time from image registration to the beginning of treatment was 24.9±6.1min. In comparison, the 20 fractions analyzed without remote coverage had an average time of 29.2±9.8min. The correlation between the console screen and the remote physician screen was R = 0.95. CONCLUSION: Our novel remote physician ART coverage practice is secure, interactive, timely, and of high visual quality. When utilizing remote physicians for ART, our department was able to increase physical distancing to lower the risk of virus transmission while providing specialty care to our patients in need.


title: Adapting to the contemporary normal in cancer management and workflow during COVID-19 situation in the Philippines: Multi-cancer center collaborative approach

text: • Cancer management adapting to the current state of health during COVID-19 pandemic. • Collaborative strategic action plan for cancer management and workflow in a developing country. • Algorithm in cancer center management during COVID-19 in a developing country. • Measures to be adopted in cancer management and workflow after COVID-19 pandemic.


Loss of taste and smell


Coronavirus Antibodies in Bat Biologists


title: Psychological influence of Coronovirus disease 2019 (COVID-19) pandemic on the general public, medical workers and patients with mental disorders and its countermeasures

text: Coronovirus disease 2019 (COVID-19) first broke out in Wuhan, Hubei Province, China in 2019, and now it spreads in more than 100 countries around the world. On January 30th, the World Health Organization (WHO) declared COVID-19 a public health emergency (PHEIC) of international concern. It was classified as a pandemic by (WHO) of the World Health Organization on March 11, 2020. With the increase in the number of cases reported by various countries every day, the COVID-19 pandemic has attracted more and more attention around the world. At the same time, this public health emergency has caused a variety of psychological problems, such as panic disorder, anxiety and depression. In addition, the Wuhan Mental Health Center's analysis of 2144 calls from the psychological hotline from February 4 to February 20, 2020 showed that general public accounted for 70%, medical workers accounted for 2.2%, patients with mental disorders accounted for 19.5%, and other personnel accounted for 8.3% (https://mp.weixin.qq.com/s/kmff1vnaLsT2d9xQkK5pwg). Therefore, while controlling the pandemic, the government should also pay attention to the mental health of the general public, medical workers and patients with mental disorders. Community mental health service system, online mental health service, telemedicine and other measures for patients with mental disorders may play a vital role during the pandemic.


title: Coronavirus spreads

text: The deadly virus that emerged in Wuhan, China, may be much more contagious than initially thought. Jessica Hamzelou reports


title: Corticosteroid Administration Is Associated With Improved Outcome in Patients With Severe Acute Respiratory Syndrome Coronavirus 2-Related Acute Respiratory Distress Syndrome

text: OBJECTIVES: To compare the clinical outcome of mechanically ventilated patients with severe acute respiratory syndrome coronavirus 2-related acute respiratory distress syndrome, who received corticosteroid with those who did not. DESIGN: Retrospective analysis. SETTING: Intensive care setting. PATIENTS: All adult mechanically ventilated patients, who were admitted to the ICU between March 20, 2020, and May 10, 2020, for severe acute respiratory syndrome coronavirus 2-related acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cohort was divided into two groups based on corticosteroid administration. The primary outcome variable was ventilator-free days at day 28. Secondary outcome variable was ICU-free days at day 30, and hospital-free days at day 30. Consecutive 61 mechanically ventilated patients with severe acute respiratory syndrome coronavirus 2-related acute respiratory distress syndrome were analyzed. Patient in corticosteroid group as compared with noncorticosteroid group have higher 28-day ventilator-free days (mean, 10.2; median, 7 [interquartile range, 0–22.3] vs mean, 4.7; median, 0 [interquartile range, 0–11]; p = 0.01).There was no significant difference noted in secondary outcomes (ICU-free days at day 30 and hospital-free days at day 30). CONCLUSIONS: Among mechanically ventilated severe acute respiratory syndrome coronavirus 2-related acute respiratory distress syndrome patients, corticosteroids use was associated with significant improvement in 28-day ventilator-free days at day 28, but no significant improvement in ICU-free days at day 30, and hospital-free days at day 30.


Commentary: Adaptations to COVID-19 or Permanent Reforms in the “New Normal”?


title: Diseases and Causes of Death in European Bats: Dynamics in Disease Susceptibility and Infection Rates

text: BACKGROUND: Bats receive increasing attention in infectious disease studies, because of their well recognized status as reservoir species for various infectious agents. This is even more important, as bats with their capability of long distance dispersal and complex social structures are unique in the way microbes could be spread by these mammalian species. Nevertheless, infection studies in bats are predominantly limited to the identification of specific pathogens presenting a potential health threat to humans. But the impact of infectious agents on the individual host and their importance on bat mortality is largely unknown and has been neglected in most studies published to date. METHODOLOGY/PRINCIPAL FINDINGS: Between 2002 and 2009, 486 deceased bats of 19 European species (family Vespertilionidae) were collected in different geographic regions in Germany. Most animals represented individual cases that have been incidentally found close to roosting sites or near human habitation in urban and urban-like environments. The bat carcasses were subjected to a post-mortem examination and investigated histo-pathologically, bacteriologically and virologically. Trauma and disease represented the most important causes of death in these bats. Comparative analysis of pathological findings and microbiological results show that microbial agents indeed have an impact on bats succumbing to infectious diseases, with fatal bacterial, viral and parasitic infections found in at least 12% of the bats investigated. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the importance of diseases and infectious agents as cause of death in European bat species. The clear seasonal and individual variations in disease prevalence and infection rates indicate that maternity colonies are more susceptible to infectious agents, underlining the possible important role of host physiology, immunity and roosting behavior as risk factors for infection of bats.


title: COVID-19: NAD(+) deficiency may predispose the aged, obese and type2 diabetics to mortality through its effect on SIRT1 activity

text: The SARS-CoV-2 hyperinflammatory response is associated with high mortality. This hypothesis suggests that a deficiency of nicotinamide adenine dinucleotide (NAD(+)) may be the primary factor related to the SARS-Cov-2 disease spectrum and the risk for mortality, as subclinical nutritional deficiencies may be unmasked by any significant increase in oxidative stress. NAD(+) levels decline with age and are also reduced in conditions associated with oxidative stress as occurs with hypertension, diabetes and obesity. These groups have also been observed to have high mortality following infection with COVID-19. Further consumption of NAD(+) in a pre-existent depleted state is more likely to cause progression to the hyperinflammatory stage of the disease through its limiting effects on the production of SIRT1. This provides a unifying hypothesis as to why these groups are at high risk of mortality and suggests that nutritional support with NAD(+) and SIRT1 activators, could minimise disease severity if administered prophylactically and or therapeutically. The significance of this, if proven, has far-reaching consequences in the management of COVID-19 especially in third world countries, where resources and finances are limited.


title: An improved thermoanalytical approach to quantifying trace levels of polymorphic impurity in drug powders

text: Abstract Accurate quantification of impurities existing as separate crystalline phases at trace levels in drug materials is an important issue in the pharmaceutical industry. In the present study, a thermoanalytical approach previously developed for quantifying trace levels of polymorphic impurity (form II metastable nuclei) in commercial salmeterol xinafoate powders has been successfully applied with slight modifications to ribavirin, an antiviral drug exhibiting roughly similar polymorph-dependent crystallization kinetics in melts to that of salmeterol xinafoate. Essentially, the approach involved modeling of the crystallization kinetics of both tested and reference drug materials in melts using the Avrami-Erofe’ev (AE) rate expression, derivation of a mathematical equation for relating the AE kinetic constant to the composition of reference polymorph mixtures, and the use of this derived equation (in the form of a calibration curve) to calculate the impurity contents of the tested samples from their computed AE constants. For ribavirin, modification of the latter equation by incorporation of an empirical exponent was found necessary to account for the composition-dependent changes in crystallization kinetics of the reference mixtures. Such modification has made possible the determination of polymorphic impurity content of as low as 0.004% (w/w) in ribavirin samples induced by different forms of grinding treatment.


title: Surveillance of upper respiratory infections using a new multiplex PCR assay compared to conventional methods during the influenza season in Taiwan

text: Abstract Objectives To improve diagnosis as part of laboratory surveillance in Taiwan, influenza-like illness (ILI) surveillance was conducted using a new multiplex PCR assay (FilmArray) and the results compared to those of conventional methods The study was performed during the winter months. Methods Throat swabs from patients with an ILI presenting to physicians in sentinel practices were collected during the 2016–2017 influenza season. Results A total of 52 samples tested positive by FilmArray Respiratory Panel. Forty percent were influenza A virus, and subtype H3N2 virus was the major epidemic strain. However, nearly 60% of ILI cases seen at sentinel sites were caused by non-influenza pathogens. The results of the FilmArray assay and cell culture were identical, and this assay was more sensitive than a rapid influenza diagnostic test. Genetic analyses revealed new influenza A H3N2 variants belonging to a novel subclade 3C.2a2. Conclusions The FilmArray assay facilitates urgent testing and laboratory surveillance for common viral and bacterial respiratory pathogens. This study demonstrated the use of a highly sensitive assay using clinical samples that is feasible for application worldwide. This may lead to an increased rate of diagnosis of viral infections and to improved patient outcomes, and in particular to a reduction in the overuse of antibiotics and antivirals.


title: Bioinformatics insight into the spike glycoprotein gene of field porcine epidemic diarrhea strains during 2011–2013 in Guangdong, China

text: Three strains of porcine epidemic diarrhea virus (PEDV) were isolated from dead or diseased pigs at different swine farms in Guangdong during 2011–2013, and their S genes were sequenced. In the same period, seven PEDV strains were also isolated in Guangdong by other laboratories. The spike sequences of 10 Guangdong isolates were compared with vaccine strains and reference pathogenic isolates using six bioinformatics tools. The results revealed that 10 Guangdong strains, excluding strain GDS03, had distinct characteristics in terms of primary structure, secondary structure, high-specificity N-glycosylation sites, potential phosphorylation sites, and palmitoylation sites. Phylogenetic analysis also confirmed these findings and revealed that all PEDV strains were clustered into three distinct groups. Ten Guangdong strains, not including GDS03, belong to Group 1, whereas four vaccine strains and GDS03 belong to Group 3, which is evolutionarily distant from Group 1. Alignment analysis of the neutralizing region amino acid sequences indicated that the amino acid substitutions of Y/D766S, T549S, and G594S that are present in the Guangdong strains, not including GDS03, were a sign of predominant genetic changes among the isolated strains. GDS03 is closely related to the 83P-5 vaccine strain, which suggests that it might represent re-isolation of the vaccine strain or vaccine variants. Taken together, these results indicate that there have been predominant new strains circulating in Guangdong from 2011 to 2013, and the circulating PEDV strains have a genetic composition that is distant from reference strains, especially the vaccine strains; however, the vaccinations might also provide some level of cross-protection, as there have been no changes in the neutralizing epitopes of SS2 and 2C10. This explains why there have been constant but infrequent outbreaks recently in comparison to late 2010 in which PEDV outbreaks were more frequent and severe. In addition, the USA-Colorado-2013 strain had the same amino acid substitutions in the neutralizing regions as the Guangdong strains except GDS03, which suggests that the information and strategies in this study may play role in PEDV variant research in other countries.


title: Nanoparticle orientationally displayed antigen epitopes improve neutralizing antibody level in a model of porcine circovirus type 2

text: Recent advancements in biotechnology have enabled the rapid identification and subsequent expression of pathogenic microbial major antigens that induce protective immune responses. However, subunit vaccines have not been successfully commercialized mainly due to the lack of sufficient levels of neutralizing antibodies (NAs). High levels of NA rely on the efficient recognition and cross-linking of multiple neutralizing epitopes with B-cell receptors (BCRs). Nanoparticles are able to display coupled antigenic arrays at high density and provide multiple binding molecular scenarios with BCRs. The high-resolution antigenic structure makes it possible to accurately display stable neutralizing epitopes. Therefore, the development of a nanovaccine that orientationally displays neutralizing epitopes is a feasible strategy. To address this hypothesis, the capsid (Cap) protein of porcine circovirus type 2 as model antigen was conjugated to gold nanoparticles (AuNPs) through direct reaction of the mercapto group of the unique cysteines with AuNPs, rendering Cap-AuNPs to have neutralizing epitopes on outer surface and an immunodominant epitope buried within the inner surface. In vitro studies showed that AuNPs promoted the phagocytosis of Cap protein and NA levels were significantly improved, meanwhile antibody levels against the immunodominant epitope was significantly reduced. In mouse studies, Cap-AuNP-immunized mice displayed a high production of interleukin (IL)-4, IL-10, and interferon-γ, suggesting that Cap-AuNPs can effectively activate CD4(+) and CD8(+) T cells and balance Th1 and Th2 cellular responses. This study presents a new vaccine design strategy based on antigen structure, where nanoparticles are coupled to antigens in well-ordered arrays and orientationally display neutralizing epitopes to enhance NA levels.


Isolation of Novel Adenovirus from Fruit Bat (Pteropus dasymallus yayeyamae)


title: Burden of respiratory viruses in patients with acute respiratory failure

text: Respiratory viruses (RVs) are ubiquitous pathogens that represent a major cause of community‐acquired pneumonia and chronic pulmonary diseases exacerbations. However, their contribution to acute respiratory failure events requiring intensive care unit admission in the era of rapid multiplex molecular assay deserves further evaluation. This study investigated the burden of viral infections in non immunocompromised patients admitted to the intensive care unit for acute respiratory failure using a multiplex molecular assay. Patients were investigated for RVs using immunofluoresence testing and a commercial multiplex molecular assay, and for bacteria using conventional culture. Half the patients (34/70, 49%) had a documented RVs infection. No other pathogen was found in 24 (71%) patients. Viral infection was detected more frequently in patients with obstructive respiratory diseases (64% vs. 29%; P = 0.0075). Multiplex molecular assay should be considered as an usefull diagnostic tool in patients admitted to the intensive care unit with acute respiratory failure, especially those with acute exacerbations of chronic obstructive pulmonary disease and asthma. J. Med. Virol. 86:1198–1202, 2014. © 2013 Wiley Periodicals, Inc.


title: Rapid identification of multiple constantly-released contaminant sources in indoor environments with unknown release time

text: Abstract The sudden release of airborne hazardous contaminants in an indoor environment can potentially lead to severe disasters, such as the spread of toxic gases, fire, and explosion. To prevent and mitigate these disasters it is critical to rapidly and accurately identify the characteristics of the contaminant sources. Although remarkable achievements have been made in identifying a single indoor contaminant source in recent years, the issues related to multiple contaminant sources are still challenging. This study presents a method for identifying the exact locations, emission rates, and release time of multiple indoor contaminant sources simultaneously released at constant rates, by considering sensor thresholds and measurement errors. The method uses a two-stage procedure for rapid source identification. Before the release of contaminants, only a limited number of time-consuming computational fluid dynamics (CFD) simulations need to be conducted. After the release of contaminants, the method can be executed in real-time. Through case studies in a three-dimensional office the method was numerically demonstrated and validated, and the results show that the method is effective and feasible. The effects of sensor threshold, measurement error and total sampling time on the source identification performance were analysed, and the limitations and applicability of the method were also discussed.


title: IL‐10 expression in pyramidal neurons after neuropathogenic coronaviral infection

text: The apoptosis of pyramidal neurons in CA2 and CA3 subregions of the hippocampus is induced after infection with Mu‐3 virus (Mu‐3), a neuropathogenic strain of the JHM virus (JHMV), at 4–5 days post‐inoculation (dpi). The viral antigens in the hippocampus are mainly found in the CD11b‐positive cells distributed in the stratum oriens located outside the pyramidal layer, and only a few pyramidal neurons are infected. Furthermore, the apoptotic cells, indicated as showing caspase 3 (Cas3) activation, consist of a high number of uninfected cells. Therefore, it is considered that the apoptotic lesions occur through the indirect effects of infection, and not as a result of direct infection with Mu‐3, similar to the reported neuronal apoptosis in the hippocampus after other types of infection. The apoptosis in the pyramidal neurons is accompanied by various types of proinflammatory cytokines depending on the causative agents. Thus, the local expression of proinflammatory cytokines was studied, revealing no correlation in the distribution of cytokine expression with the subregions showing apoptosis. However, the anti‐inflammatory cytokine IL‐10 was produced by pyramidal neurons of CA2 and CA3 at 3 dpi when there is no destructive change or viral invasion in the hippocampus.


title: Clinical Pharmacology Perspectives on the Antiviral Activity of Azithromycin and Use in COVID‐19

text: Azithromycin (AZ) is a broad‐spectrum macrolide antibiotic with a long half‐life and a large volume of distribution. It is primarily used for the treatment of respiratory, enteric, and genitourinary bacterial infections. AZ is not approved for the treatment of viral infections, and there is no well‐controlled, prospective, randomized clinical evidence to support AZ therapy in coronavirus disease 2019 (COVID‐19). Nevertheless, there are anecdotal reports that some hospitals have begun to include AZ in combination with hydroxychloroquine or chloroquine (CQ) for treatment of COVID‐19. It is essential that the clinical pharmacology (CP) characteristics of AZ be considered in planning and conducting clinical trials of AZ alone or in combination with other agents, to ensure safe study conduct and to increase the probability of achieving definitive answers regarding efficacy of AZ in the treatment of COVID‐19. The safety profile of AZ used as an antibacterial agent is well established.(1) This work assesses published in vitro and clinical evidence for AZ as an agent with antiviral properties. It also provides basic CP information relevant for planning and initiating COVID‐19 clinical studies with AZ, summarizes safety data from healthy volunteer studies, and safety and efficacy data from phase II and phase II/III studies in patients with uncomplicated malaria, including a phase II/III study in pediatric patients following administration of AZ and CQ in combination. This paper may also serve to facilitate the consideration and use of a priori–defined control groups for future research.


title: Emerging respiratory infections: The infectious disease pathology of SARS, MERS, pandemic influenza, and Legionella

text: Abstract Lower respiratory infections remain one of the top global causes of death and the emergence of new diseases continues to be a concern. In the first two decades of the 21st century, we have born witness to the emergence of newly recognized coronaviruses that have rapidly spread around the globe, including severe acute respiratory syndrome virus (SARS) and Middle Eastern respiratory syndrome virus (MERS). We have also experienced the emergence of a novel H1N1 pandemic influenza strain in 2009 that caused substantial morbidity and mortality around the world and has transitioned into a seasonal strain. Although we perhaps most frequently think of viruses when discussing emerging respiratory infections, bacteria have not been left out of the mix, as we have witnessed an increase in the number of infections from Legionella spp. since the organisms’ initial discovery in 1976. Here, we explore the basic epidemiology, clinical presentation, histopathology, and clinical laboratory diagnosis of these four pathogens and emphasize themes in humans’ evolving relationship with our natural environment that have contributed to the infectious burden. Histology alone is rarely diagnostic for these infections, but has been crucial to bettering our understanding of these diseases. Together, we rely on the diagnostic acumen of pathologists to identify the clinicopathologic features that raise the suspicion of these diseases and lead to the early control of the spread in our populations.


title: No Serologic Evidence for Zoonotic Canine Respiratory Coronavirus Infections among Immunocompetent Adults

text: Zoonotic diseases continue to emerge and threaten both human and animal health. Overcrowded shelters and breeding kennels create the perfect environment for amplified infectious disease transmission among dogs and present a critical opportunity for zoonotic pathogens to emerge and infect people who work in close contact with dogs. Coronaviruses’ widespread prevalence, extensive host range, various disease manifestations and increased frequency of recombination events all underline their potential for interspecies transmission (Methods Mol. Biol. 2008, 454, 43). The objectives of this study were to determine whether people with occupational contact with dogs were more likely to have antibodies against canine respiratory coronavirus (CRCoV) compared to persons with no dog exposure. A seroepidemiological cohort study was completed, for which 302 canine‐exposed and 99 non‐canine‐exposed study subjects enrolled in the study by providing a serum sample and completing a self‐administered questionnaire. A competitive enzyme‐linked immunosorbent assay (ELISA) was developed to detect human antibodies against CRCoV while controlling for cross‐reacting antibodies against the human coronavirus OC43. All study subjects were negative for antibodies against CRCoV by this competitive ELISA. This study supports the premise that humans are not at risk for CRCoV infections; however, infrequent cross‐species transmission of CRCoV cannot be ruled out.


title: Model for Taking Care of Patients with Early Childhood Caries during the SARS-Cov-2 Pandemic

text: Pending the availability of vaccines to contain the SARS-CoV-2 pandemic, the current solution is “social distancing” with a reduction of dental treatments to those assessed as urgent and emergency cases. These treatments also involve Early Childhood Caries (ECC) due to the fact that this disease affects preschool children (a vulnerable population) and, in addition, shows a propensity to evolve into more serious complications (dental pain, infections). A narrative review was carried out to support a protocol for treating ECC with efficacious and safe (in terms of SARS-CoV-2 transmission) procedures. Protocol involves criteria for patients’ selection remotely (telemedicine), and well-detailed criteria/equipment and hygiene procedures to combat against SARS-CoV-2 transmission. Moreover, the protocol proposes innovative caries treatments, named Minimally Invasive Treatments (MITs), well known in pedodontics for their high level of children’s acceptance during dental care. MITs allow for caries removal (particularly in primary teeth) without any high-speed rotating instrument cooled with nebulized air-water spray (with high risk of virus environmental diffusion), usually adopted during traditional treatments. For evaluating MITs effectiveness in caries management, only Systematic Review and Randomized Controlled Trials (RCTs) were included in our study, without any risk of bias assessment. The indications proposed in this protocol could support clinicians for the temporary management of ECC until the SARS-CoV-2 pandemic ends.


title: Wildlife trade, consumption and conservation awareness in southwest China

text: Commercial trade in wildlife is the major cause of species endangerment and a main threat to animal welfare in China and its neighboring countries. Driven by consumptive use for food and traditional medicine, the large volume of both legal and illegal trade in wildlife has caused great destruction to ecosystems and pushed many species to the brink of extinction. Data gathered from trading hubs at ports, boundary markets, city markets and stores, indicates the large amount of wildlife traded in the region of Guangxi, Yunnan and Qinghai provinces, a direct result of the numerous wildlife markets available. In a survey distributed in various trading places, while about half of the respondents agreed that wildlife should be protected, 60% of them had consumed wildlife at some point in the last 2 years. The results also indicated that law and regulation on wildlife trade control is insufficient. Wildlife trade controls are very limited because of bias on the utilization of wildlife as a natural resource to be exploited by the government agencies. The survey also shows that the current situation of wildlife consumption in key cities in China is serious, especially the consumption for food. The main consumption groups in China are male and young people with high education levels and good incomes. The key in public awareness publicity and education is to give them more information on the negative impacts of wildlife consumption and knowledge of protection.


title: Distinct cellular responses differentiating alcohol- and hepatitis C virus-induced liver cirrhosis

text: BACKGROUND: Little is known at the molecular level concerning the differences and/or similarities between alcohol and hepatitis C virus induced liver disease. Global transcriptional profiling using oligonucleotide microarrays was therefore performed on liver biopsies from patients with cirrhosis caused by either chronic alcohol consumption or chronic hepatitis C virus (HCV). RESULTS: Global gene expression patterns varied significantly depending upon etiology of liver disease, with a greater number of differentially regulated genes seen in HCV-infected patients. Many of the gene expression changes specifically observed in HCV-infected cirrhotic livers were expectedly associated with activation of the innate antiviral immune response. We also compared severity (CTP class) of cirrhosis for each etiology and identified gene expression patterns that differentiated ethanol-induced cirrhosis by class. CTP class A ethanol-cirrhotic livers showed unique expression patterns for genes implicated in the inflammatory response, including those related to macrophage activation and migration, as well as lipid metabolism and oxidative stress genes. CONCLUSION: Stages of liver cirrhosis could be differentiated based on gene expression patterns in ethanol-induced, but not HCV-induced, disease. In addition to genes specifically regulating the innate antiviral immune response, mechanisms responsible for differentiating chronic liver damage due to HCV or ethanol may be closely related to regulation of lipid metabolism and to effects of macrophage activation on deposition of extracellular matrix components.


title: COVID‐19 pandemic in France: health emergency experiences from the field

text: AIM: This paper describes the situation regarding COVID‐19 emergency in France as of early May 2020, the main policies to fight this virus, and the roles and responsibilities of nurses regarding their work at this time, as well as the challenges facing the profession. BACKGROUND: Europe continues to be affected by the COVID‐19 pandemic. At the time of writing France was the fourth country with the highest number of detected cases and cumulative deaths. SOURCES OF EVIDENCE: Websites of the World Health Organization, French Government, French Agency of Public Health, French National Council of Nurses and ClinicalTrials.gov database, as well as the experiences of the authors. DISCUSSION: The history of the development of the pandemic in France helps explain the establishment of the state of health emergency and containment of the population. Many decisions made had undesirable repercussions, particularly in terms of intra‐family violence, mental health disorders and the renunciation of care. Hospitals and primary care services, with significant investment by nurses, played a key role in the care of persons with and without COVID‐19. CONCLUSION: France has suffered a very high toll in terms of COVID‐19 morbidity and mortality, and effects on its people, health systems and health professionals, including nurses. IMPLICATIONS FOR NURSING PRACTICE: Nurses are recognized for their social usefulness in France. However, it is important to consider the collateral effects of this crisis on nurses and nursing and to integrate the health emergency nursing skills established during the pandemic into the standard field of nursing competence. IMPLICATIONS FOR NURSING POLICY: The nursing profession has expectations of a reflection on and revision of nursing skills as well as of its valorization in the French healthcare system, notably carried out by the French National Council Order of Nurses.


COVID -19 and sudden sensorineural hearing loss, a case report


title: Prophylactic and Therapeutic Efficacy of Human Monoclonal Antibodies against H5N1 Influenza

text: BACKGROUND: New prophylactic and therapeutic strategies to combat human infections with highly pathogenic avian influenza (HPAI) H5N1 viruses are needed. We generated neutralizing anti-H5N1 human monoclonal antibodies (mAbs) and tested their efficacy for prophylaxis and therapy in a murine model of infection. METHODS AND FINDINGS: Using Epstein-Barr virus we immortalized memory B cells from Vietnamese adults who had recovered from infections with HPAI H5N1 viruses. Supernatants from B cell lines were screened in a virus neutralization assay. B cell lines secreting neutralizing antibodies were cloned and the mAbs purified. The cross-reactivity of these antibodies for different strains of H5N1 was tested in vitro by neutralization assays, and their prophylactic and therapeutic efficacy in vivo was tested in mice. In vitro, mAbs FLA3.14 and FLD20.19 neutralized both Clade I and Clade II H5N1 viruses, whilst FLA5.10 and FLD21.140 neutralized Clade I viruses only. In vivo, FLA3.14 and FLA5.10 conferred protection from lethality in mice challenged with A/Vietnam/1203/04 (H5N1) in a dose-dependent manner. mAb prophylaxis provided a statistically significant reduction in pulmonary virus titer, reduced associated inflammation in the lungs, and restricted extrapulmonary dissemination of the virus. Therapeutic doses of FLA3.14, FLA5.10, FLD20.19, and FLD21.140 provided robust protection from lethality at least up to 72 h postinfection with A/Vietnam/1203/04 (H5N1). mAbs FLA3.14, FLD21.140 and FLD20.19, but not FLA5.10, were also therapeutically active in vivo against the Clade II virus A/Indonesia/5/2005 (H5N1). CONCLUSIONS: These studies provide proof of concept that fully human mAbs with neutralizing activity can be rapidly generated from the peripheral blood of convalescent patients and that these mAbs are effective for the prevention and treatment of H5N1 infection in a mouse model. A panel of neutralizing, cross-reactive mAbs might be useful for prophylaxis or adjunctive treatment of human cases of H5N1 influenza.


title: Interferon-γ and interleukin-4 downregulate expression of the SARS coronavirus receptor ACE2 in Vero E6 cells

text: Abstract Interferons (IFNs) inhibit severe acute respiratory syndrome coronavirus (SARS-CoV) replication and might be valuable for SARS treatment. In this study, we demonstrate that treatment of Vero E6 cells with interleukin-4 (IL-4) decreased the susceptibility of these cells to SARS-CoV infection. In contrast to IFNs, IL-4 did not show antiviral activity when administered immediately after SARS-CoV infection, suggesting that IL-4 acts early during the SARS-CoV replication cycle. Indeed, binding of recombinant SARS-CoV spike protein to Vero E6 cells was diminished on cells treated with IL-4, but also on cells exposed to IFN-γ. Consistent with these observations, IL-4 and IFN-γ downregulated cell surface expression of angiotensin-converting enzyme 2 (ACE2), the SARS-CoV receptor. Besides diminished ACE2 cell surface expression, ACE2 mRNA levels were also decreased after treatment with these cytokines. These findings suggest that IL-4 and IFN-γ inhibit SARS-CoV replication partly through downregulation of ACE2.


title: Towards Detection and Diagnosis of Ebola Virus Disease at Point-of-Care

text: Ebola outbreak-2014 (mainly Zaire strain related Ebola virus) has been declared most widely spread deadly persistent epidemic due to unavailability of rapid diagnostic, detection, and therapeutics. Ebola virus disease (EVD), a severe viral hemorrhagic fever syndrome caused by Ebola virus (EBOV) is transmitted by direct contact with the body fluids of infected person and objects contaminated with virus or infected animals. World Health Organization (WHO) has declared EVD epidemic as public health emergency of international concern with severe global economic burden. At fatal EBOV infection stage, patients usually die before the antibody response. Currently, rapid blood tests to diagnose EBOV infection include the antigen or antibodies capture using ELISA and RNA detection using RT/Q-PCR within 3–10 days after the onset of symptoms. Moreover, few nanotechnology-based colorimetric and paper-based immunoassay methods have been recently reported to detect Ebola virus. Unfortunately, these methods are limited to laboratory only. As state-of-the art (SoA) diagnostics time to confirm Ebola infection, varies from 6 hours to about 3 days, it causes delay in therapeutic approaches. Thus developing a cost-effective, rapid, sensitive, and selective sensor to detect EVD at point-of-care (POC) is certainly worth exploring to establish rapid diagnostics to decide therapeutics. This review highlights SoA of Ebola diagnostics and also a call to develop rapid, selective and sensitive POC detection of EBOV for global health care. We propose that adopting miniaturized electrochemical EBOV immunosensing can detect virus level at pM concentration within ~40 minute compared to 3 days of ELISA test at nM levels.


Brain Awareness Week, CoVID-19 infection and Neurological Sciences


title: Biomass use and COVID-19: A novel concern

text: Abstract Evidence supports the link between air pollution and COVID-19 and thus it is likely that exposure to biomass smoke is associated with COVID-19. The poor, including refugees and migrant workers staying in fragile conditions, are most vulnerable. An outbreak of COVID-19 in a place where the concept of physical distancing is next to impossible could easily overwhelm the public health system. It is thus essential to understand the consequences of being exposed to smoke in relation to COVID-19 infection.


title: No evidence of enteric viral involvement in the new neonatal porcine diarrhoea syndrome in Danish pigs

text: BACKGROUND: The aim of this study was to investigate whether the syndrome New Neonatal Porcine Diarrhoea Syndrome (NNPDS) is associated with a viral aetiology. Four well-managed herds experiencing neonatal diarrhoea and suspected to be affected by NNPDS were included in a case-control set up. A total of 989 piglets were clinically examined on a daily basis. Samples from diarrhoeic and non-diarrhoeic piglets at the age of three to seven days were selected for extensive virological examination using specific real time polymerase chain reactions (qPCRs) and general virus detection methods. RESULTS: A total of 91.7% of the animals tested positive by reverse transcription qPCR (RT-qPCR) for porcine kobuvirus 1 (PKV-1) while 9% and 3% were found to be positive for rotavirus A and porcine teschovirus (PTV), respectively. The overall prevalence of porcine astrovirus (PAstV) was 75% with 69.8% of the PAstV positive pigs infected with PAstV type 3. No animals tested positive for rotavirus C, coronavirus (TGEV, PEDV and PRCV), sapovirus, enterovirus, parechovirus, saffoldvirus, cosavirus, klassevirus or porcine circovirus type 2 (PCV2). Microarray analyses performed on a total of 18 animals were all negative, as were eight animals examined by Transmission Electron Microscopy (TEM). Using Next Generation de novo sequencing (de novo NGS) on pools of samples from case animals within all herds, PKV-1 was detected in four herds and rotavirus A, rotavirus C and PTV were detected in one herd each. CONCLUSIONS: Our detailed analyses of piglets from NNPDS-affected herds demonstrated that viruses did not pose a significant contribution to NNPDS. However, further investigations are needed to investigate if a systemic virus infection plays a role in the pathogenesis of NNPDS.


title: Field Effectiveness of Pandemic and 2009-2010 Seasonal Vaccines against 2009-2010 A(H1N1) Influenza: Estimations from Surveillance Data in France

text: BACKGROUND: In this study, we assess how effective pandemic and trivalent 2009-2010 seasonal vaccines were in preventing influenza-like illness (ILI) during the 2009 A(H1N1) pandemic in France. We also compare vaccine effectiveness against ILI versus laboratory-confirmed pandemic A(H1N1) influenza, and assess the possible bias caused by using non-specific endpoints and observational data. METHODOLOGY AND PRINCIPAL FINDINGS: We estimated vaccine effectiveness by using the following formula: VE = (PPV-PCV)/(PPV(1-PCV)) × 100%, where PPV is the proportion vaccinated in the population and PCV the proportion of vaccinated influenza cases. People were considered vaccinated three weeks after receiving a dose of vaccine. ILI and pandemic A(H1N1) laboratory-confirmed cases were obtained from two surveillance networks of general practitioners. During the epidemic, 99.7% of influenza isolates were pandemic A(H1N1). Pandemic and seasonal vaccine uptakes in the population were obtained from the National Health Insurance database and by telephonic surveys, respectively. Effectiveness estimates were adjusted by age and week. The presence of residual biases was explored by calculating vaccine effectiveness after the influenza period. The effectiveness of pandemic vaccines in preventing ILI was 52% (95% confidence interval: 30–69) during the pandemic and 33% (4–55) after. It was 86% (56–98) against confirmed influenza. The effectiveness of seasonal vaccines against ILI was 61% (56–66) during the pandemic and 19% (−10–41) after. It was 60% (41–74) against confirmed influenza. CONCLUSIONS: The effectiveness of pandemic vaccines in preventing confirmed pandemic A(H1N1) influenza on the field was high, consistently with published findings. It was significantly lower against ILI. This is unsurprising since not all ILI cases are caused by influenza. Trivalent 2009-2010 seasonal vaccines had a statistically significant effectiveness in preventing ILI and confirmed pandemic influenza, but were not better in preventing confirmed pandemic influenza than in preventing ILI. This lack of difference might be indicative of selection bias.


title: Surgeons, Ethics, and COVID-19: Early Lessons Learned

text: In response to the COVID-19 pandemic, surgeons are being forced to shift from patient-centered ethics to public health ethics. This shift will inevitably cause moral distress for surgeons as they are forced to alter elective surgical schedules and shift to other aspects of patient care. It is imperative that we realize the changes that are occurring in the current international setting of absolute scarcities so that surgeons are best equipped to navigate these challenging ethical waters.


title: When polymerase chain reaction does not help: cytomegalovirus pneumonitis associated with very low or undetectable viral load in both blood and bronchoalveolar lavage samples after lung transplantation

text: Cytomegalovirus (CMV) pneumonitis occurs frequently among solid organ transplant recipients and is classically associated with significant viral replication in both blood and bronchoalveolar lavage (BAL) samples. We present a case of a 64‐year‐old lung transplant recipient who presented with CMV pneumonitis that was diagnosed based on the association of viral inclusion in the BAL sample, rapid response to ganciclovir, and absence of other infectious etiology. Surprisingly, we observed very low or undetectable viral load both in blood and BAL samples. Diagnosis of CMV pneumonitis should rely on the association of clinical, pathological, radiological, and microbiological signs, while quantitative nucleic acid amplification testing should be interpreted with caution.


title: Molecular characterization and genogrouping of VP1 of aquatic birnavirus GC1 isolated from rockfish Sebastes schlegeli in Korea

text: The cDNA nucleotide sequence of genome segment B encoding the VP1 protein was determined for the aquatic birnavirus GC1 isolated from the rockfish Sebastes schlegeli in Korea. The VP1 protein of GC1 contains a 2,538 bp open reading frame, which encodes a protein comprising 846 amino acid residues that has a predicted MW of 94 kDa. The sequence contains 6 potential Asn-X-Ser/Thr motifs. Eight potential Ser phosphorylation sites and 1 potential Tyr phophorylation site were also identified. GC1 contains the Leu-Lys-Asn (LKN) motif instead of the typical Gly-Asp-Asp (GDD) motif found in other aquatic birnaviruses. We also identified the GLPYIGKT motif, the putative GTP-binding site at amino acid position 248. In total, the VP1 regions of 22 birnavirus strains were compared for analyzing the genetic relationship among the family Birnaviridae. Based on the deduced amino acid sequences, GC1 was observed to be more closely related to the infectious pancreatic necrosis virus (IPNV) from the USA, Japan, and Korea than the IPNV from Europe. Further, aquatic birnaviruses containing GC1 and IPNV have genogroups that are distinct from those in the genus Avibirnaviruses and Entomo-birnaviruses. The birnavirusstrains were clustered into 5 genogroups based on their amino acid sequences. The marine aquatic birnaviruses (MABVs) containing GC1 were included in the MABV genogroup; the IPNV strains isolated from Korea, Japan, and the USA were included in genogroup 1 and the IPNV strains isolated primarily from Europe were included in genogroup 2. Avibirnaviruses and entomobirnaviruses were included in genogroup 3 and 4, respectively.


title: Cancer therapy and treatments during COVID-19 era

text: The COVID-19 pandemic has put a serious strain on health treatments as well at the economies of many nations. Unfortunately, there is not currently available vaccine for SARS-Cov-2/COVID-19. Various types of patients have delayed treatment or even routine check-ups and we are adapting to a virtual world. In many cases, surgeries are delayed unless they are essential. This is also true with regards to cancer treatments and screening. Interestingly, some existing drugs and nutraceuticals have been screened for their effects on COVID-19. Certain FDA approved drugs, vitamin, natural products and trace minerals may be repurposed to treat or improve the prevention of COVID-19 infections and disease progression. This review article will summarize how the treatments of various cancer patients has changed during the COVID-19 era as well as discuss the promise of some existing drugs and other agents to be repurposed to treat this disease.


COVID‐19 Relief Law Update


title: Virus purification and enrichment by hydroxyapatite chromatography on a chip

text: Abstract The spread of infectious diseases has become a global health concern. In order to diagnose infectious diseases quickly and accurately, next-generation DNA sequencing techniques for genetic analysis of infectious viruses have been developed rapidly. However, it takes a very long time to pretreat clinical samples for genetic analysis using next-generation sequencers. We have therefore developed a microfluidic chromatography chip that can purify and enrich viruses in a sample using hydroxyapatite particles packed in a micro-column. We demonstrated the purification of virus from a mixture of virus and FBS protein, and enrichment of the virus using this novel microfluidic chip.


title: Cellular membrane cholesterol is required for porcine reproductive and respiratory syndrome virus entry and release in MARC-145 cells

text: Cholesterol represents one of the key constituents of small, dynamic, sterol- and sphingolipid-enriched domains on the plasma membrane. It has been reported that many viruses depend on plasma membrane cholesterol for efficient infection. In this study, the role of the plasma membrane cholesterol in porcine reproductive and respiratory syndrome virus (PRRSV) infection of MARC-145 cells was investigated. Pretreatment of MARC-145 cells with methyl-β-cyclodextrin (MβCD), a drug used to deplete cholesterol from cellular membrane, significantly reduced PRRSV infection in a dose-dependent manner. This inhibition was partially reversed by supplementing exogenous cholesterol following MβCD treatment, suggesting that the inhibition of PRRSV infection was specifically mediated by removal of cellular cholesterol. Further detailed studies showed that depletion of cellular membrane cholesterol significantly inhibited virus entry, especially virus attachment and release. These results indicate that the presence of cholesterol in the cellular membrane is a key component of PRRSV infection.


title: Role of chemotherapy of taeniasis in prevention of neurocysticercosis

text: Abstract Neurocysticercosis (NC) is a serious public health problem in Taenia solium endemic areas and in some immigrants and international travelers. A key intervention in preventing NC is elimination of taeniasis by chemotherapy. Currently, two safe and effective taenicides, namely niclosamide and praziquantel, are available. Both are on WHO Essential Drug list, but are often inaccessible in T. solium endemic areas. Natural remedies, still widely used in some endemic areas, are frequently carcinogenic or highly toxic and as such should be discontinued. Chemotherapeutic intervention to control T. solium taeniasis/cysticercosis, whilst theoretically feasible, has several practical obstacles. These include poor public awareness, problems with diagnosing Taenia carriers, poor availability of taenicides where needed and low priority afforded to the control of NC. These can be overcome, respectively, by effective health education, wider use of newly developed coproantigen tests, strengthening of health services infrastructure and essential drugs distribution, and increasing the priority given to prevention of NC, as a leading cause of epilepsy in T. solium endemic areas. Information is accumulating on rational approaches to population-based short-term chemotherapeutic control measures. These are: widely available modern diagnostic tools and taenicides, treatment of any case of taeniasis, confirmed or probable, focus-oriented chemotherapy, irrespective of Taenia species implicated, improved sanitation, cooperation of veterinary and medical services, linkage with programs against epilepsy and cooperation of better educated communities. Now, it remains to take an advantage of existing tools and experience.


Tracking the Traveler Without a Passport: Perspective on Surveillance of Imported Disease


title: Health care–associated infection outbreaks in pediatric long-term care facilities

text: Children in pediatric long-term care facilities (pLTCFs) have complex medical conditions and increased risk for health care–associated infections (HAIs). We performed a retrospective study from January 2010-December 2013 at 3 pLTCFs to describe HAI outbreaks and associated infection control interventions. There were 62 outbreaks involving 700 cases in residents and 250 cases in staff. The most common interventions were isolation precautions and education and in-services. Further research should examine interventions to limit transmission of infections in pLTCFs.


title: Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin–angiotensin–aldosterone inhibitors

text: AIMS: The current pandemic coronavirus SARS-CoV-2 infects a wide age group but predominantly elderly individuals, especially men and those with cardiovascular disease. Recent reports suggest an association with use of renin–angiotensin–aldosterone system (RAAS) inhibitors. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for coronaviruses. Higher ACE2 concentrations might lead to increased vulnerability to SARS-CoV-2 in patients on RAAS inhibitors. METHODS AND RESULTS: We measured ACE2 concentrations in 1485 men and 537 women with heart failure (index cohort). Results were validated in 1123 men and 575 women (validation cohort). The median age was 69 years for men and 75 years for women. The strongest predictor of elevated concentrations of ACE2 in both cohorts was male sex (estimate = 0.26, P < 0.001; and 0.19, P < 0.001, respectively). In the index cohort, use of ACE inhibitors, angiotensin receptor blockers (ARBs), or mineralocorticoid receptor antagonists (MRAs) was not an independent predictor of plasma ACE2. In the validation cohort, ACE inhibitor (estimate = –0.17, P = 0.002) and ARB use (estimate = –0.15, P = 0.03) were independent predictors of lower plasma ACE2, while use of an MRA (estimate = 0.11, P = 0.04) was an independent predictor of higher plasma ACE2 concentrations. CONCLUSION: In two independent cohorts of patients with heart failure, plasma concentrations of ACE2 were higher in men than in women, but use of neither an ACE inhibitor nor an ARB was associated with higher plasma ACE2 concentrations. These data might explain the higher incidence and fatality rate of COVID-19 in men, but do not support previous reports suggesting that ACE inhibitors or ARBs increase the vulnerability for COVID-19 through increased plasma ACE2 concentrations.


Temperature Monitoring with an Implantable Loop Recorder in a Patient with Presumed COVID-19


title: Mortality in COVID-19 patients treated with ACEIs/ARBs: re-estimated meta-analysis results following the Mehra et al. retraction

text: • A meta-analysis included a retracted study for Covid-19 patients on ACEI/ARBs. • Re-estimation of that meta-analysis confirms there is no increase in mortality. • As more studies accrue, a “living systematic review” is needed to update risk estimates.


title: Vesivirus viremia and seroprevalence in humans

text: Pathogenic caliciviruses of the genus Vesivirus circulate in oceanic ecosystems and spread to and among terrestrial mammals. Isolation of Vesivirus from natural and laboratory infections in humans led to this investigation of Vesivirus seroprevalence and viremia. Sera from four groups were tested for antibodies to Vesivirus as follows: blood donors whose units were cleared for donation, blood donors whose units were not accepted for donation solely because of elevated blood liver alanine aminotransferase (ALT) concentrations, patients with clinical hepatitis of unknown but suspected infectious cause, and patients with clinical hepatitis of unknown cause but associated with blood transfusion or dialysis. Additionally, sera were tested for Vesivirus genome by three methods: dot‐blot and two reverse transcription‐polymerase chain reaction (RT‐PCR) methods. The calculated seroprevalence against Vesivirus virions within these groups (N = 765) was 12%, 21%, 29%, and 47%, respectively (P < 0.001 for group differences). Additionally, 11 (9.8%) of 112 sera tested yielded RT‐PCR amplicons that by nucleotide sequence were distinct from each other and related to known Vesivirus. These data indicate that some blood donors in the population tested have serologic evidence of previous Vesivirus infection and some also have Vesivirus viremia. These results justify further investigation of an association between Vesivirus infection and illness in humans. J. Med. Virol. 78:693–701, 2006. © 2006 Wiley‐Liss, Inc.


title: Dudleya brittonii extract promotes survival rate and M2-like metabolic change in porcine 3D4/31 alveolar macrophages

text: OBJECTIVE: Although alveolar macrophages play a key role in the respiratory immunity of livestock, studies on the mechanism of differentiation and survival of alveolar macrophages are lacking. Therefore, we undertook to investigate changes in the lipid metabolism and survival rate, using 3D4/31 macrophages and Dudleya brittonii which has been used as a traditional asthma treatment. METHODS: 3D4/31 macrophages were used as the in vitro porcine alveolar macrophages model. The cells were activated by exposure to phorbol 12-myristate 13-acetate (PMA). Dudleya brittonii extraction was performed with distilled water. For evaluating the cell survival rate, we performed the water-soluble tetrazolium salt cell viability assay and growth curve analysis. To confirm cell death, cell cycle and intracellular reactive oxygen species (ROS) levels were measured using flow cytometric analysis by applying fluorescence dye dichlorofluorescein diacetate and propidium iodide. Furthermore, we also evaluated cellular lipid accumulation with oil red O staining, and fatty acid synthesis related genes expression levels using quantitative polymerase chain reaction (qPCR) with SYBR green dye. Glycolysis, fatty acid oxidation, and tricarboxylic acid (TCA) cycle related gene expression levels were measured using qPCR after exposure to Dudleya brittonii extract (DB) for 12 h. RESULTS: The ROS production and cell death were induced by PMA treatment, and exposure to DB reduced the PMA induced downregulation of cell survival. The PMA and DB treatments upregulated the lipid accumulation, with corresponding increase in the acetyl-CoA carboxylase alpha, fatty acid synthase mRNA expressions. DB-PMA co-treatment reduced the glycolysis genes expression, but increased the expressions of fatty acid oxidation and TCA cycle genes. CONCLUSION: This study provides new insights and directions for further research relating to the immunity of porcine respiratory system, by employing a model based on alveolar macrophages and natural materials.


title: Delayed Time-to-Treatment of an Antisense Morpholino Oligomer Is Effective against Lethal Marburg Virus Infection in Cynomolgus Macaques

text: Marburg virus (MARV) is an Ebola-like virus in the family Filovirdae that causes sporadic outbreaks of severe hemorrhagic fever with a case fatality rate as high as 90%. AVI-7288, a positively charged antisense phosphorodiamidate morpholino oligomer (PMOplus) targeting the viral nucleoprotein gene, was evaluated as a potential therapeutic intervention for MARV infection following delayed treatment of 1, 24, 48, and 96 h post-infection (PI) in a nonhuman primate lethal challenge model. A total of 30 cynomolgus macaques were divided into 5 groups of 6 and infected with 1,830 plaque forming units of MARV subcutaneously. AVI-7288 was administered by bolus infusion daily for 14 days at 15 mg/kg body weight. Survival was the primary endpoint of the study. While none (0 of 6) of the saline group survived, 83–100% of infected monkeys survived when treatment was initiated 1, 24, 48, or 96 h post-infection (PI). The antisense treatment also reduced serum viremia and inflammatory cytokines in all treatment groups compared to vehicle controls. The antibody immune response to virus was preserved and tissue viral antigen was cleared in AVI-7288 treated animals. These data show that AVI-7288 protects NHPs against an otherwise lethal MARV infection when treatment is initiated up to 96 h PI.


title: Development of a Rapid Fluorescent Immunochromatographic Test to Detect Respiratory Syncytial Virus

text: Human respiratory syncytial virus (RSV) is one of the most common viruses infecting the respiratory tracts of infants. The rapid and sensitive detection of RSV is important to minimize the incidence of infection. In this study, novel monoclonal antibodies (mAbs; B11A5 and E8A11) against RSV nucleoprotein (NP) were developed and applied to develop a rapid fluorescent immunochromatographic strip test (FICT), employing europium nanoparticles as the fluorescent material. For the FICT, the limits of detection of the antigen and virus were 1.25 µg/mL and 4.23 × 10(6) TCID(50)/mL, respectively, corresponding to 4.75 × 10(6) ± 5.8 ×10(5) (mean ± SD) RNA copy numbers per reaction mixture for RSV NP. A clinical study revealed a sensitivity of 90% (18/20) and specificity of 98.18% (108/110) for RSV detection when comparing the performance to that of reverse transcription polymerase chain reaction (RT-PCR), representing a 15% improvement in sensitivity over the SD Bioline rapid kit. This newly developed FICT could be a useful tool for the rapid diagnosis of RSV infection.


Research during SARS-CoV-2 pandemic: To “Preprint” or not to “Preprint”, that is the question


title: Beyond ventilatory support: challenges in general practice and in the treatment of critically Ill children and adolescents with SARS-CoV-2 infection

text: Severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2 infection) is a new challenge for all countries, and children are predisposed to acquire this disease Some studies have demonstrated more severe diseases in adults, but critically ill pediatric patients have been described in all ages Pulmonary involvement is the major feature, and ventilatory support is common in critical cases Nevertheless, other very important therapeutic approaches must be considered In this article, we reviewed extensively all recent medical literature to point out the main clinical attitudes to support these pediatric patients during their period in respiratory support Radiologic findings, fluid therapy, hemodynamic support, use of inotropic/vasopressors, nutritional therapy, antiviral therapy, corticosteroids, antithrombotic therapy, and immunoglobulins are analyzed to guide all professionals during hospitalization We emphasize the importance of a multi-professional approach for adequate recovery


title: When is it safe to ease lockdowns?

text: Contact tracing and a low number of new cases are crucial before lifting coronavirus restrictions, reports Jessica Hamzelou


title: “Hello are you available?” Dealing with online frauds and the role of forensic science

text: Abstract On August 6, 2019, the 119 members of the School of criminal justice, forensic science and criminology at the University of Lausanne were the target of an online scammer. His/her modus operandi consisted of email masquerading as the Director of the School in an attempt to induce the victims to buy digital gift cards and to transmit the card usage code to the perpetrator. The first author of this paper is the Director of the School, and the second is an expert in digital forensic science and a professor of the School. They worked together in real time to deal with the fraud. Because the fraud occurred in a School of forensic science and criminology, it raised many questions on a variety of overlapping dimensions. The objective of this study was, therefore, to draw lessons from this case from several perspectives ranging from forensic science to cybersecurity, and from practical to academic. The response to the incident has been treated in four typical distinguishable phases: (1) fraud detection; (2) crisis management; (3) post-incident analysis; and (4) reporting to different communities. We conclude this paper by taking lessons from the case to express the essential role of forensic knowledge and crime analysis in interpreting the information conveyed by digital traces to develop innovative cross-disciplinary models for preventing, detecting, analysing, investigating and responding to online fraud.


title: What does the COVID-19 pandemic mean for HIV, tuberculosis, and malaria control?

text: Despite its current relatively low global share of cases and deaths in Africa compared to other regions, coronavirus disease 2019 (COVID-19) has the potential to trigger other larger crises in the region. This is due to the vulnerability of health and economic systems, coupled with the high burden of human immunodeficiency virus (HIV), tuberculosis (TB), and malaria. Here we examine the potential implications of COVID-19 on the control of these major epidemic diseases in Africa. We use current evidence on disease burden of HIV, TB, and malaria, and epidemic dynamics of COVID-19 in Africa, retrieved from the literature. Our analysis shows that the current measures to control COVID-19 neglect important and complex context-specific epidemiological, social, and economic realities in Africa. There is a similarity of clinical features of TB and malaria, with those used to track COVID-19 cases. This coupled with institutional mistrust and misinformation might result in many patients with clinical features similar to those of COVID-19 being hesitant to voluntarily seek care in a formal health facility. Furthermore, most people in productive age in Africa work in the informal sector, and most of those in the formal sector are underemployed. With the current measures to control COVID-19, these populations might face unprecedented difficulties to access essential services, mainly due to reduced ability of patients to support direct and indirect medical costs, and unavailability of transportation means to reach health facilities. Therefore, if not accompanied with appropriate economic and epidemiological considerations, we anticipate that these measures might result in unprecedented difficulties among vulnerable segments of society to access essential services, including antiretroviral and prophylactic drugs among people living with HIV and Acquired Immune Deficiency Syndrome, anti-tuberculosis drugs, and curative and preventive treatments for malaria among pregnant women and children. This might increase the propensity of patients taking substandard doses and/or medicines, which has the potential to compromise drug efficacy, and worsen health inequalities in the region. COVID-19 responses at country level should include measures to protect vulnerable and under-served segments of society.


title: Assessment of Sensitivity and Specificity of Patient-Collected Lower Nasal Specimens for Sudden Acute Respiratory Syndrome Coronavirus 2 Testing

text: This prognostic study compares the diagnostic equivalence of patient-collected lower nasal specimens with that of health care worker–collected oropharyngeal specimens for sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing.


title: Complete Genome Sequence of Porcine Deltacoronavirus Isolated in Thailand in 2015

text: In Thailand, porcine deltacoronavirus (PDCoV) was first identified in November 2015. The virus was isolated from piglets experiencing diarrhea outbreak. Herein, the full-length genome sequence of the Thai PDCoV isolate P23_15_TT_1115 is reported. The results provide a clearer understanding of the molecular characteristics of PDCoV in Thailand.


Renin-angiotensin system inhibitors and COVID-19: Potential therapeutics rather than perpetrators


title: Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation

text: The RefSeq project at the National Center for Biotechnology Information (NCBI) maintains and curates a publicly available database of annotated genomic, transcript, and protein sequence records (http://www.ncbi.nlm.nih.gov/refseq/). The RefSeq project leverages the data submitted to the International Nucleotide Sequence Database Collaboration (INSDC) against a combination of computation, manual curation, and collaboration to produce a standard set of stable, non-redundant reference sequences. The RefSeq project augments these reference sequences with current knowledge including publications, functional features and informative nomenclature. The database currently represents sequences from more than 55 000 organisms (>4800 viruses, >40 000 prokaryotes and >10 000 eukaryotes; RefSeq release 71), ranging from a single record to complete genomes. This paper summarizes the current status of the viral, prokaryotic, and eukaryotic branches of the RefSeq project, reports on improvements to data access and details efforts to further expand the taxonomic representation of the collection. We also highlight diverse functional curation initiatives that support multiple uses of RefSeq data including taxonomic validation, genome annotation, comparative genomics, and clinical testing. We summarize our approach to utilizing available RNA-Seq and other data types in our manual curation process for vertebrate, plant, and other species, and describe a new direction for prokaryotic genomes and protein name management.