title: Chapter 10 Organization of Public Health Systems

text: Abstract Public health consists of a complex of activities of public and private organizations working to protect and promote the health of the population, within laws, regulations, legal precedents, and ethics to ensure individual rights as well as those of society. Elected governments in unitary or federal states have legislative, executive, and judicial functions with taxing and enforcement powers. Unitary countries have two levels of government: national and local; federal states have three: federal, state, and local. Each level has official public health responsibilities. Interaction with governmental, non-governmental, and professional organizations, and the public is vital to successful public health. Higher levels of government have greater tax resources, so cost sharing from state and national levels is essential. Low-income countries generally allocate low levels of funding to health and have weak public health infrastructures. Linkages among prevention, health promotion, and medical care are essential to meet population and individual health targets.


title: International Air Travel to Ohio, USA, and the Impact on Malaria, Influenza, and Hepatitis A

text: The State of Ohio led the United States in measles in 2014, ostensibly related to international air travel (IAT), and ranked lower than 43 other states in infectious disease outbreak preparedness. We conducted a retrospective cohort study using surveillance data of the total Ohio population of 11 million from 2010 through 2014 with a nested case control of air travelers to determine the risk of malaria, seasonal influenza hospitalizations (IH), and hepatitis A (HA) disease related to international travel and to estimate the association with domestic enplanement. IAT appeared protective for HA and IH with a risk of 0.031 (.02–.04) but for malaria was 2.7 (2.07–3.62). Enplanement increased the risk for nonendemic M 3.5 (2.5–4.9) and for HA and IH 1.39 (1.34–1.44). IAT's ratio of relative risk (RRR) of malaria to HA and IH was 87.1 (55.8–136) greater than 219 times versus domestic enplanement which was protective for malaria at 0.397 (0.282–0.559). Malaria is correlated with IAT with cases increasing by 6.9 for every 10,000 passports issued.


title: Risk factors for adverse clinical outcomes with COVID-19 in China: a multicenter, retrospective, observational study

text: Background: The risk factors for adverse events of Coronavirus Disease-19 (COVID-19) have not been well described. We aimed to explore the predictive value of clinical, laboratory and CT imaging characteristics on admission for short-term outcomes of COVID-19 patients. Methods: This multicenter, retrospective, observation study enrolled 703 laboratory-confirmed COVID-19 patients admitted to 16 tertiary hospitals from 8 provinces in China between January 10, 2020 and March 13, 2020. Demographic, clinical, laboratory data, CT imaging findings on admission and clinical outcomes were collected and compared. The primary endpoint was in-hospital death, the secondary endpoints were composite clinical adverse outcomes including in-hospital death, admission to intensive care unit (ICU) and requiring invasive mechanical ventilation support (IMV). Multivariable Cox regression, Kaplan-Meier plots and log-rank test were used to explore risk factors related to in-hospital death and in-hospital adverse outcomes. Results: Of 703 patients, 55 (8%) developed adverse outcomes (including 33 deceased), 648 (92%) discharged without any adverse outcome. Multivariable regression analysis showed risk factors associated with in-hospital death included ≥ 2 comorbidities (hazard ratio [HR], 6.734; 95% CI; 3.239-14.003, p < 0.001), leukocytosis (HR, 9.639; 95% CI, 4.572-20.321, p < 0.001), lymphopenia (HR, 4.579; 95% CI, 1.334-15.715, p = 0.016) and CT severity score > 14 (HR, 2.915; 95% CI, 1.376-6.177, p = 0.005) on admission, while older age (HR, 2.231; 95% CI, 1.124-4.427, p = 0.022), ≥ 2 comorbidities (HR, 4.778; 95% CI; 2.451-9.315, p < 0.001), leukocytosis (HR, 6.349; 95% CI; 3.330-12.108, p < 0.001), lymphopenia (HR, 3.014; 95% CI; 1.356-6.697, p = 0.007) and CT severity score > 14 (HR, 1.946; 95% CI; 1.095-3.459, p = 0.023) were associated with increased odds of composite adverse outcomes. Conclusion: The risk factors of older age, multiple comorbidities, leukocytosis, lymphopenia and higher CT severity score could help clinicians identify patients with potential adverse events.


title: Effect of Puumala hantavirus infection on human umbilical vein endothelial cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release

text: Puumala virus (PUUV) infection causes over 5000 cases of hemorrhagic fever in Europe annually and can influence the hemostatic balance extensively. Infection might lead to hemorrhage, while a recent study showed an increased risk of myocardial infarction during or shortly after PUUV infection. The mechanism by which this hantavirus influences the coagulation system remains unknown. Therefore we aimed to elucidate mechanisms explaining alterations seen in primary and secondary hemostasis during PUUV infection. By using low passage PUUV isolates to infect primary human umbilical vein endothelial cells (HUVECs) we were able to show alterations in the regulation of primary- and secondary hemostasis and in the release of fibrinolysis regulators. Our main finding was an activation of secondary hemostasis due to increased tissue factor (TF) expression leading to increased thrombin generation in a functional assay. Furthermore, we showed that during infection platelets adhered to HUVEC and subsequently specifically to PUUV virus particles. Infection of HUVEC with PUUV did not result in increased von Willebrand factor while they produced more plasminogen activator inhibitor type-1 (PAI-1) compared to controls. The PAI-1 produced in this model formed complexes with vitronectin. This is the first report that reveals a potential mechanism behind the pro-coagulant changes in PUUV patients, which could be the result of increased thrombin generation due to an increased TF expression on endothelial cells during infection. Furthermore, we provide insight into the contribution of endothelial cell responses regarding hemostasis in PUUV pathogenesis.


title: Regulation of cellular innate antiviral signaling by ubiquitin modification

text: Host pattern-recognition receptors (PRRs) recognize pathogen-associated molecular patterns generated by invading viruses and initiate a series of signaling cascades that lead to the activation of interferon-regulatory factor 3 (IRF3) and nuclear factor-κB (NF-κB) and subsequent induction of type I interferons (IFNs). Posttranslational modification of proteins by ubiquitin plays an essential role in mediating or regulating the virus-triggered PRRs-mediated signaling. Deubiquitination is the reversible process of ubiquitination and its role in regulating PRRs-mediated signaling has recently been explored. In this review, we first summarize the ubiquitination events in PRRs-mediated signaling that is triggered by viral nucleic acid and then focus on host and viral deubiquitinating enzymes-mediated regulation of virus-triggered signaling that modulates the activation of IRF3 and NF-κB and subsequent induction of type I IFNs.


title: Biological response of using municipal solid waste compost in agriculture as fertilizer supplement

text: Waste management and declining soil fertility are the two main issues experienced by all developing nations, like India. Nowadays, agricultural utilization of Municipal Solid Waste (MSW) is one of the most promising and cost effective options for managing solid waste. It is helpful in solving two current burning issues viz. soil fertility and MSW management. However, there is always a potential threat because MSW may contain pathogens and toxic pollutants. Therefore, much emphasis has been paid to composting of MSW in recent years. Application of compost from MSW in agricultural land helps in ameliorating the soil’s physico-chemical properties. Apart from that it also assists in improving biological response of cultivated land. Keeping the present situation in mind, this review critially discusses the current scenario, agricultural utilization of MSW compost, role of soil microbes and soil microbial response on municipal solid waste compost application.


Acute Profound Sensorineural Hearing Loss after COVID-19 Pneumonia


title: Animal assisted intervention: A systematic review of benefits and risks

text: Abstract Introduction The therapeutic use of animals has been debated for decades, and its use explored in a variety of settings and populations. However, there is no uniformity on naming these interventions. Evidence based knowledge is essential to implement effective strategies in hospital. This review focused on the use of animal programs for hospitalized patients, and considered the potential risks. Methods The following databases were searched: PubMed, Scopus, PsychInfo, Ebsco Animals, PROQUEST, Web of Science, CINAHL, and MEDLINE, and PRISMA guidelines were adhered to. Results Out of 432 articles were identified 36 articles suitable for inclusion into the review. Data was heterogeneous in terms of age of patient, health issue, animals used and the length of interactions, which made comparison problematic. Studies on children, psychiatric and elderly patients were the most common. The animal-intervention programs suggested various benefits such as reducing stress, pain and anxiety. Other outcomes considered were changes in vital signs, and nutritional intake. Most studies used dogs, but other animals were effectively employed. The major risks outlined were allergies, infections and animal-related accidents. Zoonosis was a possible risk, as well as common infections as Methicillin-resistant Staphylococcus Aureus. The implementation of simple hygiene protocols was effective at minimizing risk. The literature suggested that the benefits outweighed by far the risks. Conclusion The human relationship with animals can be useful and relatively safe for inpatients with various problems. Moreover, the implementation of security precautions and the careful selection of patients should minimize the risks, particularly those infection-related. Many aspects remain unclear, further studies are required.


Jede zweite akute Exazerbation viral bedingt?: Chronisch obstruktive Lungenerkrankung


title: Chapter 12 Early Warning Practice Using Internet-Based Data

text: Abstract On the Internet, there is a lot of open access information related to infectious diseases, e.g., official announcement, media news, bulletin boards, blogs, and other social media. If proper data retrieval and screening methods were applied on these Internet-based data, it would be very useful to improve the timeliness of early detection for infectious diseases. In China, we practice early warning using Internet-based data with routine intelligence screening assessment every day, and respond to any unusual event in a timely manner. Through this mechanism, the surveillance and early warning of Internet-based data for infectious disease and public health emergency plays an important supplemental role to the traditional surveillance systems.


title: Evolution of emergency medical calls during a pandemic – An emergency medical service during the COVID-19 outbreak

text: INTRODUCTION: Emergency Medical Services (EMS) are expected to be affected by a pandemic outbreak. However, the available data about trends and extents of these effects is limited. METHODS: We analyzed numbers of ambulance calls for all 136 diagnosis codes used by Magen David Adom (MDA), Israel's national EMS during 121 days between January 01 and April 30, 2020. RESULTS: There was an increase in calls for COVID-19 symptoms (cough, fever, throat pain). This trend followed the same shape as the curve for confirmed COVID-19 patients. Trends were found to increase for calls not followed by transport to the hospital as well as in calls for mental or psychiatric causes. Simultaneously, there was a decrease in calls for cardiovascular issues, pneumonia, and all injuries. CONCLUSION: Understanding these correlations may allow better preparedness of the EMS and a better response towards the public needs in the period of an epidemic or a pandemic.


title: Experimental Dual Infection of Specific Pathogen‐Free Pigs with Porcine Reproductive and Respiratory Syndrome Virus and Pseudorabies Virus

text: Twenty 6‐week‐old specific pathogen‐free pigs were divided into four groups. On day 0 of the experiment, PRRSV–PRV (n = 6) and PRRSV (n = 4) groups were intranasally inoculated with porcine reproductive and respiratory syndrome virus (PRRSV) (10(5.6) TCID(50)). On day 7, the PRRSV–PRV and PRV (n = 6) groups were intranasally inoculated with pseudorabies virus (PRV) (10(3.6) TCID(50)). Control pigs (n = 4) were kept as uninoculated negative controls. Half of the pigs in each group were euthanized and necropsied on day 14 or 21. Clinical signs such as depression and anorexia were observed in the PRRSV–PRV and PRV groups after inoculation with PRV. Although febrile response was observed after virus inoculations, the duration of that response was prolonged in the PRRSV–PRV group compared with the other groups. The lungs in the PRRSV–PRV group failed to collapse and were mottled or diffusely tan and red, whereas the lungs of the pigs in the other groups were grossly normal. Histopathologically, interstitial pneumonia was present in all PRRSV‐inoculated pigs, but the pneumonic lesions were more severe in the PRRSV–PRV group. Mean PRRSV titres of tonsil and lung in the PRRSV–PRV group were significantly (P < 0.05) higher than that in the PRRSV group on day 21. These results indicate that dual infection with PRRSV and PRV increased clinical signs and pneumonic lesions in pigs infected with both viruses, as compared to pigs infected with PRRSV or PRV only, at least in the present experimental conditions.


title: Deletions into an NH2-terminal hydrophobic domain result in secretion of rotavirus VP7, a resident endoplasmic reticulum membrane glycoprotein

text: Rotavirus, a non-enveloped reovirus, buds into the rough endoplasmic reticulum and transiently acquires a membrane. The structural glycoprotein, VP7, a 38-kD integral membrane protein of the endoplasmic reticulum (ER), presumably transfers to virus in this process. The gene for VP7 potentially encodes a protein of 326 amino acids which has two tandem hydrophobic domains at the NH2-terminal, each preceded by an in- frame ATG codon. A series of deletion mutants constructed from a full- length cDNA clone of the Simian 11 rotavirus VP7 gene were expressed in COS 7 cells. Products from wild-type, and mutants which did not affect the second hydrophobic domain of VP7, were localized by immunofluorescence to elements of the ER only. However, deletions affecting the second hydrophobic domain (mutants 42-61, 43-61, 47-61) showed immunofluorescent localization of VP7 which coincided with that of wheat germ agglutinin, indicating transport to the Golgi apparatus. Immunoprecipitable wild-type protein, or an altered protein lacking the first hydrophobic sequence, remained intracellular and endo-beta-N- acetylglucosaminidase H sensitive. In contrast, products of mutants 42- 61, 43-61, and 47-61 were transported from the ER, and secreted. Glycosylation of the secreted molecules was inhibited by tunicamycin, resistant to endo-beta-N-acetylglucosaminidase H digestion and therefore of the N-linked complex type. An unglycosylated version of VP7 was also secreted. We suggest that the second hydrophobic domain contributes to a positive signal for ER location and a membrane anchor function. Secretion of the mutant glycoprotein implies that transport can be constitutive with the destination being dictated by an overriding compartmentalization signal.


Please cite this paper as: Coleman et al. (2011) Respiratory illnesses in Canadian health care workers: a pilot study of influenza vaccine and oseltamivir prophylaxis during the 2007/2008 influenza season. Influenza and Other Respiratory Viruses 5(6), 404–408. Background Data regarding both rates of acute respiratory illness in health care workers and experience with long‐term antiviral prophylaxis are sparse. Objective To determine the efficacy and tolerability of oseltamivir prophylaxis versus seasonal influenza vaccine for the prevention of influenza among health care workers. Methods We conducted a pilot, randomized control study during the 2007/2008 influenza season in a tertiary care setting. Adult health care workers 18–69 years of age were recruited and randomly assigned in a 4:1 ratio to receive either oseltamivir (Tamiflu(®); Roche) 75 mg once daily prophylaxis or seasonal influenza (Fluviral(®)) vaccine. Results Of 56 adults enrolled, 12 received vaccine and 44 received prophylaxis. Incidence of symptomatic laboratory‐confirmed influenza was similar for participants in the vaccine and prophylaxis arms (17% and 24%, respectively; P = 0·71). Participants who developed an acute respiratory illness during the study period reported working 85% of scheduled work days, and 29% stated that they worked despite feeling miserable because they were too busy to stay home. Of 42 participants who initiated oseltamivir prophylaxis, four discontinued it owing to side effects. Median duration of oseltamivir prophylaxis was 121 days, with 34 (81%) continuing ≥12 weeks. Conclusions During an extended season of suboptimal vaccine match, 22% of health care workers receiving antiviral prophylaxis or seasonal influenza vaccine developed symptomatic laboratory‐confirmed influenza. Long‐term antiviral prophylaxis against influenza was generally well tolerated with good compliance.


title: High detection rates of nucleic acids of a wide range of respiratory viruses in the nasopharynx and the middle ear of children with a history of recurrent acute otitis media

text: Both bacteria and viruses play a role in the development of acute otitis media, however, the importance of specific viruses is unclear. In this study molecular methods were used to determine the presence of nucleic acids of human rhinoviruses (HRV; types A, B, and C), respiratory syncytial viruses (RSV; types A and B), bocavirus (HBoV), adenovirus, enterovirus, coronaviruses (229E, HKU1, NL63, and OC43), influenza viruses (types A, B, and C), parainfluenza viruses (types 1, 2, 3, 4A, and 4B), human metapneumovirus, and polyomaviruses (KI and WU) in the nasopharynx of children between 6 and 36 months of age either with (n = 180) or without (n = 66) a history of recurrent acute otitis media and in 238 middle ear effusion samples collected from 143 children with recurrent acute otitis media. The co‐detection of these viruses with Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and Moraxella catarrhalis was analyzed. HRV (58.3% vs. 42.4%), HBoV (52.2% vs. 19.7%), polyomaviruses (36.1% vs. 15.2%), parainfluenza viruses (29.4% vs. 9.1%), adenovirus (25.0% vs. 6.1%), and RSV (27.8% vs. 9.1%) were detected significantly more often in the nasopharynx of children with a history of recurrent acute otitis media compared to healthy children. HRV was predominant in the middle ear and detected in middle ear effusion of 46% of children. Since respiratory viruses were detected frequently in the nasopharynx of both children with and without a history of recurrent acute otitis media, the etiological role of specific viruses in recurrent acute otitis media remains uncertain, however, anti‐viral therapies may be beneficial in future treatment and prevention strategies for acute otitis media. J. Med. Virol. 83:2008–2017, 2011. © 2011 Wiley‐Liss, Inc.


Artificial Intelligence in Diagnosis and Management of COVID‐19 in Dermatology


title: Localization of TGN38 to the trans-Golgi network: involvement of a cytoplasmic tyrosine-containing sequence

text: Protein localization to the TGN was investigated by examining the subcellular distribution of chimeric proteins in which the cytoplasmic and/or transmembrane domains of the TGN protein, TGN38, were substituted for the analogous domains of the plasma membrane protein, Tac. Using immunofluorescence and immunoelectron microscopy, the COOH- terminal cytoplasmic domain of TGN38 was found to be sufficient for localization of the chimeric proteins to the TGN. Deletion analysis identified an 11-amino acid segment containing the critical sequence, YQRL, as being sufficient for TGN localization. TGN localization was abrogated by mutation of the tyrosine or leucine residues in this sequence to alanine, or of the arginine residue to aspartate. In addition to specifying TGN localization, the 11-amino acid segment was active as an internalization signal, although the property of internalization alone was insufficient to confer TGN localization. Overexpression of chimeric proteins containing TGN localization determinants resulted in their detection at the plasma membrane and in intracellular vesicles, and abolished detection of endogenous TGN38. These results suggest that discrete cytoplasmic determinants can mediate protein localization to the TGN, and reveal a novel role for tyrosine-based motifs in this process.


title: Managing ACS during COVID-19 infection: do not follow the traditional route

text: COVID-19 pandemic is creating havoc in the world. It is also spreading in India creating a massive healthcare problem. Few major hospitals were closed down because of the spread among healthcare personnel. Management of several commonly occurring diseases needed modifications to a lesser or greater extent because of this pandemic. Management of acute coronary syndrome (ACS) also requires certain modifications. In this opinion paper an attempt has been made to give an outline of ACS management in this changed scenario.


title: Isolation and Selection of Duck Primary Cells as Pathogenic and Innate Immunologic Cell Models for Duck Plague Virus

text: Duck plague virus (DPV) is a representative pathogen transmitted among aquatic animals that causes gross lesions and immune inhibition in geese and ducks. The mechanism of organ tropism and innate immune evasion of DPV has not been completely deciphered due to a lack of cell models to study the innate immune manipulation and pathogenicity of aquatic viruses. In the present study, we isolated five types of duck primary cells [duck embryo fibroblasts (DEFs), neurons, astrocytes, peripheral blood mononuclear cells (PBMCs), and monocytes/macrophages] to identify appropriate cell models for DPV, using tropism infection and innate immunologic assays. Cells responded differently to stimulation with DNA viruses or RNA virus analogs. DPV infection exhibited broad tropism, as the recombinant virulent strain (CHv-GFP) infected DEFs, neurons, astrocytes, and monocytes/macrophages, but not the PBMCs, as the expression of EGFP was negligible. The basal levels of innate immunity molecules were highest in monocytes/macrophages and lower in DEFs and astrocytes. Conversely, the titer and genomic copy number of the attenuated virus strain was higher in DEFs and astrocytes than in neurons and monocytes/macrophages. The titer and genomic copy number of the attenuated virus strain were higher compared with the virulent strain in DEFs, neurons, and astrocytes. The innate immune response was not significantly induced by either DPV strain in DEFs, neurons, or astrocytes. The virulent strain persistently infected monocytes/macrophages, but the attenuated strain did so abortively, and this was accompanied by the phenomenon of innate immune inhibition and activation by the virulent and attenuated strains, respectively. Blockage of IFNAR signaling promoted replication of the attenuated strain. Pre-activation of IFNAR signaling inhibited infection by the virulent strain. The selection assay results indicated that induction of innate immunity plays an essential role in controlling DPV infection, and monocytes/macrophages are an important cell model for further investigations. Our study provided practical methods for isolating and culturing duck primary cells, and our results will facilitate further investigations of organ tropism, innate immune responses, latent infection, and the effectiveness of antiviral drugs for treating DPV and potentially other aerial bird pathogens.


title: Operating room team safety and perioperative anesthetic management of patients with suspected or confirmed novel corona virus in resource limited settings: A systematic review

text: Abstract Background Novel Corona Virus is a pandemic infectious disease which affects all age groups with higher incidence in geriatric population and chronic diseases. Contact, droplet and airborne had a role for transmission of the disease during airway manoeuvres in infected patients. This study aimed to prepare the operation room and provide protection of both the patient and health care personnel. Method This systematic review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) protocol. Search engines like Pub Med through HINARI, Cochrane database, Google Scholar to get access for current and updated evidences on operating room team safety and perioperative anesthetic management for patients with suspected or confirmed novel corona virus. Discussion High risk procedures for aerosolization including endotracheal intubation, open lung surgery and airway suctioning should be managed with vented masks. Conclusion All health care personnel should wear personal protective equipment based on the class of patients during surgery. Elective procedures should be postponed to save and mobilize resources for the protection and management of the pandemic disease. Emergency procedures including burn, Cesarean section, malignant neoplasia, perforated viscus and traumatic injury should be operated with wearing of personal protective equipment.


title: Employment‐Based, For‐Profit Health Care in a Pandemic

text: The emergence of Covid‐19 in the United States has revealed a critical weakness in the health care system in the United States. The majority of people in the nation receive health care via employment‐based health insurance from providers in a competitive market. However, neither employment‐based health care nor a competitive health care market can adequately provide treatment during a global pandemic. Employment‐based health care will fail to provide care for a large number of people in any destabilizing economic event, including a pandemic. Competitive for‐profit health care systems distribute limited goods based on markets rather than health care needs. If a global pandemic results in unusually high demand for specific medical supplies, then these will be distributed suboptimally. The combined risk of suboptimal distribution of needed goods and a significant drop in health care access in a global pandemic indicates that the U.S. health care system has serious vulnerabilities that need to be addressed.


title: Prediction of class I T-cell epitopes: evidence of presence of immunological hot spots inside antigens

text: Motivation: Processing and presentation of major histocompatibility complex class I antigens to cytotoxic T-lymphocytes is crucial for immune surveillance against intracellular bacteria, parasites, viruses and tumors. Identification of antigenic regions on pathogen proteins will play a pivotal role in designer vaccine immunotherapy. We have developed a system that not only identifies high binding T-cell antigenic epitopes, but also class I T-cell antigenic clusters termed immunological hot spots. Methods: MULTIPRED, a computational system for promiscuous prediction of HLA class I binders, uses artificial neural networks (ANN) and hidden Markov models (HMM) as predictive engines. The models were rigorously trained, tested and validated using experimentally identified HLA class I T-cell epitopes from human melanoma related proteins and human papillomavirus proteins E6 and E7. We have developed a scoring scheme for identification of immunological hot spots for HLA class I molecules, which is the sum of the highest four predictions within a window of 30 amino acids. Results: Our predictions against experimental data from four melanoma-related proteins showed that MULTIPRED ANN and HMM models could predict T-cell epitopes with high accuracy. The analysis of proteins E6 and E7 showed that ANN models appear to be more accurate for prediction of HLA-A3 hot spots and HMM models for HLA-A2 predictions. For illustration of its utility we applied MULTIPRED for prediction of promiscuous T-cell epitopes in all four SARS coronavirus structural proteins. MULTIPRED predicted HLA-A2 and HLA-A3 hot spots in each of these proteins.


Molecular mimicry has been proposed as a pathogenetic mechanism for autoimmune disease, as well as a probe useful in uncovering its etiologic agents. The hypothesis is based in part on the abundant epidemiological, clinical, and experimental evidence of an association of infectious agents with autoimmune disease and observed cross‐reactivity of immune reagents with host ‘self’ antigens and microbial determinants. For our purpose, molecular mimicry is defined as similar structures shared by molecules from dissimilar genes or by their protein products. Either the molecules' linear amino acid sequences or their conformational fits may be shared, even though their origins are as separate as, for example, a virus and a normal host–self determinant. An immune response against the determinant shared by the host and virus can evoke a tissue‐specific immune response that is presumably capable of eliciting cell and tissue destruction. The probable mechanism is generation of cytotoxic cross‐reactive effector lymphocytes or antibodies that recognize specific determinants on target cells. The induction of cross‐reactivity does not require a replicating agent, and immune‐mediated injury can occur after the immunogen has been removed—a hit‐and‐run event. Hence, the viral or microbial infection that initiates the autoimmune phenomenon may not be present by the time overt disease develops. By a complementary mechanism, the microbe can induce cellular injury and release self antigens, which generate immune responses that cross‐react with additional but genetically distinct self antigens. In both scenarios, analysis of the T cells or antibodies specifically engaged in the autoimmune response and disease provides a fingerprint for uncovering the initiating infectious agent.—Oldstone, M. B. A. Molecular mimicry and immune‐mediated diseases. FASEB J. 12, 1255–1265 (1998)


title: Experience of Chicagoland acute care hospitals in preparing for Ebola virus disease, 2014–2015

text: During the 2014–2015 Ebola Virus Disease (EVD) outbreak, hospitals in the United States selected personal protective equipment (PPE) and trained healthcare personnel (HCP) in anticipation of receiving EVD patients. To improve future preparations for high-consequence infectious diseases, it was important to understand factors that affected PPE selection and training in the context of the EVD outbreak. Semistructured interviews were conducted with HCP involved with decision-making during EVD preparations at acute care hospitals in the Chicago, IL area to gather information about the PPE selection and training process. HCP who received training were surveyed about elements of training and their perceived impact and overall experience by email invitation. A total of 28 HCP from 15 hospitals were interviewed, and 55 HCP completed the survey. Factors affecting PPE selection included: changing guidance, vendor supply, performance evaluations, and perceived risk and comfort for HCP. Cost did not affect selection. PPE acquisition challenges were mitigated by: sharing within hospital networks, reusing PPE during training, and improvising with existing PPE stock. Selected PPE ensembles were similar across sites. Training included hands-on activities with trained observers, instructional videos, and simulations/drills, which were felt to increase HCP confidence. Many felt refresher training would be helpful. Hands-on training was perceived to be effective, but there is a need to establish the appropriate frequency of refresher training frequency to maintain competence. Lacking confidence in the CDC guidance, interviewed trainers described turning to other sources of information and developing independent PPE evaluation and selection. Response to emerging and/or high consequence infectious diseases would be enhanced by transparent, risk-based guidance for PPE selection and training that addresses protection level, ease of use, ensembles, and availability.


title: A Field-Proven Yeast Two-Hybrid Protocol Used to Identify Coronavirus–Host Protein–Protein Interactions

text: Over the last 2 decades, yeast two-hybrid became an invaluable technique to decipher protein–protein interaction networks. In the field of virology, it has proven instrumental to identify virus–host interactions that are involved in viral embezzlement of cellular functions and inhibition of immune mechanisms. Here, we present a yeast two-hybrid protocol that has been used in our laboratory since 2006 to search for cellular partners of more than 300 viral proteins. Our aim was to develop a robust and straightforward pipeline, which minimizes false-positive interactions with a decent coverage of target cDNA libraries, and only requires a minimum of equipment. We also discuss reasons that motivated our technical choices and compromises that had to be made. This protocol has been used to screen most non-structural proteins of murine hepatitis virus (MHV), a member of betacoronavirus genus, against a mouse brain cDNA library. Typical results were obtained and are presented in this report.


title: Rapid responses in the emergency department of Linkou Chang Gung Memorial Hospital, Taiwan effectively prevents spread of COVID-19 among healthcare workers of emergency department during outbreak: Lessons learnt from SARS

text: Linkou Chang Gung Memorial Hospital, Taiwan has been on the forefront of efforts to manage and mitigate the Coronavirus Disease 2019 (COVID-19) pandemic since 20th January 2020. Despite having one of the largest and busiest emergency departments (EDs) in the world, we have managed to maintain a “zero-infection” rate among our ED healthcare workers through various systematic approaches. The measures implemented include establishing a clear flowchart with route planning, strict infection control policies and regulation of medical equipment, and team-based segregation in the workplace. These strategies, borne of our experience during the severe acute respiratory syndrome (SARS) outbreak, can complement a network of well-trained personnel to enable EDs around the world in successfully mounting an effective defense against new airborne illness while minimizing healthcare personnel casualties.


title: Viral respiratory infections in hospitalized and community control children in Alaska,

text: Respiratory syncytial virus (RSV) in Alaska Native children from the Yukon Kuskokwim (YK) Delta is associated with a hospitalization rate five times higher than that reported for the general US child population. The role of other viral respiratory pathogens has not been studied in this population. YK Delta children <3 years of age hospitalized with respiratory infections and same aged community control children were prospectively enrolled between October 2005 and September 2007. Polymerase chain reaction detection of viruses was performed on nasopharyngeal samples. Characteristics of hospitalized and asymptomatic control children were analyzed. From October 2005 to September 2007, 440 hospitalized and 425 control children were analyzed. Respiratory viruses were detected in 90% (395) of hospitalized children: 194 (44%) rhinovirus, 131 (30%) adenovirus, 102 (23%) RSV, 77 (18%) para influenza viruses (PIV), 66 (15%) human metapneumovirus (hMPV), 23 (5%) influenza, and 25 (6%) coronavirus. Fifty‐two percent (221) of control children had a virus detected, most commonly rhinovirus (33%), and adenovirus (16%). RSV, PIV, hMPV, and influenza were significantly more common in hospitalized cases than control children, but rhinovirus, adenovirus, and coronavirus were not. RSV and hMPV were associated with higher severity of illness. In this study, RSV remains the most important virus associated with respiratory hospitalization, although hMPV and PIV were also common. RSV and hMPV were associated with more severe illness. Rhinovirus and adenovirus were detected in two‐thirds of hospitalized children, but their frequent detection in control children made their role in respiratory hospitalization uncertain. J. Med. Virol. 82:1282–1290, 2010. © 2010 Wiley‐Liss, Inc.


title: Mit Immanuel Kant in die zweite Welle der gegenwärtigen Pandemie

text: BACKGROUND: The efficacy of the most serious limitation of free movement of the German citizens since the end of the World War II and the Oil Crisis 1973 as intended countermeasure against the first wave of the pandemic is currently expected. The planning in regard to further action for the coming weeks and months has to take place now. METHODS: With the help of the principles of the German philosopher Kant, the thinking and planning is framed. RESULTS: The modelling by the researchers of the Imperial College, London, make an oversized second wave in autumn/winter 2020 most likely, if the current countermeasures are kept in place for too long. A timely relaxation of the measures is warranted to allow a staggered attack by the virus onto the population (German: “Durchseuchung”) before the next influenza season 2020/2021 without overburdening the health care infrastructure especially the respiratory care bed capacity. The tempting perspective of a vaccine available before the second wave in autumn, should not lead to any delay in the intermittent relaxation of the countermeasures. A pre-licensure marginally tested vaccine would only be eligible for people with an anyway high risk in regard to SARS-CoV‑2. CONCLUSIONS: Further, more detailed and from each other independent models on the basis of data from Germany are urgently needed. Upon these a heterogeneous trans-hierarchical committee would need to discuss and make decisions in regard to differentiated relaxations of measures given the high remaining uncertainties.


title: Metagenomic Nanopore sequencing of influenza virus direct from clinical respiratory samples

text: Influenza is a major global public health threat as a result of its highly pathogenic variants, large zoonotic reservoir, and pandemic potential. Metagenomic viral sequencing offers the potential of a diagnostic test for influenza which also provides insights on transmission, evolution and drug resistance, and simultaneously detects other viruses. We therefore set out to apply Oxford Nanopore Technology to metagenomic sequencing of respiratory samples. We generated influenza reads down to a limit of detection of 102-103 genome copies/ml in pooled samples, observing a strong relationship between the viral titre and the proportion of influenza reads (p = 4.7×10-5). Applying our methods to clinical throat swabs, we generated influenza reads for 27/27 samples with high-to-mid viral titres (Cycle threshold (Ct) values <30) and 6/13 samples with low viral titres (Ct values 30-40). No false positive reads were generated from 10 influenza-negative samples. Thus Nanopore sequencing operated with 83% sensitivity (95% CI 67-93%) and 100% specificity (95% CI 69-100%) compared to the current diagnostic standard. Coverage of full length virus was dependent on sample composition, being negatively influenced by increased host and bacterial reads. However, at high influenza titres, we were able to reconstruct >99% complete sequence for all eight gene segments. We also detected Human Coronavirus and generated a near complete Human Metapneumovirus genome from clinical samples. While further optimisation is required to improve sensitivity, this approach shows promise for the Nanopore platform to be used in the diagnosis and genetic analysis of influenza and other respiratory viruses.


title: Situación de la infección por SARS-CoV-2 en pacientes en tratamiento renal sustitutivo Informe del Registro COVID-19 de la Sociedad Española de Nefrología (S.E.N.)

text: RESUMEN La reciente aparición de la pandemia por el coronavirus SARS-CoV-2 ha impactado de forma muy importante en la población general. Los pacientes en tratamiento renal sustitutivo (TRS) no han sido ajenos a esta situación y por sus características resultan especialmente vulnerables. Presentamos los resultados del análisis del Registro COVID-19 de la S.E.N. Material y métodos: EL Registro comenzó a funcionar el 18 de marzo de 2020. Recoge variables epidemiológicas, datos del contagio y diagnóstico, clínica acompañante, tratamientos y desenlace. Se trata de un registro “on line”. Los pacientes fueron diagnosticados de infección por SARS-Cov-2 en base a los resultados de la PCR del virus, realizada tanto en pacientes que habían manifestado clínica compatible o tenían signos sospechosos como en aquellos a los que se había hecho como cribado tras algún contacto conocido con otro enfermo. Resultados: A fecha 11 de abril el Registro disponía de datos de 868 pacientes, procedentes de todas las Comunidades Autónomas. La modalidad de TRS más representada es la hemodiálisis en centro (HDC) seguida de los pacientes trasplantados. La clínica de presentación es similar a la población general. Un porcentaje muy elevado (85%) requirió ingreso hospitalario, un 8% en unidades de cuidados intensivos. Los tratamientos más utilizados fueron hidroxicloroquina, lopinavir-ritonavir y esteroides. La mortalidad es elevada y alcanza el 23%: los pacientes fallecidos estaban con más frecuencia en HDC, desarrollaban más frecuentemente neumonía y recibían en menos ocasiones lopinavir-ritonavir y esteroides. La edad y la neumonía se asociaban de forma independiente al riesgo de fallecer. Conclusiones: La infección por SARS-CoV-2 afecta ya a un número importante de pacientes españoles en TRS, fundamentalmente aquellos que están en HDC, las tasas de hospitalización son muy elevadas y la mortalidad es elevada; la edad y el desarrollo de neumonía son factores asociados a mortalidad. SUMMARY The recent appearance of the SARS-CoV-2 coronavirus pandemic has had a significant impact on the general population. Patients on renal replacement therapy (RRT) have not been unaware of this situation and due to their characteristics they are especially vulnerable. We present the results of the analysis of the COVID-19 Registry of the Spanish Society of Nephrology. Material and methods: The Registry began operating on March 18th, 2020. It collects epidemiological variables, contagion and diagnosis data, signs and symptoms, treatments and outcomes. It is an "online" registry. Patients were diagnosed with SARS-Cov-2 infection based on the results of the PCR of the virus, carried out both in patients who had manifested compatible symptoms or had suspicious signs, as well as in those who had undergone screening after some contact. acquainted with another patient. Results: As of April 11, the Registry had data on 868 patients, from all the Autonomous Communities. The most represented form of TRS is in-center hemodialysis (ICH) followed by transplant patients. Symptoms are similar to the general population. A very high percentage (85%) required hospital admission, 8% in intensive care units. The most used treatments were hydroxychloroquine, lopinavir-ritonavir, and steroids. Mortality is high and reaches 23%; deceased patients were more frequently on ICH, developed pneumonia more frequently, and received less frequently lopinavir-ritonavir and steroids. Age and pneumonia were independently associated with the risk of death. Conclusions: SARS-CoV-2 infection already affects a significant number of Spanish patients on RRT, mainly those on ICH, hospitalization rates are very high and mortality is high; age and the development of pneumonia are factors associated with mortality.


title: Heart failure exacerbation as only presenting sign of COVID-19

text: With the increasing number of confirmed cases and accumulating clinical data, our understanding of COVID-19 continues to evolve. Here we describe the case of a patient who was initially admitted for decompensated heart failure with reduced ejection fraction (HFrEF). Only later in his course did he develop fever that led to testing for severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). Although we are aware of the common respiratory failure induced by SARS-COV-2, we have scant information that describes cardiac manifestations caused by this novel virus.


docid: otfnrarh

title: Management strategies in the treatment of neonatal and pediatric gastroenteritis

text: Acute gastroenteritis, characterized by the onset of diarrhea with or without vomiting, continues to be a major cause of morbidity and mortality in children in mostly resource-constrained nations. Although generally a mild and self-limiting disease, gastroenteritis is one of the most common causes of hospitalization and is associated with a substantial disease burden. Worldwide, up to 40% of children aged less than 5 years with diarrhea are hospitalized with rotavirus. Also, some microorganisms have been found predominantly in resource-constrained nations, including Shigella spp, Vibrio cholerae, and the protozoan infections. Prevention remains essential, and the rotavirus vaccines have demonstrated good safety and efficacy profiles in large clinical trials. Because dehydration is the major complication associated with gastroenteritis, appropriate fluid management (oral or intravenous) is an effective and safe strategy for rehydration. Continuation of breastfeeding is strongly recommended. New treatments such as antiemetics (ondansetron), some antidiarrheal agents (racecadotril), and chemotherapeutic agents are often proposed, but not yet universally recommended. Probiotics, also known as “food supplement,” seem to improve intestinal microbial balance, reducing the duration and the severity of acute infectious diarrhea. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the European Society of Paediatric Infectious Diseases guidelines make a stronger recommendation for the use of probiotics for the management of acute gastroenteritis, particularly those with documented efficacy such as Lactobacillus rhamnosus GG, Lactobacillus reuteri, and Saccharomyces boulardii. To date, the management of acute gastroenteritis has been based on the option of “doing the least”: oral rehydration-solution administration, early refeeding, no testing, no unnecessary drugs.


title: Characterize health and economic vulnerabilities of workers to control the emergence of COVID-19 in an industrial zone in Vietnam

text: The detection of first COVID-19 infected industrial worker in Vietnam on 13 April 2020 prompted timely effort to examine the health problems, behaviors, and health services access of industrial workers to inform effective and appropriate COVID-19 control measures, minimizing the risk of industrial sites becoming the next disease cluster. A search strategy involving search terms corresponding to ‘health’, ‘industrial worker’, and ‘Vietnam’ was applied to search for related papers published in English on Web of Science, PubMed, and Google Scholar. Duplicates were removed, and relevant data were extracted from the full text of remaining publications. Results showed that underlying health problems, including respiratory system problems, were common among industrial workers. Many suffered occupational diseases and/or work-related injuries. Self-treatment (without medication) was the most used method when having health problems (by 28.2% to 51% of participants), followed by visiting commune health centers (24%) and self-medication (20.3%). Findings suggest a high risk of disease spreading among industrial workers and of them suffering more severe conditions when infected. Economic vulnerabilities may be the reason for workers’ reluctance to taking time off work to attend hospital/clinic. These imply a need for involving local pharmacies, commune health centers, traditional health providers or village health collaborators as local health gatekeepers who are the first point of detecting and reporting of suspected COVID-19 cases, as well as a channel where accurate information regarding COVID-19, protective equipment, and intervention packages can be delivered. Having COVID-19 testing centers at or near industrial sites are also recommended.


title: Emerging Infectious Diseases: a Review

text: PURPOSE OF REVIEW: This review highlights some of the recent concerning emerging infectious diseases, a number of them specifically that the World Health Organization has categorized as priorities for research. RECENT FINDINGS: Emerging and reemerging infectious diseases account for significant losses in not only human life, but also financially. There are a number of contributing factors, most commonly surrounding human behavior, that lead to disease emergence. Zoonoses are the most common type of infection, specifically from viral pathogens. The most recent emerging diseases in the USA are Emergomyces canadensis, the Heartland virus, and the Bourbon virus. SUMMARY: In addition to the aforementioned pathogens, the Severe Acute Respiratory Syndrome, Middle East Respiratory Syndrome, Nipah virus, New Delhi metallo-ß-lactamase-1 Enterobacteriaceae, Rift Valley Fever virus, and Crimean-Congo Hemorrhagic Fever virus are reviewed. These pathogens are very concerning with a high risk for potential epidemic, ultimately causing both significant mortality and financial costs. Research should be focused on monitoring, prevention, and treatment of these diseases.


title: Human (non‐severe acute respiratory syndrome) coronavirus infections in hospitalised children in France

text: Aim: This study has two objectives: to study the clinical symptoms associated with the detection of the four human coronaviruses (HCoVs), 229E, OC43, NL63 and HKU1 types, in the respiratory specimens sampled from hospitalised children in France between September 2004 and May 2005; and to develop a multiplex reverse transcription polymerase chain reaction (RT‐PCR) assay allowing for the simultaneous detection of the four HCoVs. Methods: 1002 respiratory specimens were tested for HCoVs. The clinical and epidemiological data were compared on the basis of the type HCoV infection. Results: A hundred coronaviruses, 33 NL63, 2229E, 27 OC43 and 38 HKU1, were detected in 97 (9.8%) of 1002 samples negative in routine tests. The clinical and epidemiological characteristics of the study children were compared in three groups, 24 OC43‐, 27 NL63‐ and 34 HKU1‐infected children. HCoVs were identified mainly in children with upper and lower respiratory tract infections (50.5% vs. 29.4%). The significant difference in clinical presentation between the three coronavirus groups was the very low association between lower respiratory tract illness and HKU1 detection. Conclusions: HCoV detection in hospitalised children without any other respiratory virus detection was associated with upper and a significant rate of lower respiratory tract illness. The four types of HCoVs were detected, and new types NL63 and HKU1 represented a substantial portion of detection. The multiplex RT‐PCR enabled a sensitive one‐time detection and the characterisation of all of the known HCoV types with the exception severe acute respiratory syndrome‐coronavirus.


title: Acute Epstein-Barr related myocarditis: An unusual but life-threatening disease in an immunocompetent patient

text: Abstract Myocarditis is an uncommon but potentially life-threatening disease. Clinical manifestations could range from subclinical disease to sudden death, due to fulminant heart failure and/or malignant ventricular arrhythmias. The most common cause of myocarditis is viral infection, including Epstein-Barr virus (EBV). Nevertheless, EBV rarely presents with cardiac involvement in immunocompetent hosts. We report a case of acute EBV-related myocarditis in a young female, complicated with malignant ventricular arrhythmias and cardiac arrest. After 20 days of hospitalization and treatment, the patient was fit for discharge on pharmacological therapy (tapering steroids, beta-blockers, amiodarone, angiotensin-converting enzyme inhibitors, and diuretics). Clinical course is described, cardiac magnetic resonance images are shown. This case underlines how myocarditis is a disease that should not be underestimated: it could present with life-threatening complications such as malignant arrhythmias and/or severe systolic dysfunction. <Learning objective: Although Epstein-Barr virus rarely presents with cardiac involvement in immunocompetent hosts, the risk should not be underestimated, as it could present with life-threatening complications.>


title: Full-length Ebola glycoprotein accumulates in the endoplasmic reticulum

text: The Filoviridae family comprises of Ebola and Marburg viruses, which are known to cause lethal hemorrhagic fever. However, there is no effective anti-viral therapy or licensed vaccines currently available for these human pathogens. The envelope glycoprotein (GP) of Ebola virus, which mediates entry into target cells, is cytotoxic and this effect maps to a highly glycosylated mucin-like region in the surface subunit of GP (GP1). However, the mechanism underlying this cytotoxic property of GP is unknown. To gain insight into the basis of this GP-induced cytotoxicity, HEK293T cells were transiently transfected with full-length and mucin-deleted (Δmucin) Ebola GP plasmids and GP localization was examined relative to the nucleus, endoplasmic reticulum (ER), Golgi, early and late endosomes using deconvolution fluorescent microscopy. Full-length Ebola GP was observed to accumulate in the ER. In contrast, GPΔmucin was uniformly expressed throughout the cell and did not localize in the ER. The Ebola major matrix protein VP40 was also co-expressed with GP to investigate its influence on GP localization. GP and VP40 co-expression did not alter GP localization to the ER. Also, when VP40 was co-expressed with the nucleoprotein (NP), it localized to the plasma membrane while NP accumulated in distinct cytoplasmic structures lined with vimentin. These latter structures are consistent with aggresomes and may serve as assembly sites for filoviral nucleocapsids. Collectively, these data suggest that full-length GP, but not GPΔmucin, accumulates in the ER in close proximity to the nuclear membrane, which may underscore its cytotoxic property.


title: Transcriptional changes detected in fecal RNA of neonatal dairy calves undergoing a mild diarrhea are associated with inflammatory biomarkers

text: After birth, a newborn calf has to adapt to an extrauterine life characterized by several physiological changes. In particular, maturation of the gastrointestinal tract in a new environment loaded with potential pathogens, which can predispose neonatal calves to develop diarrhea, and is a major cause of morbidity and mortality during the first 4 wks of life. We aimed to investigate the inflammatory adaptations at a transcriptomic level in the gastrointestinal (GI) tract to a mild diarrhea in neonatal dairy calves using RNA isolated from fresh fecal samples. Eight newborn Jersey male calves were used from birth to 5 wks of age and housed in individual pens. After birth, calves received 1.9 L of colostrum from their respective dams. Calves had ad-libitum access to water and starter grain (22% CP) and were fed twice daily a total of 5.6 L pasteurized whole milk. Starter intake, body weight (BW), fecal score, withers height (WH), and rectal temperature (RT) were recorded throughout the experiment. Blood samples were collected weekly for metabolic and inflammatory profiling from wk 0 to wk 5. Fresh fecal samples were collected weekly and immediately flash frozen until RNA was extracted using a Trizol-based method, and subsequently, an RT-qPCR analysis was performed. Orthogonal contrasts were used to evaluate linear or quadratic effects over time. Starter intake, BW, and WH increased over time. Fecal score was greatest (2.6 ± 0.3) during wk 2. The concentrations of IL-6, ceruloplasmin, and haptoglobin had a positive quadratic effect with maximal concentrations during wk 2, which corresponded to the maximal fecal score observed during the same time. The concentration of serum amyloid A decreased over time. The mRNA expression of the proinflammatory related genes TLR4, TNFA, IL8, and IL1B had a positive quadratic effect of time. A time effect was observed for the cell membrane sodium-dependent glucose transporter SLC5A1, for the major carbohydrate facilitated transporter SLC2A2, and water transport function AQP3, where SLC5A1 and AQP3 had a negative quadratic effect over time. Our data support the use of the fecal RNA as a noninvasive tool to investigate intestinal transcriptomic profiling of dairy calves experiencing diarrhea, which would be advantageous for future research including nutritional effects and health conditions.


title: Host response-based screening to identify undiagnosed cases of COVID-19and expand testing capacity

text: The COVID-19 pandemic has created unprecedented challenges in diagnostic testing. At the beginning of the epidemic, a confluence of factors resulted in delayed deployment of PCR-based diagnostic tests, resulting in lack of testing of individuals with symptoms of the disease. Although these tests are now more widely available, it is estimated that a three- to ten-fold increase in testing capacity will be required to ensure adequate surveillance as communities reopen(1). In response to these challenges, we evaluated potential roles of host-response based screening in the diagnosis of COVID-19. Previous work from our group showed that the nasopharyngeal (NP) level of CXCL10, a protein produced as part of the host response to viral infection, is a sensitive predictor of respiratory virus infection across a wide spectrum of viruses(2). Here, we show that NP CXCL10 is elevated during SARS-CoV-2 infection and use a CXCL10-based screening strategy to identify four undiagnosed cases of COVID-19 in Connecticut in early March. In a second set of samples tested at the Yale New Haven Hospital, we show that NP CXCL10 had excellent performance as a rule-out test (NPV 0.99, 95% C.I. 0.985-0.997). Our results demonstrate how biomarker-based screening could be used to leverage existing PCR testing capacity to rapidly enable widespread testing for COVID-19.


An Old Solution for a New Problem: Antiserum against Emerging Infectious Diseases


title: Filtration Efficiencies of Nanoscale Aerosol by Cloth Mask Materials Used to Slow the Spread of SARS-CoV-2

text: [Image: see text] Filtration efficiency (FE), differential pressure (ΔP), quality factor (QF), and construction parameters were measured for 32 cloth materials (14 cotton, 1 wool, 9 synthetic, 4 synthetic blends, and 4 synthetic/cotton blends) used in cloth masks intended for protection from the SARS-CoV-2 virus (diameter 100 ± 10 nm). Seven polypropylene-based fiber filter materials were also measured including surgical masks and N95 respirators. Additional measurements were performed on both multilayered and mixed-material samples of natural, synthetic, or natural-synthetic blends to mimic cloth mask construction methods. Materials were microimaged and tested against size selected NaCl aerosol with particle mobility diameters between 50 and 825 nm. Three of the top five best performing samples were woven 100% cotton with high to moderate yarn counts, and the other two were woven synthetics of moderate yarn counts. In contrast to recently published studies, samples utilizing mixed materials did not exhibit a significant difference in the measured FE when compared to the product of the individual FE for the components. The FE and ΔP increased monotonically with the number of cloth layers for a lightweight flannel, suggesting that multilayered cloth masks may offer increased protection from nanometer-sized aerosol with a maximum FE dictated by breathability (i.e., ΔP).


title: The effect of build orientation on both flexural quasi-static and fatigue behaviours of filament deposited PA6 polymer

text: The present paper aims to study the effect of manufacturing build orientation on both flexural quasi-static and fatigue behaviours of semi-crystalline polyamide 6 obtained by Fused Filament Fabrication (FFF), by considering the porosity and surface roughness. The glass transition temperature, melting temperature, and crystallinity degree were measured complementary to understand better the process. Fatigue analysis is here fully described in visco-elastic domain of material. The results highlight that the XZ build orientation is better than the XY one and suggest that porosity plays an important role. The obtained results are also compared with conventional techniques given by the literature review.


title: Development of the full-length cDNA clones of two porcine epidemic diarrhea disease virus isolates with different virulence

text: The recently emerged highly virulent variants of porcine epidemic and diarrhea virus (PEDV) remain a huge threat to the worldwide swine industry. Here, we describe the development of a bacterial artificial chromosome (BAC) reverse genetics system for PEDV based on two recent Chinese field isolates, namely CHM2013 and BJ2011C. Phylogenetically, CHM2013 is closely related to the vaccine strain SM98 whereas the isolate BJ2011C belongs to the GIIb group, a cluster that contains many recent pandemic strains. The full-length cDNA clones of the two isolates were constructed into BAC under the control of CMV promoter. The rescued viruses rBJ2011C and rCHM2013 were found to replicate at the kinetics similar to their respective parental viruses in cell culture. When tested in the 2-day-old pig model, rBJ2011C caused severe diarrhea of piglets with extensive damages to the intestinal epithelium, leading to 100% fatality within 48 hours. In contrast, the rCHM2013-inoculated piglets all survived with only very minor tissue damage observed. Thus, we have successfully established a convenient platform for PEDV genome manipulation. This study also represents the first description of a DNA-launched reverse genetics system for the highly virulent PEDV.


title: Complement Receptor 1: Disease associations and therapeutic implications

text: Abstract Exaggerated complement activation is a key event in the pathogenesis of a range of autoimmune and inflammatory diseases. Complement Receptor 1 (CR1) has emerged as a molecule of immense interest in gaining insight to the susceptibility, pathophysiology, diagnosis, prognosis and therapy of such diseases. This review brings forth a composite view of the current understanding on the structure, functions, genetics, disease associations and therapeutic implications of CR1.


title: Antibody Tests in Detecting SARS-CoV-2 Infection: A Meta-Analysis

text: The emergence of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 made imperative the need for diagnostic tests that can identify the infection. Although Nucleic Acid Test (NAT) is considered to be the gold standard, serological tests based on antibodies could be very helpful. However, individual studies are usually inconclusive, thus, a comparison of different tests is needed. We performed a systematic review and meta-analysis in PubMed, medRxiv and bioRxiv. We used the bivariate method for meta-analysis of diagnostic tests pooling sensitivities and specificities. We evaluated IgM and IgG tests based on Enzyme-linked immunosorbent assay (ELISA), Chemiluminescence Enzyme Immunoassays (CLIA), Fluorescence Immunoassays (FIA), and the Lateral Flow Immunoassays (LFIA). We identified 38 studies containing data from 7848 individuals. Tests using the S antigen are more sensitive than N antigen-based tests. IgG tests perform better compared to IgM ones and show better sensitivity when the samples were taken longer after the onset of symptoms. Moreover, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody alone. All methods yield high specificity with some of them (ELISA and LFIA) reaching levels around 99%. ELISA- and CLIA-based methods perform better in terms of sensitivity (90%–94%) followed by LFIA and FIA with sensitivities ranging from 80% to 89%. ELISA tests could be a safer choice at this stage of the pandemic. LFIA tests are more attractive for large seroprevalence studies but show lower sensitivity, and this should be taken into account when designing and performing seroprevalence studies.


title: Influenza A (H1N1) pneumonia: HRCT findings

text: OBJECTIVE: To describe aspects found on HRCT scans of the chest in patients infected with the influenza A (H1N1) virus. METHODS: We retrospectively analyzed the HRCT scans of 71 patients (38 females and 33 males) with H1N1 infection, confirmed through laboratory tests, between July and September of 2009. The HRCT scans were interpreted by two thoracic radiologists independently, and in case of disagreement, the decisions were made by consensus. RESULTS: The most common HRCT findings were ground-glass opacities (85%), consolidation (64%), or a combination of ground-glass opacities and consolidation (58%). Other findings were airspace nodules (25%), bronchial wall thickening (25%), interlobular septal thickening (21%), crazy-paving pattern (15%), perilobular pattern (3%), and air trapping (3%). The findings were frequently bilateral (89%), with a random distribution (68%). Pleural effusion, when observed, was typically minimal. No lymphadenopathy was identified. CONCLUSIONS: The most common findings were ground-glass opacities and consolidations, or a combination of both. Involvement was commonly bilateral with no axial or craniocaudal predominance in the distribution. Although the major tomographic findings in H1N1 infection are nonspecific, it is important to recognize such findings in order to include infection with the H1N1 virus in the differential diagnosis of respiratory symptoms.


title: Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins

text: Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases.


docid: aydsqzbc

title: Response to Char's comment: Comment on Li et al.: COVID‐19 patients' clinical characteristics, discharge rate, and fatality rate of meta‐analysis

text: We have read Char's comment(1). Thanks for readers’ attention and valuable feedback on our article. Following was our response to Char's question about data overlap. Firstly, the meta‐analysis reprocessed the existing data about COVID‐19 patients in published articles, and involved no other information outside of the article. This article is protected by copyright. All rights reserved.


title: Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections

text: We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection. The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia. A random library was generated from nucleic acids extracted from the nasopharyngeal aspirate and analyzed by high throughput DNA sequencing. Multiple DNA fragments were cloned that possessed limited homology to known polyomaviruses. We subsequently sequenced the entire virus genome of 5,229 bp, henceforth referred to as WU virus, and found it to have genomic features characteristic of the family Polyomaviridae. The genome was predicted to encode small T antigen, large T antigen, and three capsid proteins: VP1, VP2, and VP3. Phylogenetic analysis clearly revealed that the WU virus was divergent from all known polyomaviruses. Screening of 2,135 patients with acute respiratory tract infections in Brisbane, Queensland, Australia, and St. Louis, Missouri, United States, using WU virus–specific PCR primers resulted in the detection of 43 additional specimens that contained WU virus. The presence of multiple instances of the virus in two continents suggests that this virus is geographically widespread in the human population and raises the possibility that the WU virus may be a human pathogen.


title: Public Awareness of Nature and the Environment During the COVID-19 Crisis

text: As our behavioral patterns change due to the COVID-19 crisis, our impact on nature and the environment changes too. Pollution levels are showing significant reductions. People are more aware of the importance of access to local green and blue spaces. By analyzing online search behavior in twenty European countries, we investigate how public awareness of nature and the environment has evolved during the COVID-19 crisis. We find that the crisis goes hand in hand with a positive shift in public awareness of nature-related topics, but that awareness of environmental topics remains unaffected. While the decreasing pollution levels and media attention may reduce the overall sense of urgency to tackle pollution problems, the increased experience with local natural resources may strengthen public support for a recovery program that puts the transition towards a more sustainable economic system centrally.


title: MERS transmission and risk factors: a systematic review

text: BACKGROUND: Since Middle East respiratory syndrome (MERS) infection was first reported in 2012, many studies have analysed its transmissibility and severity. However, the methodology and results of these studies have varied, and there has been no systematic review of MERS. This study reviews the characteristics and associated risk factors of MERS. METHOD: We searched international (PubMed, ScienceDirect, Cochrane) and Korean databases (DBpia, KISS) for English- or Korean-language articles using the terms “MERS” and “Middle East respiratory syndrome”. Only human studies with > 20 participants were analysed to exclude studies with low representation. Epidemiologic studies with information on transmissibility and severity of MERS as well as studies containing MERS risk factors were included. RESULT: A total of 59 studies were included. Most studies from Saudi Arabia reported higher mortality (22–69.2%) than those from South Korea (20.4%). While the R(0) value in Saudi Arabia was < 1 in all but one study, in South Korea, the R(0) value was 2.5–8.09 in the early stage and decreased to < 1 in the later stage. The incubation period was 4.5–5.2 days in Saudi Arabia and 6–7.8 days in South Korea. Duration from onset was 4–10 days to confirmation, 2.9–5.3 days to hospitalization, 11–17 days to death, and 14–20 days to discharge. Older age and concomitant disease were the most common factors related to MERS infection, severity, and mortality. CONCLUSION: The transmissibility and severity of MERS differed by outbreak region and patient characteristics. Further studies assessing the risk of MERS should consider these factors.


title: A Syndemic of COVID-19 and methanol poisoning in Iran: Time for Iran to consider alcohol use as a public health challenge?

text: • While all activities surrounding alcohol is banned in Iran, mass methanol poisoning outbreaks (such as the one amid the COVID-19 epidemic with more than 5,000 poisonings and more than 700 deaths within only two months) have become a major public health concern. • Iran’s national policymakers should consider developing and implementing public health models to better address alcohol use problems.


docid: gvtsneoy

title: COVID-19 Infection Fatality Rate Associated with Incidence—A Population-Level Analysis of 19 Spanish Autonomous Communities

text: Previous studies have found large variations in the COVID-19 infection fatality rate (IFR). This study hypothesized that IFR would be influenced by COVID-19 epidemic intensity. We tested the association between epidemic intensity and IFR using serological results from a recent large SARS-CoV-2 serosurvey (N = 60,983) in 19 Spanish regions. The infection fatality rate for Spain as a whole was 1.15% and varied between 0.13% and 3.25% in the regions (median 1.07%, IQR 0.69–1.32%). The IFR by region was positively associated with SARS-CoV-2 seroprevalence (rho = 0.54; p = 0.0162), cases/100,000 (rho = 0.75; p = 0.002), hospitalizations/100,000 (rho = 0.78; p = 0.0001), mortality/100,000 (rho = 0.77; p = 0.0001) and case fatality rate (rho = 0.49; p = 0.0327). These results suggest that the SARS-CoV-2 IFR is not fixed. The Spanish regions with more rapid and extensive spread of SARS-CoV-2 had higher IFRs. These findings are compatible with the theory that slowing the spread of COVID-19 down reduces the IFR and case fatality rate via preventing hospitals from being overrun, and thus allowing better and lifesaving care.


title: Coronavirus entry and release in polarized epithelial cells: a review

text: Most coronaviruses cause respiratory or intestinal infections in their animal or human host. Hence, their interaction with polarized epithelial cells plays a critical role in the onset and outcome of infection. In this paper, we review the knowledge regarding the entry and release of coronaviruses, with particular emphasis on the severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses. As these viruses approach the epithelial surfaces from the apical side, it is not surprising that coronavirus cell receptors are exposed primarily on the apical domain of polarized epithelial cells. With respect to release, all possibilities appear to occur. Thus, most coronaviruses exit through the apical surface, several through the basolateral one, although the Middle East respiratory syndrome coronavirus appears to use both sides. These observations help us understand the local or systematic spread of the infection within its host as well as the spread of the virus within the host population. Copyright © 2014 John Wiley & Sons, Ltd.


title: Immobilization of Ulp1 protease on NHS-activated Sepharose: a useful tool for cleavage of the SUMO tag of recombinant proteins

text: OBJECTIVE: To fabricate an active and stable enzyme through covalent immobilization, a Ubl-specific protease (Ulp1) was used to cleave small ubiquitin-like modifier (SUMO) fusion proteins. RESULTS: We immobilized Ulp1 on N-hydroxysuccinimide (NHS)-activated Sepharose with a coupling efficiency of 1.7 mg/ml. The immobilized Ulp1 maintains 95% substrate-cleavage ability and significantly enhances pH and thermal stability, especially can withstand pH of 10.5. Besides resistance against some small molecules, the immobilized Ulp1 can tolerate 15% (v/v) DMSO and 20% (v/v) ethanol. It can be reused for more than 15 batch reactions with 90% activity retention. This provides a fast purification system to quickly obtain cleaved recombinant proteins with 95% purity from cell lysates with the application of immobilized Ulp1. CONCLUSIONS: Ulp1 used in immobilization form is a potentially useful tool for cleavage of SUMO-tagged proteins and may reduce time and cost of protein purification. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10529-017-2330-5) contains supplementary material, which is available to authorized users.


title: Estimating the reproductive number and the outbreak size of COVID-19 in Korea

text: OBJECTIVES: Since the first novel coronavirus disease 2019 (COVID-19) patient in Korea was diagnosed on January 20, 2020, 30 patients were diagnosed until February 17, 2020. However, 5,298 additional patients were confirmed until March 4, 2020. Therefore, our objective was to estimate the reproduction number (R) and evaluate the effectiveness of preventive measures. METHODS: A COVID-19 transmission model (SEIHR) was established to suit the Korean outbreak. The number of daily confirmed cases in Daegu and North Gyeongsang Province (NGP), the main area of outbreak, was used. The first patient’ symptom onset date in the Daegu/NGP outbreak was assumed as January 22, 2020. The R according to the start date of the effect of preventive measures was estimated. RESULTS: The estimated R in Hubei Province, China, was 4.0281, whereas the estimated initial R in Korea was 0.555, but later in Daegu/NGP, the value was between 3.472 and 3.543. When the transmission period decreases from 4-day to 2-day, the outbreak ends early, but the peak of the epidemic increases, and the total number of patients does not change greatly. It was found that, if transmission rate decreases, the outbreak ends early, and the size of the peak and the total number of patients also decreases. CONCLUSIONS: To end the COVID-19 epidemic, efforts to reduce the spread of the virus, such as social distancing and wearing masks, are absolutely crucial with the participation of the public, along with the policy of reducing the transmission period by finding and isolating patients as quickly as possible through the efforts of the quarantine authorities.


title: The Effectiveness and Mechanism of Toona sinensis Extract Inhibit Attachment of Pandemic Influenza A (H1N1) Virus

text: TSL-1 is a fraction of the aqueous extract from the tender leaf of Toona sinensis Roem, a nutritious vegetable. The pandemic influenza A (H1N1) virus is a recently described, rapidly contagious respiratory pathogen which can cause acute respiratory distress syndrome (ARDS) and poses a major public health threat. In this study, we found that TSL-1 inhibited viral yields on MDCK plaque formation by pandemic influenza A (H1N1) virus on infected A549 cells with high selectivity index. Meanwhile, TSL-1 also suppressed viral genome loads in infected A549 cells, quantified by qRT-PCR. This study further demonstrated that TSL-1 inhibited pandemic influenza A (H1N1) virus activity through preventing attachment of A549 cells but not penetration. TSL-1 inhibited viral attachment through significant downregulation of adhesion molecules and chemokines (VCAM-1, ICAM-1, E-selectin, IL-8, and fractalkine) compared to Amantadine. Our results suggest that TSL-1 may be used as an alternative treatment and prophylaxis against pandemic influenza A (H1N1) virus.


title: Neurological disease and encephalitis in cats experimentally infected with Borna disease virus

text: Barrier-bred cats were inoculated intracerebrally with either the rabbit-adapted Borna disease virus (BDV) strain V or a newly isolated feline BDV, obtained from a cat with natural staggering disease (SD). Three out of eight inoculated cats developed neurological signs and non-suppurative encephalitis; all three recovered from the acute stage of disease. Sero-conversion and the development of neutralizing antibodies occurred in all of the virus-inoculated cats. In addition, cats inoculated with feline BDV showed an early peripheral T cell response not present in cats inoculated with BDV strain V, suggesting that the feline virus exerted a more vigorous effect on the immune system. Using immunohistochemistry and a reverse transcriptase-polymerase chain reaction assay, BDV-specific antigen and nucleic acid could be demonstrated in brain samples from each cat with encephalitis, showing that incomplete viral clearance was probably responsible for the maintenance of inflammation. The successful induction of neurological signs and encephalitis in one cat infected with feline BDV, together with the detection of BDV-specific antigen and nucleic acid in the brain, provides strong evidence for the notion that BDV is the etiological agent behind feline SD.


docid: cvwpskwk

title: Comparing Chinese children and adults with RT-PCR positive COVID-19: A systematic review

text: BACKGROUND: The various clinical manifestations of COVID-19 with RT-PCR positive patients have been reported. However, the differences in the clinical presentation between children and adults were unclear. Thus, we aimed to investigate the differences in the clinical manifestations and imaging characteristics between Chinese children and adults with COVID-19 by systematically analyzing the data derived from some latest literatures. METHODS: An extensive search of COVID-19 papers was conducted in PubMed and Chinese medical journal network, and relevant articles were selected based on some standard requirements. The included papers were analyzed for differences in clinical manifestation between children and adults with COVID-19 after the quality evaluation with the QUADAS-2 tool. The differences in the clinical features and CT findings were analyzed using a Pearson χ(2) test or Fisher's exact test. Patients who underwent CT examination were divided into the initial examination (0-4days) and follow-up examination groups (5-14 days). RESULTS: A total of 345patients (70 children and 275 adults) with RT- PCR (+) were included in our study (5 papers for children and 5 papers for adult groups). Significant differences between children and adults were found in exposure history ( p < 0.001, χ(2) = 166.890), fever ( p=,0.016, χ(2) = 5.757), white cell count ( p < 0.001, χ(2) = 14.043), and CT features in the initial ( p < 0.001, χ(2) = 60.653) and follow-up stages ( p < 0.001, χ(2) = 52.924); and the involved lung in the follow-up stage ( p＜0.001, χ(2) = 16.776). CONCLUSIONS: Some differences have been presented between children and adults with RT-PCR positive COVID-19, which are helpful in the management and protection of children with COVID-19.


title: Challenges and recommendations for mental health providers during the COVID-19 pandemic: the experience of China’s First University-based mental health team

text: Coronavirus Disease is impacting the entire world. As the first country that has needed to confront this disease, China has responded with unprecedented and hugely successful public health initiatives. Almost simultaneous with the awareness of the potential for widespread loss of life, the first Chinese university recognizing the likely psychological impacts of COVID-19, assembled the first university-based professional team to offer pandemic-related mental health services to the Chinese public. This paper describes the work that we provided and the challenges encountered. The challenges are described in four contexts: the organizational/systemic level, the technical perspective, the therapeutic process, and the ethical aspects. We also provide recommendations on what we can do in the short term, and future improvements that can be made.


title: Comparison of visual and electronic devices for individual identification of dromedary camels under different farming conditions

text: The camel industry uses traditional (i.e., iron brands and ear tags) and modern (i.e., microchips) identification (ID) systems without having performance results of reference. Previously iron-branded (n = 45; 1 yr) and microchipped (n = 59; 7 yr) camels showed problems of healing (8.6% of brands) and reading (only 42.9% of brands and 69.5% of microchips were readable), which made their use inadvisable. With the aim of proposing suitable ID systems for different farming conditions, an on-field study was performed using a total of 528 dromedaries at 4 different locations (Egypt, n = 83; Spain, n = 304; Saudi Arabia, n = 90; and Tunisia, n = 51). The ID devices tested were visual (button ear tags, 28.5 mm diameter, n = 178; double flag ear tags, 50 by 15 mm, n = 83; both made of polyurethane) and electronic (ear tags, n = 90, and rumen boluses, n = 555). Electronic ear tags were polyurethane-loop type (75 by 9 mm) with a container in which a 22-mm transponder of full-duplex technology was lodged. Electronic boluses of 7 types, varying in dimensions (50 to 76 mm length, 11 to 21 mm width, and 12.7 to 82.1 g weight) and specific gravity (SG; 1.49 to 3.86) and each of them containing a 31-mm transponder of half-duplex technology, were all administered to the dromedaries at the beginning of the study. When a low-SG bolus was lost, a high-SG bolus was readministered. Readability rates of each ID system were evaluated during 1 to 3 yr, according to device and location, and yearly values were estimated for comparison. On a yearly basis, visual ear tag readability was not fully satisfactory; it was lower for rectangular ear tags (66.3%) than for button ear tags (80.9%). Yearly readability of electronic ear tags was 93.7%. Bolus readability dramatically varied according to their SG; the SG < 2.0 boluses were fully lost after 8 mo. In contrast, the SG > 3.0 boluses were efficiently retained (99.6 to 100%) at all locations. In conclusion, according to the expected long lifespan of camels, low ID performances were observed for iron brands, injectable microchips, and ear tags (visual and electronic), making their use inadvisable as unique ID systems in camels. The high readability of dense electronic boluses recommended their use as a permanent ID device of reference in camels.


title: The ACE2‐deficient mouse: A model for a cytokine storm‐driven inflammation

text: Angiotensin converting enzyme 2 (ACE2) plays an important role in inflammation, which is attributable at least, in part, to the conversion of the pro‐inflammatory angiotensin (Ang) II peptide into angiotensin 1‐7 (Ang 1‐7), a peptide which opposes the actions of AngII. ACE2 and AngII are present in many tissues but information on the cornea is lacking. We observed that mice deficient in the Ace2 gene (Ace2(−/−)), developed a cloudy cornea phenotype as they aged. Haze occupied the central cornea, accompanied by corneal edema and neovascularization. In severe cases with marked chronic inflammation, a cell‐fate switch from a transparent corneal epithelium to a keratinized, stratified squamous, psoriasiform‐like epidermis was observed. The stroma contained a large number of CD11c, CD68, and CD3 positive cells. Corneal epithelial debridement experiments in young ACE2‐deficient mice showed normal appearing corneas, devoid of haze. We hypothesized, however, that these mice are “primed” for a corneal inflammatory response, which once initiated, would persist. In vitro studies reveal that interleukins (IL‐1a, IL‐1b), chemokines (CCL2, CXCL8), and TNF‐α, are all significantly elevated, resulting in a cytokine storm‐like phenotype. This phenotype could be partially rescued by treatment with the AngII type 1 receptor (AT1R) antagonist, losartan, suggesting that the observed effect was mediated by AngII acting on its main receptor. Since the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) utilizes human ACE2 as the receptor for entry with subsequent downregulation of ACE2, corneal inflammation in Ace2(−/−) mice may have a similar mechanism with that in COVID‐19 patients. Thus the Ace2(−/−) cornea, because of easy accessibility, may provide an attractive model to explore the molecular mechanisms, immunological changes, and treatment modalities in patients with COVID‐19.


title: Diagnostic Reverse-Transcription Polymerase Chain Reaction Kit for Filoviruses Based on the Strain Collections of all European Biosafety Level 4 Laboratories

text: A network of European biosafety level 4 laboratories has designed the first industry-standard molecular assay for all filoviruses species, based on the strain collections of all participants. It uses 5 optimized L gene primers and 3 probes, as well as an internal control with a separate detection probe. Detection limits (probit analysis, 95% detection chance) were as follows: Zaire ebolavirus, 487 copies/mL of plasma; Sudan ebolavirus Maleo, 586 copies/mL; Sudan ebolavirus Gulu, 1128 copies/mL; Cote d'Ivoire ebolavirus, 537 copies/mL; Reston ebolavirus, 4546 copies/mL; Lake Victoria marburgvirus Musoke, 860 copies/mL; and Lake Victoria marburgvirus Ravn, 1551 copies/mL. The assay facilitates reliable detection or exclusion screening of filovirus infections.


title: Reflections arising from the COVID-19 pandemic

text: Abstract While we were drafting the recommendations for the joint contingency plan between the Spanish Society of Intensive Care and Coronary Unit Nursing (SEEIUC) and the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC), predictions were overtaken by events with regard to the magnitude of the COVID-19 pandemic. Members informed us of the lack of personal protection equipment (PPE), the rapid provision of improvised ICUs in various hospital areas and the recruitment of nurses to cover shifts. The failure to recognise the specialty of critical care nursing, included in the macro-specialty of medical–surgical nursing and not yet developed, has highlighted the urgent need to learn from our mistakes: specialisation, increase the number of nurses in teams and protect the public health system.


title: Estimating and modelling the transmissibility of Middle East Respiratory Syndrome CoronaVirus during the 2015 outbreak in the Republic of Korea

text: BACKGROUND: Emerging respiratory infections represent a significant public health threat. Because of their novelty, there are limited measures available to control their early spread. Learning from past outbreaks is important for future preparation. The Middle Eastern Respiratory Syndrome CoronaVirus (MERS‐CoV ) 2015 outbreak in the Republic of Korea (ROK) provides one such opportunity. OBJECTIVES: We demonstrated through quantitative methodologies how to estimate MERS‐CoV's transmissibility and identified the effective countermeasures that stopped its spread. METHODS: Using the outbreak data, statistical methods were employed to estimate the basic reproductive number R (0), the average number of secondary cases produced by a typical primary case during its entire infectious period in a fully susceptible population. A transmission dynamics model was also proposed to estimate R (0) and to identify the most effective countermeasures. The consistency between results will provide cross‐validation of the approaches. RESULTS: R (0) ranged from 2.5 with 95% confidence interval (CI): [1.7, 3.1] (using the sequential Bayesian method) to 7.2 with 95% CI: [5.3, 9.4] (using the Nowcasting method). Estimates from transmission model were higher but overlapped with these. Personal protection and rapid confirmation of cases were identified as the most important countermeasures. CONCLUSIONS: Our estimates were in agreement with others from the ROK outbreak, albeit significantly higher than estimates based on other small outbreaks and sporadic cases of MERS‐CoV. The large‐scale outbreak in the ROK was jointly due to the high transmissibility in the healthcare‐associated setting and the Korean culture‐associated contact behaviour. Limiting such behaviour by rapidly identifying and isolating cases and avoiding high‐risk contacts effectively stopped further transmission.


title: A novel European H5N8 influenza A virus has increased virulence in ducks but low zoonotic potential

text: We investigated in a unique setup of animal models and a human lung explant culture biological properties, including zoonotic potential, of a representative 2016 highly pathogenic avian influenza virus (HPAIV) H5N8, clade 2.3.4.4 group B (H5N8B), that spread rapidly in a huge and ongoing outbreak series in Europe and caused high mortality in waterfowl and domestic birds. HPAIV H5N8B showed increased virulence with rapid onset of severe disease and mortality in Pekin ducks due to pronounced neuro- and hepatotropism. Cross-species infection was evaluated in mice, ferrets, and in a human lung explant culture model. While the H5N8B isolate was highly virulent for Balb/c mice, virulence and transmissibility were grossly reduced in ferrets, which was mirrored by marginal replication in human lung cultures infected ex vivo. Our data indicate that the 2016 HPAIV H5N8B is avian-adapted with augmented virulence for waterfowl, but has low zoonotic potential. The here tested combination of animal studies with the inoculation of human explants provides a promising future workflow to evaluate zoonotic potential, mammalian replication competence and avian virulence of HPAIV.


title: Pulmonary Aspergillosis: An Evolving Challenge for Diagnosis and Treatment

text: Aspergillus is a mold that may lead to different clinical pictures, from allergic to invasive disease, depending on the patient’s immune status and structural lung diseases. Chronic pulmonary aspergillosis is an infection with a locally invasive presentation, reported especially in patients with chronic pulmonary disease, while aspergilloma is typically found in patients with previously formed cavities in the lungs. Allergic bronchopulmonary aspergillosis is due to a hypersensitivity reaction to Aspergillus antigens and is more frequently described in patients with moderate-severe asthma or cystic fibrosis. Invasive pulmonary aspergillosis mainly occurs in patients with neutropenia or immunodeficiency, but has increasingly been recognized as an emerging disease of non-neutropenic patients. The significance of this infection has dramatically increased in recent years, considering the high number of patients with an impaired immune state associated with the management and treatment of neoplasm, solid or hematological transplantation, autoimmune diseases, and inflammatory conditions. Moreover, prolonged steroid treatment is recognized as an important risk factor, especially for invasive disease. In this setting, critically ill patients admitted to intensive care units and/or with chronic obstructive pulmonary disease could be at higher risk for invasive infection. This review provides an update on the clinical features and risk factors of pulmonary aspergillosis. Current approaches for the diagnosis, management, and treatment of these different forms of pulmonary aspergillosis are discussed.


Global Health Security in an Era of Global Health Threats


title: Identification of an immunorelevant ORF2 epitope from porcine circovirus type 2 as a serological marker for experimental and natural infection

text: Post-weaning multisystemic wasting syndrome (PMWS) is a recently identified disease of pigs linked to the emergence of a new porcine circovirus (PCV2). We report here the characterization of immunorelevant linear B-cell epitopes of the Open Reading Frame 2-encoded protein (Orf2) from PCV2 by an enzyme-linked immunosorbent assay (ELISA) using experimental antisera collected from pigs inoculated with a PCV2 isolate. Two epitopes spanning residues 69 to 83 and 117 to 131 were specific to PCV2. Antibodies to the 117 to 131 epitope (B-133) were detected in 22% and 100% of specific pathogen-free (SPF) pig sera 6 and 11 weeks post inoculation, respectively. Cross-sectional studies performed with field sera collected from PMWS-affected herds showed B-133 antibodies in 5% of 8 to 10 week-old pigs, 38% of 13–14 week-old pigs, 62% of 16 to 19 week-old pigs, 56% of 20 to 25 week-old pigs and 45% of 26 to 31 week-old pigs. All these data suggest that epitope B-133 is a serological marker of PCV2 infection that could be used for the detection of PCV2 antibody response.


title: Case report of a patient with suspected COVID-19 with depression and fever in an epidemic stress environment

text: During the COVID-19 pandemic, the number of suspected cases, confirmed cases and those who passed away from the virus has been reported in major media and the internet, and has caused a high degree of tension. In addition, people’s outdoor activities have been limited, making it more difficult to find outlets for releasing stress. Under this situation, some people began to experience emotions of anxiety and depression. This article reports a case of depression with fever caused by the stress tension of the pandemic. The patient was highly suspected to have contracted COVID-19. The reported patient, who had a history of depression and had been to Wuhan to attend an exam, showed obvious pre-exam anxiety under the epidemic situation, which gradually increased the patient's pressure and then caused some adverse symptoms, such as insomnia, anxiety, sweating and a reoccurrent fever. Local community authorities paid close attention to him and later sent him to a general hospital in Jingmen for quarantine and treatment, as he was suspected of having COVID-19. After being hospitalised for half a month, he was ruled out from having ‘COVID-19’ and was cured of depression and discharged from the hospital. From this case, we can realise that, under the situation of the epidemic, people are easily prone to insomnia, anxiety and even depression. As clinicians in general hospitals, especially when encountering large emergencies, we must carefully inquire about the patient’s medical history while strengthening our understanding of psychiatric knowledge to improve the recognition rate for depression.