title: Searching for the cause of Kawasaki disease — cytoplasmic inclusion bodies provide new insight

text: Kawasaki disease (KD) has emerged as the most common cause of acquired heart disease in children in the developed world. The cause of KD remains unknown, although an as-yet unidentified infectious agent might be responsible. By determining the causative agent, we can improve diagnosis, therapy and prevention of KD. Recently, identification of an antigen-driven IgA response that was directed at cytoplasmic inclusion bodies in KD tissues has provided new insights that could unlock the mysteries of KD.


title: The Fear of COVID-19 Scale: Development and Initial Validation

text: BACKGROUND: The emergence of the COVID-19 and its consequences has led to fears, worries, and anxiety among individuals worldwide. The present study developed the Fear of COVID-19 Scale (FCV-19S) to complement the clinical efforts in preventing the spread and treating of COVID-19 cases. METHODS: The sample comprised 717 Iranian participants. The items of the FCV-19S were constructed based on extensive review of existing scales on fears, expert evaluations, and participant interviews. Several psychometric tests were conducted to ascertain its reliability and validity properties. RESULTS: After panel review and corrected item-total correlation testing, seven items with acceptable corrected item-total correlation (0.47 to 0.56) were retained and further confirmed by significant and strong factor loadings (0.66 to 0.74). Also, other properties evaluated using both classical test theory and Rasch model were satisfactory on the seven-item scale. More specifically, reliability values such as internal consistency (α = .82) and test–retest reliability (ICC = .72) were acceptable. Concurrent validity was supported by the Hospital Anxiety and Depression Scale (with depression, r = 0.425 and anxiety, r = 0.511) and the Perceived Vulnerability to Disease Scale (with perceived infectability, r = 0.483 and germ aversion, r = 0.459). CONCLUSION: The Fear of COVID-19 Scale, a seven-item scale, has robust psychometric properties. It is reliable and valid in assessing fear of COVID-19 among the general population and will also be useful in allaying COVID-19 fears among individuals.


Rationale For The Routine Application of Lung Ultrasound In The Management Of COVID-19 Patients In Middle To Low-Income Countries.


title: Association of particulate matter pollution and case fatality rate of COVID-19 in 49 Chinese cities

text: Abstract The COVID-19 epidemic, caused by the SARS-CoV-2 virus, has resulted in 3352 deaths in China as of April 12, 2020. This study aimed to investigate the associations between particulate matter (PM) concentrations and the case fatality rate (CFR) of COVID-19 in 49 Chinese cities, including the epicenter of Wuhan. We used the Global Moran's I to analyze spatial distribution and autocorrelation of CFRs, and then we used multivariate linear regression to analyze the associations between PM2.5 and PM10 concentrations and COVID-19 CFR. We found positive associations between PM pollution and COVID-19 CFR in cities both inside and outside Hubei Province. For every 10 μg/m3 increase in PM2.5 and PM10 concentrations, the COVID-19 CFR increased by 0.24% (0.01%–0.48%) and 0.26% (0.00%–0.51%), respectively. PM pollution distribution and its association with COVID-19 CFR suggests that exposure to such may affect COVID-19 prognosis.


title: Does Porcine Reproductive and Respiratory Syndrome Virus Potentiate Classical Swine Fever Virus Infection in Weaner Pigs?

text: Fifteen 6‐week‐old crossbred weaners weighing about 12 kg each were randomly divided into three groups of five animals each. One group of pigs was inoculated first with porcine reproductive and respiratory syndrome (PRRS) virus and then 3 days later with CSF virus. The second group received classical swine fever (CSF) virus, while the third group was inoculated with PRRS virus only. The aim of the experiment was to determine whether a primary PRRS virus infection influences the clinical outcome of experimentally induced CSF in young pigs. The PRRS virus infected weaners developed mild respiratory symptoms and recovered completely. All five weaners which were inoculated with CSF virus only showed severe clinical signs typical of the acute form of CSF. One pig had to be killed 15 days post‐inoculation (p.i.); the remaining four died between the 18th and 22nd day p.i. The clinical course of the animals inoculated with both viruses was slightly different from that of the pigs that received only CSF virus. Four out of five pigs from the PRRS/CSF group became febrile and viraemic earlier than the animals which received CSF virus only. These pigs had to be killed 15–17 days post CSF virus inoculation. One animal in this group survived the acute phase of CSF and recovered completely. It was concluded that the observed divergences of the clinical courses would not have been noticed under field conditions. Therefore these findings cast doubt on the relevance of PRRS virus infection potentiating significantly the clinical outcome of CSF in young pigs.


title: Simple Economical Solution for Personal Protection Equipment (Face Mask/Shield) for Health Care Staff During COVID 19

text: Coronavirus disease 2019 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. It has taken a toll of lots of lives since its outbreak. Infection prevention at present is an appropriate control measure in addition to other measure like hand hygiene and personal protective equipment (PPE). In our country with a large population, supplying PPE to all the health care workers of all hospitals definitely is an economic burden. Hence we have come up with an economic and simple solution for face mask. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12070-020-01863-4) contains supplementary material, which is available to authorized users.


title: Reverse genetic manipulation of the overlapping coding regions for structural proteins of the type II porcine reproductive and respiratory syndrome virus

text: Abstract The overlapping genomic regions coding for structural proteins of porcine reproductive and respiratory syndrome virus (PRRSV) poses problems for molecular dissection of the virus replication process. We constructed five mutant full-length cDNA clones with the overlapping regions unwound and 1 to 3 restriction sites inserted between two adjacent ORFs (ORF1/2, ORF4/5, ORF5/6, ORF 6/7 and ORF7/3′ UTR), which generated the recombinant viruses. Our findings demonstrated that 1) the overlapping structural protein ORFs can be physically separated, and is dispensable for virus viability; 2) such ORF separations did not interrupt the subgenomic RNA synthesis; 3) the plaque morphology, growth kinetics, and antigenicity of these mutant viruses were virtually indistinguishable from those of the parental virus in cultured cells; and 4) these mutant viruses remained genetic stable in vitro. This study lays a foundation for further molecular dissection of PRRSV replication process, and development of genetically tagged vaccines against PRRS.


title: Personal journey and perspective from psychiatric nurse and medical student to intern doctor during COVID-19

text: COVID-19 or ‘Coronavirus’ has become a global pandemic since its initial report in Wuhan, China, on November 17, 2020. It is highly infectious and poses significant health risks for those in vulnerable populations. This article aims to provide perspective into an Irish experience, through the eyes of a practicing psychiatric nurse, who has recently graduated medical school and intends to work as an intern doctor.


title: Prevention of nosocomial transmission of swine-origin pandemic influenza virus A/H1N1 by infection control bundle

text: Summary After the outbreak of severe acute respiratory syndrome in Hong Kong, the importance of preventing nosocomial transmission of respiratory viruses has become a top priority in infection control. During the containment and early mitigation phases of the swine-origin influenza virus (S-OIV) A H1N1 pandemic, an infection control bundle consisting of multiple coherent measures was organised by our infection control team to minimise nosocomial transmission. This included repeated open staff forum achieving high attendance; early recognition of index cases among inpatients by liberal testing; early relief of sick staff from work; directly observed hand hygiene practice during outbreaks; and monitoring of compliance with infection control practice. During the first 100 days (from 1 May to 8 August 2009) when the first 100 laboratory-confirmed patients with S-OIV and 12 infected healthcare workers (HCWs) were identified, a total of 836 asymptomatic exposed persons (184 patients and 652 HCWs) were required to undergo a seven-day medical surveillance. The infection control nurses monitored them for the onset of symptoms. Four (0.48%) exposed persons (one house officer, two non-clinical staff, and one patient) were virologically confirmed with S-OIV. Not wearing a surgical mask either by the exposed persons during contact with the index cases (4/4 vs 264/832, P =0.010) or vice versa (4/4 vs 300/832, P =0.017, Fisher's exact test) were found to be significant risk factors for nosocomial acquisition of S-OIV.


title: A Meta-Analysis of Multiple Whole Blood Gene Expression Data Unveils a Diagnostic Host-Response Transcript Signature for Respiratory Syncytial Virus

text: Respiratory syncytial virus (RSV) is one of the major causes of acute lower respiratory tract infection worldwide. The absence of a commercial vaccine and the limited success of current therapeutic strategies against RSV make further research necessary. We used a multi-cohort analysis approach to investigate host transcriptomic biomarkers and shed further light on the molecular mechanism underlying RSV-host interactions. We meta-analyzed seven transcriptome microarray studies from the public Gene Expression Omnibus (GEO) repository containing a total of 922 samples, including RSV, healthy controls, coronaviruses, enteroviruses, influenzas, rhinoviruses, and coinfections, from both adult and pediatric patients. We identified > 1500 genes differentially expressed when comparing the transcriptomes of RSV-infected patients against healthy controls. Functional enrichment analysis showed several pathways significantly altered, including immunologic response mediated by RSV infection, pattern recognition receptors, cell cycle, and olfactory signaling. In addition, we identified a minimal 17-transcript host signature specific for RSV infection by comparing transcriptomic profiles against other respiratory viruses. These multi-genic signatures might help to investigate future drug targets against RSV infection.


Concern coronavirus may trigger post-viral fatigue syndromes


title: Burden of disease due to human coronavirus NL63 infections and periodicity of infection

text: Abstract Background The disease burden caused by recently identified respiratory viruses like HCoV-NL63 is unknown. Objectives We determined the burden of disease due to HCoV-NL63 infections using the population-based PRI.DE cohort of children under the age of 3 with lower respiratory tract infections (LRTIs). Study design In total 1756 respiratory samples, from hospitalized children or children who visited the outpatient clinic, were tested for HCoV-NL63. Sampling covered a period of 2 years and the frequency of infection in different years was compared to other Western European studies that tested for this virus in 2 or more consecutive years. Results Sixty-nine samples were HCoV-NL63 positive, 35 were with high loads, and of these 25 were single HCoV-NL63 infections. Based on the number of children with high HCoV-NL63 infection and no additional infection, the overall annual incidence in outpatients was 7 per 1000 children per year (95% confidence interval (CI) 3–13 per 1000 children per year), which can be extrapolated to an absolute number of 16,929 visits to the physician due to an HCoV-NL63 infection in Germany per year. The estimated hospitalization rate is 22 per 100,000 children (95% CI: 7–49 per 100,000 children per year). This number reflects 522 HCoV-NL63 children in Germany per year. A large year-to-year difference in HCoV-NL63 infection frequency was observed. Combining these data with those of other studies in Western Europe revealed that HCoV-NL63 infections follow a 2-year inter-epidemic period with peaks of infection in the winters of 2000/2001, 2002/2003 and 2004/2005 (p <0.0001). Conclusions HCoV-NL63 infection in children below 3 years of age often requires a visit to the physician in an outpatient clinic, especially during peak-years, but hospitalizations are relatively infrequent.


title: Optimizing psychiatric care during the COVID‐19 pandemic

text: It is increasingly clear that there is a tension between best possible psychiatric care and efforts to reduce the spread of SARS-CoV-2. As clinicians, we now perceive several key challenges for optimal psychiatric care in the current pandemic context.


title: Aetiology of childhood pneumonia in a well vaccinated South African birth cohort: a nested case-control study of the Drakenstein Child Health Study

text: Summary Background Pneumonia is a leading cause of mortality and morbidity in children globally. The cause of pneumonia after introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) has not been well studied in low-income and middle-income countries, and most data are from cross-sectional studies of children admitted to hospital. We aimed to longitudinally investigate the incidence and causes of childhood pneumonia in a South African birth cohort. Methods We did a nested case-control study of children in the Drakenstein Child Health Study who developed pneumonia from May 29, 2012, to Dec 1, 2014. Children received immunisations including acellular pertussis vaccine and PCV13. A nested subgroup had nasopharyngeal swabs collected every 2 weeks throughout infancy. We identified pneumonia episodes and collected blood, nasopharyngeal swabs, and induced sputum specimens. We used multiplex real-time PCR to detect pathogens in nasopharyngeal swabs and induced sputum of pneumonia cases and in nasopharyngeal swabs of age-matched and site-matched controls. To show associations between organisms and pneumonia we used conditional logistic regression; results are presented as odds ratios (ORs) with 95% CIs. Findings 314 pneumonia cases occurred (incidence of 0·27 episodes per child-year, 95% CI 0·24–0·31; median age 5 months [IQR 3–9]) in 967 children during 1145 child-years of follow-up. 60 (21%) cases of pneumonia were severe (incidence 0·05 episodes per child-year [95% CI 0·04–0·07]) with a case fatality ratio of 1% (three deaths). A median of five organisms (IQR 4–6) were detected in cases and controls with nasopharyngeal swabs, and a median of six organisms (4–7) recorded in induced sputum (p=0·48 compared with nasopharyngeal swabs). Bordetella pertussis (OR 11·08, 95% CI 1·33–92·54), respiratory syncytial virus (8·05, 4·21–15·38), or influenza virus (4·13, 2·06–8·26) were most strongly associated with pneumonia; bocavirus, adenovirus, parainfluenza virus, Haemophilus influenzae, and cytomegalovirus were also associated with pneumonia. In cases, testing of induced sputum in addition to nasopharyngeal swabs provided incremental yield for detection of B pertussis and several viruses. Interpretation Pneumonia remains common in this highly vaccinated population. Respiratory syncytial virus was the most frequently detected pathogen associated with pneumonia; influenza virus and B pertussis were also strongly associated with pneumonia. Testing of induced sputum increases the yield for detection of several organisms. New vaccines and strategies are needed to address the burden of childhood pneumonia. Funding Bill & Melinda Gates Foundation, Medical Research Council South Africa, National Research Foundation South Africa, National Institute of Health, and H3Africa.


title: Interleukin‐6 Blockade Treatment for COVID‐19 associated Cytokine Release Syndrome in a Patient with Poorly Controlled Chronic Myeloid Leukaemia

text: In December 2019, a novel coronavirus pneumonia, coronavirus disease 2019 (COVID‐19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) was reported in Wuhan, China. A hyperinflammatory immune response, or cytokine release syndrome (CRS) is observed in critically unwell patients with SARS‐CoV‐2 globally. Severe lymphopenia, hyperactivated pro‐inflammatory T cells(1) and decreased regulatory T cells(2) are seen in these critically ill patients, suggesting dysregulated immune responses.


title: Likelihood of survival of coronavirus in a respiratory droplet deposited on a solid surface

text: We predict and analyze the drying time of respiratory droplets from a COVID-19 infected subject, which is a crucial time to infect another subject. Drying of the droplet is predicted by using a diffusion-limited evaporation model for a sessile droplet placed on a partially wetted surface with a pinned contact line. The variation in droplet volume, contact angle, ambient temperature, and humidity are considered. We analyze the chances of the survival of the virus present in the droplet based on the lifetime of the droplets under several conditions and find that the chances of the survival of the virus are strongly affected by each of these parameters. The magnitude of shear stress inside the droplet computed using the model is not large enough to obliterate the virus. We also explore the relationship between the drying time of a droplet and the growth rate of the spread of COVID-19 in five different cities and find that they are weakly correlated.


title: Nosocomial infections due to methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci at a university hospital in Taiwan from 1991 to 2003: resistance trends, antibiotic usage and in vitro activities of newer antimicrobial agents

text: Abstract A rapid increase of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection (from 39% in 1991 to 75% in 2003) and vancomycin-resistant enterococci (VRE) (from 1.2% in 1996 to 6.1% in 2003) at a university hospital in Taiwan was found. The noticeable rise of MRSA and VRE was significantly correlated with the increased consumption of glycopeptides, β-lactam–β-lactamase inhibitor combinations, extended-spectrum cephalosporins, carbapenems and fluoroquinolones (Pearson's correlation coefficient, P <0.05). Minimum inhibitory concentrations (MICs) of 100 non-duplicate blood isolates of MRSA (in 2003) and of 25 non-duplicate isolates of vancomycin-resistant Enterococcus faecalis and 172 vancomycin-resistant Enterococcus faecium (in 1996–2003) causing nosocomial infection recovered from various clinical specimens of patients treated at the hospital to nine antimicrobial agents were determined by the agar dilution method. All of these isolates were susceptible to linezolid and were inhibited by 0.5mg/L of tigecycline, and all MRSA isolates were inhibited by daptomycin 1mg/L, including two isolates of MRSA with heteroresistance to vancomycin. Daptomycin had two-fold better activity against vancomycin-resistant E. faecalis (MIC90, 2mg/L) than against vancomycin-resistant E. faecium (MIC90, 4mg/L). Decreased susceptibilities of vancomycin-resistant E. faecium and MRSA to quinupristin/dalfopristin (non-susceptibility 25% and 8%, respectively) were found. Telithromycin had poor activity against the isolates tested (MIC90, 8mg/L). Linezolid, daptomycin and tigecycline may represent therapeutic options for infections caused by these resistant Gram-positive organisms.


title: Strategies for Successful Catheterization Laboratory Recovery From the COVID-19 Pandemic

text: ABSTRACT As the world slowly starts to recover from the COVID-19 pandemic, healthcare systems are now thinking about resuming elective cardiovascular procedures, including procedures in the cardiac catheterization laboratories (cath lab). Rebooting cath labs will be an arduous process in part due to limited healthcare resources, new processes and fears stemming from the COVID-19 pandemic. We propose a detailed phased-in approach that considers clinical, patient-centered, and operational strategies to safely and effectively reboot cath lab programs during these unprecedented times. This model balances delivery of essential cardiovascular care while reducing exposure and preserving resources. The guiding principles detailed in this manuscript can be used by cath lab programs when restarting elective interventional procedures.


title: Chapter 6 Epidemiology and Control of Viral Diseases

text: Abstract This chapter describes aspects of the epidemiology of viral infections including routes of transmission, risk factors, methods of surveillance, and principles of control and eradication of animal viral diseases.


title: Identification of Immune complement function as a determinant of adverse SARS-CoV-2 infection outcome

text: Understanding the pathophysiology of SARS-CoV-2 infection is critical for therapeutics and public health intervention strategies. Viral-host interactions can guide discovery of regulators of disease outcomes, and protein structure function analysis points to several immune pathways, including complement and coagulation, as targets of the coronavirus proteome. To determine if conditions associated with dysregulation of the complement or coagulation systems impact adverse clinical outcomes associated with SARS-CoV-2 infection, we performed a retrospective observational study of 11,116 patients suspected of SARS-CoV-2 infection. We found that history of macular degeneration (a proxy for complement activation disorders) and history of coagulation disorders (thrombocytopenia, thrombosis, and hemorrhage) are risk factors for morbidity and mortality in SARS-CoV-2 infected patients – effects that could not be explained by age or sex. In addition, using data from the UK Biobank, we implemented a candidate driven approach to evaluate linkage between severe SARS-CoV-2 disease and genetic variation associated with complement and coagulation pathways. Among our findings, our scan identified an eQTL for CD55 (a negative regulator of complement activation) and SNPs in Complement Factor H (CFH) and Complement Component 4 Binding Protein Alpha (C4BPA), which play central roles in complement activation and innate immunity and were previously linked to Age Related Macular Degeneration (AMD) in a Genome-Wide Association Study (GWAS). In addition to providing evidence that complement function modulates SARS-CoV-2 infection outcome, the data point to several putative genetic markers of susceptibility. The results highlight the value of using a multi-modal analytical approach, combining molecular information from virus protein structure-function analysis with clinical informatics and genomics to reveal determinants and predictors of immunity, susceptibility, and clinical outcome associated with infection.


title: Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19

text: BACKGROUND: Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19). Direct detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in respiratory tract specimens informs patient, healthcare institution and public health level decision-making. The numbers of available SARS-CoV-2 nucleic acid detection tests are rapidly increasing, as is the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) recognized a significant need for frequently updated systematic reviews of the literature to inform evidence-based best practice guidance. OBJECTIVE: The IDSA’s goal was to develop an evidence-based diagnostic guideline to assists clinicians, clinical laboratorians, patients and policymakers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, we provide a conceptual framework for understanding molecular diagnostic test performance, discuss the nuance of test result interpretation in a variety of practice settings, and highlight important unmet research needs in the COVID-19 diagnostic testing space. METHODS: IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. RESULTS: The panel agreed on 15 diagnostic recommendations. CONCLUSIONS: Universal access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention and the public response to the COVID-19 pandemic. Information on the clinical performance of available tests is rapidly emerging, but the quality of evidence of the current literature is considered low to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is recommended for asymptomatic individuals with known or suspected contact with a COVID-19 case. Testing asymptomatic individuals without known exposure is suggested when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions, dictate eligibility for surgery, or inform administration of immunosuppressive therapy. Ultimately, prioritization of testing will depend on institutional-specific resources and the needs of different patient populations.


title: The Transformation of Enterovirus Replication Structures: a Three-Dimensional Study of Single- and Double-Membrane Compartments

text: All positive-strand RNA viruses induce membrane structures in their host cells which are thought to serve as suitable microenvironments for viral RNA synthesis. The structures induced by enteroviruses, which are members of the family Picornaviridae, have so far been described as either single- or double-membrane vesicles (DMVs). Aside from the number of delimiting membranes, their exact architecture has also remained elusive due to the limitations of conventional electron microscopy. In this study, we used electron tomography (ET) to solve the three-dimensional (3-D) ultrastructure of these compartments. At different time points postinfection, coxsackievirus B3-infected cells were high-pressure frozen and freeze-substituted for ET analysis. The tomograms showed that during the exponential phase of viral RNA synthesis, closed smooth single-membrane tubules constituted the predominant virus-induced membrane structure, with a minor proportion of DMVs that were either closed or connected to the cytosol in a vase-like configuration. As infection progressed, the DMV number steadily increased, while the tubular single-membrane structures gradually disappeared. Late in infection, complex multilamellar structures, previously unreported, became apparent in the cytoplasm. Serial tomography disclosed that their basic unit is a DMV, which is enwrapped by one or multiple cisternae. ET also revealed striking intermediate structures that strongly support the conversion of single-membrane tubules into double-membrane and multilamellar structures by a process of membrane apposition, enwrapping, and fusion. Collectively, our work unravels the sequential appearance of distinct enterovirus-induced replication structures, elucidates their detailed 3-D architecture, and provides the basis for a model for their transformation during the course of infection.


title: Cryo-electron microscopy structure of the SADS-CoV spike glycoprotein provides insights into an evolution of unique coronavirus spike proteins

text: The outbreak of a novel betacoronavirus (SARS-CoV-2) has aroused great public health concern. As a new coronavirus which was responsible for a large-scale outbreak of fatal disease in piglets in China, swine acute diarrhea syndrome coronavirus (SADS-CoV) originated from the same genus of horseshoe bats (Rhinolophus) as SARS-CoV and possesses a broad species tropism. In addition to human cells, it can also infect cell lines from diverse species. Given the importance of the spike glycoprotein (S) protein in viral entry and host immune responses, here we report the cryo-EM structure of the SADS-CoV S in the prefusion conformation at a resolution of 3.55 Å. Our studies reveal that SADS-CoV S structure takes an intra-subunit quaternary packing mode where the NTD and CTD from the same subunit pack together by facing each other. The comparison of NTD and CTD with that of the other four genera gives the suggestion of the evolutionary procedure of the SADS-CoV S. Moreover, SADS-CoV S has several characteristic structural features, i.e., more compact architecture of S trimer, masking of epitopes by glycan shielding, which may facilitate to viral immune evasion. These data provide new insights into the evolutionary relationships of SADS-CoV S and would deepen our understanding of their structural and functional diversity which will facilitate to vaccine development.


title: Global health diplomacy: advancing foreign policy and global health interests

text: Attention to global health diplomacy has been rising but the future holds challenges, including a difficult budgetary environment. Going forward, both global health and foreign policy practitioners would benefit from working more closely together to achieve greater mutual understanding and to advance respective mutual goals.


title: RNAi-based inhibition of porcine reproductive and respiratory syndrome virus replication in transgenic pigs

text: Abstract Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating viral disease causing heavy losses to the swine industry worldwide. Many studies have shown that transient delivery of small interfering RNA (siRNA) or adenovirus-mediated RNA interfere (RNAi) could potentially inhibit porcine reproductive and respiratory syndrome virus (PRRSV) replication in vivo and in vitro. Here, we applied RNAi to produce transgenic (TG) pigs that constitutively expressed PRRSV-specific siRNA derived from small hairpin RNA (shRNA). First, we evaluated siRNA expression in the founding and F1 generation pigs and confirmed stable transmission. Then, we detected the expression of IFN-β and protein kinase R (PKR) and found no difference among TG, non-transgenic (NTG), and wild-type pigs. Lastly, the F1 generation pigs, including TG and NTG piglets, were challenged with 3×104.5 TCID50 of JXA1, a highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV). Our results showed that the in vivo siRNA expression substantially reduced the serum HP-PRRSV titers and increased survival time by 3 days when TG pigs were compared with the NTG controls. These data suggested that RNAi-based genetic modification might be used to breed viral-resistant livestock with stable siRNA expression with no complications of siRNA toxicity.


Responding to Pandemics: What We’ve Learned from HIV/AIDS


title: Interferon-beta and interferon-gamma synergistically inhibit the replication of severe acute respiratory syndrome-associated coronavirus (SARS-CoV)

text: Abstract Recent studies have shown that interferon-gamma (IFN-γ) synergizes with IFN-α/β to inhibit the replication of both RNA and DNA viruses. We investigated the effects of IFNs on the replication of two strains of severe acute respiratory syndrome-associated coronavirus (SARS-CoV). While treatment of Vero E6 cells with 100 U/ml of either IFN-β or IFN-γ marginally reduced viral replication, treatment with both IFN-β and IFN-γ inhibited SARS-CoV plaque formation by 30-fold and replication by 3000-fold at 24 h and by > 1 × 105-fold at 48 and 72 h post-infection. These studies suggest that combination IFN treatment warrants further investigation as a treatment for SARS.


title: Impact of Ebola experiences and risk perceptions on mental health in Sierra Leone, July 2015

text: BACKGROUND: The mental health impact of the 2014–2016 Ebola epidemic has been described among survivors, family members and healthcare workers, but little is known about its impact on the general population of affected countries. We assessed symptoms of anxiety, depression and post-traumatic stress disorder (PTSD) in the general population in Sierra Leone after over a year of outbreak response. METHODS: We administered a cross-sectional survey in July 2015 to a national sample of 3564 consenting participants selected through multistaged cluster sampling. Symptoms of anxiety and depression were measured by Patient Health Questionnaire-4. PTSD symptoms were measured by six items from the Impact of Events Scale-revised. Relationships among Ebola experience, perceived Ebola threat and mental health symptoms were examined through binary logistic regression. RESULTS: Prevalence of any anxiety-depression symptom was 48% (95% CI 46.8% to 50.0%), and of any PTSD symptom 76% (95% CI 75.0% to 77.8%). In addition, 6% (95% CI 5.4% to 7.0%) met the clinical cut-off for anxiety-depression, 27% (95% CI 25.8% to 28.8%) met levels of clinical concern for PTSD and 16% (95% CI 14.7% to 17.1%) met levels of probable PTSD diagnosis. Factors associated with higher reporting of any symptoms in bivariate analysis included region of residence, experiences with Ebola and perceived Ebola threat. Knowing someone quarantined for Ebola was independently associated with anxiety-depression (adjusted OR (AOR) 2.3, 95% CI 1.7 to 2.9) and PTSD (AOR 2.095% CI 1.5 to 2.8) symptoms. Perceiving Ebola as a threat was independently associated with anxiety-depression (AOR 1.69 95% CI 1.44 to 1.98) and PTSD (AOR 1.86 95% CI 1.56 to 2.21) symptoms. CONCLUSION: Symptoms of PTSD and anxiety-depression were common after one year of Ebola response; psychosocial support may be needed for people with Ebola-related experiences. Preventing, detecting, and responding to mental health conditions should be an important component of global health security efforts.


New and emerging infectious diseases (Ebola, Middle Eastern respiratory syndrome coronavirus, carbapenem-resistant Enterobacteriaceae, Candida auris): Focus on environmental survival and germicide susceptibility


Exercise in isolating during novel coronavirus 19 - A case report of bilateral ocular trauma from elastic resistant bands


title: Complementing conventional infectious disease surveillance with national health insurance claims data in the Republic of Korea

text: Surveillance remains an important tool for timely outbreak detection and response. Many countries, including Korea, have established national infectious disease surveillance systems with clinical notification. We aimed to evaluate the National Health Insurance Claims-based Surveillance (NHICS) compared to conventional passive report-based National Infectious Diseases Surveillance (NIDS). Reported to claimed cases ratios (R/C ratio) were evaluated from monthly notifiable disease cases captured by NIDS and NHICS. The relationships between 26 infectious diseases and each surveillance system were analysed using Pearson’s correlation analysis and linear regression. There was an overall increase in R/C ratio from 2010–2017 (0.37 to 0.78). In 22 infectious diseases, there was a correlation between NIDS and NHICS. Moreover, claim-based surveillance showed less fluctuating disease incidence rates than report-based surveillance for specific infectious diseases, such as varicella, mumps, and scarlet fever. However, for infectious diseases with episodic outbreaks or low incidence, it was difficult to assess NHICS usefulness. Claim-based surveillance is less affected by limitations of conventional report-based surveillance systems, such as reporting rate. Given delays in claim systems, a claim-based surveillance is expected to be complementary to conventional systems for the detection of various infectious diseases with the advancement of bio-information technology.


title: Association between COVID-19 and cardiovascular disease

text: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19) has reached a pandemic level. SARS-CoV-2 infects host cells through ACE2 receptors, leading to COVID-19-related pneumonia. The rapid increase in confirmed cases makes the prevention and control of COVID-19 extremely serious. Real-time reverse transcription-PCR (RT-PCR) assays remain the molecular test of choice for the etiologic diagnosis of SARS-CoV-2 infection while radiographic findings (chest computed tomography [CT]) and antibody-based techniques are being introduced as supplemental tools. Novel virus also cause chronic damage to the cardiovascular system, and attention should be given to cardiovascular protection during treatment for COVID-19. Acute cardiac injury determined by elevated high-sensitivity troponin levels is commonly observed in severe cases and is strongly associated with mortality. This review suggests that cardiovascular comorbidities are common in patients with COVID-19 and such patients are at higher risk of morbidity and mortality. The continuation of clinically indicated ACE inhibitor and ARB medications is recommended in COVID-19. We review the basics of coronaviruses, novel molecular targets for the coronaviruses with a focus on COVID-19, along with their effects on the cardiovascular system.


title: Absence of Severe Acute Respiratory Syndrome-Coronavirus-2 RNA in ocular tissues

text: PURPOSE: To evaluate the status of ocular donor tissues of a COVID-19 postmortem donor. METHODS: SARS-CoV-2 was detected via a pharyngeal swab and broncho-alveolar lavage in the COVID-19 suspect. Postmortem tissue procurement and preparation were performed with personal protective equipment (PPE) and the necessary protective measures. qRT-PCR-testing was performed for the following ocular tissues and fluids: conjunctival fluid swabs, bulbar conjunctiva, corneal epithelium, corneal stroma, corneal endothelium, anterior chamber fluid, lens, iris, vitreous, retina, uvea, sclera, and optic nerve. Informed consent and Institutional Review Board approval was obtained prior to this study (196/2020BO2; Date of approval: 03/26/2020; Ethics Committee of the University of Tuebingen). RESULTS: In all ocular tissue and fluid samples no SARS-CoV-2 RNA was detected via qRT-PCR of the confirmed COVID-19 postmortem donor. CONCLUSIONS: and Importance: Late-stage COVID-19 patients might not harbor an ocular reservoir of SARS-CoV-2. The risk of transmitting SARS-CoV-2 via ocular tissues and fluids might be low. This may bear future implications for patient management in ophthalmological practice, surgery and transplantation.


title: The Impact of Coronavirus Disease 2019 on Bariatric Surgery: Redefining Psychosocial Care

text: The global outbreak of the 2019 novel coronavirus disease has had a tremendous psychological impact on individuals around the world. Individuals with obesity are susceptible to distress and psychological sequalae secondary to this pandemic, which can have detrimental effects on obesity management. In particular, individuals undergoing bariatric surgery could experience increased emotional distress, resulting in increased eating psychopathology, mental health exacerbation, and difficulties with self‐management. Addressing these challenges requires novel approaches to redefining psychosocial care before and after bariatric surgery. Emerging evidence suggests that the remote delivery of care using virtual care models, including mobile and online modalities, could extend the reach of psychosocial services to individuals after bariatric surgery and mitigate weight regain or impairment in quality of life. Because of this pandemic, the rapid integration of virtual psychosocial care in bariatric surgery programs to address patients’ needs will create new opportunities for clinical and implementational scientific research.


Disproportionate impact of COVID‐19 pandemic on head and neck cancer survivors


title: Lawsonia intracellularis infection and proliferative enteropathy in foals

text: Abstract Equine proliferative enteropathy (EPE) is a disease of foals caused by the obligate intracellular organism Lawsonia intracellularis. This organism is unique in that it causes proliferation of infected enterocytes, resulting in thickening of the intestinal epithelium, most often the small intestine. This disease affects mainly weanling foals and causes fever, lethargy, peripheral edema, diarrhea, colic and weight loss. The diagnosis of EPE may be challenging and relies on the presence of hypoproteinemia, thickening of segments of the small intestinal wall observed on abdominal ultrasonography, positive serology and molecular detection of L. intracellularis in feces. The epidemiology and genetic basis for pathogenesis for this disease is beginning to be elucidated. Phenotypic traits, genomic features, and gene expression profiles during L. intracellularis infection in vitro and in vivo are presented. In addition, this article reviews the epidemiology, pathological and clinicopathological findings, diagnosis, and control of EPE.


title: Integrated Approaches to Reveal Mechanisms by which RNA Viruses Reprogram the Cellular Environment

text: RNA viruses are major threats to global society and mass outbreaks can cause long-lasting damage to international economies. RNA and related retro viruses represent a large and diverse family that contribute to the onset of human diseases such as AIDS; certain cancers like T cell lymphoma; severe acute respiratory illnesses as seen with COVID-19; and others. The hallmark of this viral family is the storage of genetic material in the form of RNA, and upon infecting host cells, their RNA genomes reprogram the cellular environment to favor productive viral replication. RNA is a multifunctional biomolecule that not only stores and transmits heritable information, but it also has the capacity to catalyze complex biochemical reactions. It is therefore no surprise that RNA viruses use this functional diversity to their advantage to sustain chronic or lifelong infections. Efforts to subvert RNA viruses therefore requires a deep understanding of the mechanisms by which these pathogens usurp cellular machinery. Here, we briefly summarize several experimental techniques that individually inform on key physicochemical features of viral RNA genomes and their interactions with proteins. Each of these techniques provide important vantage points to understand the complexities of virus-host interactions, but we attempt to make the case that by integrating these and similar methods, more vivid descriptions of how viruses reprogram the cellular environment emerges. These vivid descriptions should expedite the identification of novel therapeutic targets.


title: On the dynamics of SEIRS epidemic model with transport-related infection

text: Abstract Transportation amongst cities is found as one of the main factors which affect the outbreak of diseases. To understand the effect of transport-related infection on disease spread, an SEIRS (Susceptible, Exposed, Infectious, Recovered) epidemic model for two cities is formulated and analyzed. The epidemiological threshold, known as the basic reproduction number, of the model is derived. If the basic reproduction number is below unity, the disease-free equilibrium is locally asymptotically stable. Thus, the disease can be eradicated from the community. There exists an endemic equilibrium which is locally asymptotically stable if the reproduction number is larger than unity. This means that the disease will persist within the community. The results show that transportation among regions will change the disease dynamics and break infection out even if infectious diseases will go to extinction in each isolated region without transport-related infection. In addition, the result shows that transport-related infection intensifies the disease spread if infectious diseases break out to cause an endemic situation in each region, in the sense of that both the absolute and relative size of patients increase. Further, the formulated model is applied to the real data of SARS outbreak in 2003 to study the transmission of disease during the movement between two regions. The results show that the transport-related infection is effected to the number of infected individuals and the duration of outbreak in such the way that the disease becomes more endemic due to the movement between two cities. This study can be helpful in providing the information to public health authorities and policy maker to reduce spreading disease when its occurs.


title: Respiratory viruses in young South African children with acute lower respiratory infections and interactions with HIV

text: Abstract Background Human rhinovirus (RV) is the most common respiratory virus and has been associated with frequent and severe acute lower respiratory infections (ALRI). The prevalence of RV species among HIV-infected children in South Africa is unknown. Objectives To describe the prevalence of respiratory viruses, including RV species, associated with HIV status and other clinical symptoms in children less than two years of age with and without ALRI in Pretoria, South Africa. Study design Nasopharyngeal aspirates were collected from 105 hospitalized ALRI cases and 53 non-ALRI controls less than two years of age. HIV status was determined. Common respiratory viruses were identified by PCR, and RV species and genotypes were identified by semi-nested PCR, sequencing and phylogenetic tree analyses. Results Respiratory viruses were more common among ALRI cases than controls (83.8% vs. 69.2%; p=0.041). RV was the most commonly identified virus in cases with pneumonia (45.6%) or bronchiolitis (52.1%), regardless of HIV status, as well as in controls (39.6%). RV-A was identified in 26.7% of cases and 15.1% of controls while RV-C was identified in 21.0% of cases and 18.9% of controls. HIV-infected children were more likely to be diagnosed with pneumonia than bronchiolitis (p<0.01). RSV was not identified in any HIV-infected cases (n=15) compared with 30.6% of HIV-uninfected cases (n=85, p=0.013), and was identified more frequently in bronchiolitis than in pneumonia cases (43.8% vs. 12.3%; p<0.01). Conclusions RV-A and RV-C are endemic in South African children and HIV infection may be protective against RSV and bronchiolitis.


title: Proposed Workflow for Rehabilitation in a Field Hospital Setting During the COVID‐19 Pandemic

text: The novel Coronavirus Disease 2019 (COVID‐19) pandemic has challenged healthcare facilities throughout the world. In many regions, the need for acute inpatient healthcare services has exceeded the capacity of hospital systems, and field hospitals are being utilized as one part of the response strategy. Given the urgency and novelty of this pandemic, healthcare systems are attempting to rapidly execute plans for field hospitals, and rehabilitative care in this environment merits particular consideration given the potential impacts of mobilization and rehabilitative therapies on morbidity, mortality, duration of ventilation, and lengths of ICU/hospital stay. In order to address this need, a model for rehabilitation in field hospitals is presented here. This article is protected by copyright. All rights reserved.


title: Replication and morphogenesis of avian coronavirus in Vero cells and their inhibition by monensin

text: Abstract Avian infectious bronchitis virus (IBV) was adapted to Vero cells by serial passage. No significant inhibition of IBV replication was observed when infected Vero cells were treated with α-amanitin or actinomycin D. In thin sections of infected cells, assembly of IBV was observed at the rough endoplasmic reticulum (RER), and mature IBV particles were located in dilated cisternae of the RER as well as in smooth cytoplasmic vesicles. In addition to typical IBV particles, enveloped particles containing numerous ribosomes were identified at later times postinfection. Monensin, a sodium ionophore which blocks glycoprotein transport to plasma membranes at the level of the Golgi complex, was found to inhibit the formation of infectious IBV. In thin sections of infected Vero cells treated with the ionophore, IBV particles were located in dilated cytoplasmic vesicles, but fewer particles were found when compared to controls. A similar pattern of virus-specific proteins was detected in control or monensin-treated IBV-infected cells, which included two glycoproteins (170000 and 24000 daltons) and a polypeptide of 52000 daltons. These results suggesl lhal the ionophore inhibits assembly of a virus which malures at intracellular membranes.


title: Promising methods for detection of novel coronavirus SARS‐CoV‐2

text: A very recent outbreak of the novel coronavirus, COVID‐19, in the city of Wuhan, China, in December 2019 and its subsequent spread within and across China have resulted in several deaths and infections. Presently, nucleic acid amplification test is essential for the confirmation of COVID infection. In this report, we summarized the six promising methods, including whole‐genome sequencing, real‐time reverse transcription polymerase chain reaction, nanopore target sequencing, antibody‐based immunoassay techniques, use of paper‐based biomolecular sensors, and the clustered regularly interspaced short palindromic repeats‐Cas system‐based technology, which can also be deployed for the detection of SARS‐CoV‐2. We further introduced the principles of these methods, discussed the scope and practicability of application of the available products and methods, and highlighted the potential approaches to develop additional products and techniques for early diagnosis of COVID‐19.


Epidemics and primary care in the UK


title: Relevance of feline interferon omega for clinical improvement and reduction of concurrent viral excretion in retrovirus infected cats from a rescue shelter

text: Abstract Feline Immnunodeficiency (FIV) and Feline Leukemia (FeLV) viruses are common infectious agents in stray cats and shelter environments. Recombinant feline interferon-ω (rFeIFNω) has shown an antiviral action not only against FIV and FeLV but also against herpesvirus (FHV-1) and calicivirus (FCV). Sixteen naturally infected FIV/FeLV cats were followed during rFeIFNω therapy in order to monitor clinical signs and to correlate with excretion of concomitant viruses (FCV, FHV-1, feline coronavirus (FCoV) and parvovirus (FPV)). Cats were submitted to clinical evaluations and concomitant virus excretion assessement. Comparing D0–D65, 10/16 cats improved clinical scores. Of the 10 cats positive for FHV-1 on D0, 4 were negative and 6 reduced viral loads. Of the 11 FCoV positive cats, 9 reduced viral loads. The 13 FCV positive cats and the FPV positive cat were negative on D65. In conclusion, rFeIFNω improves clinical signs and reduces concurrent viral excretion in naturally infected retroviral cats.


Novel Coronavirus (COVID‐19) Epidemic: What Are the Risks for Older Patients?


title: New regulatory strategies to manage medicines shortages in Europe

text: Abstract Medicine shortages have been spreading in European countries. In many cases, the unavailability of medicinal products has a substantial impact on the capability of National Healthcare Systems in ensuring the continuity of care. Shortages originate from multifactorial causes. In particular, they can be due to supply-related factors (e.g., manufacturing issues, regulatory issues, logistics, distribution) and demand-related ones (e.g., fluctuating drug demand, parallel market, tendering, price and reimbursement policies). However, some extraordinary geopolitical events (e.g., Brexit) may also affect medicines’ availability. The capability of European Regulatory Authorities and other stakeholders, which are involved in the pharmaceutical distribution chain and the healthcare assistance services, to define suitable problem-solving strategies has been limited for years by the fragmentation of the European regulatory framework, starting from the lack of a univocal definition of a medicine shortage. Only in 2019, the EMA and HMA joint task force released the first harmonized “shortage” definition in the European Economic Area (EEA) and guidance on public communication. This manuscript aims to review the current European regulatory framework on medicine shortages. To support the activities of regulators, manufacturers and other healthcare professionals, an algorithm was also proposed to be used as a harmonized procedure to determine the shortage/unavailability impact on public health and to rationalize the problem-solving strategies adopted in all different settings.


title: The quintuple penalty of obese patients in the COVID-19 pandemic

text: [Figure: see text]


title: Metastatic squamous cell carcinoma in a cat

text: A 7-year-old, spayed female Persian cat was referred for evaluation of progressive paraplegia. The cat was thin, cachectic and paraplegic on presentation. The survey radiographs showed a left caudal pulmonary lesion and lytic skeletal lesions at the right iliac crest and left distal scapula. Due to a poor prognosis for complete recovery, the owner opted for euthanasia. Post-mortem examination revealed bilaterally small and irregular kidneys, lysis of the left iliac crest and left distal scapula and a dilated left ventricular lumen with a thin interventricular septum. Histologically, all the lesions were determined to be squamous cell carcinoma. It appears that the origin or the primary site of the malignancy in this case is pulmonary as cardiac and skeletal tissues are primarily mesenchymal in origin and are less likely to develop a primary epithelial malignancy. To the best of our knowledge, there is no description of cardiac or skeletal metastatic squamous cell carcinoma in a cat.


title: Infrared Thermography of the Pig Thorax: An Assessment of Selected Regions of Interest by Computed Tomographical and Anatomical Parameters

text: Current methods of diagnosis of respiratory diseases in swine are invasive, time‐consuming and expensive. Infrared thermography (IRT) of the thorax might provide a new method of high specificity to select swine affected with lung alterations for further diagnostics. In this study, layer thickness of different tissues was determined in frozen thorax slices (FTS) by computed tomography (CT) and then related to skin temperatures measured by IRT in healthy pigs. The aim was to determine appropriate regions of interest (ROI) for evaluation of IRT images. Organ layer thicknesses measured in CT images correspond to those measured in FTS. Temperature differences between lung ROIs and abdomen ROIs were positively correlated with lung layer thickness at certain localizations, and negatively correlated with the thickness of the thorax wall and of inner organ layers. Reference values of differences between skin temperatures were established for two ROIs on the thorax with potential practical use for lung health status determination. Respective ROIs were located on vertical lines crossing the 7th (right) and the 10th (left) thoracic vertebrae. The presence of ribs affected skin temperature significantly.


title: Estimating the infection and case fatality ratio for coronavirus disease (COVID-19) using age-adjusted data from the outbreak on the Diamond Princess cruise ship, February 2020

text: Adjusting for delay from confirmation to death, we estimated case and infection fatality ratios (CFR, IFR) for coronavirus disease (COVID-19) on the Diamond Princess ship as 2.6% (95% confidence interval (CI): 0.89–6.7) and 1.3% (95% CI: 0.38–3.6), respectively. Comparing deaths on board with expected deaths based on naive CFR estimates from China, we estimated CFR and IFR in China to be 1.2% (95% CI: 0.3–2.7) and 0.6% (95% CI: 0.2–1.3), respectively.


title: Direct endothelial damage and vasculitis due to SARS‐CoV‐2 in small bowel submucosa of CoViD‐19 patient with diarrhea

text: SARS‐CoV‐2, responsible for CoViD‐19, is a new virus that can infect different cellular lines, including endothelia and epithelial cells of the gastrointestinal tract mucosa. At this level, the virus can cause different types of direct damage, even in paucisymptomatic, young patients. Virus can be detected directly with immunohistochemistry techinques. This article is protected by copyright. All rights reserved.


title: Camelid VHHs Fused to Human Fc Fragments Provide Long Term Protection Against Botulinum Neurotoxin A in Mice

text: The bacterium Clostridium botulinum is the causative agent of botulism—a severe intoxication caused by botulinum neurotoxin (BoNT) and characterized by damage to the nervous system. In an effort to develop novel C. botulinum immunotherapeutics, camelid single-domain antibodies (sdAbs, VHHs, or nanobodies) could be used due to their unique structure and characteristics. In this study, VHHs were produced using phage display technology. A total of 15 different monoclonal VHHs were selected based on their comlementarity-determining region 3 (CDR3) sequences. Different toxin lethal dose (LD(50)) challenges with each selected phage clone were conducted in vivo to check their neutralizing potency. We demonstrated that modification of neutralizing VHHs with a human immunoglobulin G (IgG)1 Fc (fragment crystallizable) fragment (fusionbody, VHH-Fc) significantly increased the circulation time in the blood (up to 14 days). At the same time, VHH-Fc showed the protective activity 1000 times higher than monomeric form when challenged with 5 LD(50). Moreover, VHH-Fcs remained protective even 14 days after antibody administration. These results indicate that this VHH-Fc could be used as an effective long term antitoxin protection against botulinum type A.


title: How to strengthen a health research system: WHO’s review, whose literature and who is providing leadership?

text: BACKGROUND: Health research is important for the achievement of the Sustainable Development Goals. However, there are many challenges facing health research, including securing sufficient funds, building capacity, producing research findings and using both local and global evidence, and avoiding waste. A WHO initiative addressed these challenges by developing a conceptual framework with four functions to guide the development of national health research systems. Despite some progress, more is needed before health research systems can meet their full potential of improving health systems. The WHO Regional Office for Europe commissioned an evidence synthesis of the systems-level literature. This Opinion piece considers its findings before reflecting on the vast additional literature available on the range of specific health research system functions related to the various challenges. Finally, it considers who should lead research system strengthening. MAIN TEXT: The evidence synthesis identifies two main approaches for strengthening national health research systems, namely implementing comprehensive and coherent strategies and participation in partnerships. The literature describing these approaches at the systems level also provides data on ways to strengthen each of the four functions of governance, securing financing, capacity-building, and production and use of research. Countries effectively implementing strategies include England, Ireland and Rwanda, whereas West Africa experienced effective partnerships. Recommended policy approaches for system strengthening are context specific. The vast literature on each function and the ever-growing evidence-base are illustrated by considering papers in just one key journal, Health Research Policy and Systems, and analysing the contribution of two national studies. A review of the functions of the Iranian system identifies over 200 relevant and mostly national records; an analysis of the creation of the English National Institute for Health Research describes the key leadership role played by the health department. Furthermore, WHO is playing leadership roles in helping coordinate partnerships within and across health research systems that have been attempting to tackle the COVID-19 crisis. CONCLUSIONS: The evidence synthesis provides a firm basis for decision-making by policy-makers and research leaders looking to strengthen national health research systems within their own national context. It identifies five crucial policy approaches — conducting situation analysis, sustaining a comprehensive strategy, engaging stakeholders, evaluating impacts on health systems, and partnership participation. The vast and ever-growing additional literature could provide further perspectives, including on crucial leadership roles for health ministries.


title: COVID-19 Pandemic: How to Use Artificial Intelligence to Choose Non-Vulnerable Workers for Positions with the Highest Possible Levels of Exposure to the Novel Coronavirus

text: The COVID-19 pandemic has affected people globally; nowadays several countries are facing a major change in daily life due to universal quarantining, closed schools, social isolation, and shelter-in-place orders. In addition, this pandemic caused an economic crisis. International Labour Organization (ILO) reported that not only COVID-19 is a serious threat to public health but also the economic and social disruption of this crisis threatens the long-term livelihoods and wellbeing of millions of people. In this short paper, we introduce our hypothesis on using artificial intelligence (AI) technology to predict which employees are most vulnerable to the infections caused by the novel coronavirus (SARS-CoV-2). Such a system can be used in a wide variety of work places such as libraries, banks, drugstores, and hotel receptions to reduce the risk of severe infections in employees as well as to ensure the safety of labor force and the sustainability of businesses and jobs.


title: Highlights of Studies in Cardiovascular Disease Prevention Presented at the 2020 American College of Cardiology Annual Scientific Session

text: PURPOSE OF REVIEW: The review highlights selected studies related to cardiovascular disease (CVD) prevention that were presented at the American College of Cardiology 2020 Virtual Scientific Session (ACC.20)/World Cardiology Congress (WCC). RECENT FINDINGS: The studies reviewed include clinical trials on the efficacy and safety of alirocumab (Study in Participants with Homozygous Familial Hypercholesterolemia [ODYSSEY HoFH]) and evinacumab in the treatment of homozygous familial hypercholesterolemia (HoFH); Evaluating the Efficacy of E-cigarettes for Smoking Cessation (E3); the use of renal denervation in the treatment of hypertension (SPYRAL HTN-OFF MED PIVOTAL); and the assessment of vericiguat in the treatment of heart failure (A Study of Vericiguat in Participants with Heart Failure with Reduce Ejection Fraction [VICTORIA]). In addition, results from the pooled analysis of phase III trials on inclisiran and secondary analysis examining eicosapentaenoic acid levels and cardiovascular outcomes from the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) were included. Finally, we discuss studies examining the use of polygenic risk score with low density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP) on lifetime cardiovascular risk. SUMMARY: The studies presented at the ACC.20/WCC represent notable contributions in the field of CVD prevention.


title: Antiviral activity of lycorine against Zika virus in vivo and in vitro

text: Abstract The emergence and re-emergence of Zika virus (ZIKV), is a cause for international concern. These highly pathogenic arboviruses represent a serious health burden in tropical and subtropical areas worldwide. Despite these burdens, antiviral therapies do not exist, and inhibitors of ZIKV are therefore urgently needed. To elucidate the anti-ZIKV effect of lycorine, we used reverse transcription-quantitative real-time PCR (qRT-PCR), immunofluorescence, Western western blot, and plaque forming assay to analyse viral RNA (vRNA), viral protein, progeny virus counts, and validated inhibitors in vitro using a variety of cell lines. Additionally, we found that lycorine acts post-infection according to time-of-addition assay, and inhibits RdRp activity. Lycorine protected AG6 mice against ZIKV-induced lethality by decreasing the viral load in the blood. Due to its potency and ability to target ZIKV infection in vivo and in vitro, lycorine might offer promising therapeutic possibilities for combatting ZIKV infections in the future.


It's Not the Heat, It's the Humidity: Effectiveness of a Rice Cooker-Steamer for Decontamination of Cloth and Surgical Face Masks and N95 Respirators


title: Purpuric rash and fever among hospitalized children aged 0–18 years: Comparison between clinical, laboratory, therapeutic and outcome features of patients with bacterial versus viral etiology

text: Background The evaluation of children with purpuric rash and fever (PRF) is controversial. Although many of them have viral infections, on occasion such patients may be infected with Neisseria meningitidis. We described all children aged 0–18 years with PRF in southern Israel during the period 2005 ̶ 2016 and compared their microbiologic, laboratory, clinical and outcome characteristics in relation to various etiologies of this syndrome. Methods Data were summarized from electronic patient and microbiology files. Viral diagnoses were made by serology and/or PCR. Results Sixty-nine children with PRF were admitted; 30 (43.48%), 9 (13.04%) and 30 (43.48%) had a syndrome of bacterial, viral or non-established etiology, respectively. N. meningitidis infection was diagnosed in 16/69 (23.19%) patients and in 16/30 (53.33%) patients with bacterial etiology; 14/30 (46.67%) patients suffered from a non-invasive bacterial disease (9 with Rickettsial disease). Adenovirus and Influenza B (3 and 2 cases, respectively) represented the most frequent etiologic agents among patients with viral etiology. More patients with PRF of bacterial etiology were older, of Bedouin ethnicity, looked ill on admission, had higher rates of meningitis and were treated more frequently with antibiotics compared with patients with non-bacterial PRF. Fatality rates among patients with bacterial, viral and non-established etiology were 5/30 (16.7%), 0% and 2/39 (5.1%). Conclusions Although PFR was uncommon, high rates of meningococcal infections were recorded in children with PRF, which was associated with high fatality rates. Rickettsial infections were frequent, emphasizing the need for a high index of suspicion for this disease in endemic geographic areas.


Midwifery in the Time of COVID‐19


title: Performance of a Taqman Assay for Improved Detection and Quantification of Human Rhinovirus Viral Load

text: Human rhinovirus (HRV) is the major aetiology of respiratory tract infections. HRV viral load assays are available but limitations that affect accurate quantification exist. We developed a one-step Taqman assay using oligonucleotides designed based on a comprehensive list of global HRV sequences. The new oligonucleotides targeting the 5′-UTR region showed high PCR efficiency (E = 99.6%, R(2) = 0.996), with quantifiable viral load as low as 2 viral copies/μl. Assay evaluation using an External Quality Assessment (EQA) panel yielded a detection rate of 90%. When tested on 315 human enterovirus-positive specimens comprising at least 84 genetically distinct HRV types/serotypes (determined by the VP4/VP2 gene phylogenetic analysis), the assay detected all HRV species and types, as well as other non-polio enteroviruses. A commercial quantification kit, which failed to detect any of the EQA specimens, produced a detection rate of 13.3% (42/315) among the clinical specimens. Using the improved assay, we showed that HRV sheds in the upper respiratory tract for more than a week following acute infection. We also showed that HRV-C had a significantly higher viral load at 2–7 days after the onset of symptoms (p = 0.001). The availability of such assay is important to facilitate disease management, antiviral development, and infection control.


title: Position Statement on the Management of Cardiac Electrophysiology and Cardiac Implantable Electronic Devices in Australia during the COVID-19 Pandemic: A Living Document()

text: The COVID-19 pandemic poses a significant stress on health resources in Australia. The Heart Rhythm Council of the Cardiac Society of Australia and New Zealand aims to provide a framework for efficient resource utilisation balanced with competing risks when appropriately treating patients with cardiac arrhythmias. This document provides practical recommendations for the electrophysiology (EP) and cardiac implantable electronic devices (CIED) services in Australia. The document will be updated regularly as new evidence and knowledge is gained with time.


title: Australian Quarantine Policy: From Centralization to Coordination with mid‐Pandemic COVID‐19 Shifts

text: By combining a historical institutionalism approach with institutional isomorphism and punctuated equilibrium, this paper analyses quarantine policy change across 120 years of Australian quarantine history. By anchoring our analysis within specific time periods (years before the Spanish flu, seven decades of inaction, and multiple post‐1997 pandemic updates and responses), we highlight when and why policies did or did not change and how constant push‐and‐pulls between State and Commonwealth institutional ownership altered policy possibilities. The heart of our analysis showcases how Australia's successful COVID‐19 response is a unique output of prior quarantine policies, institutional evolution, and mid‐pandemic alterations of key national pandemic response plans. This article is protected by copyright. All rights reserved.


Lessons learned: Commentary on patient harm related to COVID-19 prevention policies at a rural academic tertiary care facility


title: Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells

text: Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors (VDR; GATA5; SFTPC; HIF1a) and activators (HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website.


SARS-CoV2 in patients on antiviral HBV and HCV therapy in Spain


title: Clinical and radiological changes of hospitalised patients with COVID-19 pneumonia from disease onset to acute exacerbation: a multicentre paired cohort study

text: OBJECTIVES: To analyse clinical and radiological changes from disease onset to exacerbation in coronavirus infectious disease-19 (COVID-19) patients. METHODS: We reviewed clinical histories of 276 patients with confirmed COVID-19 pneumonia and extracted data on patients who met the diagnostic criteria for COVID-19 severe/fatal pneumonia and had an acute exacerbation starting with mild or common pneumonia. RESULTS: Twenty-four patients were included. Of these, 8% were smokers, 54% had been to Wuhan, and 46% had comorbidities. Before acute exacerbation, elevated lactate dehydrogenase (232.9 ± 88.7) was present, and chest CT scans showed the number of involved lobes was 4 (2–5) and total CT score was 6 (2–8). Following acute exacerbation, patients were likely to have more clinical symptoms (p < 0.01) and abnormal laboratory changes (p < 0.01). The number of involved lobes and CT score after an exacerbation significantly increased to 5 (5–5) and 12 (9–14), respectively. Receiver operating characteristic (ROC) curve showed that, when the cutoff value of CT score was 5, the sensitivity and specificity for severe pneumonia were 90% and 70%, respectively. CT findings of ground glass opacity with consolidations (91.7%), bilateral distribution (100.0%), and multifocal lesion (100.0%) were features in found in patients after exacerbation. CONCLUSIONS: There are significant changes in clinical, laboratory, and CT findings in patients from disease onset to exacerbation. An increase in the number of involved lobes or an increased CT score from the baseline may predict poor clinical outcomes. Combining an assessment of CT changes with clinical and laboratory changes could help clinical teams evaluate the prognosis. KEY POINTS: • The common chest CT signs of COVID-19 pneumonia after exacerbation were ground glass opacity (GGO) with consolidation, bilateral distribution, and multifocal lesions. • An increase in number of involved lobes or an increased CT score from the baseline may predict a poor clinical outcome. • Worsened symptoms and abnormal laboratory results are also associated with poor prognosis.


title: Porcine bocavirus NP1 negatively regulates interferon signaling pathway by targeting the DNA-binding domain of IRF9

text: Abstract To subvert host antiviral immune responses, many viruses have evolved countermeasures to inhibit IFN signaling pathway. Porcine bocavirus (PBoV), a newly identified porcine parvovirus, has received attention because it shows clinically high co-infection prevalence with other pathogens in post-weaning multisystemic wasting syndrome (PWMS) and diarrheic piglets. In this study, we screened the structural and non-structural proteins encoded by PBoV and found that the non-structural protein NP1 significantly suppressed IFN-stimulated response element (ISRE) activity and subsequent IFN-stimulated gene (ISG) expression. However, NP1 affected neither the activation and translocation of STAT1/STAT2, nor the formation of the heterotrimeric transcription factor complex ISGF3 (STAT1/STAT2/IRF9). Detailed analysis demonstrated that PBoV NP1 blocked the ISGF3 DNA-binding activity by combining with the DNA-binding domain (DBD) of IRF9. In summary, these results indicate that PBoV NP1 interferes with type I IFN signaling pathway by blocking DNA binding of ISGF3 to attenuate innate immune responses.


Combating Covid-19 Pandemic In Africa: An Urgent Call To Scale Up Laboratory Testing Capacities


title: Antiviral drug screening by assessing epithelial functions and innate immune responses in human 3D airway epithelium model

text: Abstract Respiratory viral infections cause mild to severe diseases, such as common cold, bronchiolitis and pneumonia and are associated with substantial burden for society. To test new molecules for shortening, alleviating the diseases or to develop new therapies, relevant human in vitro models are mandatory. MucilAir™, a human standardized air-liquid interface 3D airway epithelial culture holds in vitro specific mechanisms to counter invaders comparable to the in vivo situation, such as mucus production, mucociliary clearance, and secretion of defensive molecules. The objective of this study was to test the relevance of such a model for the discovery and validation of antiviral drugs. Fully differentiated 3D nasal epithelium cultures were inoculated with picornaviruses, a coronavirus and influenza A viruses in the absence or in the presence of reference antiviral drugs. Results showed that, rupintrivir efficiently inhibits the replication of respiratory picornaviruses in a dose dependent manner and prevents the impairment of the mucociliary clearance. Similarly, oseltamivir reduced the replication of influenza A viruses in a dose dependent manner and prevented the impairment of the epithelial barrier function and cytotoxicity until 4 days of infection. In addition we found that Rhinovirus B14, C15 and influenza A(H1N1) induce significant increase of β Defensins 2 and Cathelicidin release with different time course. These results reveal that a large panel of epithelial functions is modified upon viral infection and validate MucilAir™ as a pertinent tool for pre-clinical antiviral drug testing.


Classification of medically important viruses II: RNA viruses


title: Will the hidden specter of acute coronary syndrome (ACS) and ST-segment elevation myocardial infarction (STEMI) emerge from the avalanche of COVID-19?

text: There has been a huge impact of the COVID-19 pandemic on global healthcare systems. Advisories across the world have appealed to people to stay at home and observe social distancing to slow down the pandemic. However it is important to realize as to how this is affecting acute cardiovascular care. Recent studies from Europe and USA have reported > 50% reduction in hospital admissions for ACS and declining rates of coronary interventions. The possible reasons for this noticeable reduction in patients with ACS/STEMI during the COVID-19 pandemic are multi-factorial. On one hand, it is due to change in thresholds for referring patients of ACS/STEMI for cardiac catheterization, with fibrinolysis being acceptable for many stable STEMI patients and conservative management being preferred for NSTEMI patients. Theories abound on how “staying at home” strategy may have led to an reduction in acute coronary events due to healthier lifestyle, better compliance and reduced stress. Realistically however, a more disquieting reason would be a “pseudo-reduction” ie. the incidence of ACS/STEMI is actually the same, but these patients are staying away from hospitals due to fear of contracting the infection. Lockdown restrictions have also limited transport options for patients seeking to reach hospitals in time. Healthcare systems need to be prepared for an anticipated downstream deluge of such untreated patients who may present with sequelae like heart failure, reinfarction, arrhythmias, mechanical complications etc. Scientific societies should have proactive campaigns to alleviate patient concerns, and encourage them to seek timely medical attention despite the COVID-19 pandemic.


title: Características clínicas y epidemiológicas de las neumonías adquiridas en la comunidad por Mycoplasma pneumoniae en una población española, 2010-2015

text: Resumen Introducción y objetivos Mycoplasma pneumoniae (MP) es uno de los agentes etiológicos más comunes de las neumonías adquiridas en la comunidad (NAC) en niños. Objetivo: describir las características clínicas y epidemiológicas, tratamiento y evolución de los pacientes con NAC por MP (NACM) en un hospital terciario de Valencia, España. Material y métodos Se revisaron retrospectivamente las historias clínicas de los niños<14 años con NACM entre enero de 2010 y diciembre de 2015. Los pacientes con evidencia radiológica de neumonía y confirmación microbiológica de MP (PCR de exudado nasofaríngeo y/o anticuerpos IgM específicos frente a MP) se consideraron NACM. Resultados Un total de 162 pacientes se diagnosticaron de NACM; mediana de edad de 6 años (rango intercuartílico: 4-9 años). La proporción de pruebas positivas para MP en pacientes con NAC, así como el uso empírico de macrólidos, aumentó progresivamente con la edad. Hubo un pico de casos en 2011 y en 2015, con un máximo de casos en julio, agosto, noviembre y diciembre. El patrón radiológico más frecuente fue el infiltrado segmentario (62,3%), mientras que 22 (13,6%) presentaron derrame pleural. Los niños con NACM desarrollaron una clínica leve, con poca elevación de parámetros inflamatorios. Se inició tratamiento empírico con un macrólido en el 68,5% de los casos. La necesidad de ingreso hospitalario fue inversamente proporcional a la edad del paciente. Conclusiones Según este estudio, los niños con NAC de mayor edad tuvieron la mayor proporción de infección por MP, siendo poco sintomáticos y con escasa elevación de parámetros inflamatorios, pudiéndose beneficiar del tratamiento empírico con macrólidos. Por consiguiente, conocer la epidemiología de un área geográfica podría ser importante para el abordaje de las NAC en niños. Abstract Introduction and objectives Mycoplasma pneumoniae (MP) is one of the most common etiological agents of community-acquired pneumonia (CAP) in children. We aimed to describe the clinical and epidemiological characteristics, treatment and outcome of children diagnosed with community-acquired MP pneumonia (CAMP) in a tertiary hospital in Valencia, Spain. Material and methods Medical records of children <14 years with CAMP were retrospectively reviewed from January 2010 to December 2015. Patients with radiological evidence of pneumonia and microbiological confirmation of MP (PCR from nasopharyngeal swab and/or serum specific IgM) were considered CAMP. Results One hundred and sixty two children were diagnosed with CAMP; median age 6 years (IQR: 4-9). The positive MP test rate among children with CAP progressively increased with age as did the empirical use of macrolides. There were two peaks of cases in 2011 and in 2015, being July, August, November and December the seasons with the higher number of cases. The most frequent radiological pattern was segmental infiltrate (62.3%) and 22 (13.6%) children had pleural effusion. It was noteworthy the mild symptomatology and low levels of inflammatory parameters that children with CAMP had. A macrolide was empirically initiated in 68.5% of cases. Hospital admission rate was inversely proportional to patient's age. Conclusions According to this study, older, less symptomatic patients and with lower inflammatory parameters had the greatest rate of MP infection among children with CAP and thus they could benefit of empiric macrolide therapy. Therefore, knowing the epidemiology of a geographical area may be important for the management of CAP in children.


title: Central Nervous System Viral Diseases

text: The nervous system has multiple intrinsic defenses against viral infection, including the blood–brain barrier. Yet, the postmitotic nature of neurons creates a uniquely vulnerable environment susceptible to irreversible damage. Various viruses can infect the different cell types within the central nervous system, neurons, oligodendrocytes, astrocytes, and microglia. Infections can cause acute and chronic infections. While there are a large number of well-defined viral-mediated diseases of the nervous system, there are an equal number of diseases that may have an as of yet unproven viral etiology. Damage to the cells can happen via cytopathic and nonlytic mechanisms. Clearance of viruses can occur via cell-mediated and antibody-mediated processes. In some cases, viruses are never cleared from the nervous system completely, and can episodically reactivate. Understanding the potential pathways and outcomes of viral infections is necessary for determining the possible role viruses may play in a variety of diseases.


title: MOVING H5N1 STUDIES INTO THE ERA OF SYSTEMS BIOLOGY

text: The dynamics of H5N1 influenza virus pathogenesis are multifaceted and can be seen as an emergent property that cannot be comprehended without looking at the system as a whole. In past years, most of the high-throughput studies on H5N1-host interactions have focused on the host transcriptomic response, at the cellular or the lung tissue level. These studies pointed out that the dynamics and magnitude of the innate immune response and immune cell infiltration is critical to H5N1 pathogenesis. However, viral-host interactions are multidimensional and advances in technologies are creating new possibilities to systematically measure additional levels of ‘omic data (e.g. proteomic, metabolomic, and RNA profiling) at each temporal and spatial scale (from the single cell to the organism) of the host response. Natural host genetic variation represents another dimension of the host response that determines pathogenesis. Systems biology models of H5N1 disease aim at understanding and predicting pathogenesis through integration of these different dimensions by using intensive computational modeling. In this review, we describe the importance of ‘omic studies for providing a more comprehensive view of infection and mathematical models that are being developed to integrate these data. This review provides a roadmap for what needs to be done in the future and what computational strategies should be used to build a global model of H5N1 pathogenesis. It is time for systems biology of H5N1 pathogenesis to take center stage as the field moves towards a more comprehensive view of virus-host interactions.


title: The four of structural genes sequences of a porcine epidemic diarrhea virus from domestic piglet in Fujian, China

text: A prevalent PEDV strain, designated FJLY06, was isolated from Fujian, China. The four of structural genes sequences of PEDV obtained were analyzed to determine their phylogenetic relationships and homology respectively, revealing that FJLY06 was highly homologous to virulent PEDV strains. The four structural genes all differed genetically from the vaccine strain CV777. The sequence alignment results further showed that N, M and E genes of Chinese PEDV strains is highly conserved. Compared with the vaccine strain CV777, 8 mutations were detected in COE of FJLY06 S gene. The recombination analysis revealed FJLY06 is similar to other pandemic strains in China with a variant S gene, and maybe a reason for recent vaccination failures.


title: In situ detection of Australian gill-associated virus with a yellow head virus gene probe

text: Abstract A digoxigenin-labeled gene probe for yellow head virus (YHV) was used to detect gill-associated virus (GAV) in Penaeus monodon from Australia via in situ hybridization. In GAV-infected shrimp, positively reacting tissues included: lymphoid organ, gills, antennal gland, and cuticular epithelium of the stomach. This demonstrates that a YHV probe can be used as a diagnostic tool for GAV and supports previous suggestions that these two viruses are closely related.


title: Editorial: Transforming Global Health, Global Health Education, Infectious Disease, and Chronic Conditions in the 21st Century

text: Chronic and infectious diseases, including health care-associated infections and tropical diseases, represent a large portion of the global health burden. Solutions need to be found while addressing other health priorities identified by the Millennium Development Goals. A number of organizations and initiatives have been created to meet this need. Developing countries in Latin America and several African countries are taking a larger role in the development of robust health systems, capacity building, and education. Integrated, efficient, and equitable health systems that incorporate primary, secondary, and tertiary care models with a research focus are critically needed to fill this void.


title: Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa

text: Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.


title: Detection of respiratory viral and bacterial pathogens causing pediatric community-acquired pneumonia in Beijing using real-time PCR

text: OBJECTIVE: The aim of this study was to determine the etiology and prevalence of pediatric CAP in Beijing using a real-time polymerase chain reaction (PCR) technique. METHODS: Between February 15, 2011 and January 18, 2012, 371 pediatric patients with CAP were enrolled at Beijing Children's Hospital. Sixteen respiratory viruses and two bacteria were detected from tracheal aspirate specimens using commercially available multiplex real-time reverse transcription PCR (RT-PCR) kits. RESULTS: A single viral pathogen was detected in 35.3% of enrolled patients, multiple viruses in 11.6%, and virus/bacteria coinfection in 17.8%. In contrast, only 6.5% of patients had a single bacterial pathogen and 2.2% were infected with multiple bacteria. The etiological agent was unknown for 26.7% of patients. The most common viruses were respiratory syncytial virus (RSV) (43.9%), rhinovirus (14.8%), parainﬂuenza virus (9.4%), and adenovirus (8.6%). In patients under three years of age, RSV (44.6%), rhinovirus (12.8%), and Streptococcus pneumoniae (9.9%) were the most frequent pathogens. In children aged 3–7 years, S. pneumoniae (38.9%), RSV (30.6%), Haemophilus inﬂuenzae (19.4%), and adenovirus (19.4%) were most prevalent. Finally in children over seven years, RSV (47.3%), S. pneumoniae (41.9%), and rhinovirus (21.5%) infections were most frequent. CONCLUSIONS: Viral pathogens, specifically RSV, were responsible for the majority of CAP in pediatric patients. However, both S. pneumoniae and H. inﬂuenzae contributed as major causes of disease. Commercially available multiplexing real-time PCR allowed for rapid detection of the etiological agent.


title: Role of viral infections in the development and exacerbation of asthma in children

text: Viral infections are closely linked to wheezing illnesses in children of all ages. Respiratory syncytial virus (RSV) is the main causative agent of bronchiolitis, whereas rhinovirus (RV) is most commonly detected in wheezing children thereafter. Severe respiratory illness induced by either of these viruses is associated with subsequent development of asthma, and the risk is greatest for young children who wheeze with RV infections. Whether viral illnesses actually cause asthma is the subject of intense debate. RSV-induced wheezing illnesses during infancy influence respiratory health for years. There is definitive evidence that RSV-induced bronchiolitis can damage the airways to promote airway obstruction and recurrent wheezing. RV likely causes less structural damage and yet is a significant contributor to wheezing illnesses in young children and in the context of asthma. For both viruses, interactions between viral virulence factors, personal risk factors (eg, genetics), and environmental exposures (eg, airway microbiome) promote more severe wheezing illnesses and the risk for progression to asthma. In addition, allergy and asthma are major risk factors for more frequent and severe RV-related illnesses. Treatments that inhibit inflammation have efficacy for RV-induced wheezing, whereas the anti-RSV mAb palivizumab decreases the risk of severe RSV-induced illness and subsequent recurrent wheeze. Developing a greater understanding of personal and environmental factors that promote more severe viral illnesses might lead to new strategies for the prevention of viral wheezing illnesses and perhaps reduce the subsequent risk for asthma.


title: Real-time characterization of risks of death associated with the Middle East respiratory syndrome (MERS) in the Republic of Korea, 2015

text: BACKGROUND: An outbreak of the Middle East respiratory syndrome (MERS), comprising 185 cases linked to healthcare facilities, occurred in the Republic of Korea from May to July 2015. Owing to the nosocomial nature of the outbreak, it is particularly important to gain a better understanding of the epidemiological determinants characterizing the risk of MERS death in order to predict the heterogeneous risk of death in medical settings. METHODS: We have devised a novel statistical model that identifies the risk of MERS death during the outbreak in real time. While accounting for the time delay from illness onset to death, risk factors for death were identified using a linear predictor tied to a logit model. We employ this approach to (1) quantify the risks of death and (2) characterize the temporal evolution of the case fatality ratio (CFR) as case ascertainment greatly improved during the course of the outbreak. RESULTS: Senior persons aged 60 years or over were found to be 9.3 times (95 % confidence interval (CI), 5.3–16.9) more likely to die compared to younger MERS cases. Patients under treatment were at a 7.8-fold (95 % CI, 4.0–16.7) significantly higher risk of death compared to other MERS cases. The CFR among patients aged 60 years or older under treatment was estimated at 48.2 % (95 % CI, 35.2–61.3) as of July 31, 2015, while the CFR among other cases was estimated to lie below 15 %. From June 6, 2015, onwards, the CFR declined 0.3-fold (95 % CI, 0.1–1.1) compared to the earlier epidemic period, which may perhaps reflect enhanced case ascertainment following major contact tracing efforts. CONCLUSIONS: The risk of MERS death was significantly associated with older age as well as treatment for underlying diseases after explicitly adjusting for the delay between illness onset and death. Because MERS outbreaks are greatly amplified in the healthcare setting, enhanced infection control practices in medical facilities should strive to shield risk groups from MERS exposure.