title: COVID-19: Ophthalmological Aspects of the SARS-CoV 2 Global Pandemic

text: Purpose To perform a systematic analysis of articles on the ophthalmological implications of the global COVID-19 pandemic. Methods PubMed.gov was searched for relevant articles using the keywords “COVID-19”, “coronavirus”, and “SARS-CoV-2” in conjunction with “ophthalmology” and “eye”. Moreover, official recommendations of ophthalmological societies were systematically reviewed, with a focus on the American Academy of Ophthalmology (AAO) and the Royal College of Ophthalmologists (RCOphth). Results As of April 16, 2020, in total, 21 peer-reviewed articles on the ophthalmological aspects of COVID-19 were identified. Of these, 12 (57.1%) were from Asia, 6 (28.6%) from the United States of America, and 3 (14.3%) from Europe. There were 5 (23.8%) original studies, 10 (47.6%) letters, 3 (14.2%) case reports, and 3 (14.2%) reviews. These articles could be classified into the topics “Modes and prevention of (ocular) transmission”, “Ophthalmological manifestations of COVID-19”, “Clinical guidance concerning ophthalmological practice during the COVID-19 pandemic”, and “Practical recommendations for clinical infrastructure”. Practical recommendations could be extracted from official statements of the AAO and the RCOphth. Conclusion Within a short period, a growing body of articles has started to elucidate the ophthalmological implications of COVID-19. As the eye can represent a route of infection (actively via tears and passively via the nasoacrimal duct), ophthalmological care has to undergo substantial modifications during this pandemic. In the eye, COVID-19 can manifest as keratoconjunctivitis.


title: Development of a multiplex real-time RT-PCR that allows universal detection of influenza A viruses and simultaneous typing of influenza A/H1N1/2009 virus

text: Abstract On June 11, 2009, the World Health Organization declared that the influenza A/H1N1/2009 virus had become the first influenza pandemic of the 21st century. Rapid detection and differentiation from seasonal and avian influenza would be beneficial for patient management and infection control. It was the aim of this study to develop a real-time RT-PCR that can detect all influenza A viruses and offer simultaneous typing for influenza A/H1N1/2009. This would be a useful addition to existing diagnostic protocols for influenza A. Its routine use would allow laboratories to screen out influenza A/H1N1/2009 positive samples rapidly and would reduce overall testing costs.


title: Associations between passive immunity and morbidity and mortality in dairy heifers in Florida, USA

text: Abstract A prospective cohort study was undertaken to determine calf-level factors that affected calf health status between birth and 6 months of age. A convenience sample of approximately 3300 female Holstein calves born in 1991 on two large Florida dairy farms was used for the study. Data collected on each calf at birth included farm of origin, weight, height at the pelvis, birth date, and serum total protein (a measure of colostral immunoglobulin absorption). Birth season was dichotomized into summer and winter using meteorological data collected by University of Florida Agricultural Research Stations. Health data including date of initial treatment and number of treatments were collected for the diseases diarrhea, omphalitis, septicemia and pneumonia. All calves were followed for 6 months. Cumulative incidences of mortality and occurrence of diarrhea, omphalitis, septicemia and pneumonia were 0.12, 0.35, 0.11, 0.24 and 0.21, respectively. Serum total protein (TP) was a significant risk factor for mortality. The association of TP and mortality was quadratic and showed a dramatic decrease in mortality as TP increased from 4.0 to 5.0 g/dl, a small improvement from 5.0 to 6.0 g/dl and virtually no improvement in mortality rates as TP increased over 6.0 g/dl. The hazard mortality ratio was constant from birth to six months, indicating that the increased risk of mortality associated with low levels of TP was evident through six months of age. No interactions between TP, farm, season, or birth weight were found in these analyses. Serum total protein concentration was a significant risk factor for the occurrences, age of onset and severity of septicemia and pneumonia. The association between TP and septicemia was linear and an interaction with birth season was found. The association between TP and pneumonia was quadratic, and in contrast to the TP-and-septicemia relationship, the morbidity hazard ratio for pneumonia was not constant over the time measured; that is, colostral immunity protected the calf from developing pneumonia early in life, but this effect disappeared as the calf got older. Total protein was not a significant risk factor for diarrhea or omphalitis.


title: An effective immunization strategy for airborne epidemics in modular and hierarchical social contact network

text: Abstract Social contact between individuals is the chief factor for airborne epidemic transmission among the crowd. Social contact networks, which describe the contact relationships among individuals, always exhibit overlapping qualities of communities, hierarchical structure and spatial-correlated. We find that traditional global targeted immunization strategy would lose its superiority in controlling the epidemic propagation in the social contact networks with modular and hierarchical structure. Therefore, we propose a hierarchical targeted immunization strategy to settle this problem. In this novel strategy, importance of the hierarchical structure is considered. Transmission control experiments of influenza H1N1 are carried out based on a modular and hierarchical network model. Results obtained indicate that hierarchical structure of the network is more critical than the degrees of the immunized targets and the modular network layer is the most important for the epidemic propagation control. Finally, the efficacy and stability of this novel immunization strategy have been validated as well.


title: Toward unsupervised outbreak detection through visual perception of new patterns

text: BACKGROUND: Statistical algorithms are routinely used to detect outbreaks of well-defined syndromes, such as influenza-like illness. These methods cannot be applied to the detection of emerging diseases for which no preexisting information is available. This paper presents a method aimed at facilitating the detection of outbreaks, when there is no a priori knowledge of the clinical presentation of cases. METHODS: The method uses a visual representation of the symptoms and diseases coded during a patient consultation according to the International Classification of Primary Care 2(nd )version (ICPC-2). The surveillance data are transformed into color-coded cells, ranging from white to red, reflecting the increasing frequency of observed signs. They are placed in a graphic reference frame mimicking body anatomy. Simple visual observation of color-change patterns over time, concerning a single code or a combination of codes, enables detection in the setting of interest. RESULTS: The method is demonstrated through retrospective analyses of two data sets: description of the patients referred to the hospital by their general practitioners (GPs) participating in the French Sentinel Network and description of patients directly consulting at a hospital emergency department (HED). Informative image color-change alert patterns emerged in both cases: the health consequences of the August 2003 heat wave were visualized with GPs' data (but passed unnoticed with conventional surveillance systems), and the flu epidemics, which are routinely detected by standard statistical techniques, were recognized visually with HED data. CONCLUSION: Using human visual pattern-recognition capacities to detect the onset of unexpected health events implies a convenient image representation of epidemiological surveillance and well-trained "epidemiology watchers". Once these two conditions are met, one could imagine that the epidemiology watchers could signal epidemiological alerts, based on "image walls" presenting the local, regional and/or national surveillance patterns, with specialized field epidemiologists assigned to validate the signals detected.


title: Early cidofovir administration might be associated with a lower probability of respiratory failure in treating human adenovirus pneumonia: a retrospective cohort study

text: Abstract Objective To compare outcomes of early and delayed treatment with cidofovir for human adenovirus (HAdV) pneumonia. Methods A retrospective cohort study in Korean military hospitals was conducted between January 2012 and December 2018. Patients with potentially severe HAdV pneumonia with risk factors for respiratory failure were included and divided into early (within 7 days from symptom onset) and delayed (after 7 days from symptom onset) treatment groups. The primary outcome was respiratory failure development within 21 days after symptom onset. Results A total of 89 patients with potentially severe HAdV pneumonia were enrolled in the cohort; they included 62 early and 27 delayed treatment patients. All patients were males in their early 20s. Significantly fewer patients in the early treatment group progressed to respiratory failure (8/62, 12.9%), compared to the delayed group (18/27, 66.7%, p < 0.001). Early treatment was associated with a lower 21-day probability of respiratory failure by the Kaplan–Meier method (p < 0.001). On multivariate analysis, monocyte count, hypoxaemia, confusion, whole lung involvement, and early cidofovir treatment within 7 days from symptom onset were included, and monocyte count (HR 0.995, 95%CI 0.991–1.000, p 0.042), confusion (HR 4.964, 95%CI 1.189–20.721, p = 0.028), and early cidofovir treatment (HR 0.319, 95%CI 0.115–0.883, p = 0.028) were significantly associated with respiratory failure. Conclusions Early administration of cidofovir was associated with a lower hazard for respiratory failure development. It is suggested that cidofovir be administered within 7 days from symptom onset to prevent respiratory failure in patients with potentially severe HAdV pneumonia.


title: Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses

text: [Image: see text] The recent Ebola virus (EBOV) outbreak in West Africa was the largest recorded in history with over 28,000 cases, resulting in >11,000 deaths including >500 healthcare workers. A focused screening and lead optimization effort identified 4b (GS-5734) with anti-EBOV EC(50) = 86 nM in macrophages as the clinical candidate. Structure activity relationships established that the 1′-CN group and C-linked nucleobase were critical for optimal anti-EBOV potency and selectivity against host polymerases. A robust diastereoselective synthesis provided sufficient quantities of 4b to enable preclinical efficacy in a non-human-primate EBOV challenge model. Once-daily 10 mg/kg iv treatment on days 3–14 postinfection had a significant effect on viremia and mortality, resulting in 100% survival of infected treated animals [Nature2016, 531, 381−38526934220]. A phase 2 study (PREVAIL IV) is currently enrolling and will evaluate the effect of 4b on viral shedding from sanctuary sites in EBOV survivors.


title: Diversity in a honey bee pathogen: first report of a third master variant of the Deformed Wing Virus quasispecies

text: Treatment of emerging RNA viruses is hampered by the high mutation and replication rates that enable these viruses to operate as a quasispecies. Declining honey bee populations have been attributed to the ectoparasitic mite Varroa destructor and its affiliation with Deformed Wing Virus (DWV). In the current study we use next-generation sequencing to investigate the DWV quasispecies in an apiary known to suffer from overwintering colony losses. We show that the DWV species complex is made up of three master variants. Our results indicate that a new DWV Type C variant is distinct from the previously described types A and B, but together they form a distinct clade compared with other members of the Iflaviridae. The molecular clock estimation predicts that Type C diverged from the other variants ∼319 years ago. The discovery of a new master variant of DWV has important implications for the positive identification of the true pathogen within global honey bee populations.


La Pandemia de la Covid-19 desde la SEAP


title: What’s in a word? The framing of health at the regional level: ASEAN, EU, SADC and UNASUR

text: The Association of Southeast Asian Nations, the European Union, the Southern African Development Community and the Union of South American Nations have increasingly been involved in health diplomacy in the past decade, yet little is known about how they frame health as a foreign policy issue and how this has an impact on their prioritisation of policies. For this, we conducted a review of existing grey and peer-reviewed literature that address regional integration and health, as well as a documentary review according to security, development, trade, human rights, moral/ethical reasonings and global public goods frames identified in the literature. The policy frames identified responded to the challenges these regions currently face. The Association of Southeast Asian Nation’s struggle with re-emerging diseases has led to favouring a securitisation approach to health, the European Union approaches health as a cross-cutting policy issue, the Southern African Development Community presents health as a driver for development, and while the Union of South American Nations emphasises health as a human right and addresses the social determinants of health as an ethical imperative. Overall, these policy frames were useful in analysing the framing of health in foreign policy at the regional level. However, within our analysis, we identified a new frame that approaches health as an intersectoral issue. The impact of regional organisations’ forward will depend on their ability to harness their convening power and speak in a coherent voice on health matters.


Priorities for global health community in COVID‐19 pandemic


title: Cross‐Species Transmission of Deltacoronavirus and the Origin of Porcine Deltacoronavirus

text: Deltacoronavirus is the last identified Coronaviridae subfamily genus. Differing from other coronavirus (CoV) genera, which mainly infect birds or mammals, deltacoronaviruses (δ‐CoVs) reportedly infect both animal types. Recent studies show that a novel δ‐CoV, porcine deltacoronavirus (PDCoV), can also infect calves and chickens with the potential to infect humans, raising the possibility of cross‐species transmission of δ‐CoVs. Here, we explored the deep phylogenetic history and cross‐species transmission of δ‐CoVs. Virus–host co‐phylogenetic analyses showed that δ‐CoVs have undergone frequent host switches in birds, and sparrows may serve as the unappreciated hubs for avian to mammal transmission. Our molecular clock analyses show that PDCoV possibly originated in Southeast Asia in the 1990s, and that the PDCoV cluster shares a common ancestor with Sparrow‐CoV of around 1810. Our findings contribute valuable insights into the diversification, evolution, and interspecies transmission of δ‐CoVs and the origin of PDCoV, providing a model for exploring the relationships of δ‐CoVs in birds and mammals.


title: STATIONARY DISTRIBUTION AND EXTINCTION OF STOCHASTIC CORONAVIRUS (COVID-19) EPIDEMIC MODEL

text: Similar to other epidemics, the novel coronavirus (COVID-19) spread very fast and infected almost two hundreds countries around the globe since December 2019. The unique characteristics of the COVID-19 include its ability of faster expansion through freely existed viruses or air molecules in the atmosphere. Assuming that the spread of virus follows a random process instead of deterministic. The continuous time Markov Chain (CTMC) through stochastic model approach has been utilized for predicting the impending states with the use of random variables. The proposed study is devoted to investigate a model consist of three exclusive compartments. The first class includes white nose based transmission rate (termed as susceptible individuals), the second one pertains to the infected population having the same perturbation occurrence and the last one isolated (quarantined) individuals. We discuss the model’s extinction as well as the stationary distribution in order to derive the the sufficient criterion for the persistence and disease’ extinction. Lastly, the numerical simulation is executed for supporting the theoretical findings.


title: Ahlstrom-Munksjö expands mask material capacity in Italy and Finland

text: Ahlstrom-Munksjö has increased the production of face mask materials at its plants in Turin, Italy and Tampere, Finland in response to the coronavirus pandemic.


title: Building resilience against biological hazards and pandemics: COVID-19 and its implications for the Sendai Framework

text: Abstract 2020 has become the year of coping with COVID-19. This year was to be the “super year” for sustainability, a year of strengthening global actions to accelerate the transformations required for achieving the 2030 agenda. We argue that 2020 can and must be a year of both. Thus we call for more utilisation of the health-emergency disaster risk management (Health-EDRM) framework to complement current responses to COVID-19 and the patent risk of similar phenomena in the future. To make our case, we examine current responses to COVID-19 and their implications for the SFDRR. We argue that current mechanisms and strategies for disaster resilience, as outlined in the SFDRR, can enhance responses to epidemics or global pandemics such as COVID-19. In this regard, we make several general and DRR-specific recommendations. These recommendations concern knowledge and science provision in understanding disaster and health-related emergency risks, the extension of disaster risk governance to manage both disaster risks and potential health-emergencies, particularly for humanitarian coordination aspects; and the strengthening of community-level preparedness and response.


title: COVID-19 Pandemic and Challenges for Socio-economic Issues, Healthcare and National Programs in India

text: BACKGROUND AND AIMS: The nationwide lockdown was imposed in India following novel coronavirus pandemic. In this paper, we discuss socio-economic, health and healthcare challenges following lockdown, with focus on population belonging to low socio-economic stratum (SES). METHODS: A literature search was conducted using PubMed and Google Scholar In addition, existing guidelines including those by Ministry of Health and Family Welfare, Government of India, and articles from several non-academic sources (e.g. news websites etc.) were accessed. RESULTS: While the nationwide lockdown has resulted in financial losses and has affected all segments of society, the domino effect on health, healthcare and nutrition could possibly pose major setbacks to previously gained successes of National health programs. CONCLUSION: Apart from firm economic measures, all National health programs should be re-strengthened to avert possible surge of communicable (apart from COVID19) and non-communicable diseases. These efforts should be focussed on population belonging to low SES.


title: Transport of exhaled particulate matter in airborne infection isolation rooms

text: Abstract The goal of this research was to examine the characteristics of the spatial velocity and concentration profiles which might result in health care workers’ exposure to a pathogenic agent in an airborne infection isolation room (AIIR). Computational fluid dynamics simulations were performed for this purpose. This investigation expanded on the work of Huang and Tsao [The influence of air motion on bacteria removal in negative pressure isolation rooms. HVAC & R Research 2005; 11: 563–85], who studied how ventilation conditions impact dispersion of pathogenic nuclei in an AIIR by investigating the airflow conditions impacting dispersion of infectious agents in the AIIR. The work included a careful quality assurance study of the computed airflow, and final simulations were performed on a fine tetrahedral mesh with approximately 1.3×106 cells. The 1μm diameter particles were released from a 0.001225m2 area representing the nose and mouth. Two cases were investigated during the current study: continuous exhalation of pathogen-laden air from the patient and expulsion of pathogenic particles by a single cough or sneeze. Slow decay of particle concentration in the AIIR during the single cough/sneeze simulation and tendency for particle accumulation near the AIIR walls observed in the continuous breathing simulation suggest that unintended exposures are possible despite the ventilation system. Based on these findings, it is recommended that extra care be taken to assure proper functionality of personal protective equipment used in an AIIR.


CT, [(18)F]FDG-PET/CT and clinical findings before and during early Covid-19 onset in a patient affected by vascular tumour


title: Seasonality and clinical impact of human parainfluenza viruses

text: BACKGROUND: Widespread availability of rapid diagnostic testing for respiratory viruses allows more in‐depth studies of human parainfluenza viruses (HPIV). OBJECTIVES: This study aimed to assess seasonality of HPIV types 1‐4, clinical outcomes by HPIV type, and risk factors for illness severity. PATIENTS/METHODS: This retrospective study was performed from January 2013 to December 2015 in children and adults with HPIV, detected by multiplex reverse transcription polymerase chain reaction, participating in a community surveillance study of acute respiratory infections (ARIs) in New York City and patients admitted to a tertiary care center in the same neighborhood. Seasonality trends by HPIV type were compared between the community and hospital groups. The associations between HPIV type, demographics, clinical characteristics, and illness severity were assessed. RESULTS: HPIV was detected in 69 (4%) of 1753 community surveillance participants (median age 9.2 years) and 680 hospitalized patients (median age 6.8 years). Seasonality for HPIV types 1‐3 agreed with previously described patterns; HPIV‐4 occurred annually in late summer and fall. In the community cohort, 22 (32%) participants sought medical care, 9 (13%) reported antibiotic use, and 20 (29%) reported ≥1 day of missed work or school. Among hospitalized patients, 24% had ≥4 chronic conditions. Multivariable ordinal logistic regression demonstrated that increased severity of illness was significantly associated with HPIV‐4 and chronic cardiovascular and respiratory conditions in children and with age ≥65 years and chronic respiratory conditions in adults. CONCLUSIONS: HPIV‐4 presented late summer and early fall annually and was associated with increased severity of illness in hospitalized children.


title: Etiology and clinical features of viral bronchiolitis in infancy

text: BACKGROUND: Bronchiolitis is a common lower respiratory tract infection in infancy. The aim of this review is to present the clinical profile of viral bronchiolitis, the different culprit viruses and the disease severity in relation to the viral etiology. DATA SOURCES: Databases including PubMed and Google Scholar were searched for articles about the clinical features of bronchiolitis and its viral etiology. The most relevant articles to the scope of this review were analyzed. RESULTS: Currently there are two main definitions for bronchiolitis which are not identical, the European definition and the American one. The most common viral pathogen that causes bronchiolitis is respiratory syncytial virus which was identified in 1955; now many other viruses have been implicated in the etiology of bronchiolitis such as rhinovirus, adenovirus, metapneumovirus, and bocavirus. Several studies have attempted to investigate the correlation of bronchiolitis severity with the type of detected virus or viruses. However, the results were not consitent. CONCLUSIONS: For the time being, the diagnosis of bronchiolitis remains clinical. The isolation of the responsible respiratory pathogens does not seem to confer to the prognosis of the disease severity.


title: Sociodemographic and Psychological Correlates of Compliance with the COVID-19 Public Health Measures in France

text: The COVID-19 disease was first identified in Wuhan, China, in December 2019, having since spread rapidly across the world. The infection and mortality rates of the disease have forced governments to implement a wave of public health measures. Depending on the context, these range from the implementation of simple hygienic rules to measures such as social distancing or lockdowns that cause major disruptions in citizens’ daily lives. The success of these crucial public health measures rests on the public's willingness to comply. However, individual differences in following the official public health recommendations for stopping the spread of COVID-19 have not yet to our knowledge been assessed. This study aims to fill this gap by assessing the sociodemographic and psychological correlates of implementing public health recommendations that aim to halt the COVID-19 pandemic. We investigate these associations in the context of France, one of the countries that has been most severely affected by the pandemic, and which ended up under a nationwide lockdown on March 17. In the next sections we describe our theoretical expectations over the associations between sociodemographics, personality, ideology, and emotions with abiding by the COVID-19 public health measures. We then test these hypotheses using data from the French Election Study.


title: Comparative Proteomics Analysis of Anisakis simplex s.s.—Evaluation of the Response of Invasive Larvae to Ivermectin

text: Ivermectin (IVM), an antiparasitic drug, has a positive effect against Anisakis simplex s.s. infection and has been used for the treatment and prevention of anisakiasis in humans. However, the molecular mechanism of action of IVM on A. simplex s.s. remains unknown. Herein, tandem mass tag (TMT) labeling and extensive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis were used to identify the effect of IVM on the proteome of A. simplex s.s. in vitro. During the study, 3433 proteins, of which 1247 had at least two protein unique peptides, were identified. Comparative proteomics analysis revealed that 59 proteins were differentially regulated (DRPs) in IVM-treated larvae, of which 14 proteins were upregulated and 38 were downregulated after 12 h of culture, but after 24 h, 12 proteins were upregulated and 22 were downregulated. The transcription level of five randomly selected DRPs was determined by real-time PCR as a supplement to the proteomic data. The functional enrichment analysis showed that most of the DRPs were involved in oxidoreductase activity, immunogenicity, protein degradation, and other biological processes. This study has, for the first time, provided comprehensive proteomics data on A. simplex s.s. response to IVM and might deliver new insight into the molecular mechanism by which IVM acts on invasive larvae of A. simplex s.s.


title: Current Scenario of COVID-19 in Pediatric Age Group and Physiology of Immune and Thymus response

text: Abstract COVID-19 pandemic caused by SARS-CoV-2, continues to manifest with severe acute respiratory syndrome among the adults, however, it offers a convincing indication of less severity and fatality in pediatric age group (0-18 years). The current trend suggests that children may get infected but are less symptomatic with less fatality, which is concordant to earlier epidemic outbreaks of SARS-CoV and MERS-CoV, in 2002 and 2012, respectively. According to the available data, children appear to be at lower risk for COVID-19, as adults constitute for maximum number of the confirmed cases (308,592) and deaths (13,069) as on 22nd March ( https://www.worldometers.info/coronavirus ). However, rapid publications and information of the adult patients with COVID-19 is in progress and published, on the contrary, almost no comprehensive data or discussion about the COVID-19 in children is available. Therefore, in this review, we outline the epidemiology, clinical symptoms, diagnosis, treatment, prevention, possible immune response and role of thymus in children to combat the COVID-19 outbreak.


title: Social Support and Response to AIDS and Severe Acute Respiratory Syndrome

text: Negative public reactions to emerging infectious diseases can adversely affect population health. We assessed whether social support was associated with knowledge of, worry about, and attitudes towards AIDS and severe acute respiratory syndrome. Our findings suggest that social support may be central to our understanding of public responses to emerging infectious diseases.


title: Pneumonia

text: Neonatal pneumonia may occur in isolation or as one component of a larger infectious process. Bacteria, viruses, fungi, and parasites are all potential causes of neonatal pneumonia, and may be transmitted vertically from the mother or acquired from the postnatal environment. The patient's age at the time of disease onset may help narrow the differential diagnosis, as different pathogens are associated with congenital, early-onset, and late-onset pneumonia. Supportive care and rationally selected antimicrobial therapy are the mainstays of treatment for neonatal pneumonia. The challenges involved in microbiological testing of the lower airways may prevent definitive identification of a causative organism. In this case, secondary data must guide selection of empiric therapy, and the response to treatment must be closely monitored.


title: Bridging the Science-Policy Divide

text: Prolonged negotiations and insufficient policies to mitigate climate change and biodiversity loss are often attributed to policymakers’ lack of understanding of the relevant science. Conversely, what do scientists need to understand about the policymaking process in order to engage policymakers productively and communicate their research effectively in this context?


title: Knowledge, Awareness, and Compliance of Disease Surveillance and Notification Among Jordanian Physicians in Residency Programs

text: Health professionals’ knowledge and awareness of the disease surveillance is essential for reporting diseases to health departments. This study aimed to assess the knowledge and attitudes of Jordanian physicians toward public health surveillance of communicable disease. A cross-sectional study was conducted among resident doctors who were working in 4 main Ministry of Health hospitals and 2 teaching hospitals in Jordan in September 2017. A self-administered paper-based questionnaire was used to collect the data. The questionnaire collected information about sociodemographic and practice-related characteristics of physicians and included items to assess their knowledge of surveillance and reporting practices. This study included 223 physicians (152 males and 71 females). About 60.1% of the residents were graduates from medical schools in Jordan and the remaining (39.9%) were graduates from medical schools in other countries. Approximately two thirds of residents (62.3%) were doing their residency in Ministry of Health hospitals and the rest (37.7%) in 2 teaching hospitals. Only 44.8% of physicians had defined surveillance correctly. Only 27.4% of physicians had been educated or trained on surveillance. About 39.5% of physicians had filled at least one report form during their practice. The main reasons for not reporting mandatory diseases were high workload (49.8%) and being not trained on reporting diseases (46.6%). A relatively high percentage of physicians have insufficient knowledge of surveillance and reporting of notifiable communicable diseases. Training of physicians on surveillance and diseases notification is highly needed. The practice of disease notification should be enforced in Jordanian hospitals.


title: Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding

text: We report epidemiological and clinical investigations on ten pediatric SARS-CoV-2 infection cases confirmed by real-time reverse transcription PCR assay of SARS-CoV-2 RNA. Symptoms in these cases were nonspecific and no children required respiratory support or intensive care. Chest X-rays lacked definite signs of pneumonia, a defining feature of the infection in adult cases. Notably, eight children persistently tested positive on rectal swabs even after nasopharyngeal testing was negative, raising the possibility of fecal–oral transmission.


title: Obesity - a risk factor for increased COVID-19 prevalence, severity and lethality

text: Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are a group of viruses that cause infections in the human respiratory tract, which can be characterized clinically from mild to fatal. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible. The global spread of COVID-19 can be described as the worst pandemic in humanity in the last century. To date, COVID-19 has infected more than 3,000,000 people worldwide and killed more than 200,000 people. All age groups can be infected from the virus, but more serious symptoms that can possibly result in death are observed in older people and those with underlying medical conditions such as cardiovascular and pulmonary disease. Novel data report more severe symptoms and even a negative prognosis for the obese patients. A growing body of evidence connects obesity with COVID-19 and a number of mechanisms from immune system activity attenuation to chronic inflammation are implicated. Lipid peroxidation creates reactive lipid aldehydes which in a patient with metabolic disorder and COVID-19 will affect its prognosis. Finally, pregnancy-associated obesity needs to be studied further in connection to COVID-19 as this infection could pose high risk both to pregnant women and the fetus.


title: Competency assessment for infection control in the undergraduate dental curriculum

text: Objectives: This study aimed at investigating the introduction of an infection control competency assessment on undergraduate dental student's awareness and knowledge of infection control. Method: A short course, including an introductory lecture and a three component competency based assessment exercise testing student's knowledge and ability in infection control measures was incorporated into the previously established training programme. The assessment exercises included a written test of students’ knowledge of the Infection Control Policy, a unit management exercise and a hand hygiene assessment. The infection control competency was initially incorporated into the final term of the second year in 2004 and is now an established part of the 5‐year dental undergraduate degree programme. Re‐assessments were scheduled (at the start of third year) for students failing to meet the required standard as successful completion of this course was compulsory prior to students being allowed to treat their first patients. Student performance over the last 2 years on this course and during their first year on clinic were analysed to determine potential improvements in student knowledge and application in infection control. Examination results from the year 3, infection control spot test were compared with those of earlier years. In addition, the opinions, as assessed by questionnaire analysis, of dental staff and students on the infection control competency were obtained. Results: All students successfully completed the infection control competency (either at first or second attempt) and were subsequently allowed to enter clinical training in year 3. Significant improvements were seen in students passing the course at their initial attempt, 42% and 78%, in the 2004 and 2005 academic years, respectively. Also subsequent testing of these students during their first year on clinic showed marked increases in awareness and knowledge of the infection control protocols. Staff and student feedback on this course was also found to be highly supportive of the introduction of the infection control competency. Conclusion: Incorporation of additional formal pre‐clinical teaching and introduction of an infection competency potentially provides enduring knowledge and clinical application benefits.


Chronic kidney disease and SARS-CoV-2 outbreak: Lazio region organizational model


title: Reparations for Black American Descendants of Persons Enslaved in the U.S. and Their Estimated Impact on SARS-CoV-2 Transmission

text: Background In the United States, Black Americans are suffering from significantly disproportionate incidence and mortality rates of COVID-19. The potential for racial-justice interventions, including reparations payments, to ameliorate these disparities has not been adequately explored. Methods We compared the COVID-19 time-varying Rt curves of relatively disparate polities in terms of social equity (South Korea vs. Louisiana). Next, we considered a range of reproductive ratios to back-calculate the transmission rates {beta}i[->]j for 4 cells of the simplified next-generation matrix (from which R0 is calculated for structured models) for the outbreak in Louisiana. Lastly, we modeled the effect that monetary payments as reparations for Black American descendants of persons enslaved in the U.S. would have had on pre-intervention {beta}i[->]j. Results Once their respective epidemics begin to propagate, Louisiana displays Rt values with an absolute difference of 1.3 to 2.5 compared to South Korea. It also takes Louisiana more than twice as long to bring Rt below 1. We estimate that increased equity in transmission consistent with the benefits of a successful reparations program (reflected in the ratio {beta}b[->]b / {beta}w[->]w) could reduce R0 by 31 to 68%. Discussion While there are compelling moral and historical arguments for racial injustice interventions such as reparations, our study describes potential health benefits in the form of reduced SARS-CoV-2 transmission risk. As we demonstrate, a restitutive program targeted towards Black individuals would not only decrease COVID-19 risk for recipients of the wealth redistribution; the mitigating effects would be distributed across racial groups, benefitting the population at large.


title: The essential adaptors of innate immune signaling

text: Microbial components and the endogenous molecules released from damaged cells can stimulate germ-line-encoded pattern recognition receptors (PRRs) to transduce signals to the hub of the innate immune signaling network-the adaptor proteins MyD88/TRIF/MAVS/STING/Caspase-1, where integrated signals relay to the relevant transcription factors IRF3/IRF7/NF-κB/ AP-1 and the signal transducer and activator of transcription 6 (STAT6) to trigger the expression of type I interferons and inflammatory cytokines or the assembly of inflammasomes. Most pleiotropic cytokines are secreted and bind to specific receptors, activating the signaling pathways including JAK-STAT for the proliferation, differentiation and functional capacity of immune cells. This review focuses on several critical adaptors in innate immune signaling cascades and recent progress in their molecular mechanisms.


title: Mechanisms of Bioactivities of Fucoidan from the Brown Seaweed Fucus vesiculosus L. of the Barents Sea

text: The aim of this study was to elucidate some mechanisms of radical scavenging and the anti-inflammatory, anti-hyperglycemic, and anti-coagulant bioactivities of high molecular weight fucoidan from Fucus vesiculosus in several in vitro models. Fucoidan has displayed potent 1, 1-diphenyl-2-picryl hydrazil radical scavenging and reduction power activities. It significantly inhibits the cyclooxygenase-2 (COX-2) enzyme (IC(50) 4.3 μg mL(−1)) with a greater selectivity index (lg(IC(80) COX-2/IC(80)COX-1), −1.55) than the synthetic non-steroidal anti-inflammatory drug indomethacin (lg(IC(80) COX-2/IC(80)COX-1), −0.09). A concentration-dependent inhibition of hyaluronidase enzyme with an IC(50) of 2.9 μg mL(−1) was observed. Fucoidan attenuated the lipopolysaccharide-induced expression of mitogen-activated protein kinase p38. Our findings suggest that the inhibition of dipeptidyl peptidase-IV (DPP-IV) (IC(50) 1.11 μg mL(−1)) is one of the possible mechanisms involved in the anti-hyperglycemic activity of fucoidan. At a concentration of 3.2 μg mL(−1), fucoidan prolongs the activated partial thromboplastin time and thrombin time by 1.5-fold and 2.5-fold compared with a control, respectively. A significant increase of prothrombin time was observed after the concentration of fucoidan was increased above 80 μg mL(−1). This evidenced that fucoidan may have an effect on intrinsic/common pathways and little effect on the extrinsic mechanism. This study sheds light on the multiple pathways of the bioactivities of fucoidan. As far as we know, the inhibition of hyaluronidase and DPP-IV by high molecular fucoidan was studied for the first time in this work. Our results and literature data suggest that molecular weight, sulfate content, fucose content, and polyphenols may contribute to these activities. It seems that high molecular weight fucoidan has promising therapeutic applications in different pharmacological settings. Anti-oxidant, anti-inflammatory and anti-coagulant drugs have been used for the management of complications of COVID19. Taken as a whole, fucoidan could be considered as a prospective candidate for the treatment of patients with COVID19; however, additional research in this field is required.


title: Colostrum from cows immunized with a veterinary vaccine against bovine rotavirus displays enhanced in vitro anti-human rotavirus activity

text: ABSTRACT Human rotaviruses represent a major cause of severe diarrheal disease in infants and young children. The limited impact of oral vaccines on global estimates of rotavirus mortality and the suboptimal use of oral rehydration justify the need for alternative prophylactic and therapeutic strategies, especially for immunocompromised hosts. The protective effects of colostrum—the first milk produced during the initial 24 to 48 h after parturition—are well documented in the literature. In particular, the ingestion of hyperimmune bovine colostrum has been proposed as an alternative preventive approach against human rotavirus gastroenteritis. Although the immunization of pregnant cows with human rotavirus boosts the release of specific immunoglobulin G in bovine colostrum, it raises regulatory and safety issues. In this study, we demonstrated that the conventional bovine rotavirus vaccine is sufficient to enhance the anti-human rotavirus protective efficacy of bovine colostrum, thus providing a conservative approach to produce hyperimmune bovine colostrum, making it exploitable as a functional food.


title: Pharmaceutical and medicinal significance of sulfur (S(VI))-Containing motifs for drug discovery: A critical review

text: Sulfur (S(VI)) based moieties, especially, the sulfonyl or sulfonamide based analogues have showed a variety of pharmacological properties, and its derivatives propose a high degree of structural diversity that has established useful for the finding of new therapeutic agents. The developments of new less toxic, low cost and highly active sulfonamides containing analogues are hot research topics in medicinal chemistry. Currently, more than 150 FDA approved Sulfur (S(VI))-based drugs are available in the market, and they are widely used to treat various types of diseases with therapeutic power. This comprehensive review highlights the recent developments of sulfonyl or sulfonamides based compounds in huge range of therapeutic applications such as antimicrobial, anti-inflammatory, antiviral, anticonvulsant, antitubercular, antidiabetic, antileishmanial, carbonic anhydrase, antimalarial, anticancer and other medicinal agents. We believe that, this review article is useful to inspire new ideas for structural design and developments of less toxic and powerful Sulfur (S(VI)) based drugs against the numerous death-causing diseases.


title: Optimizing use of theranostic nanoparticles as a life-saving strategy for treating COVID-19 patients

text: On the 30(th) of January 2020, the World Health Organization fired up the sirens against a fast spreading infectious disease caused by a newly discovered Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and gave this disease the name COVID-19. While there is currently no specific treatment for COVID-19, several off label drugs approved for other indications are being investigated in clinical trials across the globe. In the last decade, theranostic nanoparticles were reported as promising tool for efficiently and selectively deliver therapeutic moieties (i.e. drugs, vaccines, siRNA, peptide) to target sites of infection. In addition, they allow monitoring infectious sides and treatment responses using noninvasive imaging modalities. While intranasal delivery was proposed as the preferred administration route for therapeutic agents against viral pulmonary diseases, NP-based delivery systems offer numerous benefits to overcome challenges associated with mucosal administration, and ensure that these agents achieve a concentration that is many times higher than expected in the targeted sites of infection while limiting side effects on normal cells. In this article, we have shed light on the promising role of nanoparticles as effective carriers for therapeutics or immune modulators to help in fighting against COVID-19.


title: Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: a systematic review and meta-analysis

text: Abstract Objective To better inform efforts to treat and control the current outbreak with a comprehensive characterization of COVID-19. Methods We searched PubMed, EMBASE, Web of Science, and CNKI (Chinese Database) for studies published as of March 2, 2020, and we searched references of identified articles. Studies were reviewed for methodological quality. A random-effects model was used to pool results. Heterogeneity was assessed using I2 . Publication bias was assessed using Egger's test. Results 43 studies involving 3600 patients were included. Among COVID-19 patients, fever (83.3% [95% CI 78.4–87.7]), cough (60.3% [54.2–66.3]), and fatigue (38.0% [29.8–46.5]) were the most common clinical symptoms. The most common laboratory abnormalities were elevated C-reactive protein (68.6% [58.2–78.2]), decreased lymphocyte count (57.4% [44.8–69.5]) and increased lactate dehydrogenase (51.6% [31.4–71.6]). Ground-glass opacities (80.0% [67.3–90.4]) and bilateral pneumonia (73.2% [63.4–82.1]) were the most frequently reported findings on computed tomography. The overall estimated proportion of severe cases and case-fatality rate (CFR) was 25.6% (17.4–34.9) and 3.6% (1.1–7.2), respectively. CFR and laboratory abnormalities were higher in severe cases, patients from Wuhan, and older patients, but CFR did not differ by gender. Conclusions The majority of COVID-19 cases are symptomatic with a moderate CFR. Patients living in Wuhan, older patients, and those with medical comorbidities tend to have more severe clinical symptoms and higher CFR.


title: Emerging Pharmaceutical Treatments of Novel COVID-19: A Review

text: As a new decade began, COVID-19 quickly gained importance as it became the cause of the current global pandemic. Research has been focusing on studying the structure of SARS-CoV-2 and investigates possible pharmaceutical approaches. With the number of cases increasing every day, globally, multiple drugs are being researched as possible candidates. Although multiple drugs show promise in the treatment of COVID-19 via either inhibiting viral replication or preventing fusion of the virus to the ACE2 receptors, further investigation is still warranted and necessary before the admission of any type of pharmaceutical agent. Furthermore, several supplements have also been documented in being utilized as treatment of COVID-19. The exact mechanism and efficacy of current candidate drugs are still being explored through clinical trials. Despite the advancements in current research with emerging treatments, social distancing and engaging in preventative measures remains crucial to attempt to prevent the occurrence of more cases and deaths, worldwide. This review explores various drugs and their mechanism of action which are either currently being used in clinical trials or may be used in the future for the treatment of COVID-19.


title: Modified H5 promoter improves stability of insert genes while maintaining immunogenicity during extended passage of genetically engineered MVA vaccines

text: We have engineered recombinant (r) Modified Vaccinia Ankara (MVA) to express multiple antigens under the control of either of two related vaccinia synthetic promoters (pSyn) with early and late transcriptional activity or the modified H5 (mH5) promoter which has predominant early activity. We sequentially passaged these constructs and analyzed their genetic stability by qPCR, and concluded that rMVA expressing multiple antigens using the mH5 promoter exhibit remarkable genetic stability and maintain potent immunogenicity after serial passage. In contrast, rMVA expressing antigens using engineered vaccinia synthetic E/L (pSyn I or II) promoters are genetically unstable. Progressive accumulation of antigen loss variants resulted in a viral preparation with lower immunogenicity after serial passage. Metabolic labeling, followed by cold chase revealed little difference in stability of proteins expressed from mH5 or pSyn promoter constructs. We conclude that maintenance of genetic stability which is achieved using mH5, though not with pSyn promoters, is linked to timing, not the magnitude of expression levels of foreign antigen, which is more closely associated with immunogenicity of the vaccine.


title: An Overview on the Field of Micro- and Nanotechnologies for Synthetic Peptide-Based Vaccines

text: The development of synthetic peptide-based vaccines has many advantages in comparison with vaccines based on live attenuated organisms, inactivated or killed organism, or toxins. Peptide-based vaccines cannot revert to a virulent form, allow a better conservation, and are produced more easily and safely. However, they generate a weaker immune response than other vaccines, and the inclusion of adjuvants and/or the use of vaccine delivery systems is almost always needed. Among vaccine delivery systems, micro- and nanoparticulated ones are attractive, because their particulate nature can increase cross-presentation of the peptide. In addition, they can be passively or actively targeted to antigen presenting cells. Furthermore, particulate adjuvants are able to directly activate innate immune system in vivo. Here, we summarize micro- and nanoparticulated vaccine delivery systems used in the field of synthetic peptide-based vaccines as well as strategies to increase their immunogenicity.


title: An Informatics Solution for Informing Care Delivery of Immediate Public Health Risks to Their Patients

text: This paper describes a public health alerting approach that has the potential to improve patient care during a public health outbreak and reduce healthcare costs, streamline the process of public health alert management and dissemination, and heighten the crucial feedback loop between public health officials and clinicians. The approach ties public health alerts into the diagnostic process and allows clinicians to more easily determine when an observed medical condition may be related to a more widespread disease outbreak. A prototype Alert Knowledge Repository (AKR) service using this approach was demonstrated within the Health Information and Management Systems Society (HIMSS) and the Public Health Information Network (PHIN) interoperability showcases in April and September 2009, respectively.


title: Clinical characteristics and changes of chest CT features in 307 patients with common COVID-19 pneumonia infected SARS-CoV-2: A multicenter study in Jiangsu, China

text: Abstract Objective The study was aimed to describe the clinical characteristics and evaluate the dynamic changes of chest CT features in the first week in the common type fo COVID-19 pneumonia patientsin Jiangsu Province. Methods 307 patients infected SARS-CoV-2 classified as common type were enrolled in the study. 628 chest CT scans were divided into three groups based on the time interval between symptoms and chest CT scan. The clinical characteristics were descriptively analyzed.The chest CT features were quantitatively evaluated. Mann-Whitney U test was used to test the differences in three groups and between men and women. Spearman rank correlation was used to test the association between the arterial blood gas(ABG) analysis results and chest CT scores. Results Fever (69.1%) and cough (62.8%) were common symptoms. 111(36.2%) patients were anorexia. GGO was the most common manifestation of COVID-19 pneumonia, which could be followed by consolidation and fibrosis. Lower lobe or subpleural region was the most common distribution form of lesion. More lung lobes involved in the third week. Total chest CT scores in the second week were higher than the first week. Fibrosis Scores increased in the second and third week. Total CT score, GGO score and fibrosis score of male patients were significantly higher than female in the second week. Male patients had higher consolidation score and fibrosis score than female in the third week. Total CT score and GGO score had weak to moderate correlation with arterial blood gas indices. Conclusion Changes in chest CT were difficult to assess quantitatively in the first third weeks. Male patients recovered slower than female in the second week. Although CT score had correlations with arterial blood gas indices, long-term follow-up of pulmonary function test is needed to determine the recovery of lung.


title: Treatments Administered to the First 9152 Reported Cases of COVID-19: A Systematic Review

text: The emergence of SARS-CoV-2/2019 novel coronavirus (COVID-19) has created a global pandemic with no approved treatments or vaccines. Many treatments have already been administered to COVID-19 patients but have not been systematically evaluated. We performed a systematic literature review to identify all treatments reported to be administered to COVID-19 patients and to assess time to clinically meaningful response for treatments with sufficient data. We searched PubMed, BioRxiv, MedRxiv, and ChinaXiv for articles reporting treatments for COVID-19 patients published between 1 December 2019 and 27 March 2020. Data were analyzed descriptively. Of the 2706 articles identified, 155 studies met the inclusion criteria, comprising 9152 patients. The cohort was 45.4% female and 98.3% hospitalized, and mean (SD) age was 44.4 years (SD 21.0). The most frequently administered drug classes were antivirals, antibiotics, and corticosteroids, and of the 115 reported drugs, the most frequently administered was combination lopinavir/ritonavir, which was associated with a time to clinically meaningful response (complete symptom resolution or hospital discharge) of 11.7 (1.09) days. There were insufficient data to compare across treatments. Many treatments have been administered to the first 9152 reported cases of COVID-19. These data serve as the basis for an open-source registry of all reported treatments given to COVID-19 patients at www.CDCN.org/CORONA. Further work is needed to prioritize drugs for investigation in well-controlled clinical trials and treatment protocols. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40121-020-00303-8) contains supplementary material, which is available to authorized users.


title: Hematological findings and complications of COVID‐19

text: COVID‐19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential. Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases. During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL‐6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes. Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors. Furthermore, blood hypercoagulability is common among hospitalized COVID‐19 patients. Elevated D‐Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening. Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life‐threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention. So, COVID‐19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended. Last but not least, the need for assuring blood donations during the pandemic is also highlighted.


title: Houttuynia cordata Thunb. polysaccharides ameliorates lipopolysaccharide-induced acute lung injury in mice

text: Abstract Ethnopharmacological relevance Houttuynia cordata (HC) has been used as a folk therapy to treat pulmonary infections. This study aimed to determine the role and mechanism of action of polysaccharides isolated from HC (HCP) in lipopolysaccharide (LPS)-induced ALI in the mice. Materials and methods LPS was delivered by the intratracheal route to Balb/c mice 2h before HCP (40, 80 and 160mg/kg) administration. Results The number of total cells, protein and tumor necrosis factor-α (TNF-α) concentrations in bronchoalveolar lavage fluid, the wet/dry weight ratio (w/d) of lungs and pulmonary pathology of each mouse were analyzed, it was found that HCP significantly alleviated ALI induced by LPS. Moreover, in lungs of mice, it was found that the infiltration of inflammatory cells, the expression of Toll-like receptor 4 and complement deposition were significantly decreased by HCP treatment. In vitro assays showed that C5a, a complement activation product, induced significant macrophage migration and treatment with HCP prevented it. The in vitro results also proved that LPS increased nitric oxide and pro-inflammatory cytokines (TNF-α, interleukin-6, and interleukin-1β) production, and HCP antagonized these effects of LPS. It was also found that HCP alone augmented secretion of some pro-inflammatory cytokines. Conclusion These results indicate that HCP may alleviate LPS induced lung inflammatory injury, which may be associated with its inhibitory effect on the over activation of complement and macrophages. This suggests a potential role to treat ALI.


title: The impact of the COVID‐19 lockdown in Italy on a pediatric emergency setting

text: Italy has been one of countries most affected by the COVID‐19 pandemic and the Government instituted a strict national lockdown on 9 March 2020 to limit the spread. Healthcare services were only open for emergencies or undelayable needs. This study describes the impact of the lockdown on the tertiary level Pediatric Emergency Department (PED) at the Institute for Maternal and Child Health IRCCS Burlo Garofolo, in Trieste, North East Italy. It is the only PED in the city and sees 25,000 patients aged 0‐17 annually.


title: Decreased prealbumin level is associated with increased risk of mortality in hospitalized elderly patients with COVID-19

text: Objective: Severe patients tended to have lower serum prealbumin concentration in patients with novel coronavirus (SARS-CoV-2) infected pneumonia (COVID-19). This study was performed to investigate the association of prealbumin at baseline on COVID19-related mortality in elderly patients. Methods: We non-selectively and consecutively collected participants in Tongji Hospital in Wuhan from January 17 to February 17, 2020. Univariate and multivariate logistic regression models were employed to evaluate the correlation between prealbumin and in-hospital outcomes (in-hospital mortality, ICU admission and mechanical ventilation) in elderly COVID-19 patients. Linear trend was performed by entering the median value of each category of prealbumin tertile as continuous variable and was visually confirmed by using generalized additive models. Interaction and stratified analyses were conducted as well. Results: A total of 446 COVID-19 elderly patients were included in the final analyses and the in-hospital mortality was 14.79%. 15.47% patients admitted to intensive care unit and 21.3% patients required mechanical ventilation. Compared with patients in the highest tertile, the prealbumin of patients in the lowest tertile had a 19.09-fold higher risk of death (OR = 20.09; 95% CI, 3.62 to 111.64; P = 0.0006), 25.39-fold higher risk of ICU admission (OR = 26.39; 95% CI, 4.04to 172.39; P = 0.0006) and 1.8-fold higher risk of mechanical ventilation (OR = 2.8; 95% CI, 1.15 to 6.78; P = 0.0227) after adjustment for potential confounders. There was a linear trend correlation between serum prealbumin concentration and risk of in-hospital mortality, ICU admission and mechanical ventilation in elderly patients with COVID-19 infection. Conclusion: Prealbumin is an independent risk factor of the in-hospital mortality for COVID-19 elderly patients. Assessment of prealbumin may help identify high risk elderly individuals with COVID-19.


title: SARS‐CoV‐2 immunogenicity at the crossroads

text: The outbreak of coronavirus disease 2019 (COVID-19) caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global health emergency and became a worldwide pandemic. We summarize the recent findings with respect to the function, structure and immunogenicity of the spike (S) protein, arising mutations, and implications on vaccine development and therapeutics.


What’s Important: Redeployment of the Orthopaedic Surgeon During the COVID-19 Pandemic: Perspectives from the Trenches


title: Infections à Mycoplasma pneumoniae : étude rétrospective en Basse-Normandie de 1997 à 2005. Épidémiologie –– Place de la sérologie et de la PCR pour le diagnostic

text: OBJECTIVES: The objective of this study was to evaluate the epidemiology of Mycoplasma pneumoniae (Mpn) infections in Basse-Normandie by a retrospective analysis of serological and PCR data, and to confirm the diagnostic utility of PCR and serology. METHODS: From 1997 to August 2005, 6156 serum samples and 6123 respiratory tract samples were collected from hospitalised patients and evaluated for the diagnosis of Mpn infection by PCR, serological assays, or by the two tests. During the epidemic period (2004-2005), the results of 1489 patients were analysed. RESULTS: Over the 9-y period, the seroprevalence was 40,4% and we reported on 525 cases with serologically or/and PCR proven Mpn infection, according a cyclic pattern spaced out 7 years. During the epidemic period, the seroprevalence increased to 50,2% and the rate of infections was 8.3%. The analysis of the 124 cases of Mpn infection showed typical epidemiological characteristics: a peak of incidence among the children and young adults, a summer-winter pattern and some coinfections with viral strains. For diagnosis of Mpn infection, the comparison of PCR and serological assays among 36 patients showed a concordance of only 41.7%. CONCLUSION: Mpn infections were endemic and outbreaks were observed according cyclic pattern with a high incidence specially in the children. Sensitive and specific tests were now available for early and reliable diagnosis. In children, the combination of the PCR on nasopharyngeal samples and the IgM EIA serology test were recommended. In adults, the PCR was privilegiated.


title: A 21(st) century view of infection control in everyday settings: moving from the Germ Theory of Disease to the Microbial Theory of Health

text: Background: The growing understanding of the importance of a healthy microbiome is challenging traditional thinking that resulted in the general acceptance of the germ theory of disease. We propose a more encompassing Microbial Theory of Health that will have implications for the way that we address our relationship with microbes, including hygiene policy and community-based infection control practices. Methods: This paper considers theories over the last 30 years that have impacted hygiene policy and consumer practice, from the Germ Theory of Disease and the Hygiene Hypothesis, to the Microbial Theory of Health, including the concept of Bidirectional Hygiene. Here we present a high-level review of the literature on pathogen transmission and the cycle of infection in the home and everyday settings. Results: Targeted hygiene is an evidence-based hygiene policy that is employed to prevent transmission of pathogens and the transmission of infectious diseases through targeting only sites, surfaces, and practices that are considered high risk for pathogen transmission. Targeted hygiene also discourages the indiscriminate use of broad-spectrum microbicides for lower-risk activities and surfaces. Conclusions: The Microbial Theory of Health, including age-appropriate and health-appropriate hygiene practices for home and everyday life, should usher in a new era in which pathogen reduction can be accomplished without indiscriminate elimination of potentially beneficial microbes from the human and environmental microbiomes.


title: Revisiting potential druggable targets against SARS‐CoV‐2 and repurposing therapeutics under preclinical study and clinical trials: A comprehensive review

text: Coronavirus disease‐19 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is one of the most contagious diseases in human history that has already affected millions of lives worldwide. To date, no vaccines or effective therapeutics have been discovered yet that may successfully treat COVID‐19 patients or contain the transmission of the virus. Scientific communities across the globe responded rapidly and have been working relentlessly to develop drugs and vaccines, which may require considerable time. In this uncertainty, repurposing the existing antiviral drugs could be the best strategy to speed up the discovery of effective therapeutics against SARS‐CoV‐2. Moreover, drug repurposing may leave some vital information on druggable targets that could be capitalized in target‐based drug discovery. Information on possible drug targets and the progress on therapeutic and vaccine development also needs to be updated. In this review, we revisited the druggable targets that may hold promise in the development of the anti‐SARS‐CoV‐2 agent. Progresses on the development of potential therapeutics and vaccines that are under the preclinical studies and clinical trials have been highlighted. We anticipate that this review will provide valuable information that would help to accelerate the development of therapeutics and vaccines against SARS‐CoV‐2 infection.


title: Probing genomic diversity and evolution of Streptococcus suis serotype 2 by NimbleGen tiling arrays

text: BACKGROUND: Our previous studies revealed that a new disease form of streptococcal toxic shock syndrome (STSS) is associated with specific Streptococcus suis serotype 2 (SS2) strains. To achieve a better understanding of the pathogenicity and evolution of SS2 at the whole-genome level, comparative genomic analysis of 18 SS2 strains, selected on the basis of virulence and geographic origin, was performed using NimbleGen tiling arrays. RESULTS: Our results demonstrate that SS2 isolates have highly divergent genomes. The 89K pathogenicity island (PAI), which has been previously recognized as unique to the Chinese epidemic strains causing STSS, was partially included in some other virulent and avirulent strains. The ABC-type transport systems, encoded by 89K, were hypothesized to greatly contribute to the catastrophic features of STSS. Moreover, we identified many polymorphisms in genes encoding candidate or known virulence factors, such as PlcR, lipase, sortases, the pilus-associated proteins, and the response regulator RevS and CtsR. On the basis of analysis of regions of differences (RDs) across the entire genome for the 18 selected SS2 strains, a model of microevolution for these strains is proposed, which provides clues into Streptococcus pathogenicity and evolution. CONCLUSIONS: Our deep comparative genomic analysis of the 89K PAI present in the genome of SS2 strains revealed details into how some virulent strains acquired genes that may contribute to STSS, which may lead to better environmental monitoring of epidemic SS2 strains.


title: Analysis of Epidemiological Characteristics of Notifiable Diseases Reported in Children Aged 0–14 Years from 2008 to 2017 in Zhejiang Province, China

text: This study aims to learn the characteristics of morbidity and mortality of notifiable diseases reported in children aged 0–14 years in Zhejiang Province in 2008–2017. We collated data from the China Information System for Disease Control and Prevention in Zhejiang province between 1 January 2008 and 31 December 2017 of children aged 0–14 years. From 2008 to 2017, a total of 32 types and 1,994,740 cases of notifiable diseases were reported in children aged 0–14 years, including 266 deaths in Zhejiang Province. The annual average morbidity was 2502.87/100,000, and the annual average mortality was 0.33/100,000. Male morbidity was 2886.98/100,000, and female morbidity was 2072.16/100,000, with the male morbidity rate higher than the female morbidity rate (χ(2) = 54,033.12, p < 0.01). No Class A infectious diseases were reported. The morbidity of Class B infectious diseases showed a downward trend, but that of Class C infectious diseases showed an upward trend. There were 72,041 cases in 22 kinds of Class B infectious disease and 138 death cases, with a morbidity rate of 90.39/100,000, and a mortality rate of 0.17/100,000. There were 1,922,699 cases in 10 kinds of Class C infectious disease and 128 death cases, with a morbidity rate of 2412.47/100,000, and a mortality rate of 0.16/100,000. The main high-prevalence diseases included hand-foot-and-mouth disease (1430.38/100,000), other infectious diarrheal diseases (721.40/100,000), mumps (168.83/100,000), and influenza (47.40/100,000). We should focus on the prevention and control of hand-foot and mouth disease, other infectious diarrheal diseases, mumps and influenza in children aged 0–14 years in Zhejiang Province. It is recommended to strengthen epidemic surveillance and undertake early prevention and control measures in order to reduce the younger children incidence rate of infectious diseases. Immunization planning vaccines can help achieve a significant preventive decline of infectious diseases.


title: Identification and Characterization of a 65-kDa Protein Processed from the Gene 1 Polyprotein of the Murine Coronavirus MHV-A59

text: Abstract A 65-kDa protein has been detected in mouse hepatitis virus A59 (MHV-A59)-infected DBT cells using polyclonal antibodies directed against polypeptides encoded by the 5′ 1.8 kb of gene 1. The presence of this 65-kDa protein (p65) was previously predicted from immunoprecipitation studies of gene 1 expression in MHV-A59-infected DBT cells with other antisera (1). p65 was rapidly labeled in virus-infected cells at late times of infection; however, its cleavage from the polyprotein was significantly delayed compared to the amino-terminal gene 1 polyprotein cleavage product, p28. Similar to p28, p65 was cleaved from the growing polyprotein without detectable intermediate precursors. Kinetic analysis of p65 with specific antibodies indicates that p65 is immediately adjacent to p28 in the gene 1 polyprotein. The proteolytic activity responsible for the carboxy-terminal cleavage of p65, as well as the function of the p65 protein, remains to be determined.


title: iTRAQ‐based quantitative subcellular proteomic analysis of Avibirnavirus‐infected cells

text: Infectious bursal disease virus (IBDV) enters the host cells via endocytic pathway to achieve viral replication in the cytoplasm. Here, we performed LC‐MS/MS coupled with isobaric tags for relative and absolute quantification labeling of differentially abundant proteins of IBDV‐infected cells using a subcellular fractionation strategy. We show that the viral infection regulates the abundance and/or subcellular localization of 3211 proteins during early infection. In total, 23 cellular proteins in the cytoplasmic proteome and 34 in the nuclear proteome were significantly altered after virus infection. These differentially abundant proteins are involved in such biological processes as immune response, signal transduction, RNA processing, macromolecular biosynthesis, energy metabolism, virus binding, and cellular apoptosis. Moreover, transcriptional profiles of the 25 genes corresponding to the identified proteins were analyzed by quantitative real‐time RT‐PCR. Ingenuity Pathway Analysis clustered the differentially abundant proteins primarily into the mTOR pathway, PI3K/Akt pathway, and interferon‐β signaling cascades. Confocal microscopy showed colocalization of the viral protein VP3 with host proteins heterogeneous nuclear ribonucleoprotein H1, nuclear factor 45, apoptosis inhibitor 5, nuclear protein localization protein 4 and DEAD‐box RNA helicase 42 during the virus infection. Together, these identified subcellular constituents provide important information for understanding host–IBDV interactions and underlying mechanisms of IBDV infection and pathogenesis.


title: Clinical Impact of Mixed Respiratory Viral Infection in Children with Adenoviral Infection

text: BACKGROUND: Although adenovirus (ADV) infection occurs steadily all year round in Korea and the identification of respiratory viral coinfections has been increasing following the introduction of multiplex real-time polymerase chain reaction tests, the clinical impact of viral coinfection in children with ADV infection has rarely been reported. MATERIALS AND METHODS: Medical records of children diagnosed with ADV infection were retrospectively reviewed. The enrolled children were divided into two groups based on the identified respiratory viruses: ADV group and coinfection group. Clinical and laboratory parameters were compared between the two groups. RESULTS: In total, 105 children (60 males and 45 females) with a median age of 29 months (range: 0-131 months) diagnosed with an ADV infection were enrolled. Fever (99.0%) was by far the most frequent symptom, followed by respiratory (82.9%), and gastrointestinal (22.9%) symptoms. Upper and lower respiratory tract infections were diagnosed in 56 (53.3%), and 32 (30.5%) children, respectively. Five (4.8%) children received oxygen therapy, and no child died due to ADV infection. Coinfection was diagnosed in 32 (30.5%) children, with rhinovirus (46.9%), and respiratory syncytial virus (21.9%) being the most frequent. The proportions of children younger than 24 months (P <0.001), with underlying medical conditions (P = 0.020), and diagnosed with lower respiratory tract infection (P = 0.011) were significantly higher in the coinfection group than in the ADV group. In a multivariate analysis, only the younger age was significantly associated with coinfection (P <0.001). Although more children in the coinfection group received oxygen therapy (P = 0.029), the duration of fever and hospitalization was not significantly different between the two groups. CONCLUSION: Respiratory viral coinfection with ADV occurred more frequently in children younger than 24 months of age compared with children aged 24 months or older. Respiratory viral coinfection may increase the severity of ADV infection, however, appropriate therapy prevented prolonged hospitalization and poor prognosis due to coinfection.


title: Chloroquine and hydroxychloroquine ototoxicity; potential implications for SARS-CoV-2 treatment. A brief review of the literature

text: INTRODUCTION: Current clinical evidences do not support any specific treatment against SARS-CoV-2. Chloroquine (CQ) and hydroxychloroquine (HCQ) are typically used in the treatment of rheumatoid arthritis, systemic lupus erythematosus and malaria; they have been considered for off-label and compassionate use in several countries against moderate to severe cases of COVID-19 and there's actually a massive demand of these two drugs. The aim of this paper is to briefly review the published literature, summarizing evidences about audiological implications after CQ and HCQ treatment. METHODS: We conducted a review of the literature on Medline and Pubmed platforms from 27th May 2020 to 30 May 2020. We combined MeSH terms of “chloroquine”, “hydroxychloroquine”, “ototoxicity”, “hearing loss”, “tinnitus”, “deafness” and “hearing”. Publications with relevant data were included. Selected data (authors, country and year; sample size; study design; audiological side effects) were extracted and summarized in a table. RESULTS: Of 45 initial studies, 14 met inclusion criteria. The authors found xix cases of HCQ ototoxicity; Tinnitus was reported in 2 cases, and it was found to be reversible or irreversible. Sensorineural hearing loss after HCQ use was reported in 7 patients; it was found to be irreversible or partially reversible after discontinuation of HCQ in 6 cases. Eight papers reporting CQ ototoxicity were; tinnitus was not reported by any authors. Sensorineural hearing loss after taking CQ was reported in 6 patients; it was found to be irreversible after discontinuation of CQ in 5 patients. One patient showed abnormal gait after a single intramuscular injection of CQ. Thirteen patients' Auditory Brainstem Response (ABR) were found to be abnormal, but they resolved after CQ discontinuation. CONCLUSIONS: CQ and HCQ related ototoxicity is widely reported in the literature although the pathophysiological mechanism is not well known. Current data are not sufficient enough to support the use of CQ and HCQ as therapy for COVID-19, but considering the growing demand for these two drugs and the number of people around the world who have taken and will take CQ and HCQ, it must necessarily consider the clinical and social impact of long term audiological side effects.


title: Evidence for respiratory viruses interactions in asymptomatic preschool-aged children

text: Abstract Aim To prospectively evaluate interferences between viruses of the upper respiratory tract in asymptomatic preschool children. Methods Nasal-pharyngeal swabs from 233 preschool aged children were prospectively collected over four consecutive time periods, during one school year. The samples were tested using a RT-PCR DNA/RNA microarray system for nine respiratory viruses. Results Respiratory syncytial virus (RSV) was a predictor of the presence of influenza virus (INFL) (OR: 9.12, CI: 1.52–54.75, p =0.016), and similarly, INFL predicted the presence of RSV (OR: 4.01, CI: 1.14–14.16, p =0.030). Also, rhinovirus (RV) was a predictor of adenovirus (ADV) presence (OR: 3.66, CI: 1.10–12.14, p =0.034), and similarly, ADV predicted the presence of RV (OR: 4.05, CI: 1.02–16.05, p =0.046). No other significant associations between viruses were observed. Conclusion Our results indicate that respiratory viruses found in carrier stage in asymptomatic children may interact with other viruses and even facilitate their settling in the upper respiratory tract. The pathophysiological role of these interactions is not yet clear.


title: Full Genome Virus Detection in Fecal Samples Using Sensitive Nucleic Acid Preparation, Deep Sequencing, and a Novel Iterative Sequence Classification Algorithm

text: We have developed a full genome virus detection process that combines sensitive nucleic acid preparation optimised for virus identification in fecal material with Illumina MiSeq sequencing and a novel post-sequencing virus identification algorithm. Enriched viral nucleic acid was converted to double-stranded DNA and subjected to Illumina MiSeq sequencing. The resulting short reads were processed with a novel iterative Python algorithm SLIM for the identification of sequences with homology to known viruses. De novo assembly was then used to generate full viral genomes. The sensitivity of this process was demonstrated with a set of fecal samples from HIV-1 infected patients. A quantitative assessment of the mammalian, plant, and bacterial virus content of this compartment was generated and the deep sequencing data were sufficient to assembly 12 complete viral genomes from 6 virus families. The method detected high levels of enteropathic viruses that are normally controlled in healthy adults, but may be involved in the pathogenesis of HIV-1 infection and will provide a powerful tool for virus detection and for analyzing changes in the fecal virome associated with HIV-1 progression and pathogenesis.


title: Croup Is Associated with the Novel Coronavirus NL63

text: BACKGROUND: The clinical relevance of infections with the novel human coronavirus NL63 (HCoV-NL63) has not been investigated systematically. We therefore determined its association with disease in young children with lower respiratory tract infection (LRTI). METHODS AND FINDINGS: Nine hundred forty-nine samples of nasopharyngeal secretions from children under 3 y of age with LRTIs were analysed by a quantitative HCoV-NL63-specific real-time PCR. The samples had been collected from hospitalised patients and outpatients from December 1999 to October 2001 in four different regions in Germany as part of the prospective population-based PRI.DE study and analysed for RNA from respiratory viruses. Forty-nine samples (5.2%), mainly derived from the winter season, were positive for HCoV-NL63 RNA. The viral RNA was more prevalent in samples from outpatients (7.9%) than from hospitalised patients (3.2%, p = 0.003), and co-infection with either respiratory syncytial virus or parainfluenza virus 3 was observed frequently. Samples in which only HCoV-NL63 RNA could be detected had a significantly higher viral load than samples containing additional respiratory viruses (median 2.1 × 10(6) versus 2.7 × 10(2) copies/ml, p = 0.0006). A strong association with croup was apparent: 43% of the HCoV-NL63-positive patients with high HCoV-NL63 load and absence of co-infection suffered from croup, compared to 6% in the HCoV-NL63-negative group, p < 0.0001. A significantly higher fraction (17.4%) of samples from croup patients than from non-croup patients (4.2%) contained HCoV-NL63 RNA. CONCLUSION: HCoV-NL63 infections occur frequently in young children with LRTI and show a strong association with croup, suggesting a causal relationship.


title: Corrigendum to ‘An Overview of Coronaviruses including the SARS-2 Coronavirus – Molecular Biology, Epidemiology and Clinical Implications’ [Cur Med Res Pract. (2019) Vol. 10, pages 54–64].

text: [This corrects the article DOI: 10.1016/j.cmrp.2020.04.001.].


title: CCL2, but not its receptor, is essential to restrict immune privileged central nervous system‐invasion of Japanese encephalitis virus via regulating accumulation of CD11b(+) Ly‐6C(hi) monocytes

text: Japanese encephalitis virus (JEV) is a re‐emerging zoonotic flavivirus that poses an increasing threat to global health and welfare due to rapid changes in climate and demography. Although the CCR2–CCL2 axis plays an important role in trafficking CD11b(+) Ly‐6C(hi) monocytes to regulate immunopathological diseases, little is known about their role in monocyte trafficking during viral encephalitis caused by JEV infection. Here, we explored the role of CCR2 and its ligand CCL2 in JE caused by JEV infection using CCR2‐ and CCL2‐ablated murine models. Somewhat surprisingly, the ablation of CCR2 and CCL2 resulted in starkly contrasting susceptibility to JE. CCR2 ablation induced enhanced resistance to JE, whereas CCL2 ablation highly increased susceptibility to JE. This contrasting regulation of JE progression by CCR2 and CCL2 was coupled to central nervous system (CNS) infiltration of Ly‐6C(hi) monocytes and Ly‐6G(hi) granulocytes. There was also enhanced expression of CC and CXC chemokines in the CNS of CCL2‐ablated mice, which appeared to induce CNS infiltration of these cell populations. However, our data revealed that contrasting regulation of JE in CCR2‐ and CCL2‐ablated mice was unlikely to be mediated by innate natural killer and adaptive T‐cell responses. Furthermore, CCL2 produced by haematopoietic stem cell‐derived leucocytes played a dominant role in CNS accumulation of Ly‐6C(hi) monocytes in infected bone marrow chimeric models, thereby exacerbating JE progression. Collectively, our data indicate that CCL2 plays an essential role in conferring protection against JE caused by JEV infection. In addition, blockage of CCR2, but not CCL2, will aid in the development of strategies for prophylactics and therapeutics of JE.


title: Leucocyte Subsets Effectively Predict the Clinical Outcome of Patients With COVID-19 Pneumonia: A Retrospective Case-Control Study

text: Background: The clinical characteristics of coronavirus disease 2019 (COVID-19) have been well-studied, while effective predictors for clinical outcome and research on underlying mechanisms are scarce. Methods: Hospitalized COVID-19 pneumonia patients with definitive clinical outcome (cured or died) were retrospectively studied. The diagnostic performance of the leucocyte subsets and other parameters were compared using the area under the receiver operating characteristic curve (AUC). Further, the correlations between leucocyte subsets and inflammation-related factors associated with clinical outcome were subsequently investigated. Results: Among 95 subjects included, 56 patients were cured, and 39 died. Older age, elevated aspartate aminotransferase, total bilirubin, serum lactate dehydrogenase, blood urea nitrogen, prothrombin time, D-dimer, Procalcitonin, and C-reactive protein levels, decreased albumin, elevated serum cytokines (IL2R, IL6, IL8, IL10, and TNF-α) levels, and a decreased lymphocyte count indicated poor outcome in patients with COVID-19 pneumonia. Lymphocyte subset (lymphocytes, T cells, helper T cells, suppressor T cells, natural killer cells, T cells+B cells+NK cells) counts were positively associated with clinical outcome (AUC: 0.777; AUC: 0.925; AUC: 0.900; AUC: 0.902; AUC: 0.877; AUC: 0.918, resp.). The neutrophil-to-lymphocyte ratio (NLR), neutrophil to T lymphocyte count ratio (NTR), neutrophil percentage to T lymphocyte ratio (NpTR) effectively predicted mortality (AUC: 0.900; AUC: 0.905; AUC: 0.932, resp.). Binary logistic regression showed that NpTR was an independent prognostic factor for mortality. Serum IL6 levels were positively correlated with leucocyte count, neutrophil count, and eosinophil count and negatively correlated with lymphocyte count. Conclusion: These results indicate that leucocyte subsets predict the clinical outcome of patients with COVID-19 pneumonia with high efficiency. Non-self-limiting inflammatory response is involved in the development of fatal pneumonia.


title: Single-cell transcriptome analysis of the novel coronavirus (SARS-CoV-2) associated gene ACE2 expression in normal and non-obstructive azoospermia (NOA) human male testes

text: Being infected by SARS-CoV-2 may cause damage to multiple organs in patients, such as the lung, liver and heart. Angiotensin-converting enzyme 2 (ACE2), reported as a SARS-CoV-2 receptor, is also expressed in human male testes. This suggests a potential risk in human male reproductive system. However, the characteristics of ACE2-positive cells and the expression of other SARS-CoV-2 process-related genes are still worthy of further investigation. Here, we performed singlecell RNA seq (scRNA-seq) analysis on 853 male embryo primordial germ cells (PGCs) and 2,854 normal testis cells to assess the effects of the SARS-CoV-2 virus on the male reproductive system from embryonic stage to adulthood. We also collected and constructed the scRNA-seq library on 228 Sertoli cells from three non-obstructive azoospermia (NOA) patients to assess the effects at disease state. We found that ACE2 expressing cells existed in almost all testis cell types and Sertoli cells had highest expression level and positive cells ratio. Moreover, ACE2 was also expressed in human male PGCs. In adulthood, the level of ACE2 expression decreased with the increase of age. We also found that ACE2 positive cells had high expressions of stress response and immune activation-related genes. Interestingly, some potential SARS-CoV-2 process-related genes such as TMPRSS2, BSG, CTSL and CTSB had different expression patterns in the same cell type. Furthermore, ACE2 expression level in NOA donors’ Sertoli cells was significantly decreased. Our work would help to assess the risk of SARS-CoV-2 infection in the male reproductive system. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-020-1705-0 and is accessible for authorized users.


Yoga for infirmity in geriatric population amidst COVID-19 Pandemic: Comment on “Age and Ageism in COVID-19: Elderly Mental Health-care Vulnerabilities and Needs’’


title: Case fatality risk of novel coronavirus diseases 2019 in China

text: Objective The outbreak of novel coronavirus disease 2019 (COVID-19) imposed a substantial health burden in mainland China and remains a global epidemic threat. Our objectives are to assess the case fatality risk (CFR) among COVID-19 patients detected in mainland China, stratified by clinical category and age group. Method We collected individual information on laboratory-confirmed COVID-19 cases from publicly available official sources from December 29, 2019 to February 23, 2020. We explored the risk factors associated with mortality. We used methods accounting for right-censoring and survival analyses to estimate the CFR among detected cases. Results Of 12,863 cases reported outside Hubei, we obtained individual records for 9,651 cases, including 62 deaths and 1,449 discharged cases. The deceased were significantly older than discharged cases (median age: 77 vs 39 years, p<0.001). 58% (36/62) were male. Older age (OR 1.18 per year; 95%CI: 1.14 to 1.22), being male (OR 2.02; 95%CI: 1.02 to 4.03), and being treated in less developed economic regions (e.g., West and Northeast vs. East, OR 3.93; 95%CI: 1.74 to 8.85) were mortality risk factors. The estimated CFR was 0.89-1.24% among all cases. The fatality risk among critical patients was 2-fold higher than that among severe and critical patients, and 24-fold higher than that among moderate, severe and critical patients. Conclusions Our estimates of CFR based on laboratory-confirmed cases ascertained outside of Hubei suggest that COVID-19 is not as severe as severe acute respiratory syndrome and Middle East respiratory syndrome, but more similar to the mortality risk of 2009 H1N1 influenza pandemic in hospitalized patients. The fatality risk of COVID-19 is higher in males and increases with age. Our study improves the severity assessment of the ongoing epidemic and can inform the COVID-19 outbreak response in China and beyond.


title: Defective-interfering particles of murine coronavirus: Mechanism of synthesis of defective viral RNAs

text: Abstract The mechanism of synthesis of the defective viral RNAs in cells infected with defective-interfering (DI) particles of mouse hepatitis virus was studied. Two DI-specific RNA species, DIssA of genomic size and DIssE of subgenomic size, were detected in DI-infected cells. Purified DI particles, however, were found to contain predominantly DIssA and only a trace amount of DIssE RNA. Despite its negligible amount, the DIssE RNA in virions appears to serve as the template for the synthesis of DIssE RNA in infected cells. This conclusion was supported by two studies. First, the uv target size for DIssE RNA synthesis is significantly smaller than that for DIssA. Second, when purified DIssE RNA was transfected into cells which had been infected with a helper virus, DIssE RNA could replicate itself and became a predominant RNA species in the infected cells. Thus, DIssE RNA was not synthesized from the genomic RNA of DI particles. By studying the relationship between virus dilution and the amount of intracellular viral RNA synthesis, we have further shown that DIssE RNA synthesis requires a helper function, but it does not utilize the leader sequence of the helper virus. In contrast, DIssA synthesis appears to be helper-independent and can replicate itself. Thus DIssA codes for a functional RNA polymerase.


title: How to Effectively Support Patients with Rheumatic Conditions Now and Beyond COVID‐19

text: May 2020, the COVID‐19 pandemic continues to unfold. Governments are investing in public health, clinical and research efforts to avoid the spread of the SARS‐CoV‐2 virus, reduce the number of deaths and prevent the collapse of health care systems. However, this pandemic will have unprecedented consequences for people who live with chronic conditions for the months and even years to come without coordinated actions.


Spatiotemporal evolution of case fatality rates of COVID-19 in Brazil, 2020


title: Expression of SARS-coronavirus envelope protein in Escherichia coli cells alters membrane permeability

text: Abstract To promote viral entry, replication, release, and spread to neighboring cells, many cytolytic animal viruses encode proteins responsible for modification of host cell membrane permeability and for formation of ion channels in host cell membranes during their life cycles. In this study, we show that the envelope (E) protein of severe acute respiratory syndrome-associated coronavirus can induce membrane permeability changes when expressed in Escherichia coli. E protein expressed in bacterial and mammalian cells under reducing conditions existed as monomers, but formed homodimer and homotrimer under non-reducing conditions. Site-directed mutagenesis studies revealed that two cysteine residues of the E protein were essential for oligomerization, leading to induction of membrane permeability. This is the first report demonstrating that a coronavirus-encoded protein could modify membrane permeability in E. coli cells.


title: Genetically Diverse Coronaviruses in Wild Bird Populations of Northern England

text: Infectious bronchitis virus (IBV) causes a costly respiratory viral disease of chickens. The role of wild birds in the epidemiology of IBV is poorly understood. We detected diverse coronaviruses by PCR in wildfowl and wading birds in England. Sequence analysis showed some viruses to be related to IBV.


title: Disease metaphors in new epidemics: the UK media framing of the 2003 SARS epidemic

text: Since the emergence of HIV/AIDS in the 1980s, social scientists and sociologists of health and illness have been exploring the metaphorical framing of this infectious disease in its social context. Many have focused on the militaristic language used to report and explain this illness, a type of language that has permeated discourses of immunology, bacteriology and infection for at least a century. In this article, we examine how language and metaphor were used in the UK media's coverage of another previously unknown and severe infectious disease: Severe Acute Respiratory Syndrome (SARS). SARS offers an opportunity to explore the cultural framing of a less extraordinary epidemic disease. It therefore provides an analytical counter-weight to the very extensive body of interpretation that has developed around HIV/AIDS. By analysing the total reporting on SARS of five major national newspapers during the epidemic of spring 2003, we investigate how the reporting of SARS in the UK press was framed, and how this related to media, public and governmental responses to the disease. We found that, surprisingly, militaristic language was largely absent, as was the judgemental discourse of plague. Rather, the main conceptual metaphor used was SARS as a killer. SARS as a killer was a single unified entity, not an army or force. We provide some tentative explanations for this shift in linguistic framing by relating it to local political concerns, media cultures, and spatial factors.


title: Changes in infection control policies and advancing infection control advanced practice nurse education in the Republic of Korea

text: After the Middle East respiratory syndrome outbreak of 2015, the Korean government became the payer for infection control (IC) and prevention when hospitals developed IC offices and appointed IC doctors and IC advanced practice nurses. The goal was to enhance IC for all hospitalized patients to prevent the occurrence and spread of infection among them. Measures resulted in increased demand for IC personnel, especially IC advanced practice nurses. This study addressed changes in Korea's IC policies and their impact on the IC advanced practice nursing education program.