title: Studies on the survival of canine coronavirus under different environmental conditions

text: Abstract Canine coronavirus (CCV) is a common faecal agent which is difficult to isolate. This study shows CCV to survive well at temperatures below −20°C but not at temperatures above 4°C. The presence of faecal material markedly reduced CCV survival times at temperatures ranging from 20°C to −70°C. Thus, it is suggested that diagnostic faecal material should be diluted 1:10 (w/v) with growth medium and examined at the earliest opportunity.


docid: awdqguoo

title: Association of COVID-19 infection with pregnancy outcomes in healthcare workers and general women


title: Inhibition of enterovirus 71 replication and the viral 3D polymerase by aurintricarboxylic acid

text: OBJECTIVES: Enterovirus 71 (EV71) causes serious diseases in humans. The aim of this study was to examine the effects of aurintricarboxylic acid (ATA) on EV71 replication and to explore the underlying mechanism. METHODS: To measure the activity of ATA in inhibiting the cytopathic effect (CPE) of EV71, a cell-based neutralization (inhibition of virus-induced CPE) assay was performed. The effect of ATA was further confirmed using plaque reduction and viral yield reduction assays. A time of addition assay was performed to identify the mechanisms of ATA's anti-EV71 activity. We examined the effects of ATA on the following key steps involved in virus replication: (i) translation of the internal ribosomal entry site (IRES)-mediated viral polyprotein; (ii) the proteolytic activity of viral proteases 2A and/or 3C; and (iii) the viral 3D RNA-dependent RNA polymerase (RdRp) activity. RESULTS: In this study, ATA was found to be a potent inhibitor of the replication of EV71. In the antiviral neutralization assay, ATA exhibited inhibitory activity against EV71 (TW/4643/98) and EV71 (TW/2231/98). Plaque assay further demonstrated that ATA inhibited EV71 replication with an EC(50) (effective concentration at which 50% of plaques were removed) of 2.9 µM. Studies on the mechanism of action revealed that ATA targets the early stage of the viral life cycle after viral entry. ATA was able to inhibit the RdRp activity of EV71, while neither the IRES-mediated translation of viral polyprotein nor the viral 3C protease activity was affected. CONCLUSIONS: Overall, the findings in this study suggest that ATA is able to effectively inhibit EV71 replication through interfering with the viral 3D polymerase.


title: 17β-Estradiol, a potential ally to alleviate SARS-CoV-2 infection

text: Considering that female sexual hormones may modulate the inflammatory response and also exhibit direct effects on the cells of the immune system, herein, we intend to discuss the sex differences and the role of estradiol in modulating the lung and systemic inflammatory response, focusing on its possible application as a treatment modality for SARS-CoV-2 patients. COVID-19 patients develop severe hypoxemia early in the course of the disease, which is silent most of the time. Small fibrinous thrombi in pulmonary arterioles and a tumefaction of endothelial were observed in the autopsies of fatal COVID-19 cases. Studies showed that the viral infection induces a vascular process in the lung, which included vasodilation and endothelial dysfunction. Further, the proportions of CD4+ T and CD8+ T lymphocytes were strongly reduced in patients with severe SARS-CoV-2 infection. Estradiol is connected with CD4+ T cell numbers and increases T-reg cell populations, affecting immune responses to infection. It is known that estradiol exerts a protective effect on endothelial function, activating the generation of nitric oxide (NO) via endothelial nitric oxide synthase. Estrogen attenuates the vasoconstrictor response to various stimuli and induces vasodilation in the pulmonary vasculature during stress situations like hypoxia. It exerts a variety of rapid actions, which are initiated after its coupling with membrane receptors, which in turn, may positively modulate vascular responses in pulmonary disease and help to maintain microvascular flow. Direct and indirect mechanisms underlying the effects of estradiol were investigated, and the results point to a possible protective effect of estradiol against COVID-19, indicating that it may be considered as an adjuvant therapeutic element for the treatment of patients affected by the novel coronavirus.


title: Development and validation of serological assays for viral hemorrhagic fevers and determination of the prevalence of Rift Valley fever in Borno State, Nigeria

text: BACKGROUND: Rift Valley fever (RVF) is endemic to the tropical regions of eastern and southern Africa. The seroprevalence of RVF was investigated among the human population in Borno State, Nigeria to determine the occurrence of the disease in the study area in comparison with that of Lassa fever and Crimean-Congo Hemorrhagic fever. METHODS: Recombinant nucleoprotein (rNP)-based IgG-ELISAs for the detection of serum antibodies against RVF virus (RVFV), Lassa fever virus (LASV), and Crimean-Congo hemorrhagic fever virus (CCHFV) were used to test human sera in Borno State, Nigeria. The presence of neutralizing antibody against the RVFV-glycoprotein-bearing vesicular stomatitis virus pseudotype (RVFVpv) was also determined in the human sera. RESULTS: Of the 297 serum samples tested, 42 (14.1%) were positive for the presence of RVFV-IgG and 22 (7.4%) and 7 (2.4%) of the serum samples were positive for antibodies against LASV and CCHFV, respectively. There was a positive correlation between the titers of neutralizing antibodies obtained using RVFVpv and those obtained using the conventional neutralization assay with the attenuated RVFV-MP12 strain. CONCLUSIONS: The seroprevalence of RVF was significantly higher than that of LASV and CCHF in Borno State, Nigeria. The RVFVpv-based neutralization assay developed in this study has the potential to replace the traditional assays based on live viruses for the diagnosis and seroepidemiological studies of RVF.


title: Chapter 83 Artificial intelligence in medical devices and clinical decision support systems

text: Abstract Artificial Intelligence (AI) is a broad conceptual category of computer software that is designed to mimic, emulate, or improve human decision-making. There are two broad categories of AI: rules-based expert systems (ES), and machine-learning (ML) systems.


docid: nreqluol

title: Viral Pathogenesis

text: Abstract Viral pathogenesis describes the processes by which viral infections cause diseases and involves virus–host interactions at the cellular and systemic level that determine whether a virus will cause a disease, what form that disease takes, and how severe the disease will be. Though the pathogenesis of each virus is unique, there are several common points in the virus life cycle that are shared between all pathogenic viruses, and by considering these common aspects of the virus-induced disease process, we can explore some general concepts in viral pathogenesis while illustrating some of the virus specific processes that shape disease outcomes.


title: Identification of a Novel Bat Papillomavirus by Metagenomics

text: The discovery of novel viruses in animals expands our knowledge of viral diversity and potentially emerging zoonoses. High-throughput sequencing (HTS) technology gives millions or even billions of sequence reads per run, allowing a comprehensive survey of the genetic content within a sample without prior nucleic acid amplification. In this study, we screened 156 rectal swab samples from apparently healthy bats (n = 96), pigs (n = 9), cattles (n = 9), stray dogs (n = 11), stray cats (n = 11) and monkeys (n = 20) using a HTS metagenomics approach. The complete genome of a novel papillomavirus (PV), Miniopterus schreibersii papillomavirus type 1 (MscPV1), with L1 of 60% nucleotide identity to Canine papillomavirus (CPV6), was identified in a specimen from a Common Bent-wing Bat (M. schreibersii). It is about 7.5kb in length, with a G+C content of 45.8% and a genomic organization similar to that of other PVs. Despite the higher nucleotide identity between the genomes of MscPV1 and CPV6, maximum-likelihood phylogenetic analysis of the L1 gene sequence showed that MscPV1 and Erethizon dorsatum papillomavirus (EdPV1) are most closely related. Estimated divergence time of MscPV1 from the EdPV1/MscPV1 common ancestor was approximately 60.2–91.9 millions of years ago, inferred under strict clocks using the L1 and E1 genes. The estimates were limited by the lack of reliable calibration points from co-divergence because of possible host shifts. As the nucleotide sequence of this virus only showed limited similarity with that of related animal PVs, the conventional approach of PCR using consensus primers would be unlikely to have detected the novel virus in the sample. Unlike the first bat papillomavirus RaPV1, MscPV1 was found in an asymptomatic bat with no apparent mucosal or skin lesions whereas RaPV1 was detected in the basosquamous carcinoma of a fruit bat Rousettus aegyptiacus. We propose MscPV1 as the first member of the novel Dyolambda-papillomavirus genus.


title: Quantifying bias of COVID-19 prevalence and severity estimates in Wuhan, China that depend on reported cases in international travelers

text: Risk of COVID-19 infection in Wuhan has been estimated using imported case counts of international travelers, often under the assumption that all cases in travelers are ascertained. Recent work indicates variation among countries in detection capacity for imported cases. Singapore has historically had very strong epidemiological surveillance and contact-tracing capacity and has shown in the COVID-19 epidemic evidence of a high sensitivity of case detection. We therefore used a Bayesian modeling approach to estimate the relative imported case detection capacity for other countries compared to that of Singapore. We estimate that the global ability to detect imported cases is 38% (95% HPDI 22% – 64%) of Singapore’s capacity. Equivalently, an estimate of 2.8 (95% HPDI 1.5 – 4.4) times the current number of imported cases, could have been detected, if all countries had had the same detection capacity as Singapore. Using the second component of the Global Health Security index to stratify likely case-detection capacities, we found that the ability to detect imported cases relative to Singapore among high surveillance locations is 40% (95% HPDI 22% – 67%), among intermediate surveillance locations it is 37% (95% HPDI 18% – 68%), and among low surveillance locations it is 11% (95% HPDI 0% – 42%). Using a simple mathematical model, we further find that treating all travelers as if they were residents (rather than accounting for the brief stay of some of these travelers in Wuhan) can modestly contribute to underestimation of prevalence as well. We conclude that estimates of case counts in Wuhan based on assumptions of perfect detection in travelers may be underestimated by several fold, and severity correspondingly overestimated by several fold. Undetected cases are likely in countries around the world, with greater risk in countries of low detection capacity and high connectivity to the epicenter of the outbreak.


title: Modeling, state estimation, and optimal control for the US COVID-19 outbreak

text: The novel coronavirus SARS-CoV-2 and resulting COVID-19 disease have had an unprecedented spread and continue to cause an increasing number of fatalities worldwide. While vaccines are still under development, social distancing, extensive testing, and quarantining of confirmed infected subjects remain the most effective measures to contain the pandemic. These measures carry a significant socioeconomic cost. In this work, we introduce a novel optimization-based decision-making framework for managing the COVID-19 outbreak in the US. This includes modeling the dynamics of affected populations, estimating the model parameters and hidden states from data, and an optimal control strategy for sequencing social distancing and testing events such that the number of infections is minimized. The analysis of our extensive computational efforts reveals that social distancing and quarantining are most effective when implemented early, with quarantining of confirmed infected subjects having a much higher impact. Further, we find that “on-off” policies alternating between strict social distancing and relaxing such restrictions can be effective at “flattening” the curve while likely minimizing social and economic cost.


Antigen-presenting epithelial cells can play a pivotal role in airway allergy


title: Signos de alarma al regresar de un viaje

text: Puntos para una lectura rápida • Las enfermedades importadas potencialmente de mayor gravedad son el paludismo, las arbovirosis hemorrágicas, la fiebre tifoidea y la amebosis. • Sigue siendo útil considerar que toda fiebre importada de África subsahariana es paludismo hasta poder demostrar lo contrario. • Aunque las causas más frecuentes de fiebre procedente de otros destinos son otras, la fiebre siempre obliga a descartar el paludismo. • Un paciente febril que presenta sangrado espontáneo debe ser aislado y no realizar ninguna extracción o manipulación de fluidos hasta haber contactado con las autoridades epidemiológicas territoriales. • Los pródromos clínicos suelen ser inespecíficos. No obstante, la identificación de factores de riesgo (viajes mochileros o inmigrantes en visita a familiares), sus circunstancias (pacientes que no han realizado quimioprofilaxis antipalúdica) y el periodo de aparición de la fiebre (en general menor de 2 semanas) deben alertar. • En los pacientes graves no hay que demorar el inicio de un tratamiento empírico combinado antipalúdico-antibiótico a la espera de resultados microbiológicos.


title: Adaptation of Russian population to SARS-CoV-2: Asymptomatic course, comorbidities, mortality, and other respiratory viruses – A reply to Fear versus Data: Short Communication to International Journal of Antimicrobial Agents

text: In the current research, we report results of our studying SARS-CoV-2 spread in Russia and adaptation of Russian population to it in March-June 2020. Two groups of people have been investigated: 1) 12,082 persons already proven positive for SARS-CoV-2 (clinical information is studied); 2) 7,864+4,458 persons with respiratory suspicions (PCR tests and clinical information). In the latter, SARS-CoV-2 positive persons comprised 5.37% in March and 11.42% in June 2020. A number of viral co-infections was observed for SARS-CoV-2. Rhinoviruses accounted for the largest co-infection part (7.91% of samples tested positive for SARS-CoV-2); respiratory syncytial virus 7.03%; adenoviruses 4.84%; metapneumoviruses 3.29%; parainfluenza viruses 2.42%; enterovirus D68 1.10% and some other viruses (entero-, echo-, parecho-) less than 1%. In the group of 12,537 humans, SARS-CoV-2 case fatality rate was determined to be 0.6% on average (in contrast with official Russian governmental statistics that reports 1.5% mortality). It is within range of mortality caused by other common seasonal respiratory viruses (0.01-2.21% in Russia in 2012-2020 range). Most of deaths were of people with other comorbidities, also similar with different respiratory viruses. Proportion of SARS-CoV-2 asymptomatic carriers was 56.68% in March and 70.67% in June 2020. Obviously, this new pathogen presents a substantial risk to human population, as it was not contained at the very beginning of its outbreak in Wuhan and spread to the whole world. However, measures of its surveillance, prevention and treatment must be strictly evidence-based and not dictated by fear.


title: Make Yourself at Home: Viral Hijacking of the PI3K/Akt Signaling Pathway

text: As viruses do not possess genes encoding for proteins required for translation, energy metabolism or membrane biosynthesis, they are classified as obligatory intracellular parasites that depend on a host cell to replicate. This genome limitation forces them to gain control over cellular processes to ensure their successful propagation. A diverse spectrum of virally encoded proteins tackling a broad spectrum of cellular pathways during most steps of the viral life cycle ranging from the host cell entry to viral protein translation has evolved. Since the host cell PI3K/Akt signaling pathway plays a critical regulatory role in many cellular processes including RNA processing, translation, autophagy and apoptosis, many viruses, in widely varying ways, target it. This review focuses on a number of remarkable examples of viral strategies, which exploit the PI3K/Akt signaling pathway for effective viral replication.


title: Self-similarity analysis of eubacteria genome based on weighted graph

text: Abstract We introduce a weighted graph model to investigate the self-similarity characteristics of eubacteria genomes. The regular treating in similarity comparison about genome is to discover the evolution distance among different genomes. Few people focus their attention on the overall statistical characteristics of each gene compared with other genes in the same genome. In our model, each genome is attributed to a weighted graph, whose topology describes the similarity relationship among genes in the same genome. Based on the related weighted graph theory, we extract some quantified statistical variables from the topology, and give the distribution of some variables derived from the largest social structure in the topology. The 23 eubacteria recently studied by Sorimachi and Okayasu are markedly classified into two different groups by their double logarithmic point-plots describing the similarity relationship among genes of the largest social structure in genome. The results show that the proposed model may provide us with some new sights to understand the structures and evolution patterns determined from the complete genomes.


title: Cardiac Tamponade Secondary to COVID-19

text: Abstract A 67-year-old female presented with upper respiratory symptoms and was diagnosed with COVID-19. She was found to have a large hemorrhagic pericardial effusion with echocardiographic signs of tamponade and mild left ventricular impairment. Clinical course was complicated by development of Takotsubo cardiomyopathy. She was treated with pericardiocentesis, colchicine, corticosteroids and hydroxychloroquine with improvement in symptoms.


Structure, Expression, and Intracellular Localization of the SARS-CoV Accessory Proteins 7a and 7b


docid: hkqdgcyr

title: Digital technology and COVID-19

text: The past decade has allowed the development of a multitude of digital tools. Now they can be used to remediate the COVID-19 outbreak.


title: Mathematical modeling of interaction between innate and adaptive immune responses in COVID‐19 and implications for viral pathogenesis

text: We have applied mathematical modeling to investigate the infections of the ongoing coronavirus disease‐2019 (COVID‐19) pandemic caused by SARS‐CoV‐2 virus. We first validated our model using the well‐studied influenza viruses and then compared the pathogenesis processes between the two viruses. The interaction between host innate and adaptive immune responses was found to be a potential cause for the higher severity and mortality in COVID‐19 patients. Specifically, the timing mismatch between the two immune responses has a major impact on disease progression. The adaptive immune response of the COVID‐19 patients is more likely to come before the peak of viral load, while the opposite is true for influenza patients. This difference in timing causes delayed depletion of vulnerable epithelial cells in the lungs in COVID‐19 patients while enhancing viral clearance in influenza patients. Stronger adaptive immunity in COVID‐19 patients can potentially lead to longer recovery time and more severe secondary complications. Based on our analysis, delaying the onset of adaptive immune responses during the early phase of infections may be a potential treatment option for high‐risk COVID‐19 patients. Suppressing the adaptive immune response temporarily and avoiding its interference with the innate immune response may allow the innate immunity to more efficiently clear the virus.


Pandemonium During the Pandemic: What is the Role of Health and Science Professionals?


Understanding and reducing the fear of COVID-19


title: Global epidemiology of coronavirus disease 2019 (COVID-19): disease incidence, daily cumulative index, mortality, and their association with country healthcare resources and economic status

text: ABSTRACT It has been 2 months since the first case of coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. So far, COVID-19 has affected 85 403 patients in 57 countries/territories and has caused 2924 deaths in 9 countries. However, epidemiological data differ between countries. Although China had higher morbidity and mortality than other sites, the number of new daily cases in China has been lower than outside of China since 26 February 2020. The incidence ranged from 61.44 per 1 000 000 people in the Republic of Korea to 0.0002 per 1 000 000 people in India. The daily cumulative index (DCI) of COVID-19 (cumulative cases/no. of days between the first reported case and 29 February 2020) was greatest in China (1320.85), followed by the Republic of Korea (78.78), Iran (43.11) and Italy (30.62). However, the DCIs in other countries/territories were <10 per day. Several effective measures including restricting travel from China, controlling the distribution of masks, extensive investigation of COVID-19 spread, and once-daily press conferences by the government to inform and educate people were aggressively conducted in Taiwan. This is probably the reason why there was only 39 cases (as of 29 February 2020) with a DCI of 1 case per day in Taiwan, which is much lower than that of nearby countries such as the Republic of Korea and Japan. In addition, the incidence and mortality were correlated with the DCI. However, further study and continued monitoring are needed to better understand the underlying mechanism of COVID-19.


title: Symptoms of COVID-19 Outpatients in the United States

text: BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel pathogen causing the current worldwide coronavirus disease 2019 (COVID-19) pandemic. Due to insufficient diagnostic testing in the United States, there is a need for clinical decision-making algorithms to guide testing prioritization. METHODS: We recruited participants nationwide for a randomized clinical trial. We categorized participants into three groups: 1) those with confirmed SARS-CoV-2 infection, 2) those with probable SARS-CoV-2 infection (pending test or not tested but with a confirmed COVID-19 contact), and 3) those with possible SARS-CoV-2 infection (pending test or not tested and with a contact for whom testing was pending or not performed). We compared the frequency of self-reported symptoms in each group and categorized those reporting symptoms in early infection (0 – 2 days), mid-infection (3 – 5 days), and late infection (>5 days). RESULTS: Among 1,252 symptomatic persons screened, 316 had confirmed, 393 had probable, and 543 had possible SARS-CoV-2 infection. In early infection, those with confirmed and probable SARS-CoV-2 infection shared similar symptom profiles, with fever most likely in confirmed cases (p = 0.002). Confirmed cases did not show any statistically significant differences compared to unconfirmed cases in symptom frequency at any time points. The most commonly reported symptoms in those with confirmed infection were cough (82%), fever (67%), fatigue (62%), and headache (60%), with only 52% reporting both fever and cough. CONCLUSION: Symptomatic persons with probable SARS-CoV-2 infection present similarly to those with confirmed SARS-CoV-2 infection. There was no pattern of symptom frequency over time.


title: Population vulnerability to COVID-19 in Europe: a burden of disease analysis

text: BACKGROUND: Evidence has emerged showing that elderly people and those with pre-existing chronic health conditions may be at higher risk of developing severe health consequences from COVID-19. In Europe, this is of particular relevance with ageing populations living with non-communicable diseases, multi-morbidity and frailty. Published estimates of Years Lived with Disability (YLD) from the Global Burden of Disease (GBD) study help to characterise the extent of these effects. Our aim was to identify the countries across Europe that have populations at highest risk from COVID-19 by using estimates of population age structure and YLD for health conditions linked to severe illness from COVID-19. METHODS: Population and YLD estimates from GBD 2017 were extracted for 45 countries in Europe. YLD was restricted to a list of specific health conditions associated with being at risk of developing severe consequences from COVID-19 based on guidance from the United Kingdom Government. This guidance also identified individuals aged 70 years and above as being at higher risk of developing severe health consequences. Study outcomes were defined as: (i) proportion of population aged 70 years and above; and (ii) rate of YLD for COVID-19 vulnerable health conditions across all ages. Bivariate groupings were established for each outcome and combined to establish overall population-level vulnerability. RESULTS: Countries with the highest proportions of elderly residents were Italy, Greece, Germany, Portugal and Finland. When assessments of population-level YLD rates for COVID-19 vulnerable health conditions were made, the highest rates were observed for Bulgaria, Czechia, Croatia, Hungary and Bosnia and Herzegovina. A bivariate analysis indicated that the countries at high-risk across both measures of vulnerability were: Bulgaria; Portugal; Latvia; Lithuania; Greece; Germany; Estonia; and Sweden. CONCLUSION: Routine estimates of population structures and non-fatal burden of disease measures can be usefully combined to create composite indicators of vulnerability for rapid assessments, in this case to severe health consequences from COVID-19. Countries with available results for sub-national regions within their country, or national burden of disease studies that also use sub-national levels for burden quantifications, should consider using non-fatal burden of disease estimates to estimate geographical vulnerability to COVID-19.


title: Bacterial co-infection of the respiratory tract in ventilated children with bronchiolitis; a retrospective cohort study

text: BACKGROUND: Viral bronchiolitis is the most common cause of respiratory failure requiring invasive ventilation in young children. Bacterial co-infections may complicate and prolong paediatric intensive care unit (PICU) stay. Data on prevalence, type of pathogens and its association with disease severity are limited though. These data are especially important as bacterial co-infections may be treated using antibiotics and could reduce disease severity and duration of PICU stay. We investigated prevalence of bacterial co-infection and its association with disease severity and PICU stay. METHODS: Retrospective cohort study of the prevalence and type of bacterial co-infections in ventilated children performed in a 14-bed tertiary care PICU in The Netherlands. Children less than 2 years of age admitted between December 2006 and November 2014 with a diagnosis of bronchiolitis and requiring invasive mechanical ventilation were included. Tracheal aspirates (TA) and broncho-alveolar lavages (BAL) were cultured and scored based on the quantity of bacteria colony forming units (CFU) as: co-infection (TA > 10(^5)/BAL > 10(^4) CFU), low bacterial growth (TA < 10(^5)/BAL < 10(^4) CFU), or negative (no growth). Duration of mechanical ventilation and PICU stay were collected using medical records and compared against the presence of co-infection using univariate and multivariate analysis. RESULTS: Of 167 included children 63 (37.7%) had a bacterial co-infection and 67 (40.1%) low bacterial growth. Co-infections occurred within 48 h from intubation in 52 out 63 (82.5%) co-infections. H.influenza (40.0%), S.pneumoniae (27.1%), M.catarrhalis (22.4%), and S.aureus (7.1%) were the most common pathogens. PICU stay and mechanical ventilation lasted longer in children with co-infections than children with negative cultures (9.1 vs 7.7 days, p = 0.04 and 8.1vs 6.5 days, p = 0.02). CONCLUSIONS: In this large study, bacterial co-infections occurred in more than a third of children requiring invasive ventilation for bronchiolitis and were associated with longer PICU stay and mechanical ventilation. These findings support a clinical trial of antibiotics to test whether antibiotics can reduce duration of PICU stay.


title: Arenavirus Diversity and Evolution: Quasispecies In Vivo

text: Arenaviruses exist as viral quasispecies due to the high mutation rates of the low-fidelity viral RNA-dependent RNA polymerase (RdRp). This genomic heterogeneity is advantageous to the population, allowing for adaptation to rapidly changing environments that present varying types and degrees of selective pressure. The significant variation in biological properties observed among lymphocytic choriomeningitis virus (LCMV) strains, the prototypic arenavirus, indicates to what extent a quasispecies dynamics may play a role in arenavirus adaptability and pathogenesis. Several aspects of arenavirus variability and its contribution to pathogenesis will be discussed.


docid: sbrznhdn

title: Herpesviral–bacterial interactions in periodontal diseases


title: Spillovers and diversification potential of bank equity returns from developed and emerging America

text: Abstract We examine the network spillovers, portfolio allocation characteristics and diversification potential of bank returns from developed and emerging America. We draw our results by applying a directional spillover index, the tail-event driven network (TENET) and nonlinear portfolio optimization methods on bank returns. We find that the spillovers and connectedness among banks from emerging America are noticeably smaller than those among banks from developed America. The largest emerging market spillover transmitters and receivers are the banks from Brazil, followed by the banks from Chile. The largest developed market spillover transmitter is JP Morgan Chase. The connectedness among banks from developed America is dominated by the banks from the USA, relative to those from Canada. The total connectedness of the emerging market banks is more intensified than that of the banks from developed America due to the effect of the COVID-19 pandemic. The portfolio optimization shows that in developed America, the largest banks from the USA are the largest risk contributors to total portfolio risk, whereas the banks from Canada contribute the least risk. In emerging America, the banks from Brazil contribute the most risk to total portfolio risk while the banks from Peru and one bank from Colombia contribute the least risk. The portfolio of banks from emerging America offers greater diversification potential and lower total portfolio allocation risk.


title: Viral Etiology of Acute Respiratory Infections in Pediatric Patients in Lebanon

text: BACKGROUND: Acute respiratory infections (ARI) are the leading cause of death worldwide, especially among children. The majority of these infections in children are of viral etiology. In this study, we evaluated the incidence of viral ARI among children in Lebanon. PATIENTS AND METHODS: Children presenting with symptoms of ARI were prospectively recruited between September 2009 to February 2012. Nasopharyngeal aspirates were obtained from patients and screened for 11 respiratory viruses using a multiplex Luminex-based PCR assay. RESULTS: Two hundred twenty-one patients were recruited with a median age of 1 year (IQR: 0 – 5). Out of 221 patients, 116 (52.5%) were positive for at least one virus, the majority (103/116; 88.8%) of which were in children under 6-year of age. Overall, 188 viruses were detected. Rhinovirus (RhV) was the most common virus detected in 81 (69.8%) patients followed by coxsackie virus and echovirus (CVEV) which were detected as one target in the panel in 45 (38.8%), and parainfluenza viruses (PIV types: 1, 2, 3, 4) in 24 (20.7%) patients. Coinfection with more than one virus was detected in 49 (42.9%) patients. RhV and CVEV were the most common viruses associated with co-infections and higher risk of rhinorrhea. CONCLUSIONS: Viral pathogens account for at least half of the ARIs in Lebanon, with a high frequency of co-infections being detected.


title: De Los Pulsos De Corticoides En Pacientes Con Síndrome De Liberación De Citoquinas Inducido Por Infección Por Sars-Cov-2

text: Abstract Introduction: cytokine storm syndrome (CSS) is a serious complication of COVID-19 patients. Treatment is tocilizumab. The use of glucocorticoids (GC) is controversial. In other very similar CSS, such as macrophage activation syndrome (MAS) and hemophagocytic syndrome (HFS), the main treatment are corticosteroids. Our objective is to evaluate the efficacy of GC in the CSS by COVID-19. Patients: we included 92 patients with CSS associated to COVID-19 who received GC, GC, and tocilizumab and only tocilizumab. We determine CSS markers. We evaluated mortality, intubation, and a combined variable. Results: in all cases the percentages of events were lower in the group of patients with GC was administered. The hazard ratio of the final variables with GC versus the group in which only tocilizumab was administered was lower as CGs were considered, with statistical significance for survival. Discussion: the early use of GC pulses could control SLC, with a lower requirement to use tocilizumab and a decrease in events such as intubation and death.


title: Interaction of Influenza A Viruses with Oviduct Explants of Different Avian Species

text: Infection of poultry with low pathogenic avian influenza viruses (LPAIV) is often associated with mild respiratory symptoms but may also lead to loss in egg production in laying birds. In vivo susceptibility of the reproductive tract for LPAIV infection was reported for turkeys and chickens, but virus-interaction with epithelial cells of the oviduct and possible stimulation of the local antiviral immune responses have not been characterized. In this study, we wanted to investigate the suitability of magnum organ cultures (MOC) as an in vitro model to study virus-host interactions. We compared the susceptibility of duck (Du), chicken (Ch), and turkey (Tu) MOC for three different influenza A viruses (IAV). Overall, the course of infection and the antiviral immune response varied between strains as well as host cell origin, but MOC gave reproducible results for all investigated parameters within each species. While pandemic (p) H1N1 and H9N2 efficiently replicated in MOC-Ch and MOC-Tu, MOC-Du were significantly less susceptible to infection as indicated by a reduced replication level for both viruses (p < 0.05). Overall, virus replication levels did not correlate with interferonα (IFNα) mRNA-expression levels in neither species. H9N2-infection led to a significant upregulation of interferonλ (IFNλ) mRNA expression in MOC of all species compared to the non-infected controls (p < 0.05), while a correlation with replication levels was only seen for MOC-Tu. pH1N1-infection induced only significant upregulation of IFNλ mRNA expression in MOC-Tu at 48 hours post infection (p < 0.05), but the expression pattern did not correlate with replication levels. Our results show that MOC are a suitable model to study IAV-interaction with the mucosal surface of the avian reproductive tract. The data suggest that the reproductive tract may play a role in the pathobiology of IAV in poultry.


title: Minor groove RNA triplex in the crystal structure of a ribosomal frameshifting viral pseudoknot

text: Many viruses regulate translation of polycistronic mRNA using a -1 ribosomal frameshift induced by an RNA pseudoknot. A pseudoknot has two stems that form a quasi-continuous helix and two connecting loops. A 1.6 Å crystal structure of the beet western yellow virus (BWYV) pseudoknot reveals rotation and a bend at the junction of the two stems. A loop base is inserted in the major groove of one stem with quadruple-base interactions. The second loop forms a new minor-groove triplex motif with the other stem, involving 2'-OH and triple-base interactions, as well as sodium ion coordination. Overall, the number of hydrogen bonds stabilizing the tertiary interactions exceeds the number involved in Watson–Crick base pairs. This structure will aid mechanistic analyses of ribosomal frameshifting.


docid: gtgahlqm

title: An infectious disease/fever screening radar system which stratifies higher-risk patients within ten seconds using a neural network and the fuzzy grouping method

text: Summary Objectives To classify higher-risk influenza patients within 10 s, we developed an infectious disease and fever screening radar system. Methods The system screens infected patients based on vital signs, i.e., respiration rate measured by a radar, heart rate by a finger-tip photo-reflector, and facial temperature by a thermography. The system segregates subjects into higher-risk influenza (HR-I) group, lower-risk influenza (LR-I) group, and non-influenza (Non-I) group using a neural network and fuzzy clustering method (FCM). We conducted influenza screening for 35 seasonal influenza patients and 48 normal control subjects at the Japan Self-Defense Force Central Hospital. Pulse oximetry oxygen saturation (SpO2) was measured as a reference. Results The system classified 17 subjects into HR-I group, 26 into LR-I group, and 40 into Non-I group. Ten out of the 17 HR-I subjects indicated SpO2 <96%, whereas only two out of the 26 LR-I subjects showed SpO2 <96%. The chi-squared test revealed a significant difference in the ratio of subjects showed SpO2 <96% between HR-I and LR-I group (p < 0.001). There were zero and nine normal control subjects in HR-I and LR-I groups, respectively, and there was one influenza patient in Non-I group. Conclusions The combination of neural network and FCM achieved efficient detection of higher-risk influenza patients who indicated SpO2 96% within 10 s.


title: Lipemic serum in patients with Coronavirus Disease 2019 (COVID‐19) undergoing treatment

text: We read with interest the article by Morrison et al. on acute hypertriglyceridemia secondary to tocilizumab in patients with severe COVID-19. (1) One patient also had pancreatitis, a dreaded complication of hypertriglyceridemia. Both patients were already on lopinavir/ritonavir before tocilizumab (added day 9 and day 13) was added. Propofol was briefly used. This article is protected by copyright. All rights reserved.


title: COVID-19 and community pharmacy services in Pakistan: challenges, barriers and solution for progress

text: In the wake of atrocious rise in COVID-19 cases, developed countries are leveraging a range of community pharmacy services with the goal of improving access to essential medication and healthcare services. While in the developing nations, including Pakistan, pharmacists are unable to perform COVID-19 containment roles in community, since presence of pharmacists at community pharmacy settings and delivery of pharmacy services have historically been plagued by shortcomings at various levels. In this document, we identified these shortcomings which need to be resolved on many fronts. Broadly, a number of intertwined government related, public related, academic curricula and pharmacist related, and drug retailers’ related factors refrain community pharmacists from performing and facilitating Pakistan’s fragile public and healthcare system in the midst of COVID-19 pandemic. Government led multifaceted approaches are urgently needed to strengthen this unrecognized domain and thereby effectively combat COVID-19 by utilizing community pharmacy services, as evidenced in the developed world. [Note: Part of this article is published in Pakistan Observer Newspaper; dated 17 May 2020).


title: RO 90-7501 Enhances TLR3 and RLR Agonist Induced Antiviral Response

text: Recognition of virus infection by innate pattern recognition receptors (PRRs), including membrane-associated toll-like receptors (TLR) and cytoplasmic RIG-I-like receptors (RLR), activates cascades of signal transduction pathways leading to production of type I interferons (IFN) and proinflammatory cytokines that orchestrate the elimination of the viruses. Although it has been demonstrated that PRR-mediated innate immunity plays an essential role in defending virus from infection, it also occasionally results in overwhelming production of proinflammatory cytokines that cause severe inflammation, blood vessel leakage and tissue damage. In our efforts to identify small molecules that selectively enhance PRR-mediated antiviral, but not the detrimental inflammatory response, we discovered a compound, RO 90–7501 (‘2’-(4-Aminophenyl)-[2,5′-bi-1H-benzimidazol]-5-amine), that significantly promoted both TLR3 and RLR ligand-induced IFN-β gene expression and antiviral response, most likely via selective activation of p38 mitogen-activated protein kinase (MAPK) pathway. Our results thus imply that pharmacological modulation of PRR signal transduction pathways in favor of the induction of a beneficial antiviral response can be a novel therapeutic strategy.


title: Molecular strategies to inhibit the replication of RNA viruses

text: Abstract There are virtually no antiviral drugs available for the treatment of infections with RNA viruses. This is particularly worrisome since most of the highly pathogenic and emerging viruses are, and will likely continue to be, RNA viruses. These viruses can cause acute, severe illness, including severe respiratory disease, hemorrhagic fever and encephalitis, with a high case fatality rate. It is important to have potent and safe drugs at hand that can be used for the treatment or prophylaxis of such infections. Drugs approved for the treatment of RNA virus infections (other than HIV) are the influenza M2 channel inhibitors, amantadine and rimantadine; the influenza neuraminidase inhibitors, oseltamivir and zanamivir, and ribavirin for the treatment of infections with respiratory syncytial virus and hepatitis C virus. The molecular mechanism(s) by which ribavirin inhibits viral replication, such as depletion of intracellular GTP pools and induction of error catastrophe, may not readily allow the design of analogues that are more potent/selective than the parent drug. Highly pathogenic RNA viruses belong to a variety of virus families, each having a particular replication strategy, thus offering a wealth of potential targets to selectively inhibit viral replication. We here provide a non-exhaustive review of potential experimental strategies, using small molecules, to inhibit the replication of several RNA viruses. Other approaches, such as the use of interferon or other host-response modifiers, immune serum or neutralizing antibodies, are not addressed in this review.


title: Bat lung epithelial cells show greater host species-specific innate resistance than MDCK cells to human and avian influenza viruses

text: BACKGROUND: With the recent discovery of novel H17N10 and H18N11 influenza viral RNA in bats and report on high frequency of avian H9 seroconversion in a species of free ranging bats, an important issue to address is the extent bats are susceptible to conventional avian and human influenza A viruses. METHOD: To this end, three bat species (Eidolon helvum, Carollia perspicillata and Tadarida brasiliensis) of lung epithelial cells were separately infected with two avian and two human influenza viruses to determine their relative host innate immune resistance to infection. RESULTS: All three species of bat cells were more resistant than positive control Madin-Darby canine kidney (MDCK) cells to all four influenza viruses. TB1-Lu cells lacked sialic acid α2,6-Gal receptors and were most resistant among the three bat species. Interestingly, avian viruses were relatively more replication permissive in all three bat species of cells than with the use of human viruses which suggest that bats could potentially play a role in the ecology of avian influenza viruses. Chemical inhibition of the JAK-STAT pathway in bat cells had no effect on virus production suggesting that type I interferon signalling is not a major factor in resisting influenza virus infection. CONCLUSION: Although all three species of bat cells are relatively more resistant to influenza virus infection than control MDCK cells, they are more permissive to avian than human viruses which suggest that bats could have a contributory role in the ecology of avian influenza viruses.


title: Influenza and other respiratory virus infections in outpatients with medically attended acute respiratory infection during the 2011-12 influenza season

text: BACKGROUND: Respiratory tract infections are a major cause of outpatient visits, yet only a portion is tested to determine the etiologic organism. Multiplex reverse transcriptase polymerase chain reaction (MRT-PCR) assays for detection of multiple viruses are being used increasingly in clinical settings. METHODS: During January–April 2012, outpatients with acute respiratory illness (≤7 days) were tested for influenza using singleplex RT-PCR (SRT-PCR). A subset was assayed for 18 viruses using MRT-PCR to compare detection of influenza and examine the distribution of viruses and characteristics of patients using multinomial logistic regression. RESULTS: Among 662 participants (6 months–82 years), detection of influenza was similar between the MRT-PCR and SRT-PCR (κ = 0·83). No virus was identified in 267 (40.3%) samples. Commonly detected viruses were human rhinovirus (HRV, 15·4%), coronavirus (CoV, 10·4%), respiratory syncytial virus (RSV, 8·4%), human metapneumovirus (hMPV, 8·3%), and influenza (6%). Co-detections were infrequent (6·9%) and most commonly occurred among those <18 years old. In regression analyses, compared with non-viral illnesses, RSV and hMPV were significantly more frequent in children and less frequent in 18- to 49-year-olds than in those ≥50 years (P = 0·01), fever was more common in hMPV and influenza infections (P = 0·008), nasal congestion was more frequent in CoV, HRV, hMPV, influenza and RSV infections (P = 0·001), and body mass index was higher among those with influenza (P = 0·036). CONCLUSIONS: Using MRT-PCR, a viral etiology was found in three-fifths of patients with medically attended outpatient visits for acute respiratory illness during the influenza season; co-detected viruses were infrequent. Symptoms varied by viral etiology.


title: Placebo-controlled evaluation of a modified life virus vaccine against feline infectious peritonitis: safety and efficacy under field conditions

text: Abstract A modified live virus vaccine against feline infectious peritonitis (FIP) was evaluated in a double blind, placebo-controlled field trial in two high-risk populations. The vaccine was found to be safe and efficacious in one population of cats that had low antibody titre against feline coronavirus (FCoV) at the time of vaccination. Although clinically healthy at the time of vaccination, retrospectively some vaccinees that later came down with FIP were found to be RT-PCR positive for FCoV in plasma and showed changes in blood parameters consistent with early stage of FIP. It is concluded that vaccination can protect cats with no or low FCoV antibody titres and that in some cats vaccine failure was probably due to pre-existing infection.


First International Symposium on Influenza and Other Respiratory Viruses: summary and overview Kapalua, Maui, Hawaii, December 4–6, 1998


title: Baseline characteristics and risk factors for short-term outcomes in 132 COVID-19 patients with diabetes in Wuhan China: a retrospective study

text: Abstract Aims To investigate the clinical characteristics, laboratory findings and high- resolution CT (HRCT) features and to explore the risk factors for in-hospital death and complications of coronavirus disease 2019 (COVID-19) patients with diabetes. Methods From Dec 31, 2019, to Apr 5, 2020, a total of 132 laboratory-confirmed COVID-19 patients with diabetes from two hospitals were retrospectively included in our study. Clinical, laboratory and chest CT data were analyzed and compared between the two groups with an admission glucose level of ≤11mmol/L (group 1) and >11mmol/L (group 2). Logistic regression analyses were used to identify the risk factors associated with in-hospital death and complications. Results Of 132 patients, 15 died in hospital and 113 were discharged. Patients in group 2 were more likely to require intensive care unit care (21.4% vs. 9.2%), to develop acute respiratory distress syndrome (ARDS) (23.2% vs. 9.25%) and acute cardiac injury (12.5% vs. 1.3%), and had a higher death rate (19.6% vs. 5.3%) than group 1. In the multivariable analysis, patients with admission glucose of >11 mmol/l had an increased risk of death (OR: 7.629, 95%CI: 1.391-37.984) and in-hospital complications (OR: 3.232, 95%CI: 1.393-7.498). Admission d-dimer of ≥1.5 μg/mL (OR: 6.645, 95%CI: 1.212-36.444) and HRCT score of ≥10 (OR: 7.792, 95%CI: 2.195-28.958) were associated with increased odds of in-hospital death and complications, respectively. Conclusions In COVID-19 patients with diabetes, poorly-controlled blood glucose (>11mmol/L) may be associated with poor outcomes. Admission hyperglycemia, elevated d-dimer and high HRCT score are potential risk factors for adverse outcomes and death.


title: Current status of mesenchymal stem cell therapy for immune/inflammatory lung disorders: Gleaning insights for possible use in COVID‐19

text: The broad immunomodulatory properties of human mesenchymal stem cells (MSCs) has allowed for wide application in regenerative medicine as well as immune/inflammatory diseases, including unmatched allogeneic use. The novel coronavirus disease COVID‐19 has unleashed a pandemic in record time accompanied by an alarming mortality rate mainly due to pulmonary injury and acute respiratory distress syndrome. Since there are no effective preventive or curative therapies currently, MSC therapy (MSCT) has emerged as a possible candidate despite the lack of preclinical data of MSCs for COVID‐19. Interestingly, MSCT preclinical data specifically on immune/inflammatory disorders of the lungs were among the earliest to be reported in 2003, with the first clinical use of MSCT for graft‐vs‐host disease reported in 2004. Since these first reports, preclinical data showing beneficial effects of MSC immunomodulation have accumulated substantially, and as a consequence, over a third of MSCT clinical trials now target immune/inflammatory diseases. There is much preclinical evidence for MSCT in noninfectious—including chronic obstructive pulmonary disease, asthma, and idiopathic pulmonary fibrosis—as well as infectious bacterial immune/inflammatory lung disorders, with data generally demonstrating therapeutic effects; however, for infectious viral pulmonary conditions, the preclinical evidence is more scarce with some inconsistent outcomes. In this article, we review the mechanistic evidence for clinical use of MSCs in pulmonary immune/inflammatory disorders, and survey the ongoing clinical trials—including for COVID‐19—of MSCT for these diseases, with some perspectives and comment on MSCT for COVID‐19.


docid: skpkuzyu

title: Antiviral anticoagulation

text: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a novel envelope virus that causes coronavirus disease 2019 (COVID‐19). Hallmarks of COVID‐19 are a puzzling form of thrombophilia that has elevated D‐dimer but only modest effects on other parameters of coagulopathy. This is combined with severe inflammation, often leading to acute respiratory distress and possible lethality. Coagulopathy and inflammation are interconnected by the transmembrane receptor, tissue factor (TF), which initiates blood clotting as a cofactor for factor VIIa (FVIIa)‐mediated factor Xa (FXa) generation. TF also functions from within the nascent TF/FVIIa/FXa complex to trigger profound changes via protease‐activated receptors (PARs) in many cell types, including SARS‐CoV‐2–trophic cells. Therefore, aberrant expression of TF may be the underlying basis of COVID‐19 symptoms. Evidence suggests a correlation between infection with many virus types and development of clotting‐related symptoms, ranging from heart disease to bleeding, depending on the virus. Since numerous cell types express TF and can act as sites for virus replication, a model envelope virus, herpes simplex virus type 1 (HSV1), has been used to investigate the uptake of TF into the envelope. Indeed, HSV1 and other viruses harbor surface TF antigen, which retains clotting and PAR signaling function. Strikingly, envelope TF is essential for HSV1 infection in mice, and the FXa‐directed oral anticoagulant apixaban had remarkable antiviral efficacy. SARS‐CoV‐2 replicates in TF‐bearing epithelial and endothelial cells and may stimulate and integrate host cell TF, like HSV1 and other known coagulopathic viruses. Combined with this possibility, the features of COVID‐19 suggest that it is a TFopathy, and the TF/FVIIa/FXa complex is a feasible therapeutic target.


title: Enhancing Sibling Presence in Pediatric ICU

text: Critical illness of a child affects all members of the family, including well brothers and sisters. Stress in their lives results from changes in parental behaviors, caregiving arrangements, and family relationships. These changes, along with limited understanding and information about the crisis, create feelings of confusion, loneliness, jealousy, and sadness, as well as physical symptoms and behavior changes. Educating pediatric ICU nurses about the needs and reactions of well siblings enables them to optimize support to siblings and educate parents. A sibling policy guarantees that choice and support are offered in a consistent and thorough manner to each critically ill child’s family; this helps to ensure that the family unit has the abilities to nurture the ill child and other well children.


title: Coronavirus: the geriatric emergency of 2020. Joint document of the Section on Geriatric Cardiology of the Spanish Society of Cardiology and the Spanish Society of Geriatrics and Gerontology

text: Abstract SARS-CoV-2 infection, also known as COVID-19 (coronavirus infectious disease-19), was first identified in December 2019. In Spain, the first case of this infection was diagnosed on 31 January, 2020 and, by 15 April 2020, has caused 18579 deaths, especially in the elderly. Due to the rapidly evolving situation regarding this disease, the data reported in this article may be subject to modifications. The older population are particularly susceptible to COVID-19 infection and to developing severe disease. The higher morbidity and mortality rates in older people have been associated with comorbidity, especially cardiovascular disease, and frailty, which weakens the immune response. Due to both the number of affected countries and the number of cases, the current situation constitutes an ongoing pandemic and a major health emergency. Because Spain has one of the largest older populations in the world, COVID-19 has emerged as a geriatric emergency. This document has been prepared jointly between the Geriatric Cardiology Section of the Spanish Society of Cardiology and the Spanish Society of Geriatrics and Gerontology.


title: COVID-19 in 7780 pediatric patients: A systematic review

text: BACKGROUND: Studies summarizing the clinical picture of COVID-19 in children are lacking. This review characterizes clinical symptoms, laboratory, and imaging findings, as well as therapies provided to confirmed pediatric cases of COVID-19. METHODS: Adhering to PRISMA guidelines, we searched four medical databases (PubMed, LitCovid, Scopus, WHO COVID-19 database) between December 1, 2019 to May 14, 2020 using the keywords “novel coronavirus”, “COVID-19” or “SARS-CoV-2”. We included published or in press peer-reviewed cross-sectional, case series, and case reports providing clinical signs, imaging findings, and/or laboratory results of pediatric patients who were positive for COVID-19. Risk of bias was appraised through the quality assessment tool published by the National Institutes of Health. PROSPERO registration # CRD42020182261. FINDINGS: We identified 131 studies across 26 countries comprising 7780 pediatric patients. Although fever (59·1%) and cough (55·9%) were the most frequent symptoms 19·3% of children were asymptomatic. Patchy lesions (21·0%) and ground-glass opacities (32·9%) depicted lung radiograph and computed tomography findings, respectively. Immunocompromised children or those with respiratory/cardiac disease comprised the largest subset of COVID-19 children with underlying medical conditions (152 of 233 individuals). Coinfections were observed in 5.6% of children and abnormal laboratory markers included serum D-dimer, procalcitonin, creatine kinase, and interleukin-6. Seven deaths were reported (0·09%) and 11 children (0·14%) met inclusion for multisystem inflammatory syndrome in children. INTERPRETATION: This review provides evidence that children diagnosed with COVID-19 have an overall excellent prognosis. Future longitudinal studies are needed to confirm our findings and better understand which patients are at increased risk for developing severe inflammation and multiorgan failure. FUNDING: Parker B. Francis and pilot grant from 2R25-HL126140. Funding agencies had no involvement in the study.


title: Seroprevalence of hepatitis E virus in dromedary camels, Bedouins, Muslim Arabs and Jews in Israel, 2009–2017

text: Hepatitis E virus (HEV) is an emerging cause of viral hepatitis worldwide. Recently, HEV-7 has been shown to infect camels and humans. We studied HEV seroprevalence in dromedary camels and among Bedouins, Arabs (Muslims, none-Bedouins) and Jews and assessed factors associated with anti-HEV seropositivity. Serum samples from dromedary camels (n = 86) were used to determine camel anti-HEV IgG and HEV RNA positivity. Human samples collected between 2009 and 2016 from >20 years old Bedouins (n = 305), non-Bedouin Arabs (n = 320) and Jews (n = 195), were randomly selected using an age-stratified sampling design. Human HEV IgG levels were determined using Wantai IgG ELISA assay. Of the samples obtained from camels, 68.6% were anti-HEV positive. Among the human populations, Bedouins and non-Bedouin Arabs had a significantly higher prevalence of HEV antibodies (21.6% and 15.0%, respectively) compared with the Jewish population (3.1%). Seropositivity increased significantly with age in all human populations, reaching 47.6% and 34.8% among ⩾40 years old, in Bedouins and non-Bedouin Arabs, respectively. The high seropositivity in camels and in ⩾40 years old Bedouins and non-Bedouin Arabs suggests that HEV is endemic in Israel. The low HEV seroprevalence in Jews could be attributed to higher socio-economic status.


title: Structure and Function of HLA-A*02-Restricted Hantaan Virus Cytotoxic T-Cell Epitope That Mediates Effective Protective Responses in HLA-A2.1/K(b) Transgenic Mice

text: Hantavirus infections cause severe emerging diseases in humans and are associated with high mortality rates; therefore, they have become a global public health concern. Our previous study showed that the CD8(+) T-cell epitope aa129–aa137 (FVVPILLKA, FA9) of the Hantaan virus (HTNV) nucleoprotein (NP), restricted by human leukocyte antigen (HLA)-A*02, induced specific CD8(+) T-cell responses that controlled HTNV infection in humans. However, the in vivo immunogenicity of peptide FA9 and the effect of FA9-specific CD8(+) T-cell immunity remain unclear. Here, based on a detailed structural analysis of the peptide FA9/HLA-A*0201 complex and functional investigations using HLA-A2.1/K(b) transgenic (Tg) mice, we found that the overall structure of the peptide FA9/HLA-A*0201 complex displayed a typical MHC class I fold with Val2 and Ala9 as primary anchor residues and Val3 and Leu7 as secondary anchor residues that allow peptide FA9 to bind tightly with an HLA-A*0201 molecule. Residues in the middle portion of peptide FA9 extruding out of the binding groove may be the sites that allow for recognition by T-cell receptors. Immunization with peptide FA9 in HLA-A2.1/K(b) Tg mice induced FA9-specific cytotoxic T-cell responses characterized by the induction of high expression levels of interferon-γ, tumor necrosis factor-α, granzyme B, and CD107a. In an HTNV challenge trial, significant reductions in the levels of both the antigens and the HTNV RNA loads were observed in the liver, spleen, and kidneys of Tg mice pre-vaccinated with peptide FA9. Thus, our findings highlight the ability of HTNV epitope-specific CD8(+) T-cell immunity to control HTNV and support the possibility that the HTNV-NP FA9 peptide, naturally processed in vivo in an HLA-A*02-restriction manner, may be a good candidate for the development HTNV peptide vaccines.


title: Reference forecasts for CO(2) emissions from fossil-fuel combustion and cement production in Portugal

text: We provide reference forecasts for CO(2) emissions from burning fuel fossil and cement production in Portugal based on an ARFIMA model approach and using annual data from 1950 to 2017. Our reference projections suggest a pattern of decarbonization that will cause the reduction of 3.3 Mt until 2030 and 5.1 Mt between 2030 and 2050. This scenario allows us to assess effort required by the new IPCC goals to ensure carbon neutrality by 2050. For this objective to be achieved it is necessary for emissions to be reduced by 39.9 Mt by 2050. Our results suggest that of these, only 8.4 Mt will result from the inertia of the national emissions system. The remaining reduction on emissions of 31.5 Mt of CO(2) will require additional policy efforts. Accordingly, our results suggest that about 65.5% of the reductions necessary to achieve IPCC goals require deliberate policy efforts. Finally, the presence in the data of long memory with mean reversion suggests that policies must be persistent to ensure that these reductions in emissions are also permanent.


title: Direct High‐Throughput Screening Assay for mRNA Cap Guanine‐N7 Methyltransferase Activity

text: In eukaryotes, mature mRNA is formed through modifications of precursor mRNA, one of which is 5′ cap biosynthesis, involving RNA cap guanine‐N7 methyltransferase (N7‐MTase). N7‐MTases are also encoded by some eukaryotic viruses and facilitate their replication. N7‐MTase inhibitors have therapeutic potential, but their discovery is difficult because long RNA substrates are usually required for activity. Herein, we report a universal N7‐MTase activity assay based on small‐molecule fluorescent probes. We synthesized 12 fluorescent substrate analogs (GpppA and GpppG derivatives) varying in the dye type, dye attachment site, and linker length. GpppA labeled with pyrene at the 3′‐O position of adenosine acted as an artificial substrate with properties of a turn‐off probe for all three tested N7‐MTases (human, parasite, and viral). Using this compound, a high‐throughput N7‐MTase inhibitor assay was developed and used for screening of synthetic substrate analogs and a commercial library. Several inhibitors with nanomolar activities were identified.


SFM India Oriented Guidelines for Ultrasound Establishments During the COVID 19 Pandemic


docid: fooorxbk

title: Acyclic nucleoside phosphonates with a branched 2-(2-phosphonoethoxy)ethyl chain: Efficient synthesis and antiviral activity

text: Abstract Series of novel acyclic nucleoside phosphonates (ANPs) with various nucleobases and 2-(2-phosphonoethoxy)ethyl (PEE) chain bearing various substituents in β-position to the phosphonate moiety were prepared. The influence of structural alternations on antiviral activity was studied. Several derivatives exhibit antiviral activity against HIV and vaccinia virus (middle micromolar range), HSV-1 and HSV-2 (lower micromolar range) and VZV and CMV (nanomolar range), although the parent unbranched PEE–ANPs are inactive. Adenine as a nucleobase and the methyl group attached to the PEE chain proved to be a prerequisite to afford pronounced antiviral activity.


Managing Older Adults with Presumed COVID‐19 in the Emergency Department: A Rational Approach to Rationing


title: COVID-19: Beyond the virus. The use of Photodynamic Therapy for the Treatment of Infections in the Respiratory Tract

text: • •The World today is facing a great effort for the control of infections. • •Nowadays COVID-19 is the large global outbreak and is the major public health issue. • •This letter to Editor highlighted the well-established photodynamic therapy protocol as a tool to decrease the viral and bacterial load in the respiratory tract.


title: Timing of First Respiratory Virus Detections in Infants: A Community-Based Birth Cohort Study

text: BACKGROUND: Determining timing of first virus detection episodes (fVDEs) for different respiratory viruses in infants identifies risk periods and informs preventive interventions, including vaccination. We describe the ages and nature of fVDEs in an infant birth cohort and explore factors associated with increased odds of symptomatic fVDEs. METHODS: The Observational Research in Childhood Infectious Diseases (ORChID) study is a community-based birth cohort describing acute respiratory infections in infants until their second birthday. Parents recorded daily symptoms and collected nose swabs weekly, which were batch-tested using polymerase chain reaction assays for 17 respiratory viruses. RESULTS: One hundred fifty-eight infants participated in ORChID. The median age for fVDEs was 2.9 months for human rhinovirus (HRV) but was ≥13.9 months for other respiratory viruses. Overall, 52% of HRV fVDEs were symptomatic, compared with 57%–83% of other fVDEs. Respiratory syncytial virus and human metapneumovirus fVDEs were more severe than HRV fVDEs. Older age and the winter season were associated with symptomatic episodes. CONCLUSIONS: Infants do not always experience respiratory symptoms with their fVDE. Predominance of early HRV detections highlights the need for timing any intervention early in life. fVDEs from other respiratory viruses most commonly occur when maternal vaccines may no longer provide protection.


title: Tuberculosis infection via the emergency department among inpatients in South Korea: a propensity score matched analysis of the National Inpatient Sample

text: Summary Background Emergency departments (EDs) carry a high risk of infectious disease transmission and have also been implicated in tuberculosis (TB) outbreaks. Aim To determine if patients who visit EDs have an increased risk of TB infection. Using South Korean inpatient sample data (2012), the risk of TB occurrence during 90 days after hospitalization for patients admitted via EDs was compared with that for patients admitted via outpatient clinics. Methods The data of the 2012 Health Insurance Review and Assessment Service – National Inpatient Sample were used. TB diagnosis was based on International Classification of Diseases Version 10 [all TB (A15–A19), pulmonary TB (A15-A16) and extrapulmonary TB (A17–A18)]. Findings After propensity score matching using the demographic and clinical characteristics of the patients, 191,997 patients (64,017 patients admitted via EDs and 127,908 patients admitted via outpatient clinics) were included in this study. There was no significant difference in baseline patient characteristics between the two groups. The percentage of patients with TB admitted via EDs was higher than that of patients admitted via outpatient clinics. The likelihood of active TB occurrence was 30% higher for all TB [hazard ratio (HR) 1.30; 95% confidence interval (CI) 1.12–1.52] and pulmonary TB (HR 1.30; 95% CI 1.10–1.53) in patients admitted via EDs compared with patients admitted via outpatient clinics; this difference was significant. However, no difference in the occurrence of extrapulmonary TB was observed between the two groups. Conclusions The likelihood of TB infection was greater in patients admitted via EDs than in patients admitted via outpatient clinics.


title: Interferon-β 1a and SARS Coronavirus Replication

text: A global outbreak of severe acute respiratory syndrome (SARS) caused by a novel coronavirus began in March 2003. The rapid emergence of SARS and the substantial illness and death it caused have made it a critical public health issue. Because no effective treatments are available, an intensive effort is under way to identify and test promising antiviral drugs. Here, we report that recombinant human interferon (IFN)-β 1a potently inhibits SARS coronavirus replication in vitro.


title: Levels of feline infectious peritonitis virus in blood, effusions, and various tissues and the role of lymphopenia in disease outcome following experimental infection

text: Abstract Twenty specific pathogen free cats were experimentally infected with a virulent cat-passaged type I field strain of FIPV. Eighteen cats succumbed within 2–4 weeks to effusive abdominal FIP, one survived for 6 weeks, and one seroconverted without outward signs of disease. A profound drop in the absolute count of blood lymphocytes occurred around 2 weeks post-infection (p.i.) in cats with rapid disease, while the decrease was delayed in the one cat that survived for 6 weeks. The absolute lymphocyte count of the surviving cat remained within normal range. Serum antibodies as measured by indirect immunofluorescence appeared after 2 weeks p.i. and correlated with the onset of disease signs. Viral genomic RNA was either not detectable by reverse transcription quantitative real-time PCR (RT-qPCR) or detectable only at very low levels in terminal tissues not involved directly in the infection, including hepatic and renal parenchyma, cardiac muscle, lung or popliteal lymph node. High tissue virus loads were measured in severely affected tissues such as the omentum, mesenteric lymph nodes and spleen. High levels of viral genomic RNA were also detected in whole ascitic fluid, with the cellular fraction containing 10–1000 times more viral RNA than the supernatant. Replicating virus was strongly associated with macrophages by immunohistochemistry. Virus was usually detected at relatively low levels in feces and there was no evidence of enterocyte infection. Viral genomic RNA was not detected at the level of test sensitivity in whole blood, plasma, or the white cell fraction in terminal samples from the 19 cats that succumbed or in the single survivor. These studies reconfirmed the effect of lymphopenia on disease outcome. FIPV genomic RNA was also found to be highly macrophage associated within diseased tissues and effusions as determined by RT-qPCR and immunohistochemistry but was not present in blood.


docid: xtvujuji

title: Considerations for people with diabetes during the Coronavirus Disease (COVID-19) Pandemic

text: Abstract Introduction The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) continues to cause havoc globally, resulting in unprecedented healthcare, societal and economic disruption. People with diabetes have been shown to be at higher risk of complications and death when exposed to pneumonia, influenza and other coronaviruses. Despite pandemic scale infection, there is currently limited understanding on the potential impact of SARS-CoV-2 on people with diabetes. Aims (1) To characterise the outcomes of SARS-CoV-2 for people with diabetes and (2) add value to current recommendations for healthcare providers and people with diabetes to encourage optimal management. Methods A search of PubMed, Embase and MEDLINE to March 2020 was undertaken, using search terms pertaining to diabetes, coronavirus and acute respiratory distress syndrome (ARDS). We briefly reviewed the epidemiology and pathophysiology of SARS-CoV in the context of diabetes. Conclusion People with diabetes are at greater risk of severe infection and death with COVID-19. COVID-19 has significantly impacted the daily lives of individuals living with diabetes through financial implications, food and medication scarcity and its burden on mental health. In Australia, delivery of medical care has been adapted to reduce the risk of transmission, with a particular emphasis on telehealth and remote monitoring.


title: Large-scale machine learning of media outlets for understanding public reactions to nation-wide viral infection outbreaks

text: Abstract From May to July 2015, there was a nation-wide outbreak of Middle East respiratory syndrome (MERS) in Korea. MERS is caused by MERS-CoV, an enveloped, positive-sense, single-stranded RNA virus belonging to the family Coronaviridae. Despite expert opinions that the danger of MERS might be exaggerated, there was an overreaction by the public according to the Korean mass media, which led to a noticeable reduction in social and economic activities during the outbreak. To explain this phenomenon, we presumed that machine learning-based analysis of media outlets would be helpful and collected a number of Korean mass media articles and short-text comments produced during the 10-week outbreak. To process and analyze the collected data (over 86 million words in total) effectively, we created a methodology composed of machine-learning and information-theoretic approaches. Our proposal included techniques for extracting emotions from emoticons and Internet slang, which allowed us to significantly (approximately 73%) increase the number of emotion-bearing texts needed for robust sentiment analysis of social media. As a result, we discovered a plausible explanation for the public overreaction to MERS in terms of the interplay between the disease, mass media, and public emotions.


title: 33 Other viruses

text: Publisher Summary This chapter discusses the characteristics of other viruses. The reovirus family is composed of three groups—reovirus, orbivirus, and rotavirus—and can cause infections in both man and animals. Other reoviruses are pathogenic to insects and plants. The orbivirus group consists of a large number of members, some of which are transmitted by vectors and, therefore, belong to the heterogenic arboviruses. Of the orbiviruses, the Colorado tick fever virus is the only one known to cause disease in man. As indicated by its name, the vector is a tick and the virus produces a febrile illness with myalgia. Arboviruses, that is, viruses borne by arthropod vectors and multiplying both in the arthropod and in the animal on which the arthropod is parasitic, show markedly variable morphological and biochemical characteristics. Coronavirus-like particles have been observed in fecal specimens of patients with gastroenteritis symptoms in India, Australia, Gambia, West Germany, and other countries.


title: Elevated levels of interleukin-6 and CRP predict the need for mechanical ventilation in COVID-19

text: Abstract Background COVID-19 can manifest as a viral induced hyperinflammation with multi-organ involvement. Such patients often experience rapid deterioration and need for mechanical ventilation. Currently, no prospectively validated biomarker of impending respiratory failure is available. Objective We aimed to identify and prospectively validate biomarkers that allow the identification of patients in need of impending mechanical ventilation. Methods Patients with COVID-19 hospitalized from February 29th to April 09th, 2020 were analyzed for baseline clinical and laboratory findings at admission and during the disease. Data from 89 evaluable patients were available for the purpose of analysis comprising an initial evaluation cohort (n=40) followed by a temporally separated validation cohort (n=49). Results We identified markers of inflammation, LDH and creatinine as most predictive variables of respiratory failure in the evaluation cohort. Maximal interleukin-6 (IL-6) levels before intubation showed the strongest association with the need of mechanical ventilation followed by maximal CRP. Respective AUC values for IL-6 and CRP in the evaluation cohort were 0.97 and 0.86 and similar in the validation cohort 0.90 and 0.83. The calculated optimal cutoff values in the course of disease from the evaluation cohort (IL-6> 80 pg/ml and CRP> 97 mg/l) both correctly classified 80% of patients in the validation cohort regarding their risk of respiratory failure. Conclusion Maximal levels of IL-6 followed by CRP were highly predictive of the need for mechanical ventilation. This suggests the possibility of using IL-6 or CRP levels to guide escalation of treatment in patients with COVID-19 related hyperinflammatory syndrome.


title: Genetic parameters estimated at receiving for circulating cortisol, immunoglobulin G, interleukin 8, and incidence of bovine respiratory disease in feedlot beef steers(1)

text: Bovine respiratory disease complex (i.e., shipping fever and bacterial bronchopneumonia) is a multifaceted respiratory illness influenced by numerous environmental factors and microorganisms. Bovine respiratory disease (BRD) is just one component of BRD complex. Because BRD is moderately heritable, it may be possible to reduce the incidence of BRD through genetic selection. The objectives of this study were to determine the heritability and associative genetic relationships among immune system traits (i.e., cortisol, total IgG, IgG isotypes, and IL-8) in cattle monitored for BRD incidence. At an average of 83 d after weaning (219 d age and mean = 221.7 kg [SD 4.34]), crossbred Bos taurus steer calves (n = 2,869) were received at a commercial feedlot in southeastern Colorado over a 2-yr period. At receiving, jugular blood samples were collected at 212 (yr 1) and 226 d (yr 2) of age for immune trait analyses. The BRD phenotype was defined as a binomial variable (0 = no and 1 = yes) and compared with immune system traits measured at receiving (prior to illness onset). An animal identified as BRD positive exhibited ≥ 2 clinical signs (i.e., eye or nasal discharge, cough, lethargy, rapid breathing, acute interstitial pneumonia, or acute upper respiratory syndrome and/or a rectal temperature > 39.7°C). Heritability and genetic correlation estimates for categorical variable BRD, cortisol, IgG, IgG1, IgG2, and IL-8 were estimated from a sire model using ASREML. Heritability estimates were low to moderate for BRD (0.17 ± 0.08), cortisol (0.13 ± 0.05), IgG (0.15 ± 0.05), IgG1 (0.11 ± 0.05), IgG2 (0.24 ± 0.06), and IL-8 (0.30 ± 0.06). A moderate negative genetic correlation was determined between BRD and cortisol (r(g) = −0.19 ± 0.32). Moderate positive correlations were found between BRD with IgG (0.42 ± 0.28), IgG1 (0.36 ± 0.32), and IL-8 (r(g) = 0.26 ± 0.26). Variation in the BRD phenotype and immune system traits suggested herd health improvement may be achieved through genetic selection.


title: Principles for targeting RNA with drug-like small molecules

text: RNA molecules are essential for cellular information transfer and gene regulation, and RNAs have been implicated in many human diseases. Messenger and non-coding RNAs contain highly structured elements, and evidence suggests that many of these structures are important for function. Targeting these RNAs with small molecules offers opportunities to therapeutically modulate numerous cellular processes, including those linked to “undruggable” protein targets. Despite this promise, there is currently only a single class of human-designed small molecules that target RNA used clinically – the linezolid antibiotics. A growing number of small-molecule RNA ligands are being identified, however, leading to burgeoning interest in the field. Here, we discuss principles for discovering small-molecule drugs that target RNA and argue that the overarching challenge is to identify appropriate target structures – namely in disease-causing RNAs that have high information content, and consequently appropriate ligand binding pockets. If focus is placed on such druggable binding sites in RNA, extensive knowledge of the kinds of molecules that comprise conventional drugs could then enable small-molecule drug discovery for RNA targets to become (only) roughly as difficult as for protein targets.


title: Recombinant Pseudorabies Virus (PRV) Expressing Firefly Luciferase Effectively Screened for CRISPR/Cas9 Single Guide RNAs and Antiviral Compounds

text: A Pseudorabies virus (PRV) variant has emerged in China since 2011 that is not protected by commercial vaccines, and has not been well studied. The PRV genome is large and difficult to manipulate, but it is feasible to use clustered, regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology. However, identification of single guide RNA (sgRNA) through screening is critical to the CRISPR/Cas9 system, and is traditionally time and labor intensive, and not suitable for rapid and high throughput screening of effective PRV sgRNAs. In this study, we developed a recombinant PRV strain expressing firefly luciferase and enhanced green fluorescent protein (EGFP) as a reporter virus for PRV-specific sgRNA screens and rapid evaluation of antiviral compounds. Luciferase activity was apparent as soon as 4 h after infection and was stably expressed through 10 passages. In a proof of the principle screen, we were able to identify several PRV specific sgRNAs and confirmed that they inhibited PRV replication using traditional methods. Using the reporter virus, we also identified PRV variants lacking US3, US2, and US9 gene function, and showed anti-PRV activity for chloroquine. Our results suggest that the reporter PRV strain will be a useful tool for basic virology studies, and for developing PRV control and prevention measures.


title: A model for the dynamic nuclear/nucleolar/cytoplasmic trafficking of the porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid protein based on live cell imaging

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus, in common with many other positive strand RNA viruses, encodes a nucleocapsid (N) protein which can localise not only to the cytoplasm but also to the nucleolus in virus-infected cells and cells over-expressing N protein. The dynamic trafficking of positive strand RNA virus nucleocapsid proteins and PRRSV N protein in particular between the cytoplasm and nucleolus is unknown. In this study live imaging of permissive and non-permissive cell lines, in conjunction with photo-bleaching (FRAP and FLIP), was used to investigate the trafficking of fluorescent labeled (EGFP) PRRSV-N protein. The data indicated that EGFP-PRRSV-N protein was not permanently sequestered to the nucleolus and had equivalent mobility to cellular nucleolar proteins. Further the nuclear import of N protein appeared to occur faster than nuclear export, which may account for the observed relative distribution of N protein between the cytoplasm and the nucleolus.


title: The photooxidative destruction of C.I. Basic Yellow 2 using UV/S2O8 2− process in a rectangular continuous photoreactor

text: Abstract The photooxidative decolorization of C.I. Basic Yellow 2 (BY2), was investigated using UV radiation in the presence of peroxydisulfate (S2O8 2−) in a rectangular photoreactor at experimental condition. S2O8 2− and UV-light showed negligible effect when they were used independently. Removal efficiency of BY2 was sensitive to the operational parameters such as initial concentrations of S2O8 2−, BY2, light intensity, flow rate and pH. The conversion ratios of BY2 at the volumetric flow rates of 330, 500 and 650ml/min were 84%, 79%, 51% in 30min, respectively. Our results showed that light intensity was a beneficial parameter for dye removal. The results showed that in the presence of S2O8 2−, the photooxidation quantum yield obtained was higher than direct photolysis quantum yield, suggesting that photodecay of BY2 was dominated by photooxidation. The electrical energy per order (E EO) values for decolorization of BY2 solution was calculated. Results show that applying a desired peroxydisulfate concentration can reduce the E EO.


title: Royal Flying Doctor Service COVID-19 activity and surge modelling in Australia

text: INTRODUCTION: There is a COVID-19 pandemic. We aimed to describe the characteristics of patients transported by the Royal Flying Doctor Service (RFDS) for confirmed or suspected Coronavirus disease 2019 (COVID-19), and to investigate surge capacity of, and operational implications for, the RFDS in dealing with COVID-19. METHODS: Prospective cohort study. To determine the characteristics of patients transported for confirmed or suspected COVID-19, we included patient data from 02 February 2020 to 06 May 2020. To investigate surge capacity and operational implications for RFDS in dealing with COVID-19, we built, and validated, an interactive operations area level discrete-event simulation decision support model, underpinned by RFDS aeromedical activity data from 2015 to 2019 (4-years). This model was subsequently used in a factorial in silico experiment to systematically investigate both the supply of RFDS aeromedical services and the increased rates of demand for these services, for diseases of the respiratory system. RESULTS: The RFDS conducted 291 patient episodes of care for confirmed or suspected COVID-19. This included 288 separate patients, including 136 males and 119 females (gender missing=33), with a median age of 62.0 years (IQR=43.5-74.9). The simulation decision support model we developed is capable of providing dynamic and real-time support for RFDS decision-makers in understanding the system's performance under uncertain COVID-19 demand. With increased COVID-19 related demand, the ability of the RFDS to cope will be driven by the number of aircraft available. The simulation model provided each aviation section with estimated numbers of aircraft required to meet a range of anticipated demands. CONCLUSION: Despite the lack of certainty in the actual level of COVID-19 related demand for RFDS services, modelling demonstrates that robustness of meeting such demand increases with the number of operational and medically staffed aircraft.


The BTK inhibitor ibrutinib may protect against pulmonary injury in COVID-19–infected patients


docid: cybiznxp

title: Preliminary Analysis of the Impact of COVID‐19 Outbreak on Italian Liver Transplant Programs

text: Liver Transplant Programs in Italy have faced a sequela of management and clinical decision‐making problems due to the high incidence in some regions of the country of severe acute respiratory syndrome Coronavirus 2 (SARS‐CoV‐2). The Italian Society for Organ Transplantation (SITO) and the Board of Liver Transplant Program Directors issued a survey to assess the initial impact of this pandemic event on the routine activity of 22 Italian Liver Transplant Programs. One hundred percent of participants completed the survey within a few days. The analysis is presented dividing the centers in two macro‐areas: north‐central Italy and south‐central Italy. The reason for this is that the two areas had a different incidence of the infection and because they have distinctive rates of cadaveric donation. Overall, all centers remained open although a reduction in the activity was noted. Transplant Programs reduced their outpatient activity both in terms of pre‐transplant evaluation (68% of the centers) and transplant recipient follow‐up (100%); a reduction in transplant activity was observed in the first two weeks of March only in the north‐central macro area (23 LTs vs 39 in 2018 and 60 in 2019); overall, SARS‐CoV‐2 infection was registered for 24 liver transplant recipients and 37 health care providers in liver transplant units. In the perspective of the increasing magnitude of the epidemic, more data will be required to define appropriate strategies for the increasingly complex management of liver transplant patients.


title: To test or not to test? An opportunity to restart dentistry sustainably in “COVID‐19 era”

text: COVID‐19, which appeared to originate in China in December 2019, has spread worldwide pandemically. Recently, a letter regarding COVID‐19 impact on dentistry has been published in this Journal (Prati et al. 2020). In Europe, Italy is the second most affected nation by COVID‐19 infection and the first for number of deaths (WHO SR). In March 2020, the Italian Ministry of Health ordered the suspension of all non‐urgent outpatient activities (including dentistry) in hospitals and clinics of the public health system, until the end of the lockdown (Press releases Italian Ministry of Health, 1).


title: Anaphylactic shock and lethal anaphylaxis caused by food consumption in China

text: A review of case reports of anaphylactic shock and lethal anaphylaxis caused by food consumption occurring in China was conducted. Case reports published in Chinese medical journals from 1980 to 2007 were considered in the review. According to these reports, the most common allergenic offenders were pineapple, soft-shelled turtle and crab.


Implantación emergente de un servicio de Teleneurología en la Unidad de Neuromuscular del Hospital Regional de Málaga durante la pandemia por SARS-CoV-2


title: Crystal structure of the giant panda MHC class I complex: first insights into the viral peptide presentation profile in the bear family

text: The viral cytotoxic T lymphocyte (CTL) epitope peptides presented by classical MHC-I molecules require the assembly of a peptide-MHC-I-β2m (aka pMHC-I) trimolecular complex for TCR recognition, which is the critical activation link for triggering antiviral T cell immunity. Ursidae includes 5 genera and 8 species; however, research on T cell immunology in this family, especially structural immunology, is lacking. In this study, the structure of the key trimolecular complex pMHC-1 (aka pAime-128), which binds a peptide from canine distemper virus, was solved for the first time using giant panda as a representative species of Ursidae. The structural characteristics of the giant panda pMHC-I complex, including the unique pockets in the peptide-binding groove (PBG), were analyzed in detail. Comparing the panda pMHC-I to others in the bear family and extending the comparison to other mammals revealed distinct features. The interaction between MHC-I and β2m, the features of pAime-128 involved in TCR docking and CD8 binding, the anchor sites in the PBG, and the CTL epitopes of potential viruses that infect pandas were concretely clarified. Unique features of pMHC-I viral antigen presentation in the panda were revealed by solving the three-dimensional structure of pAime-128. The distinct characteristics of pAime-128 indicate an unusual event that emerged during the evolution of the MHC system in the bear family. These results provide a new platform for research on panda CTL immunity and the design of vaccines for application in the bear family. Ursidae includes 5 genera and 8 species; however, the study of its immunology, especially structural immunology, is extremely rare to date. In this paper, we first crystallized the key complex pMHC-I, taking the giant panda as its representative species. Structural characteristics of the giant panda pMHC-I complexes, contains the unique pockets of PBG were analyzed in detail. Comparison of the panda pMHC-I in the bear family and other mammals, almost definite features was displayed. Meanwhile, the interaction between HC and LV, the unique features of pMHC-I in the CD8 binding and TCR docking, validation of anchor site in the PBG, and epitopes of potential viruses infected with the pandas, were concretely clarified. These unique characteristics of pMHC-I clearly indicate an unusual situation during the evolution of MHC molecules in the endangered pandas. These results also provide a novel platform for further study of panda T cell immunology and vaccines.


title: Immunoreactivity characterisation of the three structural regions of the human coronavirus OC43 nucleocapsid protein by Western blot: Implications for the diagnosis of coronavirus infection

text: Abstract Previous studies have reported that a prokaryotic-expressed recombinant nucleocapsid protein (NP) is a suitable reagent for the epidemiological screening of coronavirus infection. In this study, soluble recombinant human coronavirus OC43 (HCoV-OC43) NP was produced to examine the antigenicity of the HCoV-OC43 NP of betacoronavirus. Using the purified recombinant NP as an antigen, a polyclonal antibody from rabbit serum with specificity for HCoV-OC43 NP was generated; this antibody reacts specifically with HCoV-OC43 NP and does not cross-react with other human CoV NPs (including those of SARS-CoV and HCoV-229E) by Western blot. Sera from 26 young adults, 17 middle-aged and elderly patients with respiratory infection, and 15 cord blood samples were also tested. Strong reactivity to the NPs of HCoV-OC43 was observed in 96%, 82%, and 93% of the serum samples from the young adults, respiratory patients, and cord blood samples, respectively. To identify the immunoreactivities of the three structural regions of the NP that are recognised by the rabbit polyclonal antibody and human serum, the antigenicities of three protein fragments, including the N-terminal domain (aa 1-173), the central-linker region (aa 174-300), and the C-terminal domain (aa 301-448), were evaluated by Western blot. The rabbit polyclonal antibody demonstrated greater immunoreactivity to the central-linker region and the C-terminal domain than to the N-terminal domain. Three different patterns for the immunoreactivities of the three structural regions of HCoV-OC43 NP were observed in human serum, suggesting variability in the immune responses that occur during HCoV-OC43 infection in humans. The central-linker region of the NP appeared to be the most highly immunoreactive region for all three patterns observed. The goal of this study was to offer insight into the design of diagnostic tools for HCoV infection.


title: COVID-19, Hipertensión y Enfermedad cardiovascular

text: Resumen La asociación entre patología cardiovascular y mala evolución de la infección por SARS-CoV-2 resulta llamativa. Estudios publicados en diferentes países muestran que la hipertensión, diabetes, enfermedad cerebrovascular y cardiopatía isquémica son marcadamente más frecuentes en aquellos pacientes que requieren cuidados críticos o fallecen por COVID-19. Un posible nexo causal sería el daño y disfunción miocárdica producidos por el SARS-CoV-2, evidenciado en los frecuentes hallazgos de elevación de la troponina y anormalidades electrocardiográficas. Por otra parte, existen hipótesis a favor y en contra de un posible efecto deletéreo de los inhibidores de la enzima convertidora y los bloqueantes del receptor de angiotensina 2 en esta patología, no habiendo actualmente evidencia sólida que respalde contundentemente una u otra, resultando impostergable la necesidad de estudios que diluciden este interrogante. Los pacientes con enfermedad cardiovascular deberían evitar especialmente la exposición al SARS-CoV-2, no automedicarse y consultar rápidamente ante la aparición de síntomas. Abstract The association between hypertension, diabetes, cardio and cerebrovascular disease and severe and fatal COVID-19, described in different countries, is remarkable. Myocardial damage and myocardial dysfunction are postulated as a possible causal nexus. Frequent findings of elevated troponin levels and electrocardiographic anomalies support this concept. On the other hand, hypotheses in favour and against a deleterious effect of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, a usual treatment for cardiovascular disease, have been raised. There is currently no solid evidence and thus properly designed studies on this subject are urgently needed. In this context, patients with cardiovascular disease should especially avoid being exposed to the virus, should not self-medicate and rapidly seek medical advice should they show symptoms of infection.


title: The adaptation of codon usage of +ssRNA viruses to their hosts

text: Abstract Viruses depend on their host's cellular structure to survive. Most of them do not have tRNAs, their translation relies on hosts' tRNA pools. Over the course of evolution, viruses needed to optimally exploit cellular processes of their host. Thus, codon usage of a virus should coevolve with its host to efficiently and rapidly replicate. Some viruses can invade a broad spectrum of hosts (BSTVs), while others can invade a narrow spectrum only (NSTVs). Consequently, we test the hypothesis that similarity of codon usage preference and the degree of matching between BSTVs and their hosts will be lower than that of NSTVs, which only need to coevolve with few hosts. We compare the patterns of codon usage in 255 virus genomes to test this hypothesis. Our results show that NSTVs have a higher degree of matching to their hosts' tRNA pools than BSTVs. Further, analysis of the effective number of codons (ENC) infers that codon usage bias of NSTVs is relatively stronger than that of BSTVs. Thus, codon usage of NSTVs tends to better match their host than that of BSTVs. This supports the hypothesis that viruses adapt to the expression system of their host(s).


title: Transmission Kinetics and histopathology induced by European Turkey Coronavirus during experimental infection of specific pathogen free turkeys

text: Numerous viruses, mostly in mixed infections, have been associated worldwide with poult enteritis complex (PEC). In 2008 a coronavirus (Fr‐TCoV 080385d) was isolated in France from turkey poults exhibiting clinical signs compatible with this syndrome. In the present study, the median infectious dose (ID (50))(,) transmission kinetics and pathogenicity of Fr‐TCoV were investigated in 10‐day‐old SPF turkeys. Results revealed a titre of 10(4.88) ID (50)/ml with 1 ID (50)/ml being beyond the limit of genome detection using a well‐characterized qRT‐PCR for avian coronaviruses. Horizontal transmission of the virus via the airborne route was not observed however, via the oro‐faecal route this proved to be extremely rapid (one infectious individual infecting another every 2.5 hr) and infectious virus was excreted for at least 6 weeks in several birds. Histological examination of different zones of the intestinal tract of the Fr‐TCoV‐infected turkeys showed that the virus had a preference for the lower part of the intestinal tract with an abundance of viral antigen being present in epithelial cells of the ileum, caecum and bursa of Fabricius. Viral antigen was also detected in dendritic cells, monocytes and macrophages in these areas, which may indicate a potential for Fr‐TCoV to replicate in antigen‐presenting cells. Together these results highlight the importance of good sanitary practices in turkey farms to avoid introducing minute amounts of virus that could suffice to initiate an outbreak, and the need to consider that infected individuals may still be infectious long after a clinical episode, to avoid virus dissemination through the movements of apparently recovered birds.