title: Achieving Effective Informed Oversight by DMCs in COVID Clinical Trials

text: Abstract Best practices of Data Monitoring Committees (DMCs) in randomized clinical trials are well established. Independent oversight provided by DMCs is particularly important in trials conducted in public health emergencies, such as in HIV/AIDS or coronavirus epidemics. Special considerations are needed to enable DMCs to effectively address novel circumstances they face in such settings. In the COVID-19 pandemic, these include the remarkable speed in which data regarding benefits and risks of interventions are accumulated. DMCs must hold frequent virtual meetings, using state-of-the-art communication software that protects against risk for security breaches. Data capture and DMC reports should be focused on the most informative measures about benefits and risks. Since numerous clinical trials are being concurrently conducted in the COVID-19 setting, often addressing closely related scientific questions, structures for DMC oversight should be efficient and adequately informative. When these concurrently conducted trials are evaluating related regimens in related clinical settings, often individually underpowered for safety and having separate DMCs, processes should be implemented enabling these DMCs to share with each other emerging confidential evidence to better assess risks and benefits. Ideally a single DMC would monitor a portfolio of clinical trials or a trial with multiple arms, such as a platform trial.


title: Managing ocular allergy in the time of COVID‐19

text: This spring, the majority of allergic patients are confined to their homes due to COVID-19 pandemic restrictions. In the following weeks, these restrictions will be reduced andpeople will be allowed to take walks, go jogging, and return to work.Spring is the time for ocular allergy (OA) to emerge with signs and symptoms consequent to increasing pollen counts. Even when wearing a mask, the eyes may remain unprotectedleading to an increase in ocular symptoms and patients seeking treatment forOA. However, access to routine consultation may remain problematic for many patients.


title: International Guidelines And Recommendations For Surgery During Covid-19 Pandemic: A Systematic Review

text: BACKGROUND: During the COVID-19 pandemic, surgical departments were forced to re-schedule their activity giving priority to urgent procedures and non-deferrable oncological cases. There is a lack of evidence-based literature providing clinical and organizational guidelines for the management of a general surgery department. Aim of our study was to review the available recommendations published by general Surgery Societies and Health Institutions and evaluate the underlying Literature. MATERIALS AND METHODS: A review of the English Literature was conducted according to the AMSTAR and to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. RESULTS: After eligibility assessment, a total of 22 papers and statements were analyzed. Surgical societies have established criteria for triage and prioritization in order to identify procedures that can be postponed after the pandemic and those that should not. Prioritization among oncologic cases represents a difficult task: clinicians have to balance a possible delay in cancer diagnosis or treatment against the risk for a potential COVID-19 exposure. There is broad agreement among guidelines that indication to proceed with surgery should be discussed in virtual Tumor Boards taking into consideration alternative therapeutic approaches. Several guidelines deal with the role of laparoscopic surgery during the pandemic: a tailored approach is currently suggested, with a case-by-case evaluation provided that appropriate personal protective equipment is available in order to minimize the potential risk of transmission. Finally, there is a considerable agreement in the published Literature concerning the management of the personnel during the peri- and intraoperative phase and on the technical advices regarding the induction, operative and recover maneuvers in COVID-19 cases. CONCLUSIONS: During COVID-19 pandemic, it is of paramount importance to face the emergency in the most effective and efficient manner, retrieving resources from non-essential settings and, at the same time, providing care to high priority non-COVID-19 related diseases.


title: Identification of G-quadruplex forming sequences in three manatee papillomaviruses

text: The Florida manatee (Trichechus manatus latirotris) is a threatened aquatic mammal in United States coastal waters. Over the past decade, the appearance of papillomavirus-induced lesions and viral papillomatosis in manatees has been a concern for those involved in the management and rehabilitation of this species. To date, three manatee papillomaviruses (TmPVs) have been identified in Florida manatees, one forming cutaneous lesions (TmPV1) and two forming genital lesions (TmPV3 and TmPV4). We identified DNA sequences with the potential to form G-quadruplex structures (G4) across the three genomes. G4 were located on both DNA strands and across coding and non-coding regions on all TmPVs, offering multiple targets for viral control. Although G4 have been identified in several viral genomes, including human PVs, most research has focused on canonical structures comprised of three G-tetrads. In contrast, the vast majority of sequences we identified would allow the formation of non-canonical structures with only two G-tetrads. Our biophysical analysis confirmed the formation of G4 with parallel topology in three such sequences from the E2 region. Two of the structures appear comprised of multiple stacked two G-tetrad structures, perhaps serving to increase structural stability. Computational analysis demonstrated enrichment of G4 sequences on all TmPVs on the reverse strand in the E2/E4 region and on both strands in the L2 region. Several G4 sequences occurred at similar regional locations on all PVs, most notably on the reverse strand in the E2 region. In other cases, G4 were identified at similar regional locations only on PVs forming genital lesions. On all TmPVs, G4 sequences were located in the non-coding region near putative E2 binding sites. Together, these findings suggest that G4 are possible regulatory elements in TmPVs.


title: Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID‐19) implicate special control measures

text: By 27 February 2020, the outbreak of coronavirus disease 2019 (COVID‐19) caused 82 623 confirmed cases and 2858 deaths globally, more than severe acute respiratory syndrome (SARS) (8273 cases, 775 deaths) and Middle East respiratory syndrome (MERS) (1139 cases, 431 deaths) caused in 2003 and 2013, respectively. COVID‐19 has spread to 46 countries internationally. Total fatality rate of COVID‐19 is estimated at 3.46% by far based on published data from the Chinese Center for Disease Control and Prevention (China CDC). Average incubation period of COVID‐19 is around 6.4 days, ranges from 0 to 24 days. The basic reproductive number (R(0)) of COVID‐19 ranges from 2 to 3.5 at the early phase regardless of different prediction models, which is higher than SARS and MERS. A study from China CDC showed majority of patients (80.9%) were considered asymptomatic or mild pneumonia but released large amounts of viruses at the early phase of infection, which posed enormous challenges for containing the spread of COVID‐19. Nosocomial transmission was another severe problem. A total of 3019 health workers were infected by 12 February 2020, which accounted for 3.83% of total number of infections, and extremely burdened the health system, especially in Wuhan. Limited epidemiological and clinical data suggest that the disease spectrum of COVID‐19 may differ from SARS or MERS. We summarize latest literatures on genetic, epidemiological, and clinical features of COVID‐19 in comparison to SARS and MERS and emphasize special measures on diagnosis and potential interventions. This review will improve our understanding of the unique features of COVID‐19 and enhance our control measures in the future.


title: Clinical Outcome of Coronavirus Disease 2019 in Haemato‐oncology Patients

text: Since being identified in China in December 2019, coronavirus disease 2019 (Covid‐19) has rapidly evolved into a global pandemic with over 4 million cases and more than 270,000 deaths.(1) Following the first reported cases in the United Kingdom (UK) in late January 2020, numbers have continued to rise with 223,060 cases and 32,065 deaths reported as of 11(th) May 2020.(2) Initial reports from China have indicated that Covid‐19 has an overall mortality rate of 1.4%. However, the prognosis varies widely between groups, with age over 60 years and underlying conditions including hypertension, diabetes, cardiovascular disease and cancer identified as risk factors for severe disease and death.(3) The initial reports from China show that patients with cancer are over‐represented among individuals who develop severe Covid‐19 after contracting the virus.(4) Patients with haematological malignancies are expected to be at increased risk of adverse outcomes from this viral infection, due being immunosuppressed as a consequence of the underlying cancer, and from the effects of therapy.


title: Telemedicine for Outpatient Neurosurgical Oncology Care: Lessons Learned for the Future During the COVID-19 Pandemic

text: Abstract Background The 2019 Coronavirus pandemic has drastically disrupted the delivery of Neurosurgical care, especially for the already at-risk neuro-oncology population. The sudden change to clinic visits has rapidly spurned the implementation of telemedicine. A recommendation care paradigm of neuro-oncologic patients limited by telemedicine has not been reported. Methods A summary of a multi-institution experience detailing the potential benefits, pitfalls and the necessary considerations to outpatient care of neurosurgical oncology patients. Results There are limitations and advantages to incorporating telemedicine into the outpatient care of neuro-oncology patients. Telemedicine-specific considerations for each step and stakeholder of the appointment (physician, patient, scheduling, pre-visit, imaging, and physical examination) are examined. Conclusions Telemedicine, pushed to prominence during this COVID-19 pandemic, is a powerful and possibly preferential tool for the future of outpatient neuro-oncologic care.


title: First COVID-19 infections in the Philippines: a case report

text: BACKGROUND: The novel coronavirus (COVID-19) is responsible for more fatalities than the SARS coronavirus, despite being in the initial stage of a global pandemic. The first suspected case in the Philippines was investigated on January 22, 2020, and 633 suspected cases were reported as of March 1. We describe the clinical and epidemiological aspects of the first two confirmed COVID-19 cases in the Philippines, both admitted to the national infectious disease referral hospital in Manila. CASE PRESENTATION: Both patients were previously healthy Chinese nationals on vacation in the Philippines travelling as a couple during January 2020. Patient 1, a 39-year-old female, had symptoms of cough and sore throat and was admitted to San Lazaro Hospital in Manila on January 25. Physical examination was unremarkable. Influenza B, human coronavirus 229E, Staphylococcus aureus and Klebsiella pneumoniae were detected by PCR on initial nasopharyngeal/oropharyngeal (NPS/OPS) swabs. On January 30, SARS-CoV-2 viral RNA was reported to be detected by PCR on the initial swabs and she was identified as the first confirmed COVID-19 case in the Philippines. Her symptoms resolved, and she was discharged. Patient 2, a 44-year-old male, had symptoms of fever, cough, and chills. Influenza B and Streptococcus pneumoniae were detected by PCR on initial NPS/OPS swabs. He was treated for community-acquired pneumonia with intravenous antibiotics, but his condition deteriorated and he required intubation. On January 31, SARS-CoV-2 viral RNA was reported to be detected by PCR on the initial swabs, and he was identified as the 2nd confirmed COVID-19 infection in the Philippines. On February 1, the patient’s condition deteriorated, and following a cardiac arrest, it was not possible to revive him. He was thus confirmed as the first COVID-19 death outside of China. CONCLUSIONS: This case report highlights several important clinical and public health issues. Despite both patients being young adults with no significant past medical history, they had very different clinical courses, illustrating how COVID-19 can present with a wide spectrum of disease. As of March 1, there have been three confirmed COVID-19 cases in the Philippines. Continued vigilance is required to identify new cases.


title: Opportunities and Risks of Host-targeting Antiviral Strategies for Hepatitis C

text: Hepatitis C virus (HCV) infects more than 2 % of the world population with highest prevalence in parts of Africa and Asia. Past standard of care using interferon α and ribavirin had adverse effects and showed modest efficacy for some HCV genotypes spurring the development of direct acting antivirals (DAAs). Such DAAs target viral proteins and are thus better tolerated but they suffer from emergence of vial resistance. Furthermore, DAAs are often HCV genotype specific. Novel drug candidates targeting host factors required for HCV propagation, so called host-targeting antivirals (HTAs), promise to overcome both caveats. The genetic barrier to resistance is usually considered to be high for HTAs and all HCV genotypes presumably use the same host factors. Recent data, however, challenge these assumptions, at least for some HTAs. Here, we highlight the most important host-targeting strategies against hepatitis C and critically discuss their opportunities and risks.


Report from the 36(th) and the 37(th) Meetings of the Executive Committee of the International Committee on Taxomony of Viruses


Public‐private partnership: strategies for continuing urgent elective operative care during the COVID‐19 pandemic


title: Functional repertoire, molecular pathways and diseases associated with 3D domain swapping in the human proteome

text: BACKGROUND: 3D domain swapping is a novel structural phenomenon observed in diverse set of protein structures in oligomeric conformations. A distinct structural feature, where structural segments in a protein dimer or higher oligomer were shared between two or more chains of a protein structure, characterizes 3D domain swapping. 3D domain swapping was observed as a key mediator of numerous functional mechanisms and play pathogenic role in various diseases including conformational diseases like amyloidosis, Alzheimer's disease, Parkinson's disease and prion diseases. We report the first study with a focus on identifying functional classes, pathways and diseases mediated by 3D domain swapping in the human proteome. METHODS: We used a panel of four enrichment tools with two different ontologies and two annotations database to derive biological and clinical relevant information associated with 3D domain swapping. Protein domain enrichment analysis followed by Gene Ontology (GO) term enrichment analysis revealed the functional repertoire of proteins involved in swapping. Pathway analysis using KEGG annotations revealed diverse pathway associations of human proteins involved in 3D domain swapping. Disease Ontology was used to find statistically significant associations with proteins in swapped conformation and various disease categories (P-value < 0.05). RESULTS: We report meta-analysis results of a literature-curated dataset of human gene products involved in 3D domain swapping and discuss new insights about the functional repertoire, pathway associations and disease implications of proteins involved in 3D domain swapping. CONCLUSIONS: Our integrated bioinformatics pipeline comprising of four different enrichment tools, two ontologies and two annotations revealed new insights into the functional and disease correlations with 3D domain swapping. GO term enrichment were used to infer terms associated with three different GO categories. Protein domain enrichment was used to identify conserved domains enriched in swapped proteins. Pathway enrichment analysis using KEGG annotations revealed that proteins with swapped conformations are present in all six classes of KEGG BRITE hierarchy and significantly enriched KEGG pathways were observed in five classes. Five major classes of disease were found to be associated with 3D domain swapping using functional disease ontology based enrichment analysis. Five classes of human diseases: cancer, diseases of the respiratory or pulmonary system, degenerative diseases of the central nervous system, vascular disease and encephalitis were found to be significant. In conclusion, our study shows that bioinformatics based analytical approaches using curated data can enhance the understanding of functional and disease implications of 3D domain swapping.


title: The dominance of human coronavirus OC43 and NL63 infections in infants

text: Abstract Background It is unknown to what extent the human coronaviruses (HCoVs) OC43, HKU1, 229E and NL63 infect healthy children. Frequencies of infections are only known for hospitalized children. Objectives Comparing infection frequencies in children who have mild infections with frequencies in children needing hospital uptake will determine whether infection by one of the four HCoVs leads to more severe disease. In addition, the sequence of seroconversions can reveal whether infection by one HCoV protects from infection by other HCoVs. Study design Two distinct study groups were monitored: healthy children and children hospitalized due to respiratory infection. HCoV natural infection rates in healthy children were obtained by serology in 25 newborns (followed 0–20months). The frequencies of severe HCoVs infection was determined by real time RT-PCR among 1471 hospitalized infants (<2-years old) with acute respiratory tract disease. Results The majority of healthy children seroconverted for HCoV-OC43 (n =19) and HCoV-NL63 (n =17), less for HCoV-HKU1 (n =9) and HCoV-229E (n =5). Notably, HCoV-HKU1 seroconversion was absent after HCoV-OC43 infection. Also HCoV-229E infection was rarely observed after HCoV-NL63 infection (1 out of 5). In the hospital 207 (14%) out of 1471 children were HCoV positive. Again we observed most infection by HCoV-OC43 (n =85) and HCoV-NL63 (n =60), followed by HCoV-HKU1 (n =47) and HCoV-229E (n =15). Conclusions HCoV-NL63 and HCoV-OC43 infections occur frequently in early childhood, more often than HCoV-HKU1 or HCoV-229E infections. HCoV-OC43 and HCoV-NL63 may elicit immunity that protects from subsequent HCoV-HKU1 and HCoV-229E infection, respectively, which would explain why HCoV-OC43 and HCoV-NL63 are the most frequently infecting HCoVs. There are no indications that infection by one of the HCoVs is more pathogenic than others.


title: Chapter 30 Neurologic aspects of influenza viruses

text: Abstract Although influenza A and B viruses are primarily known as respiratory viruses and mainly infected only the upper respiratory tract in humans, patients with influenza often develop signs and symptoms that are not due to the respiratory system. Frequently individuals with influenza develop headaches, meningismus, and even seizures in addition to their typical respiratory symptoms. In the past decades, influenza viruses have also been associated with serious non-respiratory signs. The famous 1918 strain of influenza was associated with von Economo's encephalitis lethargica and postencephalitic parkinsonism. In the 1960s influenza virus infections in children were associated with Reye's syndrome characterized often by fatty non-inflammatory hepatic disease and an encephalopathy with marked non-inflammatory cerebral edema. Intermittently children with influenza develop focal myalgia and myositis. Guillain–Barré syndrome was epidemiologically associated with the 1978 killed influenza vaccine but not subsequent vaccines. Although occasional children with influenza have developed encephalopathy, from 2000 through 2004 there was an increase in the number of serious cases of acute necrotizing encephalopathy accompanying infection with the influenza A 2009 strain. The current H5N1 strain of bird influenza occasionally infects humans with a high mortality rate and some appear to have central nervous signs. This chapter explores what is known about these influenza neurologic associations.


title: Cell Type-Dependent RNA Recombination Frequency in the Japanese Encephalitis Virus

text: Japanese encephalitis virus (JEV) is one of approximately 70 flaviviruses, frequently causing symptoms involving the central nervous system. Mutations of its genomic RNA frequently occur during viral replication, which is believed to be a force contributing to viral evolution. Nevertheless, accumulating evidences show that some JEV strains may have actually arisen from RNA recombination between genetically different populations of the virus. We have demonstrated that RNA recombination in JEV occurs unequally in different cell types. In the present study, viral RNA fragments transfected into as well as viral RNAs synthesized in mosquito cells were shown not to be stable, especially in the early phase of infection possibly via cleavage by exoribonuclease. Such cleaved small RNA fragments may be further degraded through an RNA interference pathway triggered by viral double-stranded RNA during replication in mosquito cells, resulting in a lower frequency of RNA recombination in mosquito cells compared to that which occurs in mammalian cells. In fact, adjustment of viral RNA to an appropriately lower level in mosquito cells prevents overgrowth of the virus and is beneficial for cells to survive the infection. Our findings may also account for the slower evolution of arboviruses as reported previously.


title: Chapter Seven The roles of cytosolic quality control proteins, SGTA and the BAG6 complex, in disease

text: Abstract SGTA is a co-chaperone that, in collaboration with the complex of BAG6/UBL4A/TRC35, facilitates the biogenesis and quality control of hydrophobic proteins, protecting them from the aqueous cytosolic environment. This work includes targeting tail-anchored proteins to their resident membranes, sorting of membrane and secretory proteins that mislocalize to the cytoplasm and endoplasmic reticulum-associated degradation of misfolded proteins. Since these functions are all vital for the cell's continued proteostasis, their disruption poses a threat to the cell, with a particular risk of protein aggregation, a phenomenon that underpins many diseases. Although the specific disease implications of machinery involved in quality control of hydrophobic substrates are poorly understood, here we summarize much of the available information on this topic.


title: Outbreak of Clostridium difficile‐Associated Disease in a Small Animal Veterinary Teaching Hospital

text: An apparent outbreak of enteric disease occurred in dogs and cats at a veterinary teaching hospital. Clostridium difficile Toxin A or B or both were identified in 1 or more fecal samples from 48 of 93 (52%) dogs over a 5‐month period, 30 of which were identified in the 1st 26 days, after which strict infection control measures, including closure to elective cases, were implemented. Affected animals included in‐patients, out‐patients that were housed temporarily in the wards, and resident blood donor dogs. Infection control measures, including partial depopulation, isolation, hospital and yard cleaning, and barrier precautions, were instituted, after which, the incidence of nosocomial diarrhea decreased from 19 cases per 1,000 admissions to 2.5 cases per 1,000 admissions (P <0.001)


title: The putative protein 6 of the severe acute respiratory syndrome-associated coronavirus: Expression and functional characterization

text: Abstract The SARS-CoV open reading frame 6 (ORF6) is transcribed into mRNA6 and encodes a putative 7.5kDa accessory protein, SARS 6, with unknown function. In this study, we have confirmed the SARS 6 protein expression in lung and intestine tissues of the SARS patients and in SARS-CoV infected Vero E6 cells by immunohistochemistry. Further studies by immunoblot and confocal microscopy analyses revealed the expression and the endoplasmic reticulum (ER) localization of the recombinant SARS 6 protein in mammalian cells. Expression of SARS 6 protein in mammalian cells elicits biological activity of stimulating cellular DNA synthesis.


title: Carbon nanotubes supported tyrosinase in the synthesis of lipophilic hydroxytyrosol and dihydrocaffeoyl catechols with antiviral activity against DNA and RNA viruses

text: Abstract Hydroxytyrosol and dihydrocaffeoyl catechols with lipophilic properties have been synthesized in high yield using tyrosinase immobilized on multi-walled carbon nanotubes by the Layer-by-Layer technique. All synthesized catechols were evaluated against a large panel of DNA and RNA viruses, including Poliovirus type 1, Echovirus type 9, Herpes simplex virus type 1 (HSV-1), Herpes simplex virus type 2 (HSV-2), Coxsackievirus type B3 (Cox B3), Adenovirus type 2 and type 5 and Cytomegalovirus (CMV). A significant antiviral activity was observed in the inhibition of HSV-1, HSV-2, Cox B3 and CMV. The mechanism of action of the most active dihydrocaffeoyl derivative was investigated against a model of HSV-1 infection.


title: Prevalence of enteric pathogens in diarrheic and non-diarrheic samples from pig farms with neonatal diarrhea in the North East of Spain

text: Abstract Diarrhea is one of the major causes of neonatal mortality in pigs. In the present study, 31 pig farms with outbreaks of neonatal diarrhea were investigated in Catalonia (NE Spain) from February 2017 until June 2018. Two hundred and fifteen diarrheic samples from 1 to 7 days old piglets were tested for a panel of enteric pathogens. In 19 of the studied farms additional fecal samples from apparently healthy pen-mates were collected and tested for the same panel of infectious agents. Samples were bacteriologically cultured and tested by PCR for E. coli virulence factors genes, C. perfringens types A and C toxins (Cpα, Cpβ, Cpβ2) and C. difficile toxins (TcdA, TcdB). Moreover, Rotavirus A (RVA), Rotavirus B (RVB), Rotavirus C (RVC), porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) were also determined by RT-qPCR. More than one pathogen could be detected in all of the outbreaks. Nevertheless, RVA was the only agent that could be statistically correlated with the outcome of diarrhea. For the other viruses and bacteria analyzed significant differences between the diseased pigs and the controls were not found. In spite of this, the individual analysis of each of the studied farms indicated that other agents such as RVB, RVC, toxigenic C. difficile or pathogenic E. coli could play a relevant role in the outbreak of diarrhea. In conclusion, the large diversity of agent combinations and disease situations detected in neonatal diarrhea outbreaks of this study stand for a more personalized diagnosis and management advice at a farm level.


title: Detection of antibodies to avian infectious bronchitis virus by a recombinant nucleocapsid protein-based enzyme-linked immunosorbent assay

text: Abstract The recombinant antigen obtained by cloning and expressing two IBV nucleocapsid protein fragments (143-414 aa, 281-414 aa) in Escherichia coli was used for the detection of avian infectious bronchitis virus (IBV) specific antibodies in chicken sera by the indirect ELISA (rNpIBV-ELISA). As a result of testing 1524 serum samples the diagnostic sensitivity and specificity of rNpIBV-ELISA when comparing those of the routine whole IBV ELISA have been shown to be 93.81% and 87.36%, respectively. The agreement value was 91.5%.


title: Understanding the penetrance of intrinsic protein disorder in rotavirus proteome

text: Abstract Rotavirus is a major cause of severe acute gastroenteritis in the infants and young children. The past decade has evidenced the role of intrinsically disordered proteins/regions (IDPs)/(IDPRs) in viral and other diseases. In general, (IDPs)/(IDPRs) are considered as dynamic conformational ensembles that devoid of a specific 3D structure, being associated with various important biological phenomena. Viruses utilize IDPs/IDPRs to survive in harsh environments, to evade the host immune system, and to highjack and manipulate host cellular proteins. The role of IDPs/IDPRs in Rotavirus biology and pathogenicity are not assessed so far, therefore, we have designed this study to deeply look at the penetrance of intrinsic disorder in rotavirus proteome consisting 12 proteins encoded by 11 segments of viral genome. Also, for all human rotaviral proteins, we have deciphered molecular recognition features (MoRFs), which are disorder based binding sites in proteins. Our study shows the wide spread of intrinsic disorder in several rotavirus proteins, primarily the nonstructural proteins NSP3, NSP4, and NSP5 that are involved in viral replication, translation, viroplasm formation and/or maturation. This study may serve as a primer for understanding the role of IDPs/MoRFs in rotavirus biology, design of alternative therapeutic strategies, and development of disorder-based drugs.


title: Identification of Viruses in Patients With Postviral Olfactory Dysfunction

text: Objective: Causative viruses of postviral olfactory dysfunction (PVOD) have not yet been identified. The aim of this study was to investigate causative viruses in patients with PVOD. Study Design and Methods: Nasal discharge was collected from 24 patients with PVOD. We investigated the presence of 10 viruses in nasal discharge and examined the time course, with regard to changes in olfactory dysfunction and nasal obstruction in patients with PVOD, using questionnaires, acoustic rhinometry, and olfactory tests. Results: Rhinoviruses were detected in 10 patients by electrophoresis. Rhinoviruses were also confirmed in four patients by nucleotide sequences. Viral serotypes were identified to be human rhinovirus (HRV)‐40, HRV‐75, HRV‐78, and HRV‐80. One of the four patients complained of anosmia, whereas another complained of dysosmia. Olfactory testing did not show significant improvement at 4, 8, 11, and 24 weeks after the first visit in the four patients, although results of acoustic rhinometry significantly improved. Two of the four patients complained of olfactory dysfunction even 6 months after the first visit. Coronavirus and parainfluenza virus were detected in one patient each, and Epstein‐Barr viruses were detected in three patients. Conclusions: This study for the first time detected rhinovirus, coronavirus, parainfluenza virus, and Epstein‐Barr virus in nasal discharge of patients with PVOD. Furthermore, the present study suggests that rhinoviruses can cause olfactory dysfunction through mechanisms other than nasal obstruction and that rhinoviruses can induce various severities and different time courses of olfactory dysfunction.


title: Construction and application of surveillance and response systems for parasitic diseases in China, led by NIPD

text: Parasitic diseases have been widely epidemic in China with a long history. Great endeavours made in past 70 years led to significant decrease in morbidity and mortablity caused by several major parasitic diseases, while challenges existed to eliminate parasitic diseases. Surveillance-response system has play a crucial role in identifying public health problems, ascertaining the distribution and epidemic dynamics, discovering outbreaks and epidemic anomalies, evaluating the effects of on-site intervention activities and identifying risk factors. In this article, we reviewed the progress of the surveillance system for parasitic diseases, analysed the role of NIPD in the construction and application of surveillance-response system of parasitic diseases through elaborating the surveillance activities and typical surveillance-response events led by NIPD. Suggestion and comments for improve the surveillance-response system were put forward for further control or elimination of parasitic diseases.


title: Novel coronavirus 19 (COVID-19) associated sinus node dysfunction: a case series

text: BACKGROUND: Novel coronavirus-19 disease (COVID-19) is associated with significant cardiovascular morbidity and mortality. To date, there have not been reports of sinus node dysfunction (SND) associated with COVID-19. This case series describes clinical characteristics, potential mechanisms, and short-term outcomes of COVID-19 patients who experience de novo SND. CASE SUMMARY: We present two cases of new-onset SND in patients recently diagnosed with COVID-19. Patient 1 is a 70-year-old female with no major past medical history who was intubated for acute hypoxic respiratory failure secondary to COVID-19 pneumonia and developed new-onset sinus bradycardia without a compensatory increase in heart rate in response to relative hypotension. Patient 2 is an 81-year-old male with a past medical history of an ascending aortic aneurysm, hypertension, and obstructive sleep apnoea who required intubation for COVID-19-induced acute hypoxic respiratory failure and exhibited new-onset sinus bradycardia followed by numerous episodes of haemodynamically significant accelerated idioventricular rhythm. Two weeks following the onset of SND, both patients remain in sinus bradycardia. DISCUSSION: COVID-19-associated SND has not previously been described. The potential mechanisms for SND in patients with COVID-19 include myocardial inflammation or direct viral infiltration. Patients diagnosed with COVID-19 should be monitored closely for the development of bradyarrhythmia and haemodynamic instability.


title: Pentraxin 3 (PTX-3) Levels in Bronchoalveolar Lavage Fluid as a Lung Cancer Biomarker

text: In this study, we investigated the utility of pentraxin 3 (PTX-3) in bronchoalveolar lavage fluid (BALF) as lung cancer (LCa) diagnostic. A total of 89 LCa patients and 84 non-LCa patients who received bronchoscopy in the First Affiliated Hospital of Xi'an Jiaotong University from December 2014 to February 2015 were enrolled. LCa was subdivided according to pathological type (scale, gland, and small cell lung cancer). BALF samples were obtained during bronchoscopy and PTX-3 levels assayed by ELISA. t-tests, Mann-Whitney, and Kruskal-Wallis tests were performed for the comparison of PTX-3 levels between the different groups. Correlation analysis and receiver operating characteristic (ROC) analysis were used to analyze clinical data. The levels of PTX-3 increased in the LCa groups. PTX-3 levels were higher in the small cell lung cancer (SCLC) compared to non-small-cell lung cancer (NSCLC) groups. In LCa patients, obstructive pneumonia could upregulate the expression of PTX-3 in BALF. The area under the ROC curve of PTX-3 in BALF during LCa diagnosis, SCLC, and LCa with obstructive pneumonia was 0.949 (p ≤ 0.001), 0.672 (p < 0.05), and 0.838 (p < 0.01), respectively. In conclusion, PTX-3 in BALF has a potential value as an LCa biomarker, particularly in cases of SCLC and LCa with obstructive pneumonia.


title: An Online Clinical Exam for Fellowship Certification during COVID‐19 Pandemic

text: During the COVID‐19 pandemic, the world witnessed varied responses from educational institutions to the lockdown. Within the next few years, we will see the consequences of these responses. Despite the disruption at this critical time, candidates in their final fellowship training year still need to be certified and it is arguable that they should be certified faster than ever after passing the written component.


Antihypertensive drugs and risk of COVID-19? – Authors' reply


Intensive medicine and nursing home care in times of SARS CoV-2. A Norwegian perspective


title: Acute Respiratory Illness in Rural Haiti

text: Abstract Objectives Acute Respiratory Infection (ARI) is the most common cause of childhood morbidity and mortality in developing countries, including Haiti. Our objective was to detect pathogens found in children with ARI in rural Haiti to help develop evidence-based guidelines for treatment and prevention. Methods Retrospective study of students with ARI at four schools in rural Haiti. Viral and/or bacterial pathogens were identified by qPCR in 177 nasal swabs collected from April 2013 through November 2015. Results Most common viruses detected were Rhinovirus (36%), Influenza A (16%) and Adenovirus (7%), and bacteria were Streptococcus pneumoniae (58%) and Staphylococcus aureus (28%). Compared to older children, children aged 3–5 years had more Influenza A (28% vs. 9%, p=0.002) and Adenovirus detected (14% vs. 3%, p=0.01). Similarly, S. pneumoniae was greatest in children 3–5 years old (71% 3–5yrs; 58% 6–15 years; 25% 16–20 years; p=0.008). Children 3–10 years old presented with fever more than children 11–20 years old (22% vs 7%; p=0.02) and were more often diagnosed with pneumonia (28% vs 4%, p<0.001). Conclusions Younger children had increased fever, pneumonia, and detection of Influenza A and S. pneumoniae. These data support the need for influenza and pneumococcus vaccination in early childhood in Haiti.


title: Winthrop-University Hospital Infectious Disease Division's swine influenza (H1N1) pneumonia diagnostic weighted point score system for hospitalized adults with influenza-like illnesses (ILIs) and negative rapid influenza diagnostic tests (RIDTs)

text: Background In spring 2009, a novel strain of influenza A originating in Veracruz, Mexico, quickly spread to the United States and throughout the world. This influenza A virus was the product of gene reassortment of 4 different genetic elements: human influenza, swine influenza, avian influenza, and Eurasian swine influenza. In the United States, New York was the epicenter of the swine influenza (H1N1) pandemic. Hospital emergency departments (EDs) were inundated with patients with influenza-like illnesses (ILIs) requesting screening for H1N1. Our ED screening, as well as many others, used a rapid screening test for influenza A (QuickVue A/B) because H1N1 was a variant of influenza A. The definitive laboratory test i.e., RT-PCR for H1N1 was developed by the Centers for Disease Control (Atlanta, GA) and subsequently distributed to health departments. Because of the extraordinary volume of test requests, health authorities restricted reverse transcription polymerase chain reaction (RT-PCR) testing. Hence most EDs, including our own, were dependent on rapid influenza diagnostic tests (RIDTs) for swine influenza. A positive rapid influenza A test was usually predictive of RT-PCR H1N1 positivity, but the rapid influenza A screening test (QuickVue A/B) was associated with 30% false negatives. The inability to rely on RIDTs for H1N1 diagnosis resulted in underdiagnosing H1N1. Confronted with adults admitted with ILIs, negative RIDTs, and restricted RT-PCR testing, there was a critical need to develop clinical criteria to diagnose probable swine influenza H1N1 pneumonia. Methods During the pandemic, the Infectious Disease Division at Winthrop-University Hospital developed clinical criteria for adult admitted patients with ILIs and negative RIDTs. Similar to the one developed for the clinical diagnosis of legionnaire's disease. The Winthrop-University Hospital Infectious Disease Division's diagnostic weighted point score system for swine influenza H1N1 pneumonia is based on key clinical and laboratory features. Results During the “herald” wave of the swine influenza H1N1 pandemic, the diagnostic weighted point score system accurately identified probable swine influenza H1N1 pneumonia and accurately differentiated swine influenza H1N1 pneumonia from ILIs and other viral and bacterial community-acquired pneumonias. Conclusion In hospitalized adults with ILIs and negative RIDTs, the diagnostic weighted diagnostic point score system, may be used to make a presumptive clinical diagnosis of swine influenza H1N1 pneumonia.


title: Analysis of Stress Factors for Female Professors at Online Universities

text: The aim of this paper is to analyze the primary stress factors female professors at online universities are exposed to. The technique used for the prospective and exploratory analysis was the Delphi method. Two rounds of consultations were done with fourteen judges with broad experience in health and safety at work and university teaching who reached a consensus of opinion regarding a list of nine psychosocial risk factors. Among the most important risk factors, mental overload, time pressure, the lack of a schedule, and emotional exhaustion were highlighted. These risk factors are related to the usage and expansion of information and communication technology (ICT) and to the university system itself, which requires initiating more research in the future in order to develop the intervention programs needed to fortify the health of the affected teachers and protect them from stress and other psychosocial risks.


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title: Chapter 10 Introduction to RNA Viruses

text: Abstract RNA viruses replicate their genomes using virally encoded RNA-dependent RNA polymerase (RdRp). The RNA genome is the template for synthesis of additional RNA strands. During replication of RNA viruses, there are at least three types of RNA that must be synthesized: the genome, a copy of the genome (copy genome), and mRNAs. Some RNA viruses also synthesize copies of subgenomic mRNAs. RdRp is the key player for all of these processes. RdRps of all RNA viruses probably arose from a common ancestor. The RdRp and other proteins required for viral genome synthesis are often called the replicase complex. The replicase complex consists of the set of proteins required to produce infectious genomes. In addition to the RdRp, the replicase complex may contain RNA-helicases (to unwind highly base-paired regions of the RNA genome) and NTPases (to supply energy for the polymerization process). The number of proteins in the replicase complex differs among virus families. There may also be a requirement for host cell proteins. The RNA virus group can be subdivided based on the type of RNA that serves as the genome. Positive or plus (+)-strand RNA viruses have genomes that are functional mRNAs. Their genomes are translated shortly after penetration into the host cell to produce the RdRp (and other viral proteins) required for synthesis of additional viral RNAs. Positive-strand RNA viruses often use large complexes of cellular membranes for genome replication. They actively modify host cell membranes to construct viral replication scaffolds. There are three groups of RNA viruses whose genomes are not mRNAs. They are the negative- or minus-strand RNA viruses, the closely related ambisense RNA viruses, and double-stranded RNA viruses. For each of these groups of viruses, the first synthetic event after genome penetration is transcription. This is accomplished by viral proteins (including the RdRp) that enter cell with the genome.


title: Cancer treatment during COVID-19 pandemic: do not postpone, do it!

text: At the end of January 2020, a novel beta-coronavirus, known as severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), progressively spread in Italy. Patients with cancer are considered more prone to infections because of the immunosuppressive status due to both malignancy and anticancer treatments. From the first Italian government restrictions (23(rd) February), Modena Cancer Center adopted practical health vigilance recommendations in order to minimize the virus exposure risk without overlooking cancer management. From 23(rd) February to 31(st) March 2020, 1257 patients on active anticancer treatment for oncological or hematological malignancies, attended our Institution. All the staff activities were rescheduled following our practical COVID-19 guideline. During this period, we have tallied 9 cases of COVID-19 infection (0,71%) in cancer patients as well as 3 cases (1,66%) in health workers. The mortality rate of our cancer patients was 22%, consistent with the data reported in literature. In conclusion, following our practical health vigilance recommendations, physicians should be confident in maintaining life-saving anticancer treatment without exceedingly increasing the risk of nosocomial COVID-19 infection. The high rate of mortality suggested that all patients on active anticancer treatment with flu-like symptoms have to be carefully screen for COVID-19 infection.


title: Epidemiology of viral respiratory tract infections in a prospective cohort of infants and toddlers attending daycare

text: Abstract Background The epidemiology of respiratory tract infections (RTIs) in a daycare cohort has not been explored using molecular techniques. Objectives (1) Determine the overall incidence of RTIs in a daycare cohort using real-time reverse transcriptase polymerase chain reaction (RT-PCR). (2) Determine the relative incidence and impact of specific respiratory viruses, and characterize and compare clinical features associated with these pathogens. Study design In this prospective cohort study conducted from February 2006 to April 2008, nasal swabs were obtained from symptomatic children ages 0–30 months enrolled in fulltime daycare. RT-PCR was performed to detect respiratory syncytial virus (RSV), human metapneumovirus (MPV), influenza (Flu) viruses A and B, parainfluenza (PIV), adenovirus (AdV), human coronaviruses (CoV) and rhinovirus (RhV). Symptom diaries were completed for each illness. Results We followed 119 children (mean age 10 months; range 2–24 months) for 115 child years. The mean annual incidence of RTI per child was 4.2 the first year and 1.2 the second year of the study. At least 1 virus was identified in 67% RTIs. Co-infections were common (27% RTIs), with RhV, CoV, and AdV the most common co-pathogens. PIV was identified in 12% of RTIs with a high incidence of PIV4. The viruses with the greatest impact on our population were RSV, RhV and AdV. Conclusions Using molecular techniques, viruses were identified in approximately twice as many RTIs as previously reported in a daycare cohort. Infections with newly identified viruses, such as HMPV and CoV subtypes were less frequent and severe than infections with RSV, AdV and RhV.


title: The development of Chinese specific human cytomegalovirus polyepitope recombinant vaccine

text: Abstract Human cytomegalovirus (HCMV) infection is a major cause of morbidity in the recipients of organ transplants and in the congenitally infected infants. HCMV vaccine has emerged as an effective approach to prevent HCMV infection particularly for the development of multiple viral antigens vaccination and human leukocyte antigen (HLA)-restricted polyepitope technology. As the Chinese population makes up more than one fifth of the population worldwide, it is important to develop HCMV vaccines more specific for the Chinese population by targeting Chinese-restricted HLA alleles and antigens. In the present study, we designed a novel chimeric polyepitope vaccine based on the replication-deficient adenovirus Ad5F35, which encodes 83 HCMV T cell epitopes from 15 different HCMV antigens, restricted to 14 HLA I and 7 HLA II alleles that cover 92% of the Chinese population. Our results show that the recombinant adenovirus vaccine Ad5F35-CTL·Th can be efficiently transfected and expressed in peripheral blood mononuclear cells (PBMCs) with little cytopathic activity. Ad5F35-CTL·Th can also be endogenously processed and presented by PBMCs. Ad5F35-CTL·Th-stimulated HCMV-specific cytotoxic T lymphocytes (CTLs) showed strong cytolytic activity against HCMV polyepitope-sensitized target cells. The CTL activity was accompanied by high levels of IFN-γ production after Ad5F35-CTL·Th stimulation. The specificity and vigorous response to the recombinant adenovirus vaccine in vitro makes it a potential candidate to be used for transplantation recipients or congenitally infected infants.


title: Phosphatidylinositol 4-kinases: hostages harnessed to build panviral replication platforms

text: Several RNA viruses have recently been shown to hijack members of the host phosphatidylinositol (PtdIns) 4-kinase (PI4K) family of enzymes. They use PI4K to generate membranes enriched in phosphatidylinositide 4-phosphate (PtdIns4P or PI4P) lipids, which can be used as replication platforms. Viral replication machinery is assembled on these platforms as a supramolecular complex and PtdIns4P lipids regulate viral RNA synthesis. This article highlights these recent studies on the regulation of viral RNA synthesis by PtdIns4P lipids. It explores the potential mechanisms by which PtdIns4P lipids can contribute to viral replication and discusses the therapeutic potential of developing antiviral molecules that target host PI4Ks as a form of panviral therapy.


title: Live-attenuated bivalent measles virus-derived vaccines targeting Middle East respiratory syndrome coronavirus induce robust and multifunctional T cell responses against both viruses in an appropriate mouse model

text: Abstract Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to occur, making it one of the WHO´s targets for accelerated vaccine development. One vaccine candidate is based on live-attenuated measles virus (MV) vaccine encoding the MERS-CoV spike glycoprotein (MERS-S). MVvac2-MERS-S(H) induces robust humoral and cellular immunity against MERS-S mediating protection. Here, the induction and nature of immunity after vaccination with MVvac2-MERS-S(H) or novel MVvac2-MERS-N were further characterized. We focused on the necessity for vector replication and the nature of induced T cells, since functional CD8+ T cells contribute importantly to clearance of MERS-CoV. While no immunity against MERS-CoV or MV was detected in MV-susceptible mice after immunization with UV-inactivated virus, replication-competent MVvac2-MERS-S(H) triggered robust neutralizing antibody titers also in adult mice. Furthermore, a significant fraction of MERS CoV-specific CD8+ T cells and MV-specific CD4+ T cells simultaneously expressing IFN-γ and TNF-α were induced, revealing that MVvac2-MERS-S(H) induces multifunctional cellular immunity.


title: Telemedicina con telemonitorización en el seguimiento de pacientes con COVID-19

text: ABSTRACT Aim. To asses if telemedicine with telemonitoring is a clinically useful and secure tool in the tracking of patients with COVID-19. Methods. A prospective observational study of patients with COVID-19 diagnosis by positive PCR considered high-risk tracked with telemedicine and telemonitoring was conducted in the sanitary area of Lugo between March 17th and April 17th, 2020. Two groups of patients were included: Outpatient Tracing from the beginning and after discharge. Every patient sent a daily clinical questionnaire with temperature and oxygen saturation 3 times a day. Proactive monitoring was done by getting in touch with every patient at least once a day. Results. 313 patients (52.4% female) with a total average age of 60.9 (DS 15.9) years were included. Additionally, 2 patients refused to join the program. Since the beginning, 224 were traced outpatient and 89 after being discharged. Among the first category, 38 (16.90%) were referred to Emergency department on 43 occasions; 18 were hospitalized (8.03%), and 2 deceased. Neither deaths nor a matter of vital emergency occurred at home. When including patients after admissions monitoring was done in 304 cases. One patient re-entered (0.32%) to the hospital, and another one left the program (0.32%). The average time of monitoring was 11.64 (SD 3.58) days, and 224 (73.68%) patients were discharged during the 30 days of study. Conclusions. Our study suggests that telemedicine with home telemonitoring, used proactively, allows for monitoring high-risk patients with COVID-19 in a clinically useful and secure way.


title: Las vacunas de la gripe basadas en las partículas virus-like obtenidas mediante sistemas de expresión génica en células de insectos

text: Abstract Virus-like particles (VLPs) are multimeric protein complexes mimicking the organization of native viruses but lack the viral genome. VLPs therefore constitute a safe and effective approach for the induction of neutralizing antibodies to surface proteins. Influenza VLPs have recently been developed as a new generation of non-egg based cell culture-derived vaccine candidates against influenza infection. FluBock, a recombinant trivalent hemagglutinin (rHA) vaccine produced in insect cell culture using the baculovirus expression system, provides an attractive alternative to classical inactivated influenza vaccines. The highly purified protein vaccine, administered with a three-fold higher antigen content (135 μg), is well tolerated and results in stronger immunogenicity, a long lasting immune response and provides cross-protection against drift influenza viruses.


title: The COVID-19 rehabilitation pandemic(1)

text: The coronavirus disease 2019 (COVID-19) pandemic and the response to the pandemic are combining to produce a tidal wave of need for rehabilitation. Rehabilitation will be needed for survivors of COVID-19, many of whom are older, with underlying health problems. In addition, rehabilitation will be needed for those who have become deconditioned as a result of movement restrictions, social isolation, and inability to access healthcare for pre-existing or new non-COVID-19 illnesses. Delivering rehabilitation in the same way as before the pandemic will not be practical, nor will this approach meet the likely scale of need for rehabilitation. This commentary reviews the likely rehabilitation needs of older people both with and without COVID-19 and discusses how strategies to deliver effective rehabilitation at scale can be designed and implemented in a world living with COVID-19.


title: Molecular characterization of canine coronavirus strains circulating in Brazil

text: Abstract To characterize canine coronavirus (CCoV) circulating in diarrheic puppies in Brazil, 250 fecal samples collected between 2006 and 2012 were tested. By using RT-PCR to partially amplify the M gene, CCoV RNA was detected in 30 samples. Sequence analysis of the M protein grouped eight strains with CCoV-I and another 19 with CCoV-II prototypes. To genotype/subtype the CCoV strains and assess the occurrence of single or multiple CCoV infections, RT-PCR of the S gene was performed, and 25/30 CCoV-positive strains amplified with one or two primer pairs. For 17/25 samples, single infections were detected as follows: six CCoV-I, nine CCoV-IIa and two CCoV-IIb. Eight samples were positive for more than one genotype/subtype as follows: seven CCoV-I/IIa and one CCoV-I/IIb. Sequence analysis revealed that the CCoV-I and IIa strains shared high genetic similarity to each other and to the prototypes. The Brazilian strains of CCoV-IIb displayed an aminoacid insertion that was also described in CCoV-IIb-UCD-1 and TGEV strains. Among the 25 CCoV-positive puppies, five had a fatal outcome, all but one of which were cases of mixed infection. The current study is the first reported molecular characterization of CCoV-I, IIa and IIb strains in Brazil.


Preliminary Findings of Control of Dispersion of Aerosols and Droplets during High Velocity Nasal Insufflation Therapy Using a Simple Surgical Mask: Implications for High Flow Nasal Cannula


title: Emerging novel and antimicrobial-resistant respiratory tract infections: new drug development and therapeutic options

text: Summary The emergence and spread of antimicrobial-resistant bacterial, viral, and fungal pathogens for which diminishing treatment options are available is of major global concern. New viral respiratory tract infections with epidemic potential, such as severe acute respiratory syndrome, swine-origin influenza A H1N1, and Middle East respiratory syndrome coronavirus infection, require development of new antiviral agents. The substantial rise in the global numbers of patients with respiratory tract infections caused by pan-antibiotic-resistant Gram-positive and Gram-negative bacteria, multidrug-resistant Mycobacterium tuberculosis, and multiazole-resistant fungi has focused attention on investments into development of new drugs and treatment regimens. Successful treatment outcomes for patients with respiratory tract infections across all health-care settings will necessitate rapid, precise diagnosis and more effective and pathogen-specific therapies. This Series paper describes the development and use of new antimicrobial agents and immune-based and host-directed therapies for a range of conventional and emerging viral, bacterial, and fungal causes of respiratory tract infections.


title: Value of Chest CT as COVID 19 screening tool in children

text: Chest CT is not a suitable screening tool to rule out COVID 19 in children


title: High Prevalence of MERS-CoV Infection in Camel Workers in Saudi Arabia

text: Middle East respiratory syndrome (MERS), a highly lethal respiratory disease caused by a novel coronavirus (MERS-CoV), is an emerging disease with high potential for epidemic spread. It has been listed by the WHO and the Coalition for Epidemic Preparedness Innovations (CEPI) as an important target for vaccine development. While initially the majority of MERS cases were hospital acquired, continued emergence of MERS is attributed to community acquisition, with camels likely being the direct or indirect source. However, the majority of patients do not describe camel exposure, making the route of transmission unclear. Here, using sensitive immunological assays and a cohort of camel workers (CWs) with well-documented camel exposure, we show that approximately 50% of camel workers (CWs) in the Kingdom of Saudi Arabia (KSA) and 0% of controls were previously infected. We obtained blood samples from 30 camel herders, truck drivers, and handlers with well-documented camel exposure and from healthy donors, and measured MERS-CoV-specific enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA), and neutralizing antibody titers, as well as T cell responses. Totals of 16/30 CWs and 0/30 healthy control donors were seropositive by MERS-CoV-specific ELISA and/or neutralizing antibody titer, and an additional four CWs were seronegative but contained virus-specific T cells in their blood. Although virus transmission from CWs has not been formally demonstrated, a possible explanation for repeated MERS outbreaks is that CWs develop mild disease and then transmit the virus to uninfected individuals. Infection of some of these individuals, such as those with comorbidities, results in severe disease and in the episodic appearance of patients with MERS.


title: Direct and label-free influenza virus detection based on multisite binding to sialic acid receptors

text: A system to discriminate human or avian influenza A remains a highly sought-after tool for prevention of influenza pandemics in humans. Selective binding of the influenza A viral hemagglutinin (HA) to specific sialic acid (SA) receptors (Neu5Acα(2-6)Gal in humans, Neu5Acα(2-3)Gal in birds) is determined by the genotype of the HA and neuraminidase (NA) segments, making it one of the key characteristics that distinguishes human or avian influenza A virus. Here we demonstrate the direct detection of whole H1N1 influenza A virus using 6′-sialyllactose (Neu5Acα(2-6)Galβ(1-4)Glc, 6SL)-immobilized gold electrodes as biosensing surfaces. The sensitivity was higher than that of conventional immunochromatographic technique (ICT) for influenza virus and not restricted by genetic drift. The label-free detection technology via direct attachment of a whole virus using a chemically modified electrode is a promising means to provide a simple and rapid diagnostic system for viral infections.


title: COVID‐19 and gastrointestinal endoscopy: Importance of reducing SARS‐CoV‐2 infection risks of medical workers and preserving personal protective equipment resources

text: In December 2019, the World Health Organization (WHO) was informed of cases of pneumonia of unknown etiology detected in Wuhan, China. Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), a novel coronavirus, was identified and SARS‐CoV‐2 related disease, called coronavirus disease 2019 (COVID‐19), has spread worldwide. The WHO has declared COVID‐19 to be a pandemic on March 11, 2020. Clinical symptoms of the COVID‐19 includes cough (67.8%), fever (43.8%), fatigue (38.1%), production of sputum (33.7%), and shortness of breath (18.7%). Gastrointestinal symptoms of COVID‐19 include nausea or vomiting (5.0%), as well as diarrhea (3.8%) (1). It is estimated that 1.2% of infected subjects are asymptomatic, but the rate of severe disease is 13.9% with an overall mortality rate of 2.3% (2).


title: Pathogenesis of SARS-CoV-2 in transgenic mice expressing human angiotensin-converting enzyme 2

text: Summary COVID-19 has spread worldwide since 2019 and is now a severe threat to public health. We previously identified the causative agent as a novel SARS-related coronavirus (SARS-CoV-2) that uses human angiotensin-converting enzyme 2 (hACE2) as the entry receptor. Here, we successfully developed a SARS-CoV-2 hACE2 transgenic mouse (HFH4-hACE2 in C3B6 mice) infection model. The infected mice generated typical interstitial pneumonia and pathology that were similar to those of COVID-19 patients. Viral quantification revealed the lungs as the major site of infection, although viral RNA could also be found in the eye, heart, and brain in some mice. Virus identical to SARS-CoV-2 in full-genome sequences was isolated from the infected lung and brain tissues. Lastly, we showed that pre-exposure to SARS-CoV-2 could protect mice from severe pneumonia. Our results show that the hACE2 mouse would be a valuable tool for testing potential vaccines and therapeutics.


Rationing PPEs during a pandemic: The COVID-19 scenario


title: Structural and Evolutionary Analysis Indicate that the SARS-CoV-2 Mpro is an Inconvenient Target for Small-Molecule Inhibitors Design

text: The novel coronavirus whose outbreak took place in December 2019 continues to spread at a rapid rate worldwide. In the absence of an effective vaccine, inhibitor repurposing or de novo drug design may offer a longer-term strategy to combat this and future infections due to similar viruses. Here, we report on detailed classical and mix-solvent molecular dynamics simulations of the main protease (Mpro) enriched by evolutionary and stability analysis of the protein. The results were compared with those for a highly similar SARS Mpro protein. In spite of a high level of sequence similarity, the active sites in both proteins show major differences in both shape and size indicating that repurposing SARS drugs for COVID-19 may be futile. Furthermore, analysis of the binding site’s conformational changes during the simulation time indicates its flexibility and plasticity, which dashes hopes for rapid and reliable drug design. Conversely, structural stability of the protein with respect to flexible loop mutations indicates that the virus’ mutability will pose a further challenge to the rational design of small-molecule inhibitors. However, few residues contribute significantly to the protein stability and thus can be considered as key anchoring residues for Mpro inhibitor design.


title: Pathogenicity of severe acute respiratory coronavirus deletion mutants in hACE-2 transgenic mice

text: Abstract Recombinant severe acute respiratory virus (SARS-CoV) variants lacking the group specific genes 6, 7a, 7b, 8a, 8b and 9b (rSARS-CoV-Δ[6–9b]), the structural gene E (rSARS-CoV-ΔE), and a combination of both sets of genes (rSARS-CoV-Δ[E,6–9b]) have been generated. All these viruses were rescued in monkey (Vero E6) cells and were also infectious for human (Huh-7, Huh7.5.1 and CaCo-2) cell lines and for transgenic (Tg) mice expressing the SARS-CoV receptor human angiotensin converting enzyme-2 (hACE-2), indicating that none of these proteins is essential for the viral cycle. Furthermore, in Vero E6 cells, all the viruses showed the formation of particles with the same morphology as the wt virus, indicating that these proteins do not have a high impact in the final morphology of the virions. Nevertheless, in the absence of E protein, release of virus particles efficacy was reduced. Viruses lacking E protein grew about 100-fold lower than the wt virus in lungs of Tg infected mice but did not grow in the brains of the same animals, in contrast to the rSARS-CoV-Δ[6–9b] virus, which grew almost as well as the wt in both tissues. Viruses lacking E protein were highly attenuated in the highly sensitive hACE-2 Tg mice, in contrast to the minimal rSARS-CoV-Δ[6–9b] and wt viruses. These data indicate that E gene might be a virulence factor influencing replication level, tissue tropism and pathogenicity of SARS-CoV, suggesting that ΔE attenuated viruses are promising vaccine candidates.


title: Human cytomegalovirus-inhibitory flavonoids: Studies on antiviral activity and mechanism of action

text: Abstract We report antiviral activity against human cytomegalovirus for certain dietary flavonoids and their likely biochemical mechanisms of action. Nine out of ten evaluated flavonoids blocked HCMV replication at concentrations that were significantly lower than those producing cytotoxicity against growing or stationary phase host cells. Baicalein was the most potent inhibitor in this series (IC50 =0.4–1.2μM), including positive control ganciclovir. Baicalein and genistein were chosen as model compounds to study the antiviral mechanism(s) of action for this series. Both flavonoids significantly reduced the levels of HCMV early and late proteins, as well as viral DNA synthesis. Baicalein reduced the levels of HCMV immediate-early proteins to nearly background levels while genistein did not. The antiviral effects of genistein, but not baicalein, were fully reversible in cell culture. Pre-incubation of concentrated virus stocks with either flavonoid did not inhibit HCMV replication, suggesting that baicalein did not directly inactivate virus particles. Baicalein functionally blocked epidermal growth factor receptor tyrosine kinase activity and HCMV nuclear translocation, while genistein did not. At 24h post infection HCMV-infected cells treated with genistein continued to express immediate-early proteins and efficiently phosphorylate IE1-72. However, HCMV induction of NF-κB and increases in the levels of cell cycle regulatory proteins—events that are associated with immediate-early protein functioning – were absent. The data suggested that the primary mechanism of action for baicalein may be to block HCMV infection at entry while the primary mechanism of action for genistein may be to block HCMV immediate-early protein functioning.


Mental Health and COVID-19 in Nepal: A case of a satellite clinic


title: Basic Shock Physiology and Critical Care

text: Veterinarians practicing emergency medicine and/or working with exotic animals must be well versed in the pathophysiology of shock because many exotic pets present with an acute crisis or an acute manifestation of a chronic process causing poor organ perfusion. This article discusses the pathophysiology of shock and the systemic inflammatory response syndrome, which may lead to organ dysfunction, organ failure, sepsis, and death. The physiology of perfusion, perfusion measurements, categories of shock, and altered function of the immune system, gastrointestinal barrier, and coagulation system are discussed. Veterinarians providing emergency care to patients with shock must also be aware of comorbidities.


title: Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection

text: Summary Background The Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging virus involved in cases and case clusters of severe acute respiratory infection in the Arabian Peninsula, Tunisia, Morocco, France, Italy, Germany, and the UK. We provide a full description of a fatal case of MERS-CoV infection and associated phylogenetic analyses. Methods We report data for a patient who was admitted to the Klinikum Schwabing (Munich, Germany) for severe acute respiratory infection. We did diagnostic RT-PCR and indirect immunofluorescence. From time of diagnosis, respiratory, faecal, and urine samples were obtained for virus quantification. We constructed a maximum likelihood tree of the five available complete MERS-CoV genomes. Findings A 73-year-old man from Abu Dhabi, United Arab Emirates, was transferred to Klinikum Schwabing on March 19, 2013, on day 11 of illness. He had been diagnosed with multiple myeloma in 2008, and had received several lines of treatment. The patient died on day 18, due to septic shock. MERS-CoV was detected in two samples of bronchoalveolar fluid. Viral loads were highest in samples from the lower respiratory tract (up to 1·2 × 106 copies per mL). Maximum virus concentration in urine samples was 2691 RNA copies per mL on day 13; the virus was not present in the urine after renal failure on day 14. Stool samples obtained on days 12 and 16 contained the virus, with up to 1031 RNA copies per g (close to the lowest detection limit of the assay). One of two oronasal swabs obtained on day 16 were positive, but yielded little viral RNA (5370 copies per mL). No virus was detected in blood. The full virus genome was combined with four other available full genome sequences in a maximum likelihood phylogeny, correlating branch lengths with dates of isolation. The time of the common ancestor was halfway through 2011. Addition of novel genome data from an unlinked case treated 6 months previously in Essen, Germany, showed a clustering of viruses derived from Qatar and the United Arab Emirates. Interpretation We have provided the first complete viral load profile in a case of MERS-CoV infection. MERS-CoV might have shedding patterns that are different from those of severe acute respiratory syndrome and so might need alternative diagnostic approaches. Funding European Union; German Centre for Infection Research; German Research Council; and German Ministry for Education and Research.


title: Oral faecal microbiota transplantation for the treatment of Clostridium difficile-associated diarrhoea in a dog: a case report

text: BACKGROUND: Successful clinical outcomes of faecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection have been reported in humans and a marmoset. However, it has been unclear whether oral FMT was effective for the treatment of C. difficile-associated diarrhoea in dogs. CASE PRESENTATION: An 8-month-old, intact male French bulldog was presented with a 4-month history of intermittent large bowel diarrhoea. Physical and clinical examinations did not identify any specific causes for diarrhoea. Real-time PCR analysis and immunochromatography detected C. difficile antigen and toxin A&B genes and proteins in a faecal sample. Based on these findings, diarrhoea in the dog was considered to be induced by C. difficile-associated colitis. The dog was treated with oral FMT, in which a faecal solution obtained from a healthy beagle was orally administered to the subject. Stool consistency and frequency and faecal blood and mucus became normal 2–3 days after oral FMT, and real-time PCR analysis and immunochromatography was negative for C. difficile antigen and toxin A&B genes and proteins. No adverse events were observed. CONCLUSION: The present case report demonstrated that oral FMT was an effective treatment for C. difficile-associated diarrhoea in a dog. The findings in this report provide a rationale to evaluate clinical efficacy of oral FMT for other gastrointestinal diseases in dogs.


title: Relationship Between Antimicrobial Prescribing and Antimicrobial Resistance Among UTI Patients at Buraidah Central Hospital, Saudi Arabia

text: INTRODUCTION: Most of the decisions regarding diagnosis and treatment are based on laboratory test results. Urinary tract infections (UTIs) are among the most common infections in humans. The changing antimicrobial sensitivity in UTI requires appropriate antibiotics. Antimicrobial resistance is an emerging problem in the Kingdom of Saudi Arabia where the complete reversal of antimicrobial resistance is difficult due to irrational use of antibiotics. OBJECTIVES: This study aimed to determine the most common bacterial agents causing UTI in different seasons among patients who were admitted to Buraidah Central Hospital (BCH), Saudi Arabia. The study also evaluated the link between prescribing and resistance toward antimicrobials. MATERIALS AND METHODS: A 6-month retrospective study was conducted among adult patients who were admitted to the inpatient department at BCH. A total of 379 files were collected from microbiological laboratory for inpatients. RESULTS: Most UTI-causing bacteria prevailed in the same season. Of 15 bacterial strains, 12 were significantly correlated with 20 (of a total of 40) antibiotics that were used. Most bacteria were gram-negative. Gram-negative bacilli including Escherichia coli, Klebsiella spp., and Pseudomonadaceae and gram-positive Enterococcus faecalis were most frequently causing UTIs. CONCLUSION: Overall prevalence of antibiotic resistance was negative in bacterial isolates. However, the relationship between antimicrobial prescribing and antimicrobial resistance was significantly negative among UTI patients in BCH, Saudi Arabia.


title: Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19

text: BACKGROUND: Despite limited and conflicting data on the use of hydroxychloroquine in patients with Covid-19, the U.S. Food and Drug Administration has authorized the emergency use of this drug when clinical trials are unavailable or infeasible. Hydroxychloroquine, alone or in combination with azithromycin, is being widely used in Covid-19 therapy based on anecdotal and limited observational evidence. METHODS: We performed a retrospective analysis of data from patients hospitalized with confirmed SARS-CoV-2 infection in all United States Veterans Health Administration medical centers until April 11, 2020. Patients were categorized based on their exposure to hydroxychloroquine alone (HC) or with azithromycin (HC+AZ) as treatments in addition to standard supportive management for Covid-19. The two primary outcomes were death and the need for mechanical ventilation. We determined the association between treatment and the primary outcomes using competing risk hazard regression adjusting for clinical characteristics via propensity scores. Discharge and death were taken into account as competing risks and subdistribution hazard ratios are presented. RESULTS: A total of 368 patients were evaluated (HC, n=97; HC+AZ, n=113; no HC, n=158). Rates of death in the HC, HC+AZ, and no HC groups were 27.8%, 22.1%, 11.4%, respectively. Rates of ventilation in the HC, HC+AZ, and no HC groups were 13.3%, 6.9%, 14.1%, respectively. Compared to the no HC group, the risk of death from any cause was higher in the HC group (adjusted hazard ratio, 2.61; 95% CI, 1.10 to 6.17; P=0.03) but not in the HC+AZ group (adjusted hazard ratio, 1.14; 95% CI, 0.56 to 2.32; P=0.72). The risk of ventilation was similar in the HC group (adjusted hazard ratio, 1.43; 95% CI, 0.53 to 3.79; P=0.48) and in the HC+AZ group (adjusted hazard ratio, 0.43; 95% CI, 0.16 to 1.12; P=0.09), compared to the no HC group. CONCLUSIONS: In this study, we found no evidence that use of hydroxychloroquine, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with Covid-19. An association of increased overall mortality was identified in patients treated with hydroxychloroquine alone. These findings highlight the importance of awaiting the results of ongoing prospective, randomized, controlled studies before widespread adoption of these drugs.


title: MERS coronavirus nsp1 participates in an efficient propagation through a specific interaction with viral RNA

text: Abstract MERS-CoV is the only lethal human CoV still endemic in the Arabian Peninsula and neither vaccine nor therapeutics against MERS-CoV infection is available. The nsp1 of CoV is thought to be a major virulence factor because it suppresses protein synthesis through the degradation of host mRNA. In contrast, viral RNA circumvents the nsp1-mediated translational shutoff for an efficient propagation. In this study, we identified amino acid residue in MERS-CoV nsp1 that differ from those of SARS-CoV nsp1, and that appear to be crucial for circumventing the translational shutoff. In addition, reverse genetics analysis suggested the presence of a cis-acting element at the 5′-terminus of the nsp1-coding region, which contributes to the specific recognition of viral RNA that is required for an efficient viral replication. Our results suggest the CoVs share a common mechanism for circumventing the nsp1-mediated translational shutoff.


title: Acute multi-vessel coronary occlusion revealing COVID-19 in a young adult

text: Abstract A 42-year-old man was admitted for a ST-segment elevation myocardial infarction revealing an acute thrombosis of the left anterior descending and right coronary arteries. Following this acute multivessel coronary occlusion in a young individual at low cardiovascular risk, he was tested positive for severe acute respiratory syndrome coronavirus 2.


docid: oejemaei

title: Spread of COVID-19 through Georgia, USA. Near-term projections and impacts of social distancing via a metapopulation model

text: Epidemiological forecasts of COVID-19 spread at the country and/or state level have helped shape public health interventions. However, such models leave a scale-gap between the spatial resolution of actionable information (i.e. the county or city level) and that of modeled viral spread. States and nations are not spatially homogeneous and different areas may vary in disease risk and severity. For example, COVID-19 has age-stratified risk. Similarly, ICU units, PPE and other vital equipment are not equally distributed within states. Here, we implement a county-level epidemiological framework to assess and forecast COVID-19 spread through Georgia, where 1,933 people have died from COVID-19 and 44,638 cases have been documented as of May 27, 2020. We find that county-level forecasts trained on heterogeneity due to clustered events can continue to predict epidemic spread over multi-week periods, potentially serving efforts to prepare medical resources, manage supply chains, and develop targeted public health interventions. We find that the premature removal of physical (social) distancing could lead to rapid increases in cases or the emergence of sustained plateaus of elevated fatalities.


docid: xbedijkd

title: Respiratory Virus Infections of the Stem Cell Transplant Recipient and the Hematologic Malignancy Patient

text: Respiratory virus infections in hematologic stem cell transplant recipients and patients with hematologic malignancies are increasingly recognized as a cause of significant morbidity and mortality. The often overlapping clinical presentation makes molecular diagnostic strategies imperative for rapid diagnosis and to inform understanding of the changing epidemiology of each of the respiratory viruses. Most respiratory virus infections are managed with supportive therapy, although there is effective antiviral therapy for influenza. The primary focus should remain on primary prevention infection control procedures and isolation precautions, avoidance of ill contacts, and vaccination for influenza.


title: Cellular peptidyl-prolyl cis/trans isomerase Pin1 facilitates replication of feline coronavirus

text: Abstract Although feline coronavirus (FCoV) causes feline infectious peritonitis (FIP), which is a fatal infectious disease, there are no effective therapeutic medicines or vaccines. Previously, in vitro studies have shown that cyclosporin (CsA) and FK506 inhibit virus replication in diverse coronaviruses. CsA and FK506 are targets of clinically relevant immunosuppressive drugs and bind to cellular cyclophilins (Cyps) or FK506 binding proteins (FKBPs), respectively. Both Cyp and FKBP have peptidyl-prolyl cis-trans isomerase (PPIase) activity. However, protein interacting with NIMA (Pin1), a member of the parvulin subfamily of PPIases that differs from Cyps and FKBPs, is essential for various signaling pathways. Here we demonstrated that genetic silencing or knockout of Pin1 resulted in decreased FCoV replication in vitro. Dipentamethylene thiuram monosulfide, a specific inhibitor of Pin1, inhibited FCoV replication. These data indicate that Pin1 modulates FCoV propagation.


title: Unveiling the Origin and Transmission of 2019-nCoV

text: A novel coronavirus has caused thousands of human infections in China since December 2019, raising a global public health concern. Recent studies (Huang et al ., Chan et al ., and Zhou et al .) have provided timely insights into its origin and ability to spread among humans, informing infection prevention and control practices.


title: Phylogenetic and recombination analysis of coronavirus HKU1, a novel coronavirus from patients with pneumonia

text: Phylogenetic trees constructed using predicted amino acid sequences of putative proteins of coronavirus HKU1 (CoV-HKU1) revealed that CoV-HKU1 formed a distinct branch among group 2 coronaviruses. Of the 14 trees from p65 to nsp10, nine showed that CoV-HKU1 was clustered with murine hepatitis virus. From nsp11, the topologies of the trees changed dramatically. For the eight trees from nsp11 to N, seven showed that the CoV-HKU1 branch was the first branch. The codon usage patterns of CoV-HKU1 differed significantly from those in other group 2 coronaviruses. Split decomposition analysis revealed that recombination events had occurred between CoV-HKU1 and other coronaviruses.


title: Use of Aspergillus fumigatus real-time PCR in bronchoalveolar lavage samples (BAL) for diagnosis of invasive aspergillosis, including azole-resistant cases, in high risk haematology patients: the need for a combined use with galactomannan

text: Diagnosis of invasive aspergillosis (IA) is challenging, particularly in high-risk patients with lung lesions other than typical according to 2008-EORTC/MSG criteria. Even if microbiology is positive, they still remain unclassified according to 2008-EORTC/MSG. Quantitative polymerase chain reaction (qPCR) provides new mycological documentation of IA. This retrospective study assessed Aspergillus fumigatus real time qPCR (MycoGENIE®) in BAL to diagnose IA and identify azole-resistant strains. Clinical, radiological, and microbiological data from 114 hematology patients (69% HSCT recipients; 29% on mould active agents) from years 2012-2017 were collected; and 123 BAL samples were tested with qPCR (cutoff: Ct < 40) and galactomannan (GM, Platelia®, cutoff: 0.5 ODI). Patients were classified as proven/probable, possible, and no-IA. "Atypical-IA" referred to patients with lesions other than typical according to 2008-EORTC/MSG and positive mycology. Proven IA was diagnosed in two cases (1.6%), probable in 28 (22.8%), possible in 27 (22%), atypical in 14 (11.4%). qPCR was positive in 39 samples (31.7%). Sensitivity and specificity of qPCR for proven/probable IA (vs no-IA; atypical-IA excluded) were 40% (95% confidence interval [CI]: 23–59) and 69% (95%CI: 55–81), respectively. Sensitivity of qPCR was higher when combined with GM (83%, 95%CI: 65–94) and in those receiving mould-active agents at BAL (61%, 95%CI: 32–86). One sample had TR34/L98H mutation. In conclusion, in high-risk hematology patients with various lung lesions, A. fumigatus qPCR in BAL contributes to diagnosing IA, particularly if combined with GM and in patients receiving mould-active agents might allow detecting azole-resistant mutations in culture negative samples.


title: Enhancing workplace learning at the transition into practice. Lessons from a pandemic

text: Taking responsibility for prescribing is one of newly qualified doctors’ greatest stressors.(1) Despite being a routine task, prescribing insulin is particularly stress‐inducing. The global pandemic has made it more important to minimise transitioning students’ stress; yet there are fewer clinicians to support their accelerated transitions. We had planned an intervention during 9‐week ‘Clinical Assistantships’ immediately before qualifying. Students would write insulin ‘pre‐prescriptions’, which supervisors would endorse as prescriptions that were appropriate to dispense. A trained healthcare professional or person with diabetes (‘debriefer’) would conduct one‐to‐one Case Based discussions (CBDs) to help students learn reflectively from experience.


Pre-procedural COVID testing: The “New Normal.”


A summary of the rapid services changes made in response to staff psychological needs and maintaining care to those with cancer in light of COVID‐19


title: Missed or delayed diagnosis of ARDS: a common and serious problem

text: Clinical recognition of acute respiratory distress syndrome (ARDS) is delayed or missed entirely in a substantial proportion of patients. In the LUNG SAFE study, the largest international cohort of patients with ARDS, investigators were able to determine if ARDS was present, and at what stage the clinician made the diagnosis of ARDS. The diagnosis of ARDS was delayed or missed in two-thirds of patients, with the diagnosis missed entirely in 40% of patients, while ARDS recognition ranged from 51% in mild ARDS to 79% in severe cases. Failure to recognize ARDS in a timely fashion leads to failure to use strategies that improve survival in ARDS. Early diagnosis of ARDS may facilitate measures to abrogate progression of the lung injury, including protective mechanical ventilation, fluid restriction, and adjunctive measures proven to improve survival such as prone positioning. Information overload and a complex ‘syndrome’ diagnosis likely play key roles in ARDS under-recognition. Clinical under-recognition has important consequences particularly in terms of therapeutic options not considered. The development of approaches to enable more timely recognition has the potential to save lives.


Histopathologic Changes and SARS–CoV-2 Immunostaining in the Lung of a Patient With COVID-19


title: Emergency and essential surgical healthcare services during COVID-19 in low- and middle-income countries: A Perspective

text: The COVID-19 pandemic resulted in significant changes in health care systems worldwide, with low- and middle-income countries (LMIC) sustaining important repercussions. Specifically, alongside cancellation and postponements of non-essential surgical services, emergency and essential surgical care delivery may become affected due to the shift of human and material resources towards fighting the pandemic. For surgeries that do get carried through, new difficulties arise in protecting surgical personnel from contracting SARS-CoV-2. This scarcity in LMIC surgical ecosystems may result in higher morbidity and mortality, in addition to the COVID-19 toll. This paper aims to explore the potential consequences of COVID-19 on the emergency and essential surgical care in LMICs, to offer recommendations to mitigate damages and to reflect on preparedness for future crises. Reducing the devastating consequences of the COVID-19 pandemic on LMIC emergency and essential surgical services can be achieved through empowering communities with accurate information and knowledge on prevention, optimizing surgical material resources, providing quality training of health care personnel to treat SARS-CoV-2, and ensuring adequate personal protection equipment for workers on the frontline. While LMIC health systems are under larger strain, the experience from previous outbreaks may aid in order to innovate and adapt to the current pandemic. Protecting LMIC surgical ecosystems will be a pivotal process in ensuring that previous health system strengthening efforts are preserved, comprehensive care for populations worldwide are ensured, and to allow for future developments beyond the pandemic.


title: Perception of spokespersons' performance and characteristics in crisis communication: Experience of the 2003 severe acute respiratory syndrome outbreak in Taiwan

text: Background/Purpose To explore perception of spokespersons' performance and characteristics in response to the 2003 severe acute respiratory syndrome (SARS) outbreak. Methods This study was conducted from March to July, 2005, using semi-structured in-depth interviews to collect data. All interviews were audio-recorded and transcribed verbatim. A qualitative content analysis was employed to analyze the transcribed data. Interviewees included media reporters, media supervisors, health and medical institution executives or spokespersons, and social observers. Results Altogether, 35 interviewees were recruited for in-depth interviews, and the duration of the interview ranged from 1 hour to 2 hours. Results revealed that the most important characteristics of health/medical institutions spokespersons are professional competence and good interaction with the media. In contrast, the most important behaviors they should avoid are concealing the truth and misreporting the truth. Three major flaws of spokespersons' performance were identified: they included poor understanding of media needs and landscape; blaming the media to cover up a mistake they made in an announcement; and lack of sufficient participation in decision-making or of authorization from the head of organization. Conclusion Spokespersons of health and medical institutions play an important role in media relations during the crisis of a newly emerging infectious disease.


title: Infección por SARS-CoV-2 en el embarazo y posibilidad de transmisión al neonato: una revisión sistemática

text: Resumen En este trabajo se revisan los artículos publicados sobre COVID-19, embarazo y afectación del neonato hasta 30 de abril de 2020. Se han encontrado un total de 33 publicaciones que se refieren a 553 gestantes y 456 partos. Los síntomas más frecuentes en la embarazada fueron fiebre, tos y disnea. Cerca de dos tercios de los partos se realizaron por cesárea; el 5,9% de las mujeres requirieron ingreso en UCI y el 4% requirió ventilación mecánica. No se produjo ninguna muerte materna. Hubo prematuridad en el 22,3% de los partos y el neonato requirió ingreso en UCI en el 38,3%. Solo se informó de una muerte neonatal (0,4%) y de 13 casos de COVID-19 neonatal (3,4%). La información disponible no permite asegurar que la transmisión se produjera por vía trasplacentaria. Abstract Studies published on COVID-19, pregnancy and neonate disease until 30 April 2020 are revised. We found 33 articles including 553 pregnant women and 456 deliveries. The more frequent symptoms in the pregnant women were fever, cough and dyspnoea. About two thirds deliveries were carried out via Caesarean rate; 5.9% women were admitted in the ICU and 4% required mechanic ventilation. No maternal death was reported. Prematurity occurred in 22.3% deliveries and 38.3% neonates required admission in the ICU. Only one neonatal death was reported (0.4%) and 13 neonates (3.4%) suffered COVID-19. The available information does not allow to state whether transmission to neonates occurred transplacentarily.


title: Infectivity of attenuated poxvirus vaccine vectors and immunogenicity of a raccoonpox vectored rabies vaccine in the Brazilian Free-tailed bat (Tadarida brasiliensis)

text: Bats (Order Chiroptera) are an abundant group of mammals with tremendous ecological value as insectivores and plant dispersers, but their role as reservoirs of zoonotic diseases has received more attention in the last decade. With the goal of managing disease in free-ranging bats, we tested modified vaccinia Ankara (MVA) and raccoon poxvirus (RCN) as potential vaccine vectors in the Brazilian Free-tailed bat (Tadarida brasiliensis), using biophotonic in vivo imaging and immunogenicity studies. Animals were administered recombinant poxviral vectors expressing the luciferase gene (MVA-luc, RCN-luc) through oronasal (ON) or intramuscular (IM) routes and subsequently monitored for bioluminescent signal indicative of viral infection. No clinical illness was noted after exposure to any of the vectors, and limited luciferase expression was observed. Higher and longer levels of expression were observed with the RCN-luc construct. When given IM, luciferase expression was limited to the site of injection, while ON exposure led to initial expression in the oral cavity, often followed by secondary replication at another location, likely the gastric mucosa or gastric associated lymphatic tissue. Viral DNA was detected in oral swabs up to 7 and 9 days post infection (dpi) for MVA and RCN, respectively. While no live virus was detected in oral swabs from MVA-infected bats, titers up to 3.88 × 10(4) PFU/ml were recovered from oral swabs of RCN-infected bats. Viral DNA was also detected in fecal samples from two bats inoculated IM with RCN, but no live virus was recovered. Finally, we examined the immunogenicity of a RCN based rabies vaccine (RCN-G) following ON administration. Significant rabies neutralizing antibody titers were detected in the serum of immunized bats using the rapid fluorescence focus inhibition test (RFFIT). These studies highlight the safety and immunogenicity of attenuated poxviruses and their potential use as vaccine vectors in bats.


title: Comparison of the AdvanSure™ real-time RT-PCR and Seeplex® RV12 ACE assay for the detection of respiratory viruses

text: Abstract The AdvanSure™ RV real-time PCR kit (AdvanSure; LG Life Sciences, Korea) is based on multiplex real-time PCR and can simultaneously detect 14 respiratory viruses. We compared the performance of the AdvanSure assay with the Seeplex RV 12 ACE detection kit (Seeplex; Seegene, Seoul, South Korea), a multiplex end-point PCR assay. A total of 454 consecutive respiratory specimens were tested with both AdvanSure and Seeplex assays; AdvanSure detected 153 (33.7%) positive cases and Seeplex detected 145 (31.9%) positive cases. The positive percent agreement, negative percent agreement, and kappa value for the two assays were 87.2% (95% CI, 80.3–92.1), 91.1% (95% CI, 87.2–93.9), and 0.77 (95% CI, 0.70–0.83), respectively. Compared with the Seeplex assay, the AdvanSure assay had a shorter turnaround time (3h vs. 8h) and a shorter hands-on time (<1h vs 2h). In conclusion, the AdvanSure assay demonstrated comparable performance to the Seeplex assay.


docid: zuedsaqg

title: Assessing Ebola-related web search behaviour: insights and implications from an analytical study of Google Trends-based query volumes

text: BACKGROUND: The 2014 Ebola epidemic in West Africa has attracted public interest worldwide, leading to millions of Ebola-related Internet searches being performed during the period of the epidemic. This study aimed to evaluate and interpret Google search queries for terms related to the Ebola outbreak both at the global level and in all countries where primary cases of Ebola occurred. The study also endeavoured to look at the correlation between the number of overall and weekly web searches and the number of overall and weekly new cases of Ebola. METHODS: Google Trends (GT) was used to explore Internet activity related to Ebola. The study period was from 29 December 2013 to 14 June 2015. Pearson’s correlation was performed to correlate Ebola-related relative search volumes (RSVs) with the number of weekly and overall Ebola cases. Multivariate regression was performed using Ebola-related RSV as a dependent variable, and the overall number of Ebola cases and the Human Development Index were used as predictor variables. RESULTS: The greatest RSV was registered in the three West African countries mainly affected by the Ebola epidemic. The queries varied in the different countries. Both quantitative and qualitative differences between the affected African countries and other Western countries with primary cases were noted, in relation to the different flux volumes and different time courses. In the affected African countries, web query search volumes were mostly concentrated in the capital areas. However, in Western countries, web queries were uniformly distributed over the national territory. In terms of the three countries mainly affected by the Ebola epidemic, the correlation between the number of new weekly cases of Ebola and the weekly GT index varied from weak to moderate. The correlation between the number of Ebola cases registered in all countries during the study period and the GT index was very high. CONCLUSION: Google Trends showed a coarse-grained nature, strongly correlating with global epidemiological data, but was weaker at country level, as it was prone to distortions induced by unbalanced media coverage and the digital divide. Global and local health agencies could usefully exploit GT data to identify disease-related information needs and plan proper communication strategies, particularly in the case of health-threatening events. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-015-0090-9) contains supplementary material, which is available to authorized users.