docid: tmihxndd

title: The Ebola epidemic in West Africa: Challenges, opportunities, and policy priority areas

text: Abstract The ongoing Ebola epidemic in West Africa has drawn attention to global health inequalities, in particular the inadequacies of health care systems in sub-Saharan African countries for appropriately managing and containing infectious diseases. The purpose of this article is to examine the sociopolitical and economic conditions that created the environment for the Ebola epidemic to occur, identify challenges to and opportunities for the prevention and control of Ebola and future outbreaks, and discuss policy recommendations and priority areas for addressing the Ebola epidemic and future outbreaks in West Africa. Articles in peer-reviewed journals on health system reforms in developing countries and periodicals of international organizations were used to gather the overview reported in this article. We identify individual, structural, and community challenges that must be addressed in an effort to reduce the spread of Ebola in West Africa. The Ebola epidemic in West Africa underscores the need for the overhaul and transformation of African health care systems to build the capacity in these countries to address infectious diseases. Public-private partnerships for investment in developing countries' health care systems that involve the international community are critical in addressing the current Ebola epidemic and future outbreaks.


title: Glycyrrhizin and related compounds down-regulate production of inflammatory chemokines IL-8 and eotaxin 1 in a human lung fibroblast cell line

text: Abstract Glycyrrhizin (GL) is known to have various immunomodulating activities and has long been used clinically as an anti-allergic and anti-hepatitis agent. While the potency of GL against lung inflammatory diseases has been expected, the effect of GL on the lung has been poorly understood. Lung fibroblasts are known as a potent producer of inflammatory chemokines, IL-8 and eotaxin 1, by which neutrophils and eosinophils are strongly attracted during inflammation. Therefore, we studied the effects of GL on the production of these chemokines using a human fetal lung fibroblast cell line, HFL-1, stimulated with TNF-α and IL-4. Moreover, we examined the structure–activity relationships of GL to explore more beneficial compounds. 18α,β-GL inhibited IL-8 dose-dependently and inhibited eotaxin 1 slightly. 18α,β-Glycyrrhetic acid (GA) did not inhibit IL-8 but inhibited eotaxin 1. The effect of 18α,β-glycyrrhetic acid monoglucuronide (MGA) resembled that of 18α,β-GL but was weaker. Both 3β-[(2-O-β-d-glucopyranuronosyl-β-d-glucopyranuronosyl)oxy]-18β-11-deoxo-olean-12-en-30-oic acid (11-deoxo-GL) and 3β-[(2-O-β-d-glucopyranuronosyl-β-d-glucopyranuronosyl)oxy]-olean-11,13,(18)-dien-30-oic acid (hetero-GL) exhibited inhibitory activity with significant cytotoxicity. 3β-[(2-O-β-d-Glucopyranuronosyl-β-d-glucopyranuronosyl)oxy]-18β-olean-9,12-dien-30-oic acid (homo-GL) did not have cytotoxicity but its activity was mild like that of 18α,β-GL. 3β-[(2-O-β-d-Glucopyranuronosyl-β-d-glucopyranuronosyl)oxy]-olean-11,13(18)-dien-30-ol (hetero-30-OH-GL) and 3β-[(2-O-β-d-glucopyranuronosyl-β-d-glucopyranuronosyl)oxy]-18β-olean-9,12-dien-30-ol (homo-30-OH-GL) showed potent inhibitory effects, at concentrations lower than 18α,β-GL with no significant cytotoxicity. These results suggest that GL-related compounds are effective in reducing chemokine production and that GL-modified compounds including hetero-30-OH-GL and homo-30-OH-GL appear most beneficial in view of their inhibitory capacity with less cytotoxicity.


title: Impact of PCR for respiratory viruses on antibiotic use: Theory and practice

text: RATIONALE FOR THE STUDY: Real‐time polymerase chain reaction (PCR) for respiratory viruses is more sensitive, yet more expensive, than conventionally used direct immunofluorescence (DIF). We determined the impact of real‐time PCR, additional to DIF, on antibiotic prescription in ventilated children with lower respiratory tract infection (LRTI) at admission to the pediatric intensive care unit (PICU). METHODS: First, a multicenter survey study was performed. Subsequently, in a prospective study, children (≤5 years) with LRTI were tested at admission by DIF and PCR. Positive DIF results were reported at the end of the first working day. PICU physicians reported antibiotic treatment on the second working day. After informing them of the PCR result antibiotic treatment was reevaluated. RESULTS: The multicenter survey study (94 respondents) showed that PCR decreased antibiotic use (P < 0.001). In the prospective study 38 children were included, of which 19 (50%) were DIF positive. Of the 19 DIF negative patients 12 (63%) were treated with antibiotics before revealing the PCR result; the PCR test was positive in 9 out of 12. Revealing PCR results did not alter antibiotic treatment. In 7 DIF negative patients antibiotics not given, the PCR test was positive. CONCLUSION: In contrast to their responses to the survey study, in real‐life PICU physicians did not let their antibiotic prescription be influenced by respiratory real‐time PCR in children ventilated for LRTI. Pediatr. Pulmonol. 2011; 46:428–434. © 2010 Wiley‐Liss, Inc.


title: COVID-19 and anosmia: A review based on up-to-date knowledge

text: The pandemic of Coronavirus Disease 2019 (COVID-19) has caused a vast disaster throughout the world. There is increasing evidence that Olfactory dysfunction can present in COVID-19 patients. Anosmia can occur alone or can be accompanied by other symptoms of COVID-19, such as a dry cough. However, the pathogenic mechanism of olfactory dysfunction and its clinical characteristics in patients with COVID-19 remains unclear. Multiple cross-sectional studies have demonstrated that the incidence rate of Olfactory dysfunction in COVID-19 patients varies from 33.9–68% with female dominance. Anosmia and dysgeusia are often comorbid in COVID-19 patients. Otolaryngologists should be mindful of the symptom of anosmia in outpatients so as not to delay the diagnosis of COVID-19. In this paper, we have reviewed the relevant knowledge based on up-to-date literature.


Reply to “Concerns About Misinterpretation of Recent Scientific Data Implicating Dromedary Camels in Epidemiology of Middle East Respiratory Syndrome (MERS)”


title: De Corona Check-app: monitoring en advies

text: Met de Corona Check-app kunnen gebruikers die denken dat ze COVID-19 hebben advies krijgen op basis van de coronasymptomen die ze dagelijks invullen. De app geeft aan of de gebruiker waarschijnlijk wel of niet corona heeft en of deze al dan niet acute behandeling nodig heeft. Ook verwijst de app naar de juiste zorgverlener.


title: New molecular virus detection methods and their clinical value in lower respiratory tract infections in children

text: Summary During the past decade, several new respiratory viruses and their subgroups have been discovered. All these new viruses, as well as previously known respiratory viruses, can be detected by sensitive PCR methods, which have become popular in the diagnostic workup of respiratory viral infections. Currently, respiratory viruses can be detected in up to 95% of children with lower respiratory tract illness. On the other hand, virus detection rates in asymptomatic children are also high (up to 68%), as are coinfection rates in symptomatic children (up to 43%) and justified concerns of causality have been raised. Imposing progress has been made in developing multiplex quantitative PCR assays; here, several primer sets are run within a single PCR mixture. These PCR assays give a better understanding of the dominant viral infection, of viral infections that may be incipient and of any waning infections than does a single-target PCR. Multiplex PCR assays are also gaining popularity due to their cost-effectiveness and short throughput time compared to multiple single-target PCRs. Our understanding of the indications of virus PCRs and our ability to interpret the results from a clinical point of view have improved. This paper reviews the progress in PCR assays and discusses their role in the diagnosis of lower respiratory tract infections in children.


title: Combinatorial RNAi: A Winning Strategy for the Race Against Evolving Targets?

text: The ability to use double-stranded RNA to inhibit gene expression sequence-specifically (RNA interference, or RNAi) is currently revolutionizing science and medicine alike. Numerous pre-clinical studies are evaluating RNAi as a novel therapeutic modality in the battle against gain-of-function autosomal dominant diseases, cancer, and viral infections. One emerging concern is that RNAi mono-therapies might ultimately fail to control viruses that can escape silencing by mutation and/or RNAi suppression. Thus, sophisticated strategies are being developed that aim to avert viral resistance by combining RNAi effectors with each other or with further gene expression inhibitors. Several reports already validate this new concept of “combinatorial RNAi” (coRNAi) and illustrate its versatility by describing co-expression of RNAi triggers directed against single or multiple, viral or cellular, targets. Other studies document the successful delivery of these triggers with additional RNA- or protein-based silencers. Moreover, vectors have been engineered to blend RNAi-mediated gene inhibition with conventional gene replacement strategies. Collectively, these efforts open up exciting new therapeutic avenues but could also augment the inherent risks of RNAi technology, including immune responses, off-targeting, and oversaturation of endogenous pathways. Here, we critically review all coRNAi strategies and discuss the requirements for their transition into clinical application.


title: Exploring a Proposed WHO Method to Determine Thresholds for Seasonal Influenza Surveillance

text: INTRODUCTION: Health authorities find thresholds useful to gauge the start and severity of influenza seasons. We explored a method for deriving thresholds proposed in an influenza surveillance manual published by the World Health Organization (WHO). METHODS: For 2002-2011, we analysed two routine influenza-like-illness (ILI) datasets, general practice sentinel surveillance and a locum medical service sentinel surveillance, plus laboratory data and hospital admissions for influenza. For each sentinel dataset, we created two composite variables from the product of weekly ILI data and the relevant laboratory data, indicating the proportion of tested specimens that were positive. For all datasets, including the composite datasets, we aligned data on the median week of peak influenza or ILI activity and assigned three threshold levels: seasonal threshold, determined by inspection; and two intensity thresholds termed average and alert thresholds, determined by calculations of means, medians, confidence intervals (CI) and percentiles. From the thresholds, we compared the seasonal onset, end and intensity across all datasets from 2002-2011. Correlation between datasets was assessed using the mean correlation coefficient. RESULTS: The median week of peak activity was week 34 for all datasets, except hospital data (week 35). Means and medians were comparable and the 90% upper CIs were similar to the 95(th) percentiles. Comparison of thresholds revealed variations in defining the start of a season but good agreement in describing the end and intensity of influenza seasons, except in hospital admissions data after the pandemic year of 2009. The composite variables improved the agreements between the ILI and other datasets. Datasets were well correlated, with mean correlation coefficients of >0.75 for a range of combinations. CONCLUSIONS: Thresholds for influenza surveillance are easily derived from historical surveillance and laboratory data using the approach proposed by WHO. Use of composite variables is helpful for describing influenza season characteristics.


title: Host cell autophagy promotes BK virus infection

text: Abstract Autophagy is important for a variety for virus life cycles. We sought to determine the role of autophagy in human BK polyomavirus (BKPyV) infection. The addition excess amino acids during viral infection reduced BKPyV infection. Perturbing autophagy levels using inhibitors, 3-MA, bafilomycin A1, and spautin-1, also reduced infection, while rapamycin treatment of host cells increased infection. siRNA knockdown of autophagy genes, ATG7 and Beclin-1, corresponded to a decrease in BKPyV infection. BKPyV infection not only correlated with autophagosome formation, but also virus particles localized to autophagy-specific compartments early in infection. These data support a novel role for autophagy in the promotion of BKPyV infection.


Recent progress in the field of artificial organs


title: An Intervention to Improve Compliance with Transmission Precautions for Influenza in the Emergency Department: Successes and Challenges

text: Abstract Background: Concern with the potential for hospital-based transmission of influenza has come to the forefront due to emergency department (ED) crowding and the novel H1N1 pandemic. Compliance with infection control guidelines for influenza in the ED is generally unknown, and effective yet low-resource training is needed to educate staff on the importance of decreasing the potential for ED transmission of the virus. Objectives: This study evaluates compliance with patient assignment and transport precautions for influenza in an urban ED before and after implementation of electronic reminders. Methods: We included patients with a diagnosis of influenza for two consecutive influenza seasons, and retrospectively collected limited patient encounter data on patient location, transport, and compliance with assignment and transport precautions for both years. For the second influenza season we sent monthly reminders to all ED providers via the electronic medical record (EMR), explaining the importance and proper use of infection control precautions in patients with suspected influenza. Compliance between the two seasons was compared using descriptive statistics and chi-squared analysis. Results: Overall compliance with infection control precautions was poor, but increased with the use of electronic reminders from 29% to 45% (p = 0.015). Compliance with precautions for patients moved to the hallway or Radiology increased from 7% to 24% (p = 0.001). Conclusions: The EMR may be a useful tool for improving compliance with transmission-based precautions by implementing reminders on order sets and informational mailings, and by tracking compliance. Future study should be undertaken to determine the most effective interventions to prevent ED transmission of influenza.


title: Genome-Wide Analysis of Protein-Protein Interactions and Involvement of Viral Proteins in SARS-CoV Replication

text: Analyses of viral protein-protein interactions are an important step to understand viral protein functions and their underlying molecular mechanisms. In this study, we adopted a mammalian two-hybrid system to screen the genome-wide intraviral protein-protein interactions of SARS coronavirus (SARS-CoV) and therefrom revealed a number of novel interactions which could be partly confirmed by in vitro biochemical assays. Three pairs of the interactions identified were detected in both directions: non-structural protein (nsp) 10 and nsp14, nsp10 and nsp16, and nsp7 and nsp8. The interactions between the multifunctional nsp10 and nsp14 or nsp16, which are the unique proteins found in the members of Nidovirales with large RNA genomes including coronaviruses and toroviruses, may have important implication for the mechanisms of replication/transcription complex assembly and functions of these viruses. Using a SARS-CoV replicon expressing a luciferase reporter under the control of a transcription regulating sequence, it has been shown that several viral proteins (N, X and SUD domains of nsp3, and nsp12) provided in trans stimulated the replicon reporter activity, indicating that these proteins may regulate coronavirus replication and transcription. Collectively, our findings provide a basis and platform for further characterization of the functions and mechanisms of coronavirus proteins.


title: Emerging Bacterial, Fungal, and Viral Respiratory Infections in Transplantation

text: Kidney, liver, heart, pancreas, lung, and small intestine transplantations are viable therapeutic options for patients with end-stage organ failure. Ongoing advancements of surgical techniques, immunosuppressive regimens, and perioperative management have resulted in improved survival of allograft recipients. Despite these refinements, infections still contribute to substantial morbidity and mortality, limiting long-term success rates of these procedures. This article discusses the emerging bacterial, fungal, and viral respiratory infections in transplantation.


title: Chapter 59 Sterilization and Disinfection

text: Abstract Sterilization and disinfection are the basic components of hospital infection control activities. Every day, a number of hospitals are performing various surgical procedures. Even more number of invasive procedures are being performed in different health care facilities. The medical device or the surgical instrument that comes in contact with the sterile tissue or the mucus membrane of the patient during the various processes is associated with increased risk of introduction of pathogens into the patient's body. Moreover, there is chance of transmission of infection from patient to patient; from patient or to health care personnel, and vice versa; or from the environment to the patient through the improper sterilized or disinfected devices. Hence, medical personnel, laboratory people and the health care providers should have better knowledge regarding these techniques to prevent the spread of these pathogens.


title: Chapter One The viral replication organelles within cells studied by electron microscopy

text: Abstract Transmission electron microscopy (TEM) has been crucial to study viral infections. As a result of recent advances in light and electron microscopy, we are starting to be aware of the variety of structures that viruses assemble inside cells. Viruses often remodel cellular compartments to build their replication factories. Remarkably, viruses are also able to induce new membranes and new organelles. Here we revise the most relevant imaging technologies to study the biogenesis of viral replication organelles. Live cell microscopy, correlative light and electron microscopy, cryo-TEM, and three-dimensional imaging methods are unveiling how viruses manipulate cell organization. In particular, methods for molecular mapping in situ in two and three dimensions are revealing how macromolecular complexes build functional replication complexes inside infected cells. The combination of all these imaging approaches is uncovering the viral life cycle events with a detail never seen before.


title: Chapter 499 Nairovirus Deubiquitinylating Peptidase

text: The third edition of the Handbook of Proteolytic Enzymes aims to be a comprehensive reference work for the enzymes that cleave proteins and peptides, and contains over 800 chapters. Each chapter is organized into sections describing the name and history, activity and specificity, structural chemistry, preparation, biological aspects, and distinguishing features for a specific peptidase. The subject of Chapter 499 is Nairovirus Deubiquitinylating Peptidase. Keywords Bunyavirus, Crimean-Congo haemorrhagic fever virus, Dugbe virus, innate immunity, ISG15Gylation, nairovirus peptidase, ovarian tumor domain, viral deubiquitinase, viral immune evasion.


title: Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus-related coronavirus model

text: BACKGROUND: Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those institutions without such facilities or 2019-nCoV. This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV-related coronavirus model. METHODS: A 2019-nCoV-related pangolin coronavirus GX_P2V/pangolin/2017/Guangxi was described. Whether GX_P2V uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA) -mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2V infection. The anti-viral activities and anti-viral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively. RESULTS: The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs, including cepharanthine (CEP), selamectin, and mefloquine hydrochloride, exhibited complete inhibition of cytopathic effects in cell culture at 10 μmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC(50)] of 0.98 μmol/L. The viral RNA yield in cells treated with 10 μmol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48 ± 0.02] × 10(−4)vs. 1.00 ± 0.12, t = 150.38, P < 0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 μmol/L CEP at 48 h p.i. Furthermore, we found CEP had potent anti-viral activities against both viral entry (0.46 ± 0.12, vs.1.00 ± 0.37 t = 2.42, P < 0.05) and viral replication ([6.18 ± 0.95] × 10(−4)vs. 1.00 ± 0.43, t = 3.98, P < 0.05). CONCLUSIONS: Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin, and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and further study of CEP for treatment of 2019-nCoV infection is warranted.


title: Nidovirales

text: Nidoviruses form a phylogenetically compact but diverse group of enveloped positive-stranded RNA viruses with the largest RNA genome known. They infect a broad range of hosts, including humans, other mammals, birds, fish, and shrimp. Nidovirus infection starts by binding to a receptor on the cell surface, and fusion of the viral and cellular membranes mediated by one of the major surface glycoproteins. Following genome uncoating, the translation of the two overlapping replicase open reading frames (ORFs) yields two large polyprotein precursors that undergo autoproteolysis to produce the mature nonstructural proteins that eventually assemble into a membrane-bound, replication–transcription complex. The complex, which also contains several cellular proteins, mediates negative-strand RNA synthesis, amplification of the genome RNA, and production of a nested set of subgenomic messenger RNAs (sg mRNAs). Whereas nidovirus genome replication proceeds through the synthesis of a full-length negative-strand RNA, transcription involves the synthesis of subgenome-length, negative-strand templates for mRNA synthesis. In arteriviruses and coronaviruses, and probably bafiniviruses, transcription involves a mechanism of discontinuous negative-strand synthesis (template switch) to equip each subgenomic RNA with a 5′ common leader sequence identical to the genomic 5′ end. Except for the largest torovirus sg RNA, torovirus and ronivirus sgRNAs do not share such a common leader sequence and discontinuous RNA synthesis does not appear to be involved in this case. New nidovirus particles are assembled in the cytoplasm. There is increasing evidence that nidovirus infections modify a variety of host cell functions and structures, and induce a variety of immune and stress responses.


docid: nserrspn

title: Inter nation social lockdown versus medical care against COVID-19, a mild environmental insight with special reference to India

text: Abstract Infection by coronavirus (CoV-19) has led to emergence of a pandemic called as Coronavirus Disease (COVID-19) that has so far affected about 210 countries. The dynamic data indicate that the pandemic by CoV-19 so far has infected 2,403,963 individuals, and among these 624,698 have recovered while, it has been fatal for 165,229. Without much experience, currently, the medicines that are clinically being evaluated for COVID-19 include chloroquine, hydroxychloroquine, azithromycin, tocilizumab, lopinavir, ritonavir, tocilizumab and corticosteroids. Therefore, countries such as Italy, USA, Spain and France with the most advanced health care system are partially successful to control CoV-19 infection. India being the 2nd largest populous country, where, the healthcare system is underdeveloped, major portion of population follow unhygienic lifestyle, is able to restrict the rate of both infection and death of its citizens from COVID-19. India has followed an early and a very strict social distancing by lockdown and has issued advisory to clean hands regularly by soap and/or by alcohol based sterilizers. Rolling data on the global index of the CoV infection is 13,306, and the index of some countries such as USA (66,148), Italy (175,055), Spain (210,126), France (83,363) and Switzerland (262,122) is high. The index of India has remained very low (161) so far, mainly due to early implementation of social lockdown, social distancing, and sanitizing hands. However, articles on social lockdown as a preventive measure against COVID-19 in PubMed are scanty. It has been observed that social lockdown has also drastic impacts on the environment especially on reduction of NO2 and CO2 emission. Slow infection rate under strict social distancing will offer time to researchers to come up with exact medicines/vaccines against CoV-19. Therefore, it is concluded that stringent social distancing via lockdown is highly important to control COVID-19 and also to contribute for self-regeneration of nature.


title: Treatment of late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: the role of corticosteroids

text: We aimed to evaluate the treatments, particularly the role of corticosteroids, in patients with late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). One hundred and sixty-three consecutive patients who underwent non-T-cell-depleted allo-HSCT and met the criterion of LOHC after allo-HSCT were enrolled in this study. The median time from allo-HSCT to the occurrence of LOHC was 29 (range, 4–155) days. Pathogens identified in blood and/or urine samples from 143 patients were mostly viruses. All of the patients with LOHC received intravenous fluid hydration, alkalization, and forced diuresis, of which 2 patients achieved complete remission (CR) after these treatments. The remaining 161 patients received anti-infection therapies and 71 achieved CR after the therapies. Corticosteroids were additionally applied to 83 out of 90 patients who did not achieve CR after anti-infection therapies, and 88.0% (n = 73) of them showed a grade 3 to 4 LOHC at the beginning of corticosteroid therapy. Thirty-five patients showed an immediate response (CR or downgraded at least one grade) within 1 week after the beginning of the corticosteroid therapy. Sixty-four patients (77.1%) achieved CR after corticosteroid therapy, and the median period from the beginning of corticosteroid therapy to CR was 17 days. Thus, we observed that viruses were the most common pathogens in LOHC after allo-HSCT and that anti-infection therapies were critical. For patients not showing a satisfactory response to anti-infection therapies, additional corticosteroid therapy may help to achieve CR.


title: Mapping of Health Literacy and Social Panic Via Web Search Data During the COVID-19 Public Health Emergency: Infodemiological Study

text: BACKGROUND: Coronavirus disease (COVID-19) is a type of pneumonia caused by a novel coronavirus that was discovered in 2019. As of May 6, 2020, 84,407 cases and 4643 deaths have been confirmed in China. The Chinese population has expressed great concern since the COVID-19 outbreak. Meanwhile, an average of 1 billion people per day are using the Baidu search engine to find COVID-19–related health information. OBJECTIVE: The aim of this paper is to analyze web search data volumes related to COVID-19 in China. METHODS: We conducted an infodemiological study to analyze web search data volumes related to COVID-19. Using Baidu Index data, we assessed the search frequencies of specific search terms in Baidu to describe the impact of COVID-19 on public health, psychology, behaviors, lifestyles, and social policies (from February 11, 2020, to March 17, 2020). RESULTS: The search frequency related to COVID-19 has increased significantly since February 11th. Our heat maps demonstrate that citizens in Wuhan, Hubei Province, express more concern about COVID-19 than citizens from other cities since the outbreak first occurred in Wuhan. Wuhan citizens frequently searched for content related to “medical help,” “protective materials,” and “pandemic progress.” Web searches for “return to work” and “go back to school” have increased eight-fold compared to the previous month. Searches for content related to “closed community and remote office” have continued to rise, and searches for “remote office demand” have risen by 663% from the previous quarter. Employees who have returned to work have mainly engaged in the following web searches: “return to work and prevention measures,” “return to work guarantee policy,” and “time to return to work.” Provinces with large, educated populations (eg, Henan, Hebei, and Shandong) have been focusing on “online education” whereas medium-sized cities have been paying more attention to “online medical care.” CONCLUSIONS: Our findings suggest that web search data may reflect changes in health literacy, social panic, and prevention and control policies in response to COVID-19.


title: Epidemic predictions in an imperfect world: modelling disease spread with partial data

text: ‘Big-data’ epidemic models are being increasingly used to influence government policy to help with control and eradication of infectious diseases. In the case of livestock, detailed movement records have been used to parametrize realistic transmission models. While livestock movement data are readily available in the UK and other countries in the EU, in many countries around the world, such detailed data are not available. By using a comprehensive database of the UK cattle trade network, we implement various sampling strategies to determine the quantity of network data required to give accurate epidemiological predictions. It is found that by targeting nodes with the highest number of movements, accurate predictions on the size and spatial spread of epidemics can be made. This work has implications for countries such as the USA, where access to data is limited, and developing countries that may lack the resources to collect a full dataset on livestock movements.


title: Novel roles of DC-SIGNR in colon cancer cell adhesion, migration, invasion, and liver metastasis

text: BACKGROUND: Tumor metastasis is an essential cause of the poor prognosis of colon cancer. DC-SIGNR is a C-type lectin that is frequently found on human liver sinusoidal endothelial cells. LSECtin, which is a homologue of DC-SIGNR, has been demonstrated to participate in colon cancer liver metastasis. Due to the similarities in the expression pattern and structure of the two proteins, we speculated that DC-SIGNR could also be involved in this process. METHODS: Colon cancer cells were treated with the DC-SIGNR protein or control IgG, after which cell migration, invasion, and morphology were assayed. Xenograft mouse models were used to determine the role of DC-SIGNR in colon cancer liver metastasis in vivo. In addition, a human gene expression array was used to detect differential gene expression in colon cancer cells stimulated with the DC-SIGNR protein. The serum level of DC-SIGNR was examined in colon cancer patients by ELISA, and the significance of DC-SIGNR was determined. RESULTS: In our research, we investigated whether DC-SIGNR promotes colon cancer cell adhesion, migration, and invasion. Knocking down mouse DC-SIGNR decreased the liver metastatic potency of colon cancer cells and increased survival time. Expressing human DC-SIGNR enhanced colon cancer liver metastasis. Furthermore, DC-SIGNR conferred metastatic capability on cancer cells by upregulating various metallothionein isoforms. To validate the above results, we also found that the serum DC-SIGNR level was statistically higher in colon cancer patients with liver metastasis compared with those without metastasis. CONCLUSIONS: These results imply that DC-SIGNR may promote colon carcinoma hepatic metastasis and could serve as a promising therapeutic target for anticancer treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13045-016-0383-x) contains supplementary material, which is available to authorized users.


title: Unprecedented economic attack on Sub-Sahara African economies: coronavirus: How severe is the perceived slump?

text: This paper postulates the impact of coronavirus on Sub-Saharan African (SSA) economies and resilience to the pandemic. Relief measures instituted by World Bank Group (WBG) and International Monetary Fund (IMF) to help in the prevention, detection and treatment of coronavirus amidst SSA non-monetary measures and business support interventions are highlighted. The underlying economic challenges likely to impede WBG and IMF relief measures in SSA such as health infrastructure and resource deficiency, unsustainable high debt levels and drought effects due to climate change are analysed. Ranking the inadequate doctor-to-population ratio from 2015 to 2017, SSA ratio stood at less than 1 per 1000 population recommended World Health Organisation standard. On the credit front, other creditors such as China have contributed to prevailing economic challenges as China Official Development Assistance (ODA) to SSA debt ratio is depicted at 55% in 2016 from a low ratio of 17% in 2009. The economic challenges are further buttressed by estimated monthly tourism sector loss of US$8.8 billion per month for SSA countries during the pandemic. SSA self-employed informal sector that accounts for 76% (International Labour Organisation 2018) is equally affected amid lockdowns, business losses, closures and job losses. Economic growth is forecasted to drop to 1.8%, from a previous estimate of 3.2% according to United Nations Economic Commission (2020) due to a trade fall with developed and emerging markets. Recovery is aligned to good resilience in inherent cyber risk, oil intensity and urbanisation rate and policies to enhance production and the agriculture sector.


The maternity response to COVID-19: an example from one maternity unit in Taiwan


title: Optimization of Microwave-Assisted Extraction for the Determination of Glycyrrhizin in Menthazin Herbal Drug by Experimental Design Methodology

text: In the present study, a microwave-assisted extraction (MAE) method has been investigated for the extraction of glycyrrhizin from Menthazin herbal drug. The extracted samples have been analyzed by a developed reversed-phase liquid chromatography with ultraviolet detection. The separation was performed by a Eurospher-100 C(8) reversed-phase column (250 × 4.6 mm i.d., 5 μm) and the mobile phase consisted of methanol:acetonitrile:water:glacial acetic acid (30:30:40:1 v/v/v/v) with a flow rate of 0.8 mL min(−1). The extraction procedure has been screened by a two level full factorial design for determination of statistically significant parameters. Thereafter, the identified parameters, extraction temperature, time and solvent volume were optimized by a Box–Behnken design. The proposed mathematical model was based on analysis of variance results and correctly explained the behavior of the response in the experimental domain. R (2) value adjusted for numbers of degrees of freedom was 0.9915 and P-value for lack of fit, 0.8499 at the 95% confidence level, P > 0.05. The optimal condition identified were extraction temperature, 70 °C, time, 13.8 min and solvent volume 2.0 mL. To evaluate the applicability of the proposed MAE method, results were compared with those obtained with the liquid extraction method. Extraction efficiency and precision were higher when MAE has been used. The proposed method allows extracting the glycyrrhizin in a small quantity of solvent and faster than the liquid extraction method.


title: Trends and prediction in daily incidence and deaths of COVID-19 in the United States: a search-interest based model

text: BACKGROUND AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) infected more than 586,000 patients in the U.S. However, its daily incidence and deaths in the U.S. are poorly understood. Internet search interest was found correlated with COVID-19 daily incidence in China, but not yet applied to the U.S. Therefore, we examined the association of internet search-interest with COVID-19 daily incidence and deaths in the U.S. METHODS: We extracted the COVDI-19 daily incidence and death data in the U.S. from two population-based datasets. The search interest of COVID-19 related terms was obtained using Google Trends. Pearson correlation test and general linear model were used to examine correlations and predict future trends, respectively. RESULTS: There were 555,245 new cases and 22,019 deaths of COVID-19 reported in the U.S. from March 1 to April 12, 2020. The search interest of COVID, “COVID pneumonia,” and “COVID heart” were correlated with COVDI-19 daily incidence with ~12-day of delay (Pearson’s r=0.978, 0.978 and 0.979, respectively) and deaths with 19-day of delay (Pearson’s r=0.963, 0.958 and 0.970, respectively). The COVID-19 daily incidence and deaths appeared to both peak on April 10. The 4-day follow-up with prospectively collected data showed moderate to good accuracies for predicting new cases (Pearson’s r=−0.641 to −0.833) and poor to good accuracies for daily new deaths (Pearson’s r=0.365 to 0.935). CONCLUSIONS: Search terms related to COVID-19 are highly correlated with the trends in COVID-19 daily incidence and deaths in the U.S. The prediction-models based on the search interest trend reached moderate to good accuracies.


docid: dbjtonnx

title: The spectrum of pathological changes in severe acute respiratory syndrome (SARS)

text: Aims: To analyse the lung pathology of severe acute respiratory syndrome (SARS) and correlate the findings with the time sequence of the disease. Methods and results: Ten patients with a clinical diagnosis of SARS, and virological confirmation of SARS coronavirus infection were identified. Histology in most cases showed diffuse alveolar damage, from early to late phases, and the changes corresponded to the time sequence. Other variable features include multinucleated giant cells, pneumocytes with cytomegaly and variable amounts of inflammatory cells and foamy macrophages. One case showed superimposed bronchopneumonia. No viral inclusions were found. Coronavirus particles were identified in pneumocytes by electron microscopy. Conclusions: The predominant pathological process of SARS is diffuse alveolar damage and, in patients who die from the disease, there is evidence of organization and fibrosis. There are apparently no histological features specific for this disease, and the aetiological diagnosis depends on virological and ultrastructural studies.


title: The Conserved Coronavirus Macrodomain Promotes Virulence and Suppresses the Innate Immune Response during Severe Acute Respiratory Syndrome Coronavirus Infection

text: ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the Coronavirinae, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3’s de-ADP-ribosylation activity in vitro. Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations. These mutations led to virus attenuation and a modest reduction of viral loads in infected mice, despite normal replication in cell culture. Further, macrodomain mutant virus elicited an early, enhanced interferon (IFN), interferon-stimulated gene (ISG), and proinflammatory cytokine response in mice and in a human bronchial epithelial cell line. Using a coinfection assay, we found that inclusion of mutant virus in the inoculum protected mice from an otherwise lethal SARS-CoV infection without reducing virus loads, indicating that the changes in innate immune response were physiologically significant. In conclusion, we have established a novel function for the SARS-CoV macrodomain that implicates ADP-ribose in the regulation of the innate immune response and helps to demonstrate why this domain is conserved in CoVs.


title: COVID-19 and climate: global evidence from 117 countries

text: Visual inspection of world maps shows that coronavirus disease 2019 (COVID-19) is less prevalent in countries closer to the equator, where heat and humidity tend to be higher. Scientists disagree how to interpret this observation because the relationship between COVID-19 and climatic conditions may be confounded by many factors. We regress confirmed COVID-19 cases per million inhabitants in a country against the country’s distance from the equator, controlling key confounding factors: air travel, distance to Wuhan, testing intensity, cell phone usage, vehicle concentration, urbanization, and income. A one-degree increase in absolute latitude is associated with a 2.6% increase in cases per million inhabitants (p value <0.001). The Northern hemisphere may see a decline in new COVID-19 cases during summer and a resurgence during winter.


title: The Multifaceted Roles of Autophagy in Flavivirus-Host Interactions

text: Autophagy is an evolutionarily conserved cellular process in which intracellular components are eliminated via lysosomal degradation to supply nutrients for organelle biogenesis and metabolic homeostasis. Flavivirus infections underlie multiple human diseases and thus exert an immense burden on public health worldwide. Mounting evidence indicates that host autophagy is subverted to modulate the life cycles of flaviviruses, such as hepatitis C virus, dengue virus, Japanese encephalitis virus, West Nile virus and Zika virus. The diverse interplay between autophagy and flavivirus infection not only regulates viral growth in host cells but also counteracts host stress responses induced by viral infection. In this review, we summarize the current knowledge on the role of autophagy in the flavivirus life cycle. We also discuss the impacts of virus-induced autophagy on the pathogeneses of flavivirus-associated diseases and the potential use of autophagy as a therapeutic target for curing flavivirus infections and related human diseases.


title: Priming with rAAV encoding RBD of SARS-CoV S protein and boosting with RBD-specific peptides for T cell epitopes increase T cell responses and provide protection against SRAS-CoV infection

text: Development of vaccines against severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is crucial in the prevention of SARS reemergence. The receptor-binding domain (RBD) of SARS-CoV spike (S) protein is an important target in developing safe and effective SARS vaccines. Our previous study has demonstrated that vaccination with adeno-associated virus encoding RBD (RBD-rAAV) induces high titer of neutralizing antibodies. In this study, we further assessed the immune responses and protective effect of the immunization with RBD-rAAV prime/RBD-specific T cell peptide boost, as compared to those of vaccinations with RBD-rAAV and RBD-peptides alone. Our results indicated that RBD-rAAV prime/RBD-peptide boost induced similar Th1 and neutralizing antibody responses, but stronger Th2 and CTL responses than RBD-rAAV prime/boost. The resulting immune responses protected the vaccinated mice from subsequent SARS-CoV challenge, which was evidenced by lower level of viral replication in mouse lung tissues. However, no significant immune responses and protective effect were detected in mice vaccinated with RBD-peptides or blank AAV alone. Since T cell epitopes are highly conserved and boosting with peptides may induce the production of effector memory T cells, our results suggest that the vaccination protocol used may be ideal for providing effective, universal and long-term protection against SARS-CoV infection.


title: Proteases facilitate the endosomal escape of porcine epidemic diarrhea virus during entry into host cells

text: Abstract Exogenous and endogenous proteases play important roles in porcine epidemic diarrhea virus (PEDV) entry and replication. The roles of proteases in the viral endosomal escape and replication using trypsin (KD) or elastase (AA)-adapted US PEDV strains were studied. While PEDV KD and AA require different exogenous protease for efficient replication in cells, PEDV KD was more dependent on the protease than PEDV AA. There was no marked difference in viral trafficking between them during the entry events. Both PEDV were observed in the endosomes with or without protease at 1 h after virus inoculation. With protease, viral signals in the endosomes disappeared after 4 h, and newly synthesized viral proteins were detected in the ER after 6 h. However, without protease, viruses remained in the endosomes up to 24 h, which correlated with limited virus replication. Inhibitors of cathepsins, endogenous proteases, significantly reduced the replication of both PEDV by interfering with the viral endosomal escape.


title: Evaluation of echinacea for the prevention and treatment of the common cold: a meta-analysis

text: Summary Echinacea is one of the most commonly used herbal products, but controversy exists about its benefit in the prevention and treatment of the common cold. Thus, we did a meta-analysis evaluating the effect of echinacea on the incidence and duration of the common cold. 14 unique studies were included in the meta-analysis. Incidence of the common cold was reported as an odds ratio (OR) with 95% CI, and duration of the common cold was reported as the weighted mean difference (WMD) with 95% CI. Weighted averages and mean differences were calculated by a random-effects model (DerSimonian-Laird methodology). Heterogeneity was assessed by the Q statistic and review of L'Abbé plots, and publication bias was assessed through the Egger weighted regression statistic and visual inspection of funnel plots. Echinacea decreased the odds of developing the common cold by 58% (OR 0·42; 95% CI 0·25–0·71; Q statistic p<0·001) and the duration of a cold by 1·4 days (WMD −1·44, −2·24 to −0·64; p=0·01). Similarly, significant reductions were maintained in subgroup analyses limited to Echinaguard/Echinacin use, concomitant supplement use, method of cold exposure, Jadad scores less than 3, or use of a fixed-effects model. Published evidence supports echinacea's benefit in decreasing the incidence and duration of the common cold.


title: Asthma exacerbations: Origin, effect, and prevention

text: Asthma is the most common chronic respiratory disease, affecting up to 10% of adults and 30% of children in the Western world. Despite advances in asthma management, acute exacerbations continue to occur and impose considerable morbidity on patients and constitute a major burden on health care resources. Respiratory tract viruses have emerged as the most frequent triggers for exacerbations in both children and adults; however, the mechanisms underlying these remain poorly understood. More recently, it has become increasingly clear that interactions might exist between viruses and other triggers, increasing the likelihood of an exacerbation. In this article we begin with an overview of the health, economic, and social burden that exacerbations of asthma carry with them. This is followed by a review of the pathogenesis of asthma exacerbations, highlighting the various triggers responsible and multiple interactions that exist between them. The final section first addresses what preventative measures are currently available for asthma exacerbations and subsequently examines which of the new treatments in development might lessen the burden of exacerbations in the future.


title: Evaluation of applied public health emergency system at Prince Mohammed International Airport in Almedinah during Hajj season 2014: a qualitative case study

text: BACKGROUND: During the Hajj season 2014, several public health measures were applied by the Ministry of Health at Prince Mohammed International Airport in Almedinah. However, several operational defects affected the provision of preventive health services for passengers and airport workers. This study aims to evaluate the applied public health emergency system at the airport, detect any potential gaps and to provide appropriate operational solutions. METHODS: This is a qualitative case study conducted at Prince Mohammed International Airport in Almedinah during the 2014 Hajj season, September 2014. Data were collected via semi-structured interviews, focus groups and policy document reviews. Interviews were conducted with the 14 individuals of the airport’s decision makers and relevant health practitioners. Data were recorded via taking notes during interviews and data coding was performed to produce the main themes and subthemes of the study. RESULTS: The main findings of the study revealed three main defects affecting the applied public health emergency system at the airport. The main themes were mainly related to shortage in logistics related to public health emergency systems, shortage in proper documentation of policies and lack of documented protocols of communications among airport stakeholders. CONCLUSIONS: The study highlighted the main factors hindering the application of public health emergency measures at the airport. A Public Health Emergency Contingency Plan was proposed as a method to regulate the process of providing logistics for public health preventive services, the method of producing documented policies and methods of producing Memoranda of Understandings as communication regulators.


docid: dufsielh

title: Interferon alfacon 1 inhibits SARS-CoV infection In human bronchial epithelial Calu-3 cells

text: The primary targets for SARS-CoV infection are the epithelial cells in the respiratory and intestinal tract. The angiotensin-converting enzyme 2 (ACE-2) has been identified as a functional receptor for SARS-CoV. ACE-2 has been shown to be expressed at the apical domain of polarized Calu-3 cells. In this report, interferon alfacon 1 was examined for inhibitory activities against SARS-CoV on human lung carcinoma epithelial Calu-3 cell line and the other three African green monkey kidney epithelial cell lines. Interferon alfacon 1 demonstrated significant antiviral activity in neutral red uptake assay and virus yield reduction assay. The data might provide an important insight into the mechanism of pathogenesis of SARS-CoV allowing further development of antiviral therapies for treating SARS infections.


COVID‐19 and emergency surgery


title: Changes in implementation of personal protective measures by ordinary Japanese citizens: A longitudinal study from the early phase to the community transmission phase of the COVID-19 outbreak

text: OBJECTIVES: To clarify changes in the implementation of personal protective measures among ordinary Japanese citizens from the early phase of the COVID-19 outbreak to the community transmission phase. METHODS: This longitudinal, internet-based survey included 2,141 people (50.8% men; 20-79 years). The baseline and follow-up surveys were conducted from February 25-27, 2020 and April 1-6, 2020, respectively. Participants were asked how often they implemented the 5 personal protective measures recommended by the World Health Organization (hand hygiene, social distancing, avoiding touching the eyes, nose and mouth, respiratory etiquette, and self-isolation) in the baseline and follow-up surveys. RESULTS: The prevalence of 3 of the 5 personal protective measures significantly improved in the community transmission phase compared to the early phase. Social distancing measures showed significant improvement, from 67.4% to 82.2%. However, the prevalence of avoiding touching the eyes, nose and mouth, which had the lowest prevalence in the early phase, showed no significant improvement (approximately 60%). Multivariate logistic regression analysis revealed, men and persons of low-income households made fewer improvements than women and persons of high-income households. CONCLUSIONS: The prevalence of personal protective measures by ordinary citizens is improving, however there is potential for improvement, especially in regard to avoiding touching eyes, nose and mouth.


title: Characterization of the cleavage of signal peptide at the C-terminus of hepatitis C virus core protein by signal peptide peptidase

text: Production of hepatitis C virus (HCV) core protein requires the cleavages of polyprotein by signal peptidase and signal peptide peptidase (SPP). Cleavage of signal peptide at the C-terminus of HCV core protein by SPP was characterized in this study. The spko mutant (mutate a.a. 189–193 from ASAYQ to PPFPF) is more efficient than the A/F mutant (mutate a.a 189 and 191 from A to F) in blocking the cleavage of signal peptide by signal peptidase. The cleavage efficiency of SPP is inversely proportional to the length of C-terminal extension of the signal peptide: the longer the extension, the less efficiency the cleavage is. Thus, reducing the length of C-terminal extension of signal peptide by signal peptidase cleavage could facilitate further cleavage by SPP. The recombinant core protein fused with signal peptide from the C-terminus of p7 protein, but not those from the C-termini of E1 and E2, could be cleaved by SPP. Therefore, the sequence of the signal peptide is important but not the sole determinant for its cleavage by SPP. Replacement of the HCV core protein E.R.-associated domain (a.a. 120–150) with the E.R.-associated domain (a.a.1–50) of SARS-CoV membrane protein results in the failure of cleavage of this recombinant protein by SPP, though this protein still is E.R.-associated. This result suggests that not only E.R.-association but also specific protein sequence is important for the HCV core protein signal peptide cleavage by SPP. Thus, our results suggest that both sequences of the signal peptide and the E.R.-associated domain are important for the signal peptide cleavage of HCV core protein by SPP. Electronic Supplementary MaterialThe online version of this article (doi: 10.1007/s11373-006-9127-1) contains supplementary material, which is available to authorized users.


2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Health Care Settings


title: Synthesis of a novel hepatitis C virus protein by ribosomal frameshift

text: Hepatitis C virus (HCV) is an important human pathogen that affects ∼100 million people worldwide. Its RNA genome codes for a polyprotein, which is cleaved by viral and cellular proteases to produce at least 10 mature viral protein products. We report here the discovery of a novel HCV protein synthesized by ribosomal frameshift. This protein, which we named the F protein, is synthesized from the initiation codon of the polyprotein sequence followed by ribosomal frameshift into the −2/+1 reading frame. This ribosomal frameshift requires only codons 8–14 of the core protein‐coding sequence, and the shift junction is located at or near codon 11. An F protein analog synthesized in vitro reacted with the sera of HCV patients but not with the sera of hepatitis B patients, indicating the expression of the F protein during natural HCV infection. This unexpected finding may open new avenues for the development of anti‐HCV drugs.


title: Experimental reproduction of winter dysentery in lactating cows using BCV — comparison with BCV infection in milk-fed calves

text: Abstract Infection models were developed for adult cows and for young calves using the same strain of bovine coronavirus (BCV), which for the first time allows experimental reproduction of winter dysentery (WD) in seronegative lactating cows. The cattle were infected through direct contact with an experimentally inoculated calf. All experimental cattle shed faecal BCV with development of diarrhoea, being profusely watery with small amounts of blood in the most severely affected animals, including both cows and calves. The cows, in contrast to the calves, showed depressed general condition and appetite leading to a marked decrease in milk yield. Further age-associated differences were a shorter incubation period in the two youngest calves, but with milder fever and milder decrease in white blood cell counts. These findings shed light on the apparent epidemiological differences between WD and calf BCV diarrhoea suggesting that, (1) the same strains of BCV cause natural outbreaks of calf diarrhoea and WD, (2) seronegative cows are more severely affected by the infection than seronegative conventionally reared calves, and (3) unaffected general condition in diarrhoeic calves may lead to underestimation of the occurrence of calf diarrhoea in WD outbreaks. In response to infection, all cattle produced early interferon type 1 in serum and, except for one calf, in nasal secretions. A finding not previously reported is the detection of interferon type 1 responses in bovine milk. All cattle developed high IgM antibody responses and long-lasting IgA antibody responses both systemically and locally. The serum IgM antibody responses came earlier in most of the calves than in the cows. Prolonged IgM antibody responses were detected in serum and milk, while those in nasal secretions were much shorter. BCV-specific IgA was present in nasal secretions from all cattle throughout the 6 months follow-up. The IgA antibody response in serum was detected up to 17 months post-infection and the duration showed an age-related variation indicating a more prominent IgA memory in the adult cattle and in the older calves than in the younger ones. BCV-specific IgG was detected in all cattle during the experimental period of up to 22 months. In conclusion, WD was reproduced in seronegative lactating cows. The cows showed a more severe general diseases than seronegative calves infected concurrently. Very long-lasting IgA antibody responses were detected both systemically and locally.


title: Is Your Interventional Radiology Service Ready for SARS?: The Singapore Experience

text: The recent epidemic of severe acute respiratory syndrome caught many by surprise. Hitherto, infection control has not been in the forefront of radiological practice. Many interventional radiology (IR) services are therefore not equipped to deal with such a disease. In this review, we share our experience from the interventional radiologist’s perspective, report on the acute measures instituted within our departments and explore the long-term effects of such a disease on the practice of IR.


Influenza Will Not Miss Opportunities


title: Prophylaxis and Therapy for Chikungunya Virus Infection

text: BackgroundChikungunya virus (CHIKV) is a recently reemerged arbovirus responsible for a massive outbreak of infection in the Indian Ocean region and India that has a very significant potential to spread globally because of the worldwide distribution of its mosquito vectors. CHIKV induces a usually self-limited disease in humans that is characterized by fever, arthralgia, myalgia, and rash; however, cases of severe CHIKV infection have recently been described, particularly in adults with underlying condition and neonates born to viremic mothers MethodsHuman polyvalent immunoglobulins were purified from plasma samples obtained from donors in the convalescent phase of CHIKV infection, and the preventive and curative effects of these immunoglobulins were investigated in 2 mouse models of CHIKV infection that we developed ResultsCHIKV immunoglobulins contain anti-CHIKV antibodies and exhibit a high in vitro neutralizing activity and a powerful prophylactic and therapeutic efficacy against CHIKV infection in vivo, including in the neonate ConclusionsAdministration of CHIKV immunoglobulins may constitute a safe and efficacious prevention strategy and treatment for individuals exposed to CHIKV who are at risk of severe infection, such as neonates born to viremic mothers and adults with underlying conditions. These results provide a proof-of-concept for purifying human immunoglobulins from plasma samples from patients in the convalescent phase of an emerging infectious disease for which neither prevention nor treatment is available


title: Viewpoint | Handwashing and COVID-19: Simple, right there…?

text: COVID-19 is a disease with no proven pharmaceutical intervention and no proven vaccine. In such circumstances, prevention is all we have. The role of handwashing in the prevention of communicable diseases has been known for over a century, yet it remains severely neglected as a public health investment, to be periodically re-discovered during pandemic-scale infections. Over 26% of the global population has no access to a handwashing station in the home; for many low-income countries this proportion rises to over 50%. In other instances, the water is unaffordable or the supply has been shut off on account of unpaid bills. But when there is no water in the home or yard, or no mechanism for delivering enough water, good hand-washing is extremely difficult. Well before COVID-19, global cost-benefit analyses of water and sanitation investments, with benefits measured in time-savings as well as health, showed significant net benefits in all sub-regions of the developing world. This Viewpoint paper argues that, in the current crisis and its aftermath, it is imperative for governments and donors to prioritize and generously fund affordable, reliable, and accessible water services in underserved regions of the world. More than ever before, this is a foundational investment for health, dignity and development.


title: Global Dynamics of a Virus Dynamical Model with Cell-to-Cell Transmission and Cure Rate

text: The cure effect of a virus model with both cell-to-cell transmission and cell-to-virus transmission is studied. By the method of next generation matrix, the basic reproduction number is obtained. The locally asymptotic stability of the virus-free equilibrium and the endemic equilibrium is considered by investigating the characteristic equation of the model. The globally asymptotic stability of the virus-free equilibrium is proved by constructing suitable Lyapunov function, and the sufficient condition for the globally asymptotic stability of the endemic equilibrium is obtained by constructing suitable Lyapunov function and using LaSalle invariance principal.


title: The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges

text: Ubiquitin Proteasome System (UPS) is an adaptable and finely tuned system that sustains proteostasis network under a large variety of physiopathological conditions. Its dysregulation is often associated with the onset and progression of human diseases; hence, UPS modulation has emerged as a promising new avenue for the development of treatments of several relevant pathologies, such as cancer and neurodegeneration. The clinical interest in proteasome inhibition has considerably increased after the FDA approval in 2003 of bortezomib for relapsed/refractory multiple myeloma, which is now used in the front-line setting. Thereafter, two other proteasome inhibitors (carfilzomib and ixazomib), designed to overcome resistance to bortezomib, have been approved for treatment-experienced patients, and a variety of novel inhibitors are currently under preclinical and clinical investigation not only for haematological malignancies but also for solid tumours. However, since UPS collapse leads to toxic misfolded proteins accumulation, proteasome is attracting even more interest as a target for the care of neurodegenerative diseases, which are sustained by UPS impairment. Thus, conceptually, proteasome activation represents an innovative and largely unexplored target for drug development. According to a multidisciplinary approach, spanning from chemistry, biochemistry, molecular biology to pharmacology, this review will summarize the most recent available literature regarding different aspects of proteasome biology, focusing on structure, function and regulation of proteasome in physiological and pathological processes, mostly cancer and neurodegenerative diseases, connecting biochemical features and clinical studies of proteasome targeting drugs.


title: Chapter 16 Avian Immunosuppressive Diseases and Immunoevasion

text: Subclinical immunosuppression in chickens is an important but often underestimated factor in the subsequent development of clinical disease. Immunosuppression can be caused by pathogens such as chicken infectious anemia virus, infectious bursal disease virus, reovirus, and some retroviruses (e.g., reticuloendotheliosis virus). Mycotoxins and stress, often caused by poor management practices, can also cause immunosuppression. The effects on the innate and acquired immune responses and the mechanisms by which mycotoxins, stress and infectious agents cause immunosuppression are discussed. Immunoevasion is a common ploy by which viruses neutralize or evade immune responses. DNA viruses such as herpesvirus and poxvirus have multiple genes, some of them host-derived, which interfere with effective innate or acquired immune responses. RNA viruses may escape acquired humoral and cellular immune responses by mutations in protective antigenic epitopes (e.g., avian influenza viruses), while accessory non-structural proteins or multi-functional structural proteins interfere with the interferon system (e.g., Newcastle disease virus).


What should virologists be teaching their students?


title: Relationship between the Clinical Characteristics and Intervention Scores of Infants with Apparent Life-threatening Events

text: We investigated the clinical presentations, diagnostic and therapeutic modalities, and prognosis from follow-up of infants with apparent life-threatening events (ALTE). In addition, the relationship between the clinical characteristics of patients and significant intervention scores was analyzed. We enrolled patients younger than 12 months who were diagnosed with ALTE from January 2005 to December 2012. There were 29 ALTE infants with a peak incidence of age younger than 1 month (48.3%). The most common symptoms for ALTE diagnosis were apnea (69.0%) and color change (58.6%). Eleven patients appeared normal upon arrival at hospital but 2 patients required cardiopulmonary resuscitation during the initial ALTE. The most common ALTE cause was respiratory disease, including respiratory infection and upper airway anomalies (44.8%). There were 20 cases of repeat ALTE and 2 cases of death during hospitalization. Four patients (15.4%) experienced recurrence of ALTE after discharge and 4 patients (15.4%) showed developmental abnormalities during the follow-up period. The patients with ALTE during sleep had lower significant intervention scores (P=0.015) compared to patients with ALTE during wakefulness and patients with previous respiratory symptoms had higher significant intervention scores (P=0.013) than those without previous respiratory symptoms. Although not statistically significant, there was a weak positive correlation between the patient's total ALTE criteria and total significant intervention score (Fig. 2, r=0.330, P=0.080). We recommend that all ALTE infants undergo inpatient observation and evaluations with at least 24 hr of cardiorespiratory monitoring, and should follow up at least within a month after discharge. GRAPHICAL ABSTRACT: [Image: see text]


docid: hulpncpi

title: A chimeric bovine enteric calicivirus: evidence for genomic recombination in genogroup III of the Norovirus genus of the Caliciviridae

text: Abstract The Norovirus genus of the Caliciviridae encompasses viruses that cause outbreaks of gastroenteritis in human and viruses that have been associated with diarrhea in cattle. The two bovine noroviruses, Bo/Newbury2/76/UK and Bo/Jena/80/DE, represent two distinct genetic clusters in the newly described genogroup III. In the present study, Jena-like polymerase sequences were identified for the first time in the UK, but one of these, Bo/Thirsk10/00/UK, was a chimeric virus. Bo/Thirsk10/00/UK had a Jena-like polymerase gene but Newbury2-like capsid and ORF3 genes by comparison of their genome organization, nucleotide, and amino acid identities and phylogenetic analyses. The present study is one of few studies to clearly demonstrate the existence of chimeric genomes in the Norovirus genus and the first, to our knowledge, to identify a chimeric genome in genogroup III. It provides additional support that genomic recombination is part of the natural evolution of noroviruses and is relevant to the diagnosis and immunological control of norovirus diarrhea outbreaks.


title: Enterovirus A71 capsid protein VP1 increases blood–brain barrier permeability and virus receptor vimentin on the brain endothelial cells

text: Enterovirus A71 (EV-A71) is the major cause of severe hand-foot-and-mouth diseases (HFMD), especially encephalitis and other nervous system diseases. EV-A71 capsid protein VP1 mediates virus attachment and is the important virulence factor in the EV-A71pathogenesis. In this study, we explored the roles of VP1 in the permeability of blood–brain barrier (BBB). Sera albumin, Evans blue, and dextran leaked into brain parenchyma of the 1-week-old C57BL/6J mice intracranially injected with VP1 recombinant protein. VP1 also increased the permeability of the brain endothelial cells monolayer, an in vitro BBB model. Tight junction protein claudin-5 was reduced in the brain tissues or brain endothelial cells treated with VP1. In contrast, VP1 increased the expression of virus receptor vimentin, which could be blocked with VP1 neutralization antibody. Vimentin expression in the VP1-treated brain endothelial cells was regulated by TGF-β/Smad-3 and NF-κB signal pathways. Moreover, vimentin over-expression was accompanied with compromised BBB. From these studies, we conclude that EV-A71 virus capsid protein VP1 disrupted BBB and increased virus receptor vimentin, which both may contribute to the virus entrance into brain and EV-A71 CNS infection.


title: Respiratory Antiviral Immunity and Immunobiotics: Beneficial Effects on Inflammation-Coagulation Interaction during Influenza Virus Infection

text: Influenza virus (IFV) is a major respiratory pathogen of global importance, and the cause of a high degree of morbidity and mortality, especially in high-risk populations such as infants, elderly, and immunocompromised hosts. Given its high capacity to change antigenically, acquired immunity is often not effective to limit IFV infection and therefore vaccination must be constantly redesigned to achieve effective protection. Improvement of respiratory and systemic innate immune mechanisms has been proposed to reduce the incidence and severity of IFV disease. In the last decade, several research works have demonstrated that microbes with the capacity to modulate the mucosal immune system (immunobiotics) are a potential alternative to beneficially modulate the outcome of IFV infection. This review provides an update of the current status on the modulation of respiratory immunity by orally and nasally administered immunobiotics, and their beneficial impact on IFV clearance and inflammatory-mediated lung tissue damage. In particular, we describe the research of our group that investigated the influence of immunobiotics on inflammation–coagulation interactions during IFV infection. Studies have clearly demonstrated that hostile inflammation is accompanied by dysfunctional coagulation in respiratory IFV disease, and our investigations have proved that some immunobiotic strains are able to reduce viral disease severity through their capacity to modulate the immune-coagulative responses in the respiratory tract.


title: Anticipated and current preventive behaviors in response to an anticipated human-to-human H5N1 epidemic in the Hong Kong Chinese general population

text: BACKGROUND: The prevalence of self-reported preventive behaviors in response to an anticipated local human-to-human H5N1 transmission outbreak and factors associated with such behaviors have not been examined. METHODS: A random, anonymous, cross-sectional telephone survey of 503 Hong Kong Chinese adults. RESULTS: The public in Hong Kong is likely to adopt self-protective behaviors (e.g., wearing face mask in public venues (73.8%), increasing the frequency of handwashing (86.7%)) and behaviors that protect others (e.g., wearing face masks when experiencing influenza-like illness (ILI, 92.4%), immediately seeking medical consultation (94.2%), making declarations when crossing the border with ILI (87.1%), complying to quarantine policies (88.3%)). Multivariate analyses indicated that factors related to age, full-time employment, perceived susceptibility, perceived efficacy of preventive measures, perceived higher fatality as compared to SARS, perceived chance of a major local outbreak, and being worried about self/family members contracting the virus were significantly associated with the inclination to adopt self-protective measures. Similar analyses showed that education level, variables related to perceived efficacy, perceived major local outbreak and such were significantly associated with various behaviors directed towards protecting others. CONCLUSION: In the event of a human-to-human H5N1 outbreak, the public in Hong Kong is likely to adopt preventive measures that may help contain the spread of the virus in the community.


title: Why lockdown? Why national unity? Why global solidarity? Simplified arithmetic tools for decision-makers, health professionals, journalists and the general public to explore containment options for the 2019 novel coronavirus

text: As every country in the world struggles with the ongoing COVID-19 pandemic, it is essential that as many people as possible understand the epidemic containment, elimination and exclusion strategies required to tackle it. Simplified arithmetic models of COVID-19 transmission, control and elimination are presented in user-friendly Shiny and Excel formats that allow non-specialists to explore, query, critique and understand the containment decisions facing their country and the world at large. Although the predictive model is broadly applicable, the simulations presented are based on parameter values representative of the United Republic of Tanzania, which is still early enough in its epidemic cycle and response to avert a national catastrophe. The predictions of these models illustrate (1) why ambitious lock-down interventions to crush the curve represent the only realistic way for individual countries to contain their national-level epidemics before they turn into outright catastrophes, (2) why these need to be implemented so early, so stringently and for such extended periods, (3) why high prevalence of other pathogens causing similar symptoms to mild COVID-19 precludes the use of contact tracing as a substitute for lock down interventions to contain and eliminate epidemics, (4) why partial containment strategies intended to merely flatten the curve, by maintaining epidemics at manageably low levels, are grossly unrealistic, and (5) why local elimination may only be sustained after lock down ends if imported cases are comprehensively excluded, so international co-operation to conditionally re-open trade and travel between countries certified as free of COVID-19 represents the best strategy for motivating progress towards pandemic eradication at global level. The three sequential goals that every country needs to emphatically embrace are contain, eliminate and exclude. As recently emphasized by the World Health Organization, success will require widespread genuine national unity and unprecedented global solidarity.


title: Toxocariasis After Slug Ingestion Characterized by Severe Neurologic, Ocular, and Pulmonary Involvement

text: Human toxocariasis is generally a benign, self-curing disease, and neurologic involvement is quite exceptional. In this study, we report a case of toxocariasis caused by ingestion of an unusual transport host, namely live slugs. The clinical picture comprised eosinophilic lung involvement with severe neurologic disorders in relation to vasculitis as well as retinal detachment.


title: Architecture and self-assembly of the SARS-CoV-2 nucleocapsid protein

text: The COVID-2019 pandemic is the most severe acute public health threat of the twenty-first century. To properly address this crisis with both robust testing and novel treatments, we require a deep understanding of the life cycle of the causative agent, the SARS-CoV-2 coronavirus. Here, we examine the architecture and self-assembly properties of the SARS-CoV-2 nucleocapsid (N) protein, which binds viral RNA and assembles into a filament that is packaged into new virions. We determined a 1.4 Å resolution crystal structure of this protein’s N2b domain, revealing a compact, intertwined dimer very similar to that of related coronaviruses SARS-CoV and MERS-CoV. Using size exclusion chromatography and multi-angle light scattering, we find that this domain forms a dimer in solution, and that addition of the C-terminal spacer B/N3 domain mediates tetramer formation. Using hydrogen-deuterium exchange mass spectrometry, we find evidence that at least part of this putatively disordered domain is structured, potentially forming an α-helix that either self-associates or docks against the N2b domain to mediate tetramer formation. Finally, we map the locations of over 4,400 individual amino acid substitutions in the N protein from (~)17,000 SARS-CoV-2 genome sequences, and find that they are strongly clustered in the protein’s N2a linker domain. The nearly 300 substitutions identified within the N1b and N2b domains cluster away from their functional RNA binding and dimerization interfaces. Overall, this work reveals the architecture and self-assembly properties of a key protein in the SARS-CoV-2 life cycle. As the N protein is a common target of patient antibodies, this work will also benefit ongoing efforts to develop robust and specific serological tests, and could also benefit the analysis of patient-derived antibodies.


title: Intervention strategies for emerging respiratory virus infections: policy and public health considerations

text: Respiratory viruses have emerged and re-emerged in humans for hundreds of years. In the recent past avian and animal influenza viruses have caused human disease ranging from conjunctivitis to respiratory illnesses, including the 2009–10 A(H1N1)pdm09 pandemic. Coronaviruses, human metapneumovirus (hMPV) and enteroviruses have also impacted humans globally. Since the likely public health impacts are common, plans and policies for intervention strategies can be developed, encompassing early detection through surveillance and diagnostics, as well as treatment and prevention through clinical and non-clinical interventions. The global comprehensiveness of these varies according to differing resources, competing health priorities and the causative agent, yet, irrespective of this, activities must be proportional to the threat. Pandemics and severe epidemics enable policies to be tested and gaps identified.


title: The Porcine Deltacoronavirus Replication Organelle Comprises Double-Membrane Vesicles and Zippered Endoplasmic Reticulum with Double-Membrane Spherules

text: Porcine deltacoronavirus (PDCoV) was first identified in Hong Kong in 2012 from samples taken from pigs in 2009. PDCoV was subsequently identified in the USA in 2014 in pigs with a history of severe diarrhea. The virus has now been detected in pigs in several countries around the world. Following the development of tissue culture adapted strains of PDCoV, it is now possible to address questions regarding virus–host cell interactions for this genera of coronavirus. Here, we presented a detailed study of PDCoV-induced replication organelles. All positive-strand RNA viruses induce the rearrangement of cellular membranes during virus replication to support viral RNA synthesis, forming the replication organelle. Replication organelles for the Alpha-, Beta-, and Gammacoronavirus genera have been characterized. All coronavirus genera induced the formation of double-membrane vesicles (DMVs). In addition, Alpha- and Betacoronaviruses induce the formation of convoluted membranes, while Gammacoronaviruses induce the formation of zippered endoplasmic reticulum (ER) with tethered double-membrane spherules. However, the structures induced by Deltacoronaviruses, particularly the presence of convoluted membranes or double-membrane spherules, are unknown. Initially, the dynamics of PDCoV strain OH-FD22 replication were assessed with the onset of viral RNA synthesis, protein synthesis, and progeny particle release determined. Subsequently, virus-induced membrane rearrangements were identified in infected cells by electron microscopy. As has been observed for all other coronaviruses studied to date, PDCoV replication was found to induce the formation of double-membrane vesicles. Significantly, however, PDCoV replication was also found to induce the formation of regions of zippered endoplasmic reticulum, small associated tethered vesicles, and double-membrane spherules. These structures strongly resemble the replication organelle induced by avian Gammacoronavirus infectious bronchitis virus.


title: COVID‐19 patients' clinical characteristics, discharge rate, and fatality rate of meta‐analysis

text: The aim of this study was to analyze the clinical data, discharge rate, and fatality rate of COVID‐19 patients for clinical help. The clinical data of COVID‐19 patients from December 2019 to February 2020 were retrieved from four databases. We statistically analyzed the clinical symptoms and laboratory results of COVID‐19 patients and explained the discharge rate and fatality rate with a single‐arm meta‐analysis. The available data of 1994 patients in 10 literatures were included in our study. The main clinical symptoms of COVID‐19 patients were fever (88.5%), cough (68.6%), myalgia or fatigue (35.8%), expectoration (28.2%), and dyspnea (21.9%). Minor symptoms include headache or dizziness (12.1%), diarrhea (4.8%), nausea and vomiting (3.9%). The results of the laboratory showed that the lymphocytopenia (64.5%), increase of C‐reactive protein (44.3%), increase of lactic dehydrogenase (28.3%), and leukocytopenia (29.4%) were more common. The results of single‐arm meta‐analysis showed that the male took a larger percentage in the gender distribution of COVID‐19 patients 60% (95% CI [0.54, 0.65]), the discharge rate of COVID‐19 patients was 52% (95% CI [0.34,0.70]), and the fatality rate was 5% (95% CI [0.01,0.11]).


title: Clinical and Laboratory Features of Severe Acute Respiratory Syndrome Vis-À-Vis Onset of Fever

text: Study objectives: Severe acute respiratory syndrome (SARS) is a rapidly progressive disease caused by a novel coronavirus (CoV) infection. However, the disease presentation is nonspecific. The aim of this study was to define clearly the presentation, clinical progression, and laboratory data in a group of patients who had SARS. Design: Retrospective observational study. Setting: A tertiary care medical center with 51 negative-pressure isolation rooms in Taipei, Taiwan. Patients: Fifty-three patients with SARS seen between April 27 and June 16, 2003. Results: Fever (ie, temperature > 38°C) was the most common symptom (98%) and the earliest. When admitted to the isolation unit of the hospital for observation, most patients reported nonspecific symptoms associated with their fever. Only two patients with preexisting illnesses had cough on the same day the fever began. Eventually, 39 patients (74%) developed cough, beginning at a mean (± SD) time of 4.5 ± 1.9 days after fever onset, and 35 patients (66%) had diarrhea beginning at a mean time of 6.0 ± 3.3 days after fever onset. Thirty-one patients (59%) had abnormal findings on chest radiographs on hospital admission, and all but 1 patient (98%) eventually developed lung infiltrates that were consistent with pneumonia. The majority of patients (63%) first developed unifocal infiltrates at a mean time of 4.5 ± 2.1 days after fever onset, while in 37% of patients the initial infiltrates were multifocal, appearing at a mean time of 5.8 ± 1.3 days after fever onset. Common laboratory findings included lymphopenia (on hospital admission, 70%; during hospitalization, 95%), thrombocytopenia (on hospital admission, 28%; during hospitalization, 40%), elevated lactate dehydrogenase (on hospital admission, 58%; during hospitalization, 88%), creatine kinase (on hospital admission, 18%; during hospitalization, 32%), and aspartate aminotransferase or alanine aminotransferase levels (on hospital admission, 27%; during hospitalization, 62%). Throat or nasopharyngeal swab for SARS-CoV by reverse transcriptase polymerase chain reaction (PCR) and real-time PCR was positive in 40 of the 47 patients (85%) in whom the test was performed. Conclusions: None of the presenting symptoms or laboratory findings are pathognomonic for SARS. Even though cough developed in a majority of patients, it did not occur until later in the disease course, suggesting that a cough preceding or concurrent with the onset of fever is less likely to indicate SARS. While PCR for SARS-CoV appears to be the best early diagnostic test currently available, it is clear that better methods are needed to differentiate between SARS and non-SARS illness on initial presentation.


docid: irnlsrgt

title: Lesiones Cutáneas En Paciente Con Infección Por Sars-Cov-2


Chilblains and COVID19 infection: causality or coincidence? How to proceed?


docid: gdpiaxbr

title: Cryptosporidium infection in herds with and without calf diarrhoeal problems

text: A case–control study was designed to investigate the role of different Cryptosporidium spp. in Swedish dairy herds with and without calf diarrhoeal problems. Faecal samples were collected from preweaned calves, young stock and cows. Cryptosporidium oocysts were detected by sodium chloride flotation and epifluorescence microscopy. Molecular diagnostics were used to identify Cryptosporidium species. Samples containing C. parvum were further analysed to determine subtypes. Calf faecal samples were also analysed for rotavirus, coronavirus and Escherichia coli F5+. Total protein was assessed in 1- to 8-day-old calves. A questionnaire was used to identify differences in management routines. Cryptosporidium infection was diagnosed in all herds, with equal prevalence in case and control herds in all three age groups. Cryptosporidium parvum, Cryptosporidium bovis, Cryptosporidium ryanae and Cryptosporidium andersoni were all identified, as were rotavirus, coronavirus and E. coli F5+. C. ryanae and C. andersoni were only detected in non-diarrhoeal samples, whereas the other pathogens were detected in both diarrhoeal and non-diarrhoeal samples. Diarrhoea was more common in case herd calves. Disinfection of single pens was more common in case herds and several other management routines seemed to differ although results were not significant.


title: Clinical Characteristics and Outcomes of Hospitalized and Critically Ill Children and Adolescents with Coronavirus Disease 2019 (COVID-19) at a Tertiary Care Medical Center in New York City

text: OBJECTIVE: To describe the clinical profiles and risk factors for critical illness in hospitalized children and adolescents with COVID-19. STUDY DESIGN: Children 1 month to 21 years with COVID-19 from a single tertiary care children’s hospital between March 15-April 13, 2020 were included. Demographic and clinical data were collected. RESULTS: 67 children tested positive for COVID-19; 21 (31.3%) were managed as outpatients. Of 46 admitted patients, 33 (72%) were admitted to the general pediatric medical unit and 13 (28%) to the pediatric intensive care unit (PICU). Obesity and asthma were highly prevalent but not significantly associated with PICU admission (p=0.99). Admission to the PICU was significantly associated with higher C-reactive protein, procalcitonin, and pro-B type natriuretic peptide levels and platelet counts (p<0.05 for all). Patients in the PICU were more likely to require high-flow nasal cannula (p=0.0001) and were more likely to have received Remdesivir through compassionate release (p<0.05). Severe sepsis and septic shock syndromes were observed in 7 (53.8%) PICU patients. Acute respiratory distress syndrome (ARDS) was observed in 10 (77%) PICU patients, 6 of whom (46.2%) required invasive mechanical ventilation for a median of 9 days. Of the 13 patients in the PICU, 8 (61.5%) were discharged home, and 4 (30.7%) patients remain hospitalized on ventilatory support at day 14. One patient died after withdrawal of life-sustaining therapy because of metastatic cancer. CONCLUSIONS: We describe a higher than previously recognized rate of severe disease requiring PICU admission in pediatric patients admitted to the hospital with COVID-19.


title: The endoplasmic reticulum—Golgi intermediate compartment

text: Abstract The recent identification of an endoplasmic reticulum-Golgi intermediate compartment has added to the complexity of the structural and functional organization of the early secretory pathway. Protein sorting along the endoplasmic reticulum-Golgi pathway depends on different signals and mechanisms, some of which guarantee recycling from various levels of the Golgi apparatus to biosynthetically earlier compartments.


title: COVID‐19 and the Gender Gap in Work Hours

text: School and daycare closures due to the COVID‐19 pandemic have increased caregiving responsibilities for working parents. As a result, many have changed their work hours to meet these growing demands. In this study, we use panel data from the U.S. Current Population Survey to examine changes in mothers’ and fathers’ work hours from February through April, 2020, the period of time prior to the widespread COVID‐19 outbreak in the U.S. and through its first peak. Using person‐level fixed effects models, we find that mothers with young children have reduced their work hours four to five times more than fathers. Consequently, the gender gap in work hours has grown by 20 to 50 percent. These findings indicate yet another negative consequence of the COVID‐19 pandemic, highlighting the challenges it poses to women's work hours and employment.


title: A New Drug–Drug Interaction Between Hydroxychloroquine and Metformin? A Signal Detection Study

text: INTRODUCTION: Hydroxychloroquine was recently promoted in patients infected with COVID-19 infection. A recent experimental study has suggested an increased toxicity of hydroxychloroquine in association with metformin in mice. OBJECTIVE: The present study was undertaken to investigate the reality of this putative drug–drug interaction between hydroxychloroquine and metformin using pharmacovigilance data. METHODS: Using VigiBase(®), the WHO pharmacovigilance database, we performed a disproportionality analysis (case/non-case study). Cases were reports of fatal outcomes with the drugs of interest and non-cases were all other reports for these drugs registered between 1 January 2000 and 31 December 2019. Data with hydroxychloroquine (or metformin) alone were compared with the association hydroxychloroquine + metformin. Results are reported as ROR (reporting odds ratio) with their 95% confidence interval. RESULTS: Of the 10,771 Individual Case Safety Reports (ICSR) involving hydroxychloroquine, 52 were recorded as ‘fatal outcomes’. In comparison with hydroxychloroquine alone, hydroxychloroquine + metformin was associated with an ROR value of 57.7 (23.9–139.3). In comparison with metformin alone, hydroxychloroquine + metformin was associated with an ROR value of 6.0 (2.6–13.8). CONCLUSION: Our study identified a signal for the association hydroxychloroquine + metformin that appears to be more at risk of fatal outcomes (particularly by completed suicides) than one of the two drugs when given alone.


title: Are we there yet? The transition from response to recovery for the COVID-19 pandemic

text: Abstract There is no corner of the planet that has not been impacted by the rapid spread of the novel coronavirus, COVID-19. While the COVID-19 pandemic has already had far-reaching socioeconomic consequences commonly associated with natural hazards (such as disruption to society, economic damage, and loss of lives), the response of governments around the world has been unparalleled and unlike anything seen before. Governments are faced with a myriad of multi-dimensional effects of the pandemic, including direct impacts on public health systems and population health and indirect socioeconomic effects including disruption to every single sector of the economy and mass unemployment. There is, additionally, the growing realisation that the timescale associated with this crisis may permanently change the very foundations of societies ‘normal’ day-to-day life. As the world transitions to recovering from COVID-19, those developing that recovery need support in adjusting and improving their policies and measures. The situation seems dire, the stakes are high. Literature about the transition between the response and recovery phase in relation to pandemics is scarce. Further complication is that the pandemic will not allow countries to simply transition to the full-scale recovery, instead, a rebound from recovery to response phase is expected for a certain period until the immunization is in place. Pandemics indeed force us to think beyond typical emergency management structures; the cycles of the disaster risk management in the case of biological and other natural hazards are not exactly the same and no one-size-fits-all approach may be used. Still, some parallels may be drawn with the efforts to combat natural hazards and some lessons may be used from previous and the current pandemic. Based on these experiences and reflections, this paper provides a set of policy directions to be considered during the transition towards, as well as throughout, this transition phase. It is suggested that meeting this global, multi-dimensional, and complex challenge will require considerable international collaboration (even convention) and macro-scale changes to global and national policies. The recovery issues are mainly going to be dominated by politics, economics and social science. Necessary for an effective recovery, the pandemic response needs to be a holistic response, combined with an improved data ecosystem between the public health system and the community. We should also view this outbreak and our response to it as an opportunity to learn lessons and reaffirm our universal commitment to sustainable development and enhancing wellbeing around the world.


title: Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients

text: The SARS-CoV-2 pandemic has unprecedented implications for public health, social life, and the world economy. Because approved drugs and vaccines are not available, new options for COVID-19 treatment and prevention are in high demand. To identify SARS-CoV-2-neutralizing antibodies, we analyzed the antibody response of 12 COVID-19 patients from 8 to 69 days after diagnosis. By screening 4,313 SARS-CoV-2-reactive B cells, we isolated 255 antibodies from different time points as early as 8 days after diagnosis. Of these, 28 potently neutralized authentic SARS-CoV-2 (IC(100) as low as 0.04 μg/mL), showing a broad spectrum of variable (V) genes and low levels of somatic mutations. Interestingly, potential precursors were identified in naive B cell repertoires from 48 healthy individuals who were sampled before the COVID-19 pandemic. Our results demonstrate that SARS-CoV-2-neutralizing antibodies are readily generated from a diverse pool of precursors, fostering hope for rapid induction of a protective immune response upon vaccination.


title: Defining the interval for monitoring potential adverse events following immunization (AEFIs) after receipt of live viral vectored vaccines

text: Abstract Live viral vectors that express heterologous antigens of the target pathogen are being investigated in the development of novel vaccines against serious infectious agents like HIV and Ebola. As some live recombinant vectored vaccines may be replication-competent, a key challenge is defining the length of time for monitoring potential adverse events following immunization (AEFI) in clinical trials and epidemiologic studies. This time period must be chosen with care and based on considerations of pre-clinical and clinical trials data, biological plausibility and practical feasibility. The available options include: (1) adapting from the current relevant regulatory guidelines; (2) convening a panel of experts to review the evidence from a systematic literature search to narrow down a list of likely potential or known AEFI and establish the optimal risk window(s); and (3) conducting “near real-time“ prospective monitoring for unknown clustering’s of AEFI in validated large linked vaccine safety databases using Rapid Cycle Analysis for pre-specified adverse events of special interest (AESI) and Treescan to identify previously unsuspected outcomes. The risk window established by any of these options could be used along with (4) establishing a registry of clinically validated pre-specified AESI to include in case-control studies. Depending on the infrastructure, human resources and databases available in different countries, the appropriate option or combination of options can be determined by regulatory agencies and investigators.