title: Necrotizing periodontal disease: oral manifestation of COVID‐19

text: We read with interest the series of cases reported by Martín Carreras‐Presas et al. (2020). We believe that the described oral vesiculobullous manifestations were suggestive of coronavirus disease 2019 (COVID‐19) co‐infections, which at present, are overlooked and poorly understood (Cox et al., 2020). Increased disease severity and mortality amongst individuals with respiratory viral infections are often attributed to subsequent bacterial co‐infections, accounting for approximately 95% of deaths during the 1918 Spanish flu pandemic (Morens et al., 2008).


title: Coronavirus disease 2019 (COVID-19) associated coagulopathy and its impact on outcomes in Shenzhen, China: A retrospective cohort study

text: Background: Early detection of suspected critical patients infected with coronavirus disease 2019 (COVID-19) is very important for the treatment of patients. This study aimed to investigate the role of COVID-19 associated coagulopathy (CAC) to preview and triage. Methods and Results: A cohort study was designed from government designated COVID-19 treatment center. CAC was defined as International Society on Thrombosis and Haemostasis (ISTH) score ≥2. Data from 117 patients COVID-19 were reviewed on admission. The primary and secondary outcomes were admission to Intensive Care Unit (ICU), the use of mechanical ventilation, vital organ dysfunction, discharges of days 14, 21 and 28 from admission and hospital mortality. Among them, admission to ICU was increased progressively from 16.1% in patients with non-CAC to 42.6% in patients with CAC (P < 0.01). Likely, invasive ventilation and noninvasive ventilation were increased from 1.8%, 21.4% in patients with non-CAC to 21.3%, 52.5% in patients with CAC, respectively (P < 0.01). The incidences of acute hepatic injury and acute respiratory distress syndrome in non-CAC and CAC were 28.6% vs. 62.3%, 8.9% vs. 27.9%, respectively (P < 0.01). The discharges of days 14, 21 and 28 from admission were more in non-CAC than those of CAC (P < 0.05). Multiple logistic regression results showed that ISTH score ≥2 was obviously associated with the admission to ICU (OR 4.07, 95% CI 1.47–11.25 P = 0.007) and the use of mechanical ventilation (OR 5.54, 95% CI 2.01–15.28 P = 0.001) in patients with COVID-19. Conclusion: All results show ISTH score ≥2 is an important indicator to preview and triage for COVID-19 patients.


Impact of COVID-19 on IR Fellowship


title: Obstetricians on the Coronavirus Disease 2019 (COVID-19) Front Lines and the Confusing World of Personal Protective Equipment

text: As health care systems struggle to maintain adequate supplies of personal protective equipment, there is confusion and anxiety among obstetricians and others about how to best protect themselves, their coworkers, and their patients. Although use of personal protective equipment is a critical strategy to protect health care personnel from coronavirus disease 2019 (COVID-19), other strategies also need to be implemented on labor and delivery units to reduce the risk of health care–associated transmission, including screening of all pregnant women who present for care (case identification), placing a mask on and rapidly isolating ill pregnant women, and minimizing the number of personnel who enter the room of an ill patient (physical distancing). Although the mechanism of transmission of COVID-19 is not known with certainty, current evidence suggests that COVID-19 is transmitted primarily through respiratory droplets. Therefore, strict adherence to hand hygiene and consistent use of recommended personal protective equipment are cornerstones for reducing transmission. In addition, it is critical that health care professionals receive training on and practice correct donning (putting on) and doffing (removing) of personal protective equipment and avoid touching their faces as well as their facial protection to minimize self-contamination.


title: Remdesivir and Tocilizumab: Mix or Match

text: To date, no therapy has demonstrated definite efficacy for patients with COVID‐19. Antiviral, as well as, anti‐inflammatory approaches, as these represented by remdesivir (RDV) and tocilizumab (TCZ) use, have been recently put forward. However, data upon optimal choice of one over the other, or potential need for regimen combination, remains an open question. We hereby report two well‐matched cases of SARS‐CoV‐2 (+) patients, developing respiratory failure, both receiving TCZ following severe inflammatory response, with or without RDV. We argue that, RDV administration is pivotal early in the course of the disease, since TCZ use alone cannot ensure inflammation control. This article is protected by copyright. All rights reserved.


SARS‐CoV2‐related myocarditis‐like syndroms: Shakespeare´s question: What´s in a name?


docid: rsajugmp

title: Acute Disseminated Encephalomyelitis in Children and Adolescents: A Single Center Experience

text: Abstract Background Acute disseminated encephalomyelitis is an immune-mediated disease that produces multiple inflammatory lesions in the brain and spinal cord. Methods This study retrospectively evaluated 15 children with acute disseminated encephalomyelitis in children and adolescents from a single institution in Adana, Turkey. Results The patients presented in a seasonal distribution, with 73.3%: (11/15) presenting in winter or spring. The majority of patients (13/15, 86.7%) had a history of acute febrile illness 2 to 40 days before presentation, and five children had serologic evidence of specific triggers: mycoplasma (2 children), influenza-A (H1N1) (1 child), or Epstein-Barr virus. All children were treated with a standard protocol of 3 to 5 days of intravenous administration of methylprednisolone and intravenous immunoglobulin for patients who continued to deteriorate. Oseltamivir and clarithromycin were administered in patients with influenza-A (H1N1) and mycoplasma according to the serology. In 13 patients, all neurologic signs and symptoms resolved after treatment. Only one patient was left with severe neurologic sequelae and another child had recurrent attacks and was ultimately diagnosed with possible multiple sclerosis. Conclusions The present series demonstrates that acute disseminated encephalomyelitis in children occurs predominantly in winter or spring and often follows an upper respiratory tract illness for those along the southern coast of Anatolia (Mediterranean region). Early treatment with immunomodulative agents is recommended and is likely to result in a favorable outcome or full recovery. This study also suggests benefit from antiviral and antibiotic treatment initiated as soon as possible after the onset of illness.


title: “Yes, but will it work for my patients?” Driving clinically relevant research with benchmark datasets

text: Benchmark datasets have a powerful normative influence: by determining how the real world is represented in data, they define which problems will first be solved by algorithms built using the datasets and, by extension, who these algorithms will work for. It is desirable for these datasets to serve four functions: (1) enabling the creation of clinically relevant algorithms; (2) facilitating like-for-like comparison of algorithmic performance; (3) ensuring reproducibility of algorithms; (4) asserting a normative influence on the clinical domains and diversity of patients that will potentially benefit from technological advances. Without benchmark datasets that satisfy these functions, it is impossible to address two perennial concerns of clinicians experienced in computational research: “the data scientists just go where the data is rather than where the needs are,” and, “yes, but will this work for my patients?” If algorithms are to be developed and applied for the care of patients, then it is prudent for the research community to create benchmark datasets proactively, across specialties. As yet, best practice in this area has not been defined. Broadly speaking, efforts will include design of the dataset; compliance and contracting issues relating to the sharing of sensitive data; enabling access and reuse; and planning for translation of algorithms to the clinical environment. If a deliberate and systematic approach is not followed, not only will the considerable benefits of clinical algorithms fail to be realized, but the potential harms may be regressively incurred across existing gradients of social inequity.


title: Detection and occurrence of indicator organisms and pathogens

text: This review paper focuses on detection and quantification techniques of indicator organisms that can be used for water quality assessment. The environmental pathogens that are critical to understand and better evaluate water quality are also discussed in this paper. Several recent studies using culture‐independent methods such as microbial source tracking, pulsed field gel electrophoresis, mitochondrial DNA, and next generation sequencing to assess various environmental samples and water bodies have been reviewed. PRACTITIONER POINTS: Various waterborne pathogens and cases of outbreak occurances due to presence of pathogens are studied in this review paper. Recent studies for detecting major indicator organisms to evaluate the presence of pathogens in water bodies are reviewed. Culture‐independent techniques as robust tools to detect and quantify waterborne pathogens are discussed in this review paper.


title: Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity

text: Abstract Objectives We hypothesized that immune response may contribute to progression of coronavirus disease-19 (COVID-19) at the second week of illness. Therefore, we compared cell-mediated immune (CMI) responses between severe and mild COVID-19 cases. Methods We examined peripheral blood mononuclear cells of laboratory-confirmed COVID-19 patients from their first and third weeks of illness. Severe pneumonia was defined as an oxygen saturation ≤ 93% at room air. Expressions of molecules related to T-cell activation and functions were analyzed by flow cytometry. Results The population dynamics of T cells at the first week were not different between the two groups. However, total numbers of CD4+ and CD8 + T cells tended to be lower in the severe group at the third week of illness. Expressions of Ki-67, PD-1, perforin, and granzyme B in CD4+ or CD8+ T cells were significantly higher in the severe group than in the mild group at the third week. In contrast to the mild group, the levels of their expression did not decrease in severe group. Conclusions Severe COVID-19 had higher degree of proliferation, activation, and cytotoxicity of T-cells at the late phase of illness without cytotoxic T-cell contraction, which might contribute to the development of severe COVID-19.


title: Willingness to seek laboratory testing for SARS-CoV-2 with home, drive-through, and clinic-based specimen collection locations

text: BACKGROUND: SARS-CoV-2 virus testing for persons with COVID-19 symptoms, and contact tracing for those testing positive, will be critical to successful epidemic control. Willingness of persons experiencing symptoms to seek testing may determine the success of this strategy. METHODS: A cross-sectional, online survey in the United States measured willingness to seek testing if feeling ill under different specimen collection scenarios: home-based saliva, home-based swab, drive-through facility swab, and clinic-based swab. Instructions clarified that home-collected specimens would be mailed to a laboratory for testing. We presented similar willingness questions regarding testing during follow-up care. RESULTS: Of 1435 participants, comprising a broad range of sociodemographic groups, 92% were willing to test with a home saliva specimen, 88% with home swab, 71% with drive-through swab, and 60% with clinic collected swab. Moreover, 68% indicated they would be more likely to get tested if there was a home testing option. There were no significant differences in willingness items across sociodemographic variables or for those currently experiencing COVID-19 symptoms. Results were nearly identical for willingness to receive testing for follow-up COVID-19 care. CONCLUSIONS: We observed a hierarchy of willingness to test for SARS-CoV-2, ordered by the degree of contact required. Home specimen collection options could result in up to one-third more symptomatic persons seeking testing, facilitating contact tracing and optimal clinical care. Remote specimen collection options may ease supply chain challenges and decrease the likelihood of nosocomial transmission. As home specimen collection options receive regulatory approval, they should be scaled rapidly by health systems.


Manifestaciones neurológicas de la infección por SARS-CoV-2


title: HIV and Shifting epicenters for COVID-19, an alert for some countries

text: Were southern hemisphere countries right to undertake national lockdown during their summer time? Were they right to blindly follow the self-isolation wave that hit European countries in full winter? As a southern hemisphere country like South Africa stands now as the most COVID-19 and HIV affected country in Africa, we use in this paper, recent COVID-19 data to provide a statistical and comparative analysis that may alert southern hemisphere countries entering the winter season. After that, we use a generalized simple mathematical model of HIV-COVID-19 together with graphs, curves and tables to compare the pandemic situation in countries that were once the epicenter of the the disease, such as China, Italy, Spain, United Kingdom (UK) and United States of America (USA). We perform stability and bifurcation analysis and show that the model contains a forward and a backward bifurcation under certain conditions. We also study different scenarios of stability/unstability equilibria for the model. The fractional (generalized) COVID-19 model is solved numerically and a predicted prevalence for the COVID-19 is provided. Recall that Brazil and South Africa share number of similar social features like Favellas (Brazil) and Townships (South Africa) with issues like promiscuity, poverty, and where social distanciation is almost impossible to observe. We can now ask the following question: Knowing its HIV situation, is South Africa the next epicenter in weeks to come when winter conditions, proven to be favorable to the spread of the new coronavirus are comfily installed?


title: Exposure to coronavirus news on mainstream media: The role of risk perceptions and depression

text: OBJECTIVE: The mainstream media tend to rely on news content that will increase risk perceptions of pandemic outbreaks to stimulate public response and persuade people to comply with preventive behaviours. The objective of this study was to examine associations between exposure to coronavirus disease (COVID‐19) news, risk perceptions, and depressive symptoms. METHODS: Cross‐sectional data were collected from 501 participants who were ≥18 years. Exposure to COVID‐19 news was assessed as our exposure variable. We screened for depression (outcome variable) with the Patient Health Questionnaire and examined the roles of risk perceptions. Multiple linear regressions and mediation analysis with 1000 bootstrap resamples were conducted. RESULTS: Participants were 55.29% female, 67.86% White with mean age 32.44 ± 11.94 years. After controlling for sociodemographic and socio‐economic factors, news exposure was positively associated with depressive symptoms β = .11; 95% confidence interval (95%CI) = 0.02–0.20. Mediation analysis showed that perceived vulnerability to COVID‐19 mediated 34.4% of this relationship (β = .04; 95%CI = 0.01–0.06). CONCLUSION: Perceived vulnerability to COVID‐19 can serve as a pathway through which exposure to COVID‐19 news on mainstream media may be associated with depressive symptoms. Based on our findings, we offered recommendations for media–health partnership, practice, and research.


PERSISTENT CORONAVIRUS INFECTION OF PROGENITOR OLIGODENDROCYTES


title: A call to arms: helping family, friends and communities navigate the COVID-19 infodemic

text: With information on COVID-19 evolving daily, the public is confronted with a mix of partial information, conflicting information and sometimes outright misinformation. Who should they turn to for the truth? In the context of acute uncertainty, I discuss what scientists can do to help mitigate the misinformation about what we do know and give some context to help decision-making in the unfolding story of COVID-19.


title: Full-Length Genome Sequence of a Plaque-Cloned Virulent Porcine Epidemic Diarrhea Virus Isolate (USA/Iowa/18984/2013) from a Midwestern U.S. Swine Herd

text: Porcine epidemic diarrhea (PED) was recognized in U.S. swine for the first time in early 2013. A plaque-purified PED virus (PEDV) isolate (USA/Iowa/18984/2013) was obtained from a diarrheic piglet. The isolate is genetically close to other previously reported U.S. PEDVs and recent Chinese PEDVs and was virulent when inoculated into neonatal pigs.


title: Chemokine expression during mouse hepatitis virus-induced encephalitis: Contributions of the spike and background genes

text: Infection of mice with mouse hepatitis virus (MHV) strain JHM (RJHM) induces lethal encephalitis, with high macrophage and neutrophil, but minimal T-cell, infiltration into the brain when compared to the neuroattenuated strain RA59. To determine if chemokine expression corresponds with the cellular infiltrate, chemokine protein and RNA levels from the brains of infected mice were quantified. RJHM-infected mice had lower T-cell (CXCL9, CXCL10), but higher macrophage-attracting (CCL2), chemokine proteins compared to RA59. RJHM also induced significantly higher CXCL2 (a neutrophil chemoattractant) mRNA compared to RA59. The neurovirulent spike gene chimera SJHM/RA59 induces high levels of T cells and macrophages in the brain compared to the attenuated SA59/RJHM chimera. Accordingly, SJHM/RA59 induced higher levels of CXCL9, CXCL10, and CCL2 protein compared to SA59/RJHM. Chemokine mRNA patterns were in general agreement. Thus, chemokine patterns correspond with the cellular infiltrate, and the spike protein influences levels of macrophage, but not T-cell, chemokines.


title: COVID-19 et rhinologie: conseils de bonne pratique, de la consultation au bloc opératoire

text: RESUME Cet article a pour but de proposer aux rhinologistes des conseils sur la façon d’adapter leur pratique courante dans le contexte de l’épidémie de COVID-19. L’objectif général de ces recommandations est de protéger les soignants du COVID-19 tout en continuant les soins urgents afin d’éviter une perte de chance aux patients. Nous présentons ici les recommandations concernant l’activité de consultation, la prescription médicamenteuse et l’activité chirurgicale en rhinologie.


title: Expression of angiotensin-converting enzyme 2 and proteases in COVID-19 patients: a potential role of cellular FURIN in the pathogenesis of SARS-CoV-2

text: Recently, a mini-review was published in the Medical Hypotheses journal by Usul Afsar entitled 2019-nCoV-SARS-CoV-2 (COVID-19) infection: Cruciality of Furin and relevance with cancer. Previous studies have pointed out that disruption of the proteolytic cleavage of proteins can promote infectious and non-infectious diseases. The last few weeks have been marked by an important revelation concerning the pathophysiology of SARS-CoV-2. This new coronavirus disease (COVID-19) is a highly contagious and transmissible acute respiratory infectious disorder. SARS-CoV-2 is composed of RNA-dependent RNA polymerase and structural proteins including Spike protein (S protein). Interestingly, the FURIN, one of the proproteins of the convertase family, play a crucial role in the maturation of viral glycoproteins. In addition, many viruses including coronaviruses, exploit FURIN for the activation of their glycoproteins. Recent data indicate that SARS-CoV-2 enters human cells by binding to angiotensin-converting enzyme 2. Subsequently, the S protein is cleaved by receptor transmembrane serine protease 2 with the help of FURIN which facilitates the entry of the virus into the cell after binding. Furthermore, it seems that FURIN is implicated in the pathogenesis of SRS-CoV-2 and potentially in the increased rates of human-to-human transmission.


Right Ventricular Longitudinal Strain: a new prognostic tool for COVID-19?


title: Incidence of Medically Attended Respiratory Syncytial Virus and Influenza Illnesses in Children 6–59 Months Old During Four Seasons

text: Background. Respiratory syncytial virus (RSV) and influenza are significant causes of seasonal respiratory illness in children. The incidence of influenza and RSV hospitalization is well documented, but the incidence of medically attended, laboratory-confirmed illness has not been assessed in a well defined community cohort. Methods. Children aged 6–59 months with medically attended acute respiratory illness were prospectively enrolled during the 2006–2007 through 2009–2010 influenza seasons in a Wisconsin community cohort. Nasal swabs were tested for RSV and influenza by multiplex reverse-transcription polymerase chain reaction. The population incidence of medically attended RSV and influenza was estimated separately and standardized to weeks 40 through 18 of each season. Results. The cohort included 2800–3073 children each season. There were 2384 children enrolled with acute respiratory illness; 627 (26%) were positive for RSV and 314 (13%) for influenza. The mean age was 28 months (standard deviation [SD] = 15) for RSV-positive and 38 months (SD = 16) for influenza-positive children. Seasonal incidence (cases per 10 000) was 1718 (95% confidence interval [CI], 1602–1843) for RSV and 768 (95% CI, 696–848) for influenza. Respiratory syncytial virus incidence was highest among children 6–11 (2927) and 12–23 months old (2377). Influenza incidence was highest (850) in children 24–59 months old. The incidence of RSV was higher than influenza across all seasons and age groups. Conclusions. The incidence of medically attended RSV was highest in children 6–23 months old, and it was consistently higher than influenza. The burden of RSV remains high throughout the first 2 years of life.


title: Assessing the value of PCR assays in oral fluid samples for detecting African swine fever, classical swine fever, and foot-and-mouth disease in U.S. swine

text: INTRODUCTION: Oral fluid sampling and testing offers a convenient, unobtrusive mechanism for evaluating the health status of swine, especially grower and finisher swine. This assessment evaluates the potential testing of oral fluid samples with real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) to detect African swine fever, classical swine fever, or foot-and-mouth disease for surveillance during a disease outbreak and early detection in a disease-free setting. METHODS: We used a series of logical arguments, informed assumptions, and a range of parameter values from literature and industry practices to examine the cost and value of information provided by oral fluid sampling and rRT-PCR testing for the swine foreign animal disease surveillance objectives outlined above. RESULTS: Based on the evaluation, oral fluid testing demonstrated value for both settings evaluated. The greatest value was in an outbreak scenario, where using oral fluids would minimize disruption of animal and farm activities, reduce sample sizes by 23%-40%, and decrease resource requirements relative to current individual animal sampling plans. For an early detection system, sampling every 3 days met the designed prevalence detection threshold with 0.95 probability, but was quite costly. LIMITATIONS: Implementation of oral fluid testing for African swine fever, classical swine fever, or foot-and-mouth disease surveillance is not yet possible due to several limitations and information gaps. The gaps include validation of PCR diagnostic protocols and kits for African swine fever, classical swine fever, or foot-and-mouth disease on swine oral fluid samples; minimal information on test performance in a field setting; detection windows with low virulence strains of some foreign animal disease viruses; and the need for confirmatory testing protocol development.


title: The role of essential organ-based comorbidities in the prognosis of COVID-19 infection patients

text: Objectives: To assess the role of essential organ-based comorbidities in the prognosis of COVID-19 patients. Methods: All consecutive patients diagnosed with COVID-19 admitted to the Zhongnan Hospital of Wuhan University from 11 January to 16 March 2020 were enrolled in this retrospective cohort study. Results: A total of 212 COVID-19 patients were included. COVID-19 patients with heart, liver and kidneycomorbidity, compared to patients without related comorbidities, were more likely to have cardiac injuries [9.1%(3/33) vs 2.2%(4/179), P = 0.043], liver injuries [13.0%(3/23) vs 3.2%(6/189), P = 0.027], kidney injury [54.5%(6/11) vs 2.0%(4/201), P < 0.001], and higher risk of mortality [Heart-comorbidity: 6.1%(2/33) vs 0.6%(1/179), P = 0.014; Liver-comorbidity: 8.7%(2/23) vs 0.5%(1/189), P = 0.002; Kidney-comorbidity: 27.3%(3/11) vs 1.0%(2/201), P < 0.001. Mortality was higher in patients with more severe Grade of organ injuries [Heart-injury: P = 0.044; Liver-injury: P = 0.020; Kidney-injury: P = 0.030]. Conclusion: Male, older, co-existing of heart, liver, and kidney comorbidities, especially those with severe Grade organ injuries, had a poor prognosis after SARS-CoV-2 infection.


title: Pathogenic epitopes, heterologous immunity and vaccine design

text: Substantial research has been directed towards the development of a new generation of vaccines that are based on the inclusion of immunogenic epitopes in recombinant vectors. Here we examine the evidence that under certain conditions immunogenic epitopes can do more harm than good and might therefore be considered pathogenic. We suggest that the specific removal of such pathogenic epitopes from vaccines might increase their prophylactic potential, while minimizing the risk of side-effects from vaccine use.


title: Influenza A (H1N1) transmission by road traffic between cities and towns

text: Influenza A (H1N1) was spread widely between cities and towns by road traffic and had a major impact on public health in China in 2009. Understanding regulation of its transmission is of great significance with urbanization ongoing and for mitigation of damage by the epidemic. We analyzed influenza A (H1N1) spatiotemporal transmission and risk factors along roads in Changsha, and combined diffusion velocity and floating population size to construct an epidemic diffusion model to simulate its transmission between cities and towns. The results showed that areas along the highways and road intersections had a higher incidence rate than other areas. Expressways and county roads played an important role in the rapid development stage and the epidemic peak, respectively, and intercity bus stations showed a high risk of disease transmission. The model simulates the intensity and center of disease outbreaks in cities and towns, and provides a more complete simulation of the disease spatiotemporal process than other models.


title: Typical or atypical pneumonia and severe acute respiratory symptoms in PICU

text: BACKGROUND AND AIMS: Mycoplasma pneumoniae (MP) is a common childhood pathogen associated with atypical pneumonia (AP). It is often a mild disease and seldom results in paediatric intensive care (PICU) admission. In 2003, World Health Organization (WHO) coined the word SARS (severe acute respiratory syndrome) in patients with severe acute respiratory symptoms (sars) for an outbreak of AP in Hong Kong due to a novel coronavirus. In 2012, another outbreak of coronavirus AP occurred in the Middle East. Confusing case definitions such as MERS (Middle East respiratory syndrome) and SARI (severe acute respiratory infections) were coined. This paper aims to present a case of MP with sars, ARDS, pneumonia and pleural effusion during the MERS epidemics, and review the incidence and mortality of severe AP with MP. METHODS: We presented a case of MP with sars, acute respiratory distress syndrome (ARDS), pneumonia and pleural effusion during the MERS epidemics, and performed a literature review on the incidence and mortality of severe AP with MP requiring PICU care. RESULTS: In early 2013, an 11‐year‐old girl presented with sars, ARDS (acute respiratory distress syndrome), right‐sided pneumonia and pleural effusion. She was treated with multiple antibiotics. Streptococcus pneumoniae was not isolated in this girl with ‘typical’ pneumonia by symptomatology and chest radiography, but tracheal aspirate identified MP instead. The respiratory equations are computed with PaO(2)/FiO(2) consistent with severe lung injury. Literature on the incidence and mortality of severe AP with MP requiring PICU care is reviewed. Six, 165 and 293 articles were found when PubMed (a service of the U.S. National Library of Medicine) was searched for the terms ‘mycoplasma’ and ‘ICU’, ‘mycoplasma’ and ‘mortality’, and ‘mycoplasma' and ‘severe’. Mortality and PICU admission associated with MP is general low and rarely reported. Experimental and clinical studies have suggested that the pathogenesis of lung injuries in MP infection is associated with a cell‐mediated immune reaction, and high responsiveness to corticosteroid therapy has been reported especially for severe disease. Management of severe mycoplasma infection in the PICU includes general cardiopulmonary support and specific antimicrobial treatment. Macrolide resistance genotypes have been detected. CONCLUSION: We urge health organizations to refrain from the temptation of coining unnecessary new terminology to describe essentially the same conditions each and every time when outbreaks of AP occur.


title: Serial Multiple Mediation Analyses: How to Enhance Individual Public Health Emergency Preparedness and Response to Environmental Disasters

text: Recent environmental disasters have revealed the government’s limitations in real-time response and mobilization to help the public, especially when disasters occur in large areas at the same time. Therefore, enhancing the ability to prepare for public health emergencies at the grassroots level and extend public health emergency response mechanisms to communities, and even to individual families, is a research question that is of practical significance. This study aimed to investigate mechanisms to determine how media exposure affects individual public health emergency preparedness (PHEP) to environmental disasters; specifically, we examined the mediating role of knowledge and trust in government. The results were as follows: (1) knowledge had a significant mediating effect on the relationship between media exposure and PHEP; (2) trust in government had a significant mediating effect on the relationship between media exposure and PHEP; (3) knowledge and trust in government had significant multiple mediating effects on the relationship between media exposure and PHEP.


Evidencia viva frente al SARS-CoV-2


docid: zgbbihpb

title: Caring for Miners During the Coronavirus Disease‐2019 (COVID‐19) Pandemic


title: Involvement of digestive system in COVID-19: manifestations, pathology, management and challenges

text: The pandemic of novel coronavirus disease (COVID-19) has developed as a tremendous threat to global health. Although most COVID-19 patients present with respiratory symptoms, some present with gastrointestinal (GI) symptoms like diarrhoea, loss of appetite, nausea/vomiting and abdominal pain as the major complaints. These features may be attributable to the following facts: (a) COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its receptor angiotensin converting enzyme 2 (ACE2) was found to be highly expressed in GI epithelial cells, providing a prerequisite for SARS-CoV-2 infection; (b) SARS-CoV-2 viral RNA has been found in stool specimens of infected patients, and 20% of patients showed prolonged presence of SARS-CoV-2 RNA in faecal samples after the virus converting to negative in the respiratory system. These findings suggest that SARS-CoV-2 may be able to actively infect and replicate in the GI tract. Moreover, GI infection could be the first manifestation antedating respiratory symptoms; patients suffering only digestive symptoms but no respiratory symptoms as clinical manifestation have also been reported. Thus, the implications of digestive symptoms in patients with COVID-19 is of great importance. In this review, we summarise recent findings on the epidemiology of GI tract involvement, potential mechanisms of faecal–oral transmission, GI and liver manifestation, pathological/histological features in patients with COVID-19 and the diagnosis, management of patients with pre-existing GI and liver diseases as well as precautions for preventing SARS-CoV-2 infection during GI endoscopy procedures.


title: Using Web and Social Media for Influenza Surveillance

text: Analysis of Google influenza-like-illness (ILI) search queries has shown a strongly correlated pattern with Centers for Disease Control (CDC) and Prevention seasonal ILI reporting data. Web and social media provide another resource to detect increases in ILI. This paper evaluates trends in blog posts that discuss influenza. Our key finding is that from 5th October 2008 to 31st January 2009, a high correlation exists between the frequency of posts, containing influenza keywords, per week and CDC influenza-like-illness surveillance data.


title: Structure of Mpro from COVID-19 virus and discovery of its inhibitors

text: A new coronavirus (CoV) identified as COVID-19 virus is the etiological agent responsible for the 2019-2020 viral pneumonia outbreak that commenced in Wuhan1–4. Currently there is no targeted therapeutics and effective treatment options remain very limited. In order to rapidly discover lead compounds for clinical use, we initiated a program of combined structure-assisted drug design, virtual drug screening and high-throughput screening to identify new drug leads that target the COVID-19 virus main protease (Mpro). Mpro is a key CoV enzyme, which plays a pivotal role in mediating viral replication and transcription, making it an attractive drug target for this virus5,6. Here, we identified a mechanism-based inhibitor, N3, by computer-aided drug design and subsequently determined the crystal structure of COVID-19 virus Mpro in complex with this compound. Next, through a combination of structure-based virtual and high-throughput screening, we assayed over 10,000 compounds including approved drugs, drug candidates in clinical trials, and other pharmacologically active compounds as inhibitors of Mpro. Six of these inhibit Mpro with IC50 values ranging from 0.67 to 21.4 μM. Ebselen also exhibited promising antiviral activity in cell-based assays. Our results demonstrate the efficacy of this screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases where no specific drugs or vaccines are available.


title: Severe Enteric Disease in an Animal Shelter Associated with Dual Infections by Canine Adenovirus Type 1 and Canine Coronavirus

text: An outbreak of dual infection in dogs with canine adenovirus type 1 (CAV‐1) and canine coronavirus (CCV) infection is reported in an animal shelter that comprised approximately 200 adults stray dogs and 30 puppies. Twenty puppies died 7–8 days after the onset of the clinical signs (severe enteritis, leucopoenia, respiratory distress and dehydration). Both CAV‐1 and CCV were isolated from tissue or swab samples. Antibodies to CCV and, at high levels, to CAV‐1 also were detected in several puppies. The principal histological findings were atrophy of small intestinal villi, lymphoid depletion, hepatitis and bronchopneumonia. The persistence of CCV in the faeces, observed by the polymerase chain reaction assay, was longer than previously reported. Results demonstrated the serious consequences which may occur with dual infections by CAV‐1 and CCV in assembled groups of dogs that are housed in poorly managed kennels with inadequate vaccination programmes.


title: Complement-Mediated Neutralization of Dengue Virus Requires Mannose-Binding Lectin

text: Mannose-binding lectin (MBL) is a key soluble pathogen recognition protein of the innate immune system that binds specific mannose-containing glycans on the surfaces of microbial agents and initiates complement activation via the lectin pathway. Prior studies showed that MBL-dependent activation of the complement cascade neutralized insect cell-derived West Nile virus (WNV) in cell culture and restricted pathogenesis in mice. Here, we investigated the antiviral activity of MBL in infection by dengue virus (DENV), a related flavivirus. Using a panel of naïve sera from mouse strains deficient in different complement components, we showed that inhibition of infection by insect cell- and mammalian cell-derived DENV was primarily dependent on the lectin pathway. Human MBL also bound to DENV and neutralized infection of all four DENV serotypes through complement activation-dependent and -independent pathways. Experiments with human serum from naïve individuals with inherent variation in the levels of MBL in blood showed a direct correlation between the concentration of MBL and neutralization of DENV; samples with high levels of MBL in blood neutralized DENV more efficiently than those with lower levels. Our studies suggest that allelic variation of MBL in humans may impact complement-dependent control of DENV pathogenesis.


title: Current practices for treatment of respiratory syncytial virus and other non‐influenza respiratory viruses in high‐risk patient populations: a survey of institutions in the Midwestern Respiratory Virus Collaborative

text: BACKGROUND: The optimal treatment for respiratory syncytial virus (RSV) infection in adult immunocompromised patients is unknown. We assessed the management of RSV and other non‐influenza respiratory viruses in Midwestern transplant centers. METHODS: A survey assessing strategies for RSV and other non‐influenza respiratory viral infections was sent to 13 centers. RESULTS: Multiplex polymerase chain reaction assay was used for diagnosis in 11/12 centers. Eight of 12 centers used inhaled ribavirin (RBV) in some patient populations. Barriers included cost, safety, lack of evidence, and inconvenience. Six of 12 used intravenous immunoglobulin (IVIG), mostly in combination with RBV. Inhaled RBV was used more than oral, and in the post‐stem cell transplant population, patients with lower respiratory tract infection (LRTI), graft‐versus‐host disease, and more recent transplantation were treated at higher rates. Ten centers had experience with lung transplant patients; all used either oral or inhaled RBV for LRTI, 6/10 treated upper respiratory tract infection (URTI). No center treated non‐lung solid organ transplant (SOT) recipients with URTI; 7/11 would use oral or inhaled RBV in the same group with LRTI. Patients with hematologic malignancy without hematopoietic stem cell transplantation were treated with RBV at a similar frequency to non‐lung SOT recipients. Three of 12 centers, in severe cases, treated parainfluenza and metapneumovirus, and 1/12 treated coronavirus. CONCLUSIONS: Treatment of RSV in immunocompromised patients varied greatly. While most centers treat LRTI, treatment of URTI was variable. No consensus was found regarding the use of oral versus inhaled RBV, or the use of IVIG. The presence of such heterogeneity demonstrates the need for further studies defining optimal treatment of RSV in immunocompromised hosts.


title: Epidemiology of Human and Animal Viral Diseases

text: Viral disease epidemiology is the study of the determinants, dynamics, and distribution of viral diseases in populations. The risk of infection or disease in a population is determined by characteristics of the virus, the host, and the host population, as well as behavioral, environmental, and ecological factors that affect virus transmission from one host to another. Viral disease epidemiology has come to have a major role in clarifying the etiologic role of particular viruses and viral variants as the cause of specific diseases, in improving our understanding of the overall nature of specific viral diseases, and in determining factors affecting host susceptibility and immunity, in unraveling modes of transmission, in clarifying the interaction of viruses with environmental determinants of disease, in determining the safety, efficacy, and utility of vaccines and antiviral drugs, and especially in alerting and directing disease prevention and control actions. Information on incidence, prevalence, and morbidity and mortality rates contributes directly to the establishment of priorities for prevention and control programs, whether this involves vaccine or drug development and delivery, environmental and hygienic improvements, enhancement of nutritional status, personal or community behavior, agricultural and food processing enhancements, reservoir host and vector control, and international cooperation and communication.


title: Obesity is the comorbidity more strongly associated for Covid-19 in Mexico. A case-control study

text: Some comorbidities are associated with severe coronavirus disease (Covid-19) but it is unclear whether some increase susceptibility to Covid-19. In this case-control Mexican study we found that obesity represents the strongest predictor for Covid-19 followed by diabetes and hypertension in both sexes and chronic renal failure in females only. Active smoking was associated with decreased odds of Covid-19. These findings indicate that these comorbidities are not only associated with severity of disease but also predispose for getting Covid-19. Future research is needed to establish the mechanisms involved in each comorbidity and the apparent “protective” effect of cigarette smoking.


title: The role of imaging in 2019 novel coronavirus pneumonia (COVID-19)

text: Almost the entire world, not only China, is currently experiencing the outbreak of a novel coronavirus that causes respiratory disease, severe pneumonia, and even death. The outbreak began in Wuhan, China, in December of 2019 and is currently still ongoing. This novel coronavirus is highly contagious and has resulted in a continuously increasing number of infections and deaths that have already surpassed the SARS-CoV outbreak that occurred in China between 2002 and 2003. It is now officially a pandemic, announced by WHO on the 11th of March. Currently, the 2019 novel coronavirus (SARS-CoV-2) can be identified by virus isolation or viral nucleic acid detection; however, false negatives associated with the nucleic acid detection provide a clinical challenge and thus make the imaging examination crucial. Imaging exams have been a main clinical diagnostic criteria for the 2019 novel coronavirus disease (COVID-19) in China. Imaging features of multiple patchy areas of ground glass opacity and consolidation predominately in the periphery of the lungs are characteristic manifestations on chest CT and extremely helpful in the early detection and diagnosis of this disease, which aids prompt diagnosis and the eventual control of this emerging global health emergency. Key Points • In December 2019, China, an outbreak of pneumonia caused by a novel, highly contagious coronavirus raised grave concerns and posed a huge threat to global public health. • Among the infected patients, characteristic findings on CT imaging include multiple, patchy, ground-glass opacity, crazy-paving pattern, and consolidation shadows, mainly distributed in the peripheral and subpleural areas of both lungs, which are very helpful for the frontline clinicians. • Imaging examination has become the indispensable means not only in the early detection and diagnosis but also in monitoring the clinical course, evaluating the disease severity, and may be presented as an important warning signal preceding the negative RT-PCR test results. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00330-020-06827-4) contains supplementary material, which is available to authorized users.


title: Approach to a Child with Sore Throat

text: Sore throat is one of the common reasons for outpatient and emergency visits among children. It could be because of several etiologies; of these bacterial pharyngitis is the most important. Major challenge for the clinician is to diagnose group A beta hemolytic streptococcus (GABHS) pharyngitis and diphtheria, which are associated with serious complications. Throat swab smear with culture and rapid antigen tests are useful for making the diagnosis but the later may not be available in resource poor settings. Many clinical scores have been devised to diagnose GABHS with variable success but usually clinical features, epidemiological criteria and expert clinical judgment with or without supportive investigations indicate need for antibiotics. A child with sore throat and toxic look may have diphtheria or parapharyngeal/retropharyngeal abscess, and therefore should be hospitalized.


title: Age‐related rhesus macaque models of COVID‐19

text: BACKGROUND: Since December 2019, an outbreak of the Corona Virus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) in Wuhan, China, has become a public health emergency of international concern. The high fatality of aged cases caused by SARS‐CoV‐2 was a need to explore the possible age‐related phenomena with non‐human primate models. METHODS: Three 3‐5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS‐CoV‐2, and then analyzed by clinical signs, viral replication, chest X‐ray, histopathological changes and immune response. RESULTS: Viral replication of nasopharyngeal swabs, anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS‐CoV‐2 challenge. Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema, notably, old monkeys exhibited diffuse severe interstitial pneumonia. Viral antigens were detected mainly in alveolar epithelial cells and macrophages. CONCLUSION: SARS‐CoV‐2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys. Rhesus macaque models infected with SARS‐CoV‐2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS‐CoV‐2 infection.


docid: mqhowppc

title: Pathological Role of Angiotensin II in Severe COVID-19

text: The activated renin–angiotensin system induces a prothrombotic state resulting from the imbalance between coagulation and fibrinolysis. Angiotensin II is the central effector molecule of the activated renin–angiotensin system and is degraded by the angiotensin-converting enzyme 2 to angiotensin (1–7). The novel coronavirus infection (classified as COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as acute respiratory distress syndrome, sepsis, and death in a proportion of patients, mostly elderly patients with preexisting comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor to enter the target cells, resulting in activation of the renin–angiotensin system. After downregulating the angiotensin-converting enzyme 2, the vasoconstrictor angiotensin II is increasingly produced and its counterregulating molecules angiotensin (1–7) reduced. Angiotensin II increases thrombin formation and impairs fibrinolysis. Elevated levels were strongly associated with viral load and lung injury in patients with severe COVID-19. Therefore, the complex clinical picture of patients with severe complications of COVID-19 is triggered by the various effects of highly expressed angiotensin II on vasculopathy, coagulopathy, and inflammation. Future treatment options should focus on blocking the thrombogenic and inflammatory properties of angiotensin II in COVID-19 patients.


title: High Resolution Analysis of Respiratory Syncytial Virus Infection In Vivo

text: Human respiratory syncytial virus (HRSV) is a major cause of pediatric infection and also causes disease in the elderly and those with underlying respiratory problems. There is no vaccine for HRSV and anti-viral therapeutics are not broadly applicable. To investigate the effect of HRSV biology in children, nasopharyngeal aspirates were taken from children with different viral loads and a combined high throughput RNAseq and label free quantitative proteomics approach was used to characterize the nucleic acid and proteins in these samples. HRSV proteins were identified in the nasopharyngeal aspirates from infected children, and their abundance correlated with viral load (Ct value), confirming HRSV infection. Analysis of the HRSV genome indicated that the children were infected with sub-group A virus and that minor variants in nucleotide frequency occurred in discrete clusters along the HRSV genome, and within a patient clustered distinctly within the glycoprotein gene. Data from the samples were binned into four groups; no-HRSV infection (control), high viral load (Ct < 20), medium viral load (Ct = 20–25), and low viral load (Ct > 25). Cellular proteins associated with the anti-viral response (e.g., ISG15) were identified in the nasopharyngeal aspirates and their abundance was correlated with viral load. These combined approaches have not been used before to study HRSV biology in vivo and can be readily applied to the study the variation of virus host interactions.


Clinical outcomes of COVID-19 in elderly male patients


Planet’s population on the move, infections on the rise


title: Analysing the Combined Health, Social and Economic Impacts of the Corovanvirus Pandemic Using Agent-Based Social Simulation

text: During the COVID-19 crisis there have been many difficult decisions governments and other decision makers had to make. E.g. do we go for a total lock down or keep schools open? How many people and which people should be tested? Although there are many good models from e.g. epidemiologists on the spread of the virus under certain conditions, these models do not directly translate into the interventions that can be taken by government. Neither can these models contribute to understand the economic and/or social consequences of the interventions. However, effective and sustainable solutions need to take into account this combination of factors. In this paper, we propose an agent-based social simulation tool, ASSOCC, that supports decision makers understand possible consequences of policy interventions, but exploring the combined social, health and economic consequences of these interventions.


title: Viral Diarrhea

text: Viral gastroenteritis is among the most common illnesses affecting humans and has greatest impact at the extremes of age. The spectrum of disease can range from asymptomatic infections to severe disease with dehydration. Intensive investigation of enteric infections in the past three decades has made it increasingly clear that viruses cause a significant proportion of enteric illnesses worldwide. In contrast to bacterial pathogens, enteric viruses cannot multiply outside their host; hence, the original inoculum into the common source determines infectivity. Prevention of contamination of food and water will help control primary cases, whereas careful nursing and handwashing prevent secondary cases.


docid: slmlhqnb

title: Dengue Virus Glycosylation: What Do We Know?

text: In many infectious diseases caused by either viruses or bacteria, pathogen glycoproteins play important roles during the infection cycle, ranging from entry to successful intracellular replication and host immune evasion. Dengue is no exception. Dengue virus glycoproteins, envelope protein (E) and non-structural protein 1 (NS1) are two popular sub-unit vaccine candidates. E protein on the virion surface is the major target of neutralizing antibodies. NS1 which is secreted during DENV infection has been shown to induce a variety of host responses through its binding to several host factors. However, despite their critical role in disease and protection, the glycosylated variants of these two proteins and their biological importance have remained understudied. In this review, we seek to provide a comprehensive summary of the current knowledge on protein glycosylation in DENV, and its role in virus biogenesis, host cell receptor interaction and disease pathogenesis.


title: Bereavement Care in the Wake of COVID-19: Offering Condolences and Referrals

text: The COVID-19 pandemic is causing deaths with forced separations that deny final goodbyes and traditional mourning rituals. These conditions threaten survivors' mental health, leaving them vulnerable to enduring psychological distress. This article describes resources for clinicians to use when circumstances make it difficult to provide ideal bereavement care.


title: The Impact of COVID-19 on Tourist Satisfaction with B&B in Zhejiang, China: An Importance–Performance Analysis

text: After the outbreak of COVID-19 (especially in the stage of tourism recovery), the bed and breakfast (B&B) tourism industry faced big challenges in improving its health strategies. B&Bs are very important for the tourism industry in China and many other countries. However, few studies have studied the impact of B&Bs, under COVID-19, on tourism in China. Our paper is among one of the first studies to investigate the impact of COVID-19 on tourist satisfaction with B&Bs in China. The work/travel restrictions started from 20 January 2020, and work/after travel resumed from 20 February 2020 in Zhejiang, China. Data were collected from 588 tourists (who experienced B&Bs in Zhejiang, China) from a WeChat online survey, from 1 March to 15 March 2020. The current study attempted to fill the gap by studying the changing tourist satisfaction levels with B&Bs before/after COVID-19. Moreover, some suggestions are given to the B&B industry for tourism resumption after COVID-19 by an importance–performance analysis (IPA).


Legacy


title: Impact of a Hypothetical Infectious Disease Outbreak on US Exports and Export-Based Jobs

text: We estimated the impact on the US export economy of an illustrative infectious disease outbreak scenario in Southeast Asia that has 3 stages starting in 1 country and, if uncontained, spreads to 9 countries. We used 2014-2016 West Africa Ebola epidemic–related World Bank estimates of 3.3% and 16.1% reductions in gross domestic product (GDP). We also used US Department of Commerce job data to calculate export-related jobs at risk to any outbreak-related disruption in US exports. Assuming a direct correlation between GDP reductions and reduced demand for US exports, we estimated that the illustrative outbreak would cost from approximately $13 million to approximately $64 million (1 country) to $8 billion to $41 billion (9 countries) and place 1,500 to almost 1.4 million export-related US jobs at risk. Our analysis illustrates how global health security is enhanced, and the US economy is protected, when public health threats are rapidly detected and contained at their source.


title: Hospitalized Children with 2009 Pandemic Influenza A (H1N1): Comparison to Seasonal Influenza and Risk Factors for Admission to the ICU

text: BACKGROUND: Limited data are available describing the clinical presentation and risk factors for admission to the intensive care unit for children with 2009 H1N1 infection. METHODS: We conducted a retrospective chart review of all hospitalized children with 2009 influenza A (H1N1) and 2008–09 seasonal influenza at The Children's Hospital, Denver, Colorado. RESULTS: Of the 307 children identified with 2009 H1N1 infections, the median age was 6 years, 61% were male, and 66% had underlying medical conditions. Eighty children (26%) were admitted to the ICU. Thirty-two (40%) of the ICU patients required intubation and 17 (53%) of the intubated patients developed acute respiratory distress syndrome (ARDS). Four patients required extracorporeal membrane oxygenation. Eight (3%) of the hospitalized children died. Admission to the ICU was significantly associated with older age and underlying neurological condition. Compared to the 90 children admitted during the 2008–09 season, children admitted with 2009 H1N1 influenza were significantly older, had a shorter length of hospitalization, more use of antivirals, and a higher incidence of ARDS. CONCLUSIONS: Compared to the 2008–09 season, hospitalized children with 2009 H1N1 influenza were much older and had more severe respiratory disease. Among children hospitalized with 2009 H1N1 influenza, risk factors for admission to the ICU included older age and having an underlying neurological condition. Children under the age of 2 hospitalized with 2009 H1N1 influenza were significantly less likely to require ICU care compared to older hospitalized children.


One Size Does Not Fit All: How to Rapidly Deploy Intubation Practice Changes in a Pediatric Hospital During the Coronavirus Disease 2019 Pandemic


docid: xemxtssg

title: N6-methyladenosine regulates PEDV replication and host gene expression

text: Methylation of the N6 position of adenosine (m(6)A) is a widespread RNA modification that is critical for various physiological and pathological processes. Although this modification was also found in the RNA of several viruses almost 40 years ago, its biological functions during viral infection have been elucidated recently. Here, we investigated the effects of viral and host RNA methylation during porcine epidemic diarrhea virus (PEDV) infection. The results demonstrated that the m(6)A modification was abundant in the PEDV genome and the host methyltransferases METTL3 and METTL14 and demethylase FTO were involved in the regulation of viral replication. The knockdown of the methyltransferases increased PEDV replication while silencing the demethylase decreased PEDV output. Moreover, the proteins of the YTHDF family regulated the PEDV replication by affecting the stability of m(6)A-modified viral RNA. In particular, PEDV infection could trigger an increasement of m(6)A in host RNA and decrease the expression of FTO. The m(6)A modification sites in mRNAs and target genes were also altered during PEDV infection. Additionally, part of the host responses to PEDV infection was controlled by m(6)A modification, which could be reversed by the expression of FTO. Taken together, our results identified the role of m(6)A modification in PEDV replication and interactions with the host.


title: Cryptosporidiosis caused by Cryptosporidium parvum subtype IIdA15G1 at a dairy farm in Northwestern China

text: BACKGROUND: Cryptosporidium spp. are zoonotic parasites responsible for diarrhoeal diseases in animals and humans worldwide. Cattle are the most common mammalian species in which Cryptosporidium is detected, with pre-weaned calves considered to be reservoirs for zoonotic C. parvum. In October 2013, severe diarrhoea was observed in 396 pre-weaned calves at a farm in the Ningxia Autonomous Region of Northwestern China. 356 of the infected calves died despite antibiotic therapy. FINDINGS: 252 faecal samples were collected from the investigated farm. The identity of Cryptosporidium species was determined by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) analysis, and by DNA sequence analysis of the small subunit (SSU) rRNA gene. C. parvum was subtyped using sequence analysis of the 60 kDa glycoprotein (gp60) gene. The highest infection rate of 83.3% (40/48) was seen in 2–3-week-old calves with diarrhoea, corresponding to the age at which animals died. Three Cryptosporidium species were identified, including C. parvum (n = 51), C. bovis (n = 1), and C. ryanae (n = 1). All C. parvum isolates were further identified as subtype IIdA15G1. CONCLUSIONS: Cryptosporidium parvum was likely to be most responsible for diarrhoea and death. This is the first report of a cryptosporidiosis outbreak caused by C. parvum IIdA15G1 in Chinese dairy cattle.


docid: mhwqgjbg

title: One Academic Health System’s Early (and Ongoing) Experience Responding to COVID-19: Recommendations From the Initial Epicenter of the Pandemic in the United States

text: On January 19, 2020, the first case of a patient with coronavirus disease 2019 (COVID-19) in the United States was reported in Washington State. On February 29, 2020, a patient infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) passed away in a hospital in Seattle-King County, the first reported COVID-19-related death in the United States. That same day, a skilled nursing and rehabilitation facility in the county reported that several of its residents tested positive for SARS-CoV-2 and that many staff had symptoms compatible with COVID-19. The University of Washington Medicine health system (UW Medicine), which is based in Seattle-King County and provides quaternary care for the region, was one of several health care organizations called upon to address this growing crisis. What ensued was a series of swiftly enacted decisions and activities at UW Medicine, in partnership with local, state, and national public health agencies, to respond to the COVID-19 pandemic. Tapping into the multipronged mission areas of academic medicine, UW Medicine worked to support the community, innovate in science and clinical practice; lead policy and practice guideline development; and adopt changes as the crisis unfolded. In doing so, health system leaders had to balance their commitments to students, residents and fellows, researchers, faculty, staff, and hospital and health center entities, while ensuring that patients continued to receive cutting-edge, high-quality, safe care. In this Invited Commentary, the authors highlight the work and challenges UW Medicine has faced in responding to the global COVID-19 pandemic.


title: MERS Coronavirus Neutralizing Antibodies in Camels, Eastern Africa, 1983–1997

text: To analyze the distribution of Middle East respiratory syndrome coronavirus (MERS-CoV)–seropositive dromedary camels in eastern Africa, we tested 189 archived serum samples accumulated during the past 30 years. We identified MERS-CoV neutralizing antibodies in 81.0% of samples from the main camel-exporting countries, Sudan and Somalia, suggesting long-term virus circulation in these animals.


Children may be less affected than adults by novel coronavirus (COVID‐19)


title: Interactions of Dimethylarsinic Acid, Total Arsenic and Zinc Affecting Rice Crop Management and Human Health in Cambodia

text: BACKGROUND. In parts of Cambodia and in many other parts of the world, irrigation of rice with groundwater results in arsenic (As) accumulation in soil and rice, leading to health concerns associated with rice consumption. At times, some As is present as relatively nontoxic, non-regulated, dimethylarsinic acid (DMA). Low levels of zinc (Zn) have been found in rice from Bangladesh, Cambodia, and China where As levels in rice are high. Furthermore, there have been claims that Zn deficiency is responsible for stunting the growth of children in Cambodia and elsewhere, however in rural Asia, rice is the major source of Zn. Current data are inadequate for both Zn and DMA in Cambodian rice. OBJECTIVES. The present study aimed to provide a preliminary evaluation of the relationship between the content of Zn and DMA in rice grain in Preak Russey, an area with elevated levels of As in groundwater and to improve the management of Zn deficiency in rice. METHODS. Rice agriculture was evaluated along the Mekong River in Cambodia. Analyses for metals, total As, and As species in rice and water were conducted by inductively coupled plasma mass spectrometry. Analysis of total Zn and As in soils and total Zn in rice were analyzed using X-ray fluorescence (XRF) spectrometry. RESULTS. Rice in Preak Russey had Zn concentrations less than a third the level recommended by the United Nations World Food Programme. There was a significant (p < 0.05) negative correlation between the Zn content of rice and DMA in rice with the lowest Zn and highest DMA levels occurring near irrigation wells, the source of As. CONCLUSIONS. The highest levels of DMA in rice were associated with Zn deficiency in rice. COMPETING INTERESTS. The authors declare no competing financial interests


title: mRNA maturation in giant viruses: variation on a theme

text: Giant viruses from the Mimiviridae family replicate entirely in their host cytoplasm where their genes are transcribed by a viral transcription apparatus. mRNA polyadenylation uniquely occurs at hairpin-forming palindromic sequences terminating viral transcripts. Here we show that a conserved gene cluster both encode the enzyme responsible for the hairpin cleavage and the viral polyA polymerases (vPAP). Unexpectedly, the vPAPs are homodimeric and uniquely self-processive. The vPAP backbone structures exhibit a symmetrical architecture with two subdomains sharing a nucleotidyltransferase topology, suggesting that vPAPs originate from an ancestral duplication. A Poxvirus processivity factor homologue encoded by Megavirus chilensis displays a conserved 5′-GpppA 2′O methyltransferase activity but is also able to internally methylate the mRNAs’ polyA tails. These findings elucidate how the arm wrestling between hosts and their viruses to access the translation machinery is taking place in Mimiviridae.


title: Mortality among dentists in Taiwan, 1985–2009

text: Background/Purpose Controversy exists in the literature regarding whether dentists with multiple occupational exposures suffer from premature mortality. A cohort mortality study was conducted to evaluate the survival outcome and determine if potential exposure to harmful agents leads to premature mortality among dentists. Methods Using the Life Table Analysis System, we calculated standardized mortality ratios (SMRs) for a cohort of 11,700 dentists affiliated with the Taiwan Dental Association. These dentists were followed from 1985–2009. Reference rates were derived from cause-, gender-, and age-specific mortality rates of the general population of Taiwan and 18,664 Taiwanese internists, who were considered to be more socioeconomically proximal to dentists. A Cox proportional hazard model was also constructed to determine multiple risk factors associated with mortality. Results Compared with the general population, dentists in Taiwan consistently demonstrated reduced from all-cause mortality. However, compared with internists, significant and excess mortality were observed in dentists for overall mortality (SMR=1.13; 95% confidence interval [CI]=1.00–1.26), drowning (SMR=6.62; 95% CI=2.15–15.45), and heart diseases (SMR=1.66; 95% CI=1.22–2.21). After adjusting for other risk factors, the Cox model showed an increased hazard ratio of 1.17 (95% CI=1.01–1.37) for dentists. Conclusion Taiwanese dentists demonstrated significant elevated SMRs for overall causes, drowning, and heart diseases. Careful precaution should be taken to reduce these trends. Future studies are also needed for in-depth exploration of the mechanisms regarding how professional stress and exposure contribute to the increased risk of mortality in Taiwanese dentists.


title: Chapter 12 Clinical Trials of Vaccines for Biodefense and Emerging and Neglected Diseases

text: Abstract The development of safe and effective vaccines for the prevention and control of emerging and neglected infectious diseases is an international priority, as is the development of similar control measures for bioterrorist threats. International standards have been established to ensure the protection of human subjects and the scientific integrity of clinical trial study design and data collection. A general overview of the history of the regulatory guidelines and ethical principles underpinning the vaccine development process is provided, with an emphasis on clinical trials conducted in the United States. The contemporary vaccine development process involves sequential assessment of safety, immunogenicity, and efficacy in phase1, 2, and 3 clinical trials. The process is not always linear or straightforward, and adaptive flexible clinical trial designs can increase the likelihood of a successful outcome. Because the efficacy of vaccines for a number of the diseases discussed in this volume cannot be tested directly in humans, alternative approaches have been developed to address this challenge. The major elements of typical clinical trial protocol are discussed, and a checklist of essential documents supporting the trial is provided. As novel vaccine approaches and technologies emerge, the regulatory and ethical considerations will need to be revisited and adapted to respond to the ever-changing landscape.


title: Molecular detection of viruses in Kenyan bats and discovery of novel astroviruses, caliciviruses and rotaviruses

text: This is the first country-wide surveillance of bat-borne viruses in Kenya spanning from 2012–2015 covering sites perceived to have medium to high level bat-human interaction. The objective of this surveillance study was to apply a non-invasive approach using fresh feces to detect viruses circulating within the diverse species of Kenyan bats. We screened for both DNA and RNA viruses; specifically, astroviruses (AstVs), adenoviruses (ADVs), caliciviruses (CalVs), coronaviruses (CoVs), flaviviruses, filoviruses, paramyxoviruses (PMVs), polyomaviruses (PYVs) and rotaviruses. We used family-specific primers, amplicon sequencing and further characterization by phylogenetic analysis. Except for filoviruses, eight virus families were detected with varying distributions and positive rates across the five regions (former provinces) studied. AstVs (12.83%), CoVs (3.97%), PMV (2.4%), ADV (2.26%), PYV (1.65%), CalVs (0.29%), rotavirus (0.19%) and flavivirus (0.19%). Novel CalVs were detected in Rousettus aegyptiacus and Mops condylurus while novel Rotavirus-A-related viruses were detected in Taphozous bats and R. aegyptiacus. The two Rotavirus A (RVA) strains detected were highly related to human strains with VP6 genotypes I2 and I16. Genotype I16 has previously been assigned to human RVA-strain B10 from Kenya only, which raises public health concern, particularly considering increased human-bat interaction. Additionally, 229E-like bat CoVs were detected in samples originating from Hipposideros bats roosting in sites with high human activity. Our findings confirm the presence of diverse viruses in Kenyan bats while providing extended knowledge on bat virus distribution. The detection of viruses highly related to human strains and hence of public health concern, underscores the importance of continuous surveillance. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s12250-016-3930-2 and is accessible for authorized users.


docid: gqzelcxn

title: Construction and Characterization of Single-Chain Variable Fragment Antibody Library Derived from Germline Rearranged Immunoglobulin Variable Genes

text: Antibody repertoires for library construction are conventionally harvested from mRNAs of immune cells. To examine whether germline rearranged immunoglobulin (Ig) variable region genes could be used as source of antibody repertoire, an immunized phage-displayed scFv library was prepared using splenocytic genomic DNA as template. In addition, a novel frame-shifting PCR (fsPCR) step was introduced to rescue stop codon and to enhance diversity of the complementarity-determining region 3 (CDR3). The germline scFv library was initially characterized against the hapten antigen phenyloxazolone (phOx). Sequence analysis of the phOx-selective scFvs indicated that the CDRs consisted of novel as well as conserved motifs. In order to illustrate that the diversity of CDR3 was increased by the fsPCR step, a second scFv library was constructed using a single scFv clone L3G7C as a template. Despite showing similar binding characteristics towards phOx, the scFv clones that were obtained from the L3G7C-derived antibody library gave a lower non-specific binding than that of the parental L3G7C clone. To determine whether germline library represented the endogenous immune status, specific scFv clones for nucleocapsid (N) protein of SARS-associated coronavirus (SCoV) were obtained both from naïve and immunized germline scFv libraries. Both libraries yielded specific anti-N scFvs that exhibited similar binding characteristics towards recombinant N protein, except the immunized library gave a larger number of specific anti-N scFv, and clones with identical nucleotide sequences were found. In conclusion, highly diversified antibody library can be efficiently constructed using germline rearranged immunoglobulin variable genes as source of antibody repertoires and fsPCR to diversify the CDR3.


title: Single stranded (ss)RNA-mediated antiviral response against infectious laryngotracheitis virus infection

text: BACKGROUND: Single stranded ribonucleic acid (ssRNA) binds to toll-like receptor (TLR)7 leading to recruitment of immune cells and production of pro-inflammatory cytokines, which has been shown in mammals. In chickens, synthetic ssRNA analog, resiquimod, has been shown to elicit antiviral response against infectious bursal disease virus infection. The objective of this study was to determine the innate host responses activated by the pre-hatch in ovo administration of resiquimod against infectious laryngotracheitis virus (ILTV) infection in chickens post-hatch. RESULTS: First, we observed that in ovo treatment of resiquimod at embryo day (ED) 18 increases macrophage recruitment in respiratory and gastrointestinal tissues of chicken day 1 post-hatch in addition to interleukin (IL)-1β in lungs. Second, we observed that in ovo treatment of resiquimod reduces ILTV cloacal shedding at 7 days post-infection (dpi) when challenged at day 1 post-hatch coinciding with higher macrophage recruitment. In vitro, we found that resiquimod enhances production of nitric oxide (NO) and IL-1β and not type 1 interferon (IFN) activity in avian macrophages. Although, the antiviral response against ILTV is associated with the enhanced innate immune response, it is not dependent on any of the innate immune mediators observed as has been shown in vitro using avian macrophage. CONCLUSION: This study provides insights into the mechanisms of antiviral response mediated by resiquimod, particularly against ILTV infection in chicken.


docid: yapmcvps

title: Death anxiety in the time of COVID-19: theoretical explanations and clinical implications

text: The recent COVID-19 pandemic has triggered a surge in anxiety across the globe. Much of the public’s behavioural and emotional response to the virus can be understood through the framework of terror management theory, which proposes that fear of death drives much of human behaviour. In the context of the current pandemic, death anxiety, a recently proposed transdiagnostic construct, appears especially relevant. Fear of death has recently been shown to predict not only anxiety related to COVID-19, but also to play a causal role in various mental health conditions. Given this, it is argued that treatment programmes in mental health may need to broaden their focus to directly target the dread of death. Notably, cognitive behavioural therapy (CBT) has been shown to produce significant reductions in death anxiety. As such, it is possible that complementing current treatments with specific CBT techniques addressing fears of death may ensure enhanced long-term symptom reduction. Further research is essential in order to examine whether treating death anxiety will indeed improve long-term outcomes, and prevent the emergence of future disorders in vulnerable populations. KEY LEARNING AIMS: (1).. To understand terror management theory and its theoretical explanation of death anxiety in the context of COVID-19. (2).. To understand the transdiagnostic role of death anxiety in mental health disorders. (3).. To understand current treatment approaches for directly targeting death anxiety, and the importance of doing so to improve long-term treatment outcomes.


title: Coping with being cooped up: Social distancing during COVID-19 among 60+ in the United States

text: OBJECTIVES. This study examined the impact of sheltering in place and social distancing among adults aged 60 and older during the 2020 outbreak of COVID-19 in the United States. METHODS. Using convenience sampling respondents were asked to complete a web-administered survey to explore impact of social distancing on loneliness, stress, and behavioral changes. The analytic sample consisted of 833 responses of persons aged 60 and older. RESULTS. A large portion reported being stressed (36%), and/or being lonely (42.5%). Nearly 1/3 stated that their sense of loneliness increased during the time of social distancing. Respondents reported engaging in more solitary activity (and fewer in-person activities), using email and text messages more than usual, and spending more time on computers/tablet than usual. Approximately 2/3 reported using more social media than usual. These differed significantly by younger (age 60-70) and older (71+) respondents. Additionally, changes in physical activity, drinking, recreational drug use and sleeping pattern changes differed by age. CONCLUSIONS. Social distancing has significant consequences on loneliness and health behaviors among adults in the United States, many of which differ by age group. Results have implications for continued shelter in place practices, but also for any older adult that may be homebound for other reasons.


title: Tuberculosis prevention in healthcare workers in China 10 years after the severe acute respiratory syndrome pandemic

text: BSL3 and respiratory isolation wards protect healthcare workers from nosocomial TB infection in China http://ow.ly/PGvSl


title: Burden of Human Metapneumovirus Infections in Cancer Patients: Risk Factors and Outcomes

text: BACKGROUND: Human metapneumovirus (hMPV) causes upper and lower respiratory tract infections (URI and LRI, respectively) in healthy and immunocompromised patients; however, its clinical burden in patients with cancer remains unknown. METHODS: In a retrospective study of all laboratory-confirmed hMPV infections treated at our institution between April 2012 and May 2015, we determined clinical characteristics, risk factors for progression to LRI, treatment, and outcomes in patients with cancer. RESULTS: We identified 181 hMPV infections in 90 (50%) patients with hematologic malignancies (HM), 57 (31%) hematopoietic cell transplantation (HCT) recipients, and 34 patients (19%) with solid tumors. Most patients (92%) had a community-acquired infection, presented with URI (67%), and 43% developed LRI (59 presented with LRI and 19 progressed from URI to LRI). On multivariable analysis, an underlying HM (adjusted odds ratio [aOR], 3.11(1.12-8.64); P=0.029), nosocomial infection (aOR, 26.9 (2.79-259.75); P=0.004), and hypoxia (SpO2 ≤ 92%) at presentation (aOR, 9.61(1.98-46.57); P = 0.005) were independent factors associated with LRI. All-cause mortality at 30 days from hMPV diagnosis was low (4%) and patients with LRI had a 10% mortality rate at day 30 from diagnosis; whereas, patients with URI had 0% mortality rate. CONCLUSIONS: hMPV infections in patients with cancer may cause significant morbidity, especially for those with underlying HM who may develop an LRI. Despite high morbidity and the lack of directed antiviral therapy for hMPV infections, mortality at day 30 from this infection remained low in this studied population.


title: 12 IBCs – A cornerstone of public trust in research

text: Abstract For four decades the NIH Guidelines have served as the framework for the oversight of research with recombinant and synthetic nucleic acid molecules. IBCs are a vital component in that system of oversight as the entity that ensures the safe conduct of this type of research at the local level. IBC review also provides a public window into the procedures utilized by institutions to manage biohazards, thereby protecting human health, animal health, and the environment. It is both because of their biosafety responsibilities, as well as the manner in which they offer transparency to the public, that IBCs play a central role in fostering public trust in the safety of the life science research enterprise.


title: Autoantibodies against human epithelial cells and endothelial cells after severe acute respiratory syndrome (SARS)‐associated coronavirus infection

text: The severe acute respiratory syndrome (SARS) is caused by infection with the SARS‐associated coronavirus (SARS‐CoV) and characterized by severe pulmonary inflammation and fibrosis. In this study, the development of autoantibodies against human epithelial cells and endothelial cells in patients with SARS at different time periods (the first week: phase I, 1 month after the disease onset: phase II/phase III) were investigated. Antibodies in sera of patients and healthy controls against: (1) A549 human pulmonary epithelial cell‐line, (2) human umbilical venous endothelial cells (HUVEC), (3) primary human pulmonary endothelial cells (HPEC) were detected by cell‐based ELISA and indirect immunofluorescence staining. The results revealed that serum levels of IgG anti‐A549 cells antibodies, IgG anti‐HUVEC antibodies, and IgM anti‐HPEC antibodies were significantly higher in SARS patients at phase II/phase III than those in healthy controls. Sera from SARS patients at phase II/phase III could mediate complement dependent cytotoxicity against some A549 cells and HPEC. It is concluded that some autoantibodies against human epithelial cells and endothelial cells would be developed after SARS‐CoV infection and this phenomenon may indicate post‐infectious cellular injury and also induce SARS‐induced immunopathology. J. Med. Virol. 77:1–7, 2005. © 2005 Wiley‐Liss, Inc.


Tackling the COVID-19 challenge—a view from the DOJ


title: Immune checkpoint inhibitors: A physiology-driven approach to the treatment of COVID-19

text: While confirmed cases of infections of the deadly coronavirus disease 2019 (COVID-19) have exceeded 4.7 million globally, scientists are pushing forward with efforts to develop vaccines and treatments in an attempt to slow the pandemic and lessen the disease’s damage. Although no proven effective therapies to treat COVID-19 patients or for managing their complications currently exist, the rapidly expanding knowledge regarding severe acute respiratory syndrome–coronavirus 2 and its interplay with hosts provide a significant number of potential drug targets, and the potential to repurpose drugs already tested in other diseases. Herein we report the biological rationale of immuno-activating drugs and a brief summary of literature data on the potential therapeutic value of immune checkpoint inhibitors that have been recently tested beyond cancer treatment for their potential to restore cellular immuno-competence.


title: COVID-19 serial interval estimates based on confirmed cases in public reports from 86 Chinese cities

text: As a novel coronavirus (COVID-19) continues to spread widely and claim lives worldwide, its transmission characteristics remain uncertain. Here, we present and analyze the serial intervals–the time period between the onset of symptoms in an index (infector) case and the onset of symptoms in a secondary (infectee) case–of 339 confirmed cases of COVID-19 identified from 264 cities in mainland China prior to February 19, 2020. Here, we provide the complete dataset in both English and Chinese to support further COVID-19 research and modeling efforts.


Where have the gatherings gone? Reweaving the social fabric in the time of pandemic and interpersonal distancing


title: Studying Communication Problems for Emergency Management of SARS and H7N9 in China

text: BACKGROUND: Severe Acute Respiratory Syndrome (SARS) and Influenza A virus Subtype H7N9 (H7N9) have both had a great impact on China in the 21(st) century, causing significant negative impacts on health, the economy, and even global security. The control efforts for SARS were heavily criticized, the H7N9 response, 10 years later was acknowledged to be much better. AIMS: This article explores communication for emergency management of SARS in 2003 and H7N9 in 2013 in China, to provide useful evidence for government and practitioner on management improvement for infectious disease outbreaks response in China and international community in the future. METHODS: This study uses a qualitative case study approach, including in-depth interviews, literature review, and document, to analysis the emergency management of SARS in 2003 and H7N9 in 2013 in China, identified the problems of communication with the emergency management process for SARS and H7N9. RESULTS: The control efforts for SARS were slow to be mobilized and were heavily criticized and generally considered to be suboptimal, as the poor handling of SARS exposed serious communication problems in the then emergency management system processes. The H7N9 response, 10 years later, was acknowledged to be much better. CONCLUSION: Communication is very important in the prevention and control of infectious diseases. From SARS to H7N9, the progress had been made in information disclosure.


title: ABSL-4 Aerobiology Biosafety and Technology at the NIH/NIAID Integrated Research Facility at Fort Detrick

text: The overall threat of a viral pathogen to human populations is largely determined by the modus operandi and velocity of the pathogen that is transmitted among humans. Microorganisms that can spread by aerosol are considered a more challenging enemy than those that require direct body-to-body contact for transmission, due to the potential for infection of numerous people rather than a single individual. Additionally, disease containment is much more difficult to achieve for aerosolized viral pathogens than for pathogens that spread solely via direct person-to-person contact. Thus, aerobiology has become an increasingly necessary component for studying viral pathogens that are naturally or intentionally transmitted by aerosol. The goal of studying aerosol viral pathogens is to improve public health preparedness and medical countermeasure development. Here, we provide a brief overview of the animal biosafety level 4 Aerobiology Core at the NIH/NIAID Integrated Research Facility at Fort Detrick, Maryland, USA.


Chapter 61 Mucosal Veterinary Vaccines: Comparative Vaccinology


title: Homozygous L-SIGN (CLEC4M) plays a protective role in SARS coronavirus infection

text: Severe acute respiratory syndrome (SARS) is caused by infection of a previously undescribed coronavirus (CoV). L-SIGN, encoded by CLEC4M (also known as CD209L), is a SARS-CoV binding receptor that has polymorphism in its extracellular neck region encoded by the tandem repeat domain in exon 4. Our genetic risk association study shows that individuals homozygous for CLEC4M tandem repeats are less susceptible to SARS infection. L-SIGN is expressed in both non-SARS and SARS-CoV–infected lung. Compared with cells heterozygous for L-SIGN, cells homozygous for L-SIGN show higher binding capacity for SARS-CoV, higher proteasome-dependent viral degradation and a lower capacity for trans infection. Thus, homozygosity for L-SIGN plays a protective role during SARS infection. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ng1698) contains supplementary material, which is available to authorized users.


The invention of the swine-flu pandemic


title: The UNITAID Patent Pool Initiative: Bringing Patents Together for the Common Good

text: Developing and delivering appropriate, affordable, well-adapted medicines for HIV/AIDS remains an urgent challenge: as first-line therapies fail, increasing numbers of people require costly second-line therapy; one-third of ARVs are not available in pediatric formulations; and certain key first- and second-line triple fixed-dose combinations do not exist or sufficient suppliers are lacking. UNITAID aims to help solve these problems through an innovative initiative for the collective management of intellectual property (IP) rights – a patent pool for HIV medicines. The idea behind a patent pool is that patent holders - companies, governments, researchers or universities - voluntarily offer, under certain conditions, the IP related to their inventions to the patent pool. Any company that wants to use the IP to produce or develop medicines can seek a license from the pool against the payment of royalties, and may then produce the medicines for use in developing countries (conditional upon meeting agreed quality standards). The patent pool will be a voluntary mechanism, meaning its success will largely depend on the willingness of pharmaceutical companies to participate and commit their IP to the pool. Generic producers must also be willing to cooperate. The pool has the potential to provide benefits to all.


title: Epidemiology characteristics of human coronaviruses in patients with respiratory infection symptoms and phylogenetic analysis of HCoV-OC43 during 2010-2015 in Guangzhou

text: Human coronavirus (HCoV) is one of the most common causes of respiratory tract infection throughout the world. To investigate the epidemiological and genetic variation of HCoV in Guangzhou, south China, we collected totally 13048 throat and nasal swab specimens from adults and children with fever and acute upper respiratory infection symptoms in Gunazhou, south China between July 2010 and June 2015, and the epidemiological features of HCoV and its species were studied. Specimens were screened for HCoV by real-time RT-PCR, and 7 other common respiratory viruses were tested simultaneously by PCR or real-time PCR. HCoV was detected in 294 cases (2.25%) of the 13048 samples, with most of them inpatients (251 cases, 85.4% of HCoV positive cases) and young children not in nursery (53.06%, 156 out of 294 HCoV positive cases). Four HCoVs, as OC43, 229E, NL63 and HKU1 were detected prevalent during 2010–2015 in Guangzhou, and among the HCoV positive cases, 60.20% were OC43, 16.67% were 229E, 14.97% were NL63 and 7.82% were HKU1. The month distribution showed that totally HCoV was prevalent in winter, but differences existed in different species. The 5 year distribution of HCoV showed a peak-valley distribution trend, with the detection rate higher in 2011 and 2013 whereas lower in 2010, 2012 and 2014. The age distribution revealed that children (especially those <3 years old) and old people (>50 years) were both high risk groups to be infected by HCoV. Of the 294 HCoV positive patients, 34.69% (101 cases) were co-infected by other common respiratory viruses, and influenza virus was the most common co-infecting virus (30/101, 29.70%). Fifteen HCoV-OC43 positive samples of 2013–2014 were selected for S gene sequencing and phylogenetic analysis, and the results showed that the 15 strains could be divided into 2 clusters in the phylogenetic tree, 12 strains of which formed a separate cluster that was closer to genotype G found in Malaysia. It was revealed for the first time that genotype B and genotype G of HCoV-OC43 co-circulated and the newly defined genotype G was epidemic as a dominant genotype during 2013–2014 in Guanzhou, south China.


PERNIOSIS DEL CONFINAMIENTO, UNA VIEJA CONOCIDA EN EL CONTEXTO DEL COVID-19


title: RNA Modifications Modulate Activation of Innate Toll-Like Receptors

text: Self/foreign discrimination by the innate immune system depends on receptors that identify molecular patterns as associated to pathogens. Among others, this group includes endosomal Toll-like receptors, among which Toll-like receptors (TLR) 3, 7, 8, and 13 recognize and discriminate mammalian from microbial, potentially pathogen-associated, RNA. One of the discriminatory principles is the recognition of endogenous RNA modifications. Previous work has identified a couple of RNA modifications that impede activation of TLR signaling when incorporated in synthetic RNA molecules. Of note, work that is more recent has now shown that RNA modifications in their naturally occurring context can have immune-modulatory functions: Gm, a naturally occurring ribose-methylation within tRNA resulted in a lack of TLR7 stimulation and within a defined sequence context acted as antagonist. Additional RNA modifications with immune-modulatory functions have now been identified and recent work also indicates that RNA modifications within the context of whole prokaryotic or eukaryotic cells are indeed used for immune-modulation. This review will discuss new findings and developments in the field of immune-modulatory RNA modifications.


title: Novel in vitro booster vaccination to rapidly generate antigen-specific human monoclonal antibodies

text: Vaccines remain the most effective tool to prevent infectious diseases. Here, we introduce an in vitro booster vaccination approach that relies on antigen-dependent activation of human memory B cells in culture. This stimulation induces antigen-specific B cell proliferation, differentiation of B cells into plasma cells, and robust antibody secretion after a few days of culture. We validated this strategy using cells from healthy donors to retrieve human antibodies against tetanus toxoid and influenza hemagglutinin (HA) from H1N1 and newly emergent subtypes such as H5N1 and H7N9. Anti-HA antibodies were cross-reactive against multiple subtypes, and some showed neutralizing activity. Although these antibodies may have arisen as a result of previous influenza infection, we also obtained gp120-reactive antibodies from non–HIV-infected donors, indicating that we can generate antibodies without prior antigenic exposure. Overall, our novel approach can be used to rapidly produce therapeutic antibodies and has the potential to assess the immunogenicity of candidate antigens, which could be exploited in future vaccine development.


title: The impact of COVID-19 on the degree of dependence and structure of risk-return relationship: A quantile regression approach

text: This paper examines the impact of the novel coronavirus (COVID-19) on the degree and structure of risk-return dependence in the US. The results from quantile regression (QR) indicate a left-tailed asymmetric dependence structure of sectoral returns with market portfolio. Following the COVID-19 outbreak, degree of dependence among returns and market portfolio have increased in the higher quantiles. Further, the outbreak has converted left-tailed dependence into a right-tailed dependence. Interaction among Google Search Index for coronavirus (GSIC) and returns also examined. Findings reveal an asymmetric GSIC-return dependence that is significant in tails.


title: COVID-19 pandemic in Panama: lessons of the unique risks and research opportunities for Latin America

text: The Republic of Panama has the second most unequally distributed wealth in Central America, has recently entered the list of countries affected by the COVID-19 pandemic, and has one of the largest testing rate per inhabitant in the region and consequently the highest incidence rate of COVID-19, making it an ideal location to discuss potential scenarios for assessing epidemic preparedness, and to outline research opportunities in the Region of the Americas. We address two timely important questions: What are the unique risks of COVID-19 in Panama that could help other countries in the Region be better prepared? And what kind of scientific knowledge can Panama contribute to the regional and global study of COVID-19? This paper provides suggestions about how the research community could support local health authorities plan for different scenarios and decrease public anxiety. It also presents basic scientific opportunities about emerging pandemic pathogens towards promoting global health from the perspective of a middle income country.


docid: zmoayelz

title: Advances of bioinformatics tools applied in virus epitopes prediction

text: In recent years, the in silico epitopes prediction tools have facilitated the progress of vaccines development significantly and many have been applied to predict epitopes in viruses successfully. Herein, a general overview of different tools currently available, including T cell and B cell epitopes prediction tools, is presented. And the principles of different prediction algorithms are reviewed briefly. Finally, several examples are present to illustrate the application of the prediction tools.


SARS CoV‐2 aggravates cellular metabolism mediated complications in COVID‐19 infection


title: Case-Fatality Risk Estimates for COVID-19 Calculated by Using a Lag Time for Fatality

text: We estimated the case-fatality risk for coronavirus disease cases in China (3.5%); China, excluding Hubei Province (0.8%); 82 countries, territories, and areas (4.2%); and on a cruise ship (0.6%). Lower estimates might be closest to the true value, but a broad range of 0.25%–3.0% probably should be considered.


title: COVID‐19 and the use of immunomodulatory and biologic agents for severe cutaneous disease: An Australian/New Zealand consensus statement

text: Patients on immunomodulators, including biologic agents and new small molecular inhibitors, for cutaneous disease, represent a potentially vulnerable population during the COVID‐19 pandemic. There is currently insufficient evidence to determine whether patients on systemic immunomodulators are at increased risk of developing COVID‐19 disease or more likely to have severe disease. As such, clinicians need to assess the benefit‐to‐risk ratio on a case‐by‐case basis. In patients with suspected or confirmed COVID‐19 disease, all immunomodulators used for skin diseases should be immediately withheld, with the possible exception of systemic corticosteroid therapy, which needs to be weaned. In patients who develop symptoms or signs of an upper respiratory tract infection, but COVID‐19 is not yet confirmed, consider dose reduction or temporarily cessation for 1–2 weeks. In otherwise well patients, immunomodulators and biologics should be continued. In all patients, and their immediate close contacts, the importance of preventative measures to minimise human‐to‐human transmission cannot be overemphasised.