title: Identification of a 24-kDa Polypeptide Processed from the Coronavirus Infectious Bronchitis Virus 1a Polyprotein by the 3C-like Proteinase and Determination of Its Cleavage Sites

text: Abstract We report here the identification of a 24-kDa polypeptide in IBV-infected Vero cells by immunoprecipitation with a region-specific antiserum raised in rabbits against the IBV sequence encoded between nucleotides 10928 and 11493. Coexpression, deletion, and mutagenesis studies have demonstrated that this protein is encoded by ORF 1a from nucleotide 10915 to 11544 and is released from the 1a polyprotein by the 3C-like proteinase-mediated proteolysis. A previously predicted Q-S (Q3462S3463) dipeptide bond encoded by the IBV sequence from nucleotide 10912 to 10917 is identified as the N-terminal cleavage site, and a Q-N (Q3672N3673) dipeptide bond encoded by the IBV sequence between nucleotides 11542 and 11547 is identified as the C-terminal cleavage site of the 24-kDa polypeptide.


title: Cullin4 Is Pro-Viral during West Nile Virus Infection of Culex Mosquitoes

text: Although mosquitoes serve as vectors of many pathogens of public health importance, their response to viral infection is poorly understood. It also remains to be investigated whether viruses deploy some mechanism to be able to overcome this immune response. Here, we have used an RNA-Seq approach to identify differentially regulated genes in Culex quinquefasciatus cells following West Nile virus (WNV) infection, identifying 265 transcripts from various cellular pathways that were either upregulated or downregulated. Ubiquitin-proteasomal pathway genes, comprising 12% of total differentially regulated genes, were selected for further validation by real time RT-qPCR and functional analysis. It was found that treatment of infected cells with proteasomal inhibitor, MG-132, decreased WNV titers, indicating importance of this pathway during infection process. In infection models, the Culex ortholog of mammalian Cul4A/B (cullin RING ubiquitin ligase) was found to be upregulated in vitro as well as in vivo, especially in midguts of mosquitoes. Gene knockdown using dsRNA and overexpression studies indicated that Culex Cul4 acts as a pro-viral protein by degradation of CxSTAT via ubiquitin-proteasomal pathway. We also show that gene knockdown of Culex Cul4 leads to activation of the Jak-STAT pathway in mosquitoes leading to decrease viral replication in the body as well as saliva. Our results suggest a novel mechanism adopted by WNV to overcome mosquito immune response and increase viral replication.


title: Introduction to Tropical Medicine

text: Tropical medicine deals with infectious and noninfectious diseases geographically located between the tropics of Cancer and Capricorn. It encompasses diseases that result from poverty, poor sanitation, infrastructure, and inadequate health resources. Lack of availability of clean water and food made with unhygienic practices add to the morbidity of these diseases. The tropics are reeling under the onslaught of climate change, deforestation, and air, water, and soil pollution, which worsens an already fragile health system. This article provides an overview of the definition, classification, geophysical problems, syndromic approach to common tropical infections, diagnostic challenges in the tropics, and access to medicines.


title: Aerobic bacteriological studies on the respiratory tracts of apparently healthy and pneumonic camels (Camelus dromedaries) in selected districts of Afar Region, Ethiopia

text: A cross-sectional study was conducted to isolate and identify bacterial species from the respiratory tract of apparently healthy and pneumonic camels in Asayita and Dubti woredas in the Afar Region, Ethiopia. From a total of 74 lung tissue and 74 tracheal swab samples Staphylococcus aureus, 16.3%, Streptococcus equi subsp. equi, 13.0%, and Pasteurella multocida, 10.9%, were dominant isolates from pneumonic lungs; Escherichia coli, 12.7%, Proteus species, 10.9%, and Klebsiella pneumoniae, 9.1%, were the majority in the normal lungs. The majority of the isolates colonized both anatomical sites investigated. There was a statistically significant association between the health status of the camels as well as the anatomical site studied with the isolation rates of the major respiratory pathogens (p < 0.05). Furthermore, the isolates were susceptible to norfloxacin, streptomycin, and gentamicin but resistant to ampicillin and tetracycline on in vitro test. Further studies on the pathogenicity of the major isolates are recommended.


title: Étude prospective de l’écologie virale hivernale dans un service de réanimation pédiatrique

text: Résumé Le but de cette étude prospective était d’évaluer l’épidémiologie des virus respiratoires chez les enfants hospitalisés dans une unité de réanimation et de soins continus pédiatriques pendant 3 mois d’hiver, en 2012–2013. Ont été inclus tous les enfants admis en réanimation pédiatrique du centre hospitalier universitaire (CHU) de Caen et ayant bénéficié d’une recherche d’infection par un virus respiratoire à partir d’un prélèvement nasal analysé par amplification génique (PCR) multiplex. Sur 105 enfants admis, 84 répondaient aux critères d’inclusion. Trente-sept enfants présentaient un ou plusieurs symptômes respiratoires à l’admission. Cinquante-quatre échantillons étaient positifs (64,3 %) avec 70 virus détectés. Le virus dont la prévalence était la plus élevée était le virus respiratoire syncytial (VRS) (n =28 ; 40,0 %), suivi par le rhinovirus (n =24 ; 34,3 %). Parmi les enfants sans symptômes respiratoires, 42,6 % étaient infectés par un ou plusieurs virus. Aucune différence de durée d’hospitalisation, de durée de ventilation mécanique n’a été mise en évidence en fonction du virus détecté. La principale limite de cette étude est l’analyse par PCR, beaucoup plus sensible que d’autres méthodes de détection, notamment chez des sujets asymptomatiques sur le plan respiratoire. Cette étude révèle cependant un taux élevé d’infections respiratoires causées par des virus chez les enfants qui ne présentent pas de symptômes respiratoires à leur admission en unité de réanimation et soins continus. Elle suggère un intérêt du dépistage de ces infections virales à l’admission des enfants et un bénéfice à l’extension des mesures d’isolement pour tous les enfants en réanimation pédiatrique. Summary Introduction Viral respiratory infections are common in children, most of which are due to a virus. They can lead to serious infections, and these children may require treatment in a pediatric intensive care unit (PICU). This prospective study evaluated the epidemiology of respiratory viruses and associated illnesses among children hospitalized in a PICU during the three winter months of 2012–2013. Methods All the children admitted to the PICU, University Hospital of Caen, France, were included. Nasal swabs were collected and specimens were tested using a single real-time PCR (polymerase chain reaction). Results Of the 105 patients admitted to the PICU during the study period, 84 fulfilled the inclusion criteria. The “respiratory group” included 37 patients with respiratory symptoms at admission while the “nonrespiratory group” included 47 patients with no respiratory symptoms. The 84 nasal swabs collected included 54 that were considered positive (64.3%) and 70 viruses were detected. The most commonly detected virus was RSV (n =28; 40.0% positive samples), followed by HRV (n =24; 34.3%). Viruses were more frequently detected in the respiratory (86.5%) than in the nonrespiratory (42.6%) group (P <0.001). Statistical analysis by subgroups revealed that RSV infections were significantly more frequent in the respiratory group (54.1%) than in the nonrespiratory group (6.4%) (P <0.001). There was no difference for HRV (32.4% and 27.7%) or for the other viruses. No difference in duration of hospitalization or duration of mechanical ventilation was demonstrated depending on the virus detected. Discussion The use of the very sensitive multiplex PCR technique increased virus detection rates in both symptomatic and asymptomatic subjects. Conclusion We have confirmed the frequency of RSV infections in a PICU and found that many patients without respiratory symptoms have respiratory infections caused by viruses. The impact of these infections on patient outcome should now be analyzed in order to demonstrate the role played by respiratory viruses.


title: De novo transcriptome reconstruction and annotation of the Egyptian rousette bat

text: BACKGROUND: The Egyptian Rousette bat (Rousettus aegyptiacus), a common fruit bat species found throughout Africa and the Middle East, was recently identified as a natural reservoir host of Marburg virus. With Ebola virus, Marburg virus is a member of the family Filoviridae that causes severe hemorrhagic fever disease in humans and nonhuman primates, but results in little to no pathological consequences in bats. Understanding host-pathogen interactions within reservoir host species and how it differs from hosts that experience severe disease is an important aspect of evaluating viral pathogenesis and developing novel therapeutics and methods of prevention. RESULTS: Progress in studying bat reservoir host responses to virus infection is hampered by the lack of host-specific reagents required for immunological studies. In order to establish a basis for the design of reagents, we sequenced, assembled, and annotated the R. aegyptiacus transcriptome. We performed de novo transcriptome assembly using deep RNA sequencing data from 11 distinct tissues from one male and one female bat. We observed high similarity between this transcriptome and those available from other bat species. Gene expression analysis demonstrated clustering of expression profiles by tissue, where we also identified enrichment of tissue-specific gene ontology terms. In addition, we identified and experimentally validated the expression of novel coding transcripts that may be specific to this species. CONCLUSION: We comprehensively characterized the R. aegyptiacus transcriptome de novo. This transcriptome will be an important resource for understanding bat immunology, physiology, disease pathogenesis, and virus transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2124-x) contains supplementary material, which is available to authorized users.


title: Single amino acid substitution (G42E) in the receptor binding domain of mouse mammary tumour virus envelope protein facilitates infection of non-murine cells in a transferrin receptor 1-independent manner

text: BACKGROUND: Mouse mammary tumour virus (MMTV) is a betaretrovirus that infects rodent cells and uses mouse tranferrin receptor 1 (TfR1) for cell entry. Several MMTV strains have been shown to productively infect, in addition to murine cells, various heterologous cell lines including those of human origin, albeit less efficiently than murine cells. Furthermore, there have been reports that the continued passage of MMTV in heterologous cell lines gives rise to novel variants that are able to infect naive non-murine cells with higher efficiency than the parental virus. RESULTS: We show that MMTV(C3H), like other MMTV strains, that had undergone a number of replication cycles in non-murine cells displayed an increased replication kinetic, as compared to parental virus, when applied on naive human cells. Sequence analysis of several replication kinetic variants and the parental virus, together with calculation of the ratio of non-synonymous to synonymous mutations at individual codons, revealed that several regions within the viral genome were under strong positive selection pressure during viral replication in human cells. The mutation responsible, at least in part, for the phenotypic change was subsequently mapped to the segment of env encoding the receptor binding site (F(40)HGFR(44)). Introduction of the identified mutation, leading to single amino acid substitution (G42E), into egfp-containing recombinant MMTV virions enhanced their ability to bind to and infect human cells. Interestingly, neither the replication kinetic mutant nor the parental virus required human TfR1 for infection. Knock-out of TFR1 gene from the human genome did not decrease the susceptibility of Hs578T cells to virus infection. Furthermore, the expression of human TfR1, in contrast to mouse TfR1, did not enhance the susceptibility of MMTV-resistant Chinese hamster ovary cells. Thus, human TfR1 is dispensable for infection and another cell surface molecule mediates the MMTV entry into human cells. CONCLUSION: Taken together, our data explain the mechanism enabling MMTV to form ‘host-range variants’ in non-murine cells that has been known for a long time, the basis of which remained obscure. Our findings may expand our understanding of how viruses gain capability to cross species-specific barriers to infect new hosts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-015-0168-2) contains supplementary material, which is available to authorized users.


title: COVID 19 and Ethnicity: Spot light on the global rheumatology issues in developing and developed countries

text: A key issue in the response to the coronavirus disease 2019 (COVID‐19) pandemic is the internationally recognised observation that COVID‐19 disproportionally affects the Black and Minority Ethnic Population (BAME) (1). We focus predominantly on the countries of the UK, USA, and India COVID‐19 rheumatology challenges and examples. This unprecedented public health crisis started in China in Dec 2019, following an infection caused by a novel coronavirus strain, named as SARS‐CoV2 (2). The World Health Organisation in March 2020 declared this public health emergency as a pandemic (2). COVID‐19 pandemic has moved from country to country peaking at different times despite implementation of strict preventive measures, including complete lock down periods with varied success. Case fatality and mortality rates have been highly variable across nations as well as different ethnic groups (3).


title: Respiratory viruses in airline travellers with influenza symptoms: Results of an airport screening study

text: Abstract Background There is very little known about the prevalence and distribution of respiratory viruses, other than influenza, in international air travellers and whether symptom screening would aid in the prediction of which travellers are more likely to be infected with specific respiratory viruses. Objectives In this study, we investigate whether, the use of a respiratory symptom screening tool at the border would aid in predicting which travellers are more likely to be infected with specific respiratory viruses. Study design Data were collected from travellers arriving at Christchurch International Airport, New Zealand, during the winter 2008, via a symptom questionnaire, temperature testing, and respiratory sampling. Results Respiratory viruses were detected in 342 (26.0%) of 1313 samples obtained from 2714 symptomatic travellers. The most frequently identified viruses were rhinoviruses (128), enteroviruses (77) and influenza B (48). The most frequently reported symptoms were stuffy or runny nose (60%), cough (47%), sore throat (27%) and sneezing (24%). Influenza B infections were associated with the highest number of symptoms (mean of 3.4) followed by rhinoviruses (mean of 2.2) and enteroviruses (mean of 1.9). The positive predictive value (PPV) of any symptom for any respiratory virus infection was low at 26%. Conclusions The high prevalence of respiratory virus infections caused by viruses other than influenza in this study, many with overlapping symptotology to influenza, has important implications for any screening strategies for the prediction of influenza in airline travellers.


Evaluation of endodontic competency in the COVID‐19 era: Problem, solution and results


title: Impact of Personal Protective Equipment on Surgical Performance During the COVID-19 Pandemic

text: BACKGROUND: The Severe Acute Respiratory Syndrome Coronavirus 2 pandemic has exposed surgeons to hazardous working conditions, imposing the need for personal protective equipment (PPE) use during surgery. The use of such equipment may affect their non-technical skills, augment fatigue, and affect performance. This study aimed to assess the surgeons’ perceptions of the impact of wearing PPE during emergency surgery throughout the pandemic. METHODS: An international cooperation group conducted an anonymous online survey among surgeons from over 30 countries, to assess perceptions about the impact of PPE use on non-technical skills, overall comfort, decision making, and surgical performance during emergency surgery on COVID-19 patients. RESULTS: Responses to the survey (134) were received from surgeons based on 26 countries. The vast majority (72%) were males. More than half of the respondents (54%) felt that their surgical performance was hampered with PPE. Visual impairment was reported by 63%, whereas 54% had communication impediments. Less than half (48%) felt protected with the use of PPE, and the same proportion perceived that the use of such equipment influenced their decision making. Decreased overall comfort was cited by 66%, and 82% experienced increased surgical fatigue. CONCLUSIONS: Surgeons perceived impediment for both visibility and communication, and other non-technical skills while using PPE on emergency surgery in COVID-19 patients. Their perceived lack of protection and comfort and increased fatigue may have inhibited their optimal surgical performance. More attention should be placed in the design of more user-friendly equipment, given the possibility of a second wave of the pandemic.


title: Hospital pharmacists’ pharmaceutical care for hospitalized patients with COVID-19: Recommendations and guidance from clinical experience

text: Abstract Objective To discuss hospital pharmacists’ role in providing pharmaceutical care for hospitalized patients with COVID-19 to promote patient care and management during the pandemic. Method Based on the method of evidence-based pharmacy, clinical evidence of therapeutical drugs for COVID-19 were retrieved and summarized. Based on clinical experience Chinese hospital pharmacists gained from providing pharmaceutical care services during COVID-19 pandemic, taking COVID-19 hospitalized patients’ needs into consideration, the methods and strategies hospital pharmacists shall use to provide pharmaceutical care were analyzed and summarized. Results Hospital pharmacists shall support pharmaceutical care services by participating in making evidence-based decisions for medication, monitoring and evaluation of medication safety and efficacy, providing strengthened care for special population and patients with combined underlying diseases, monitoring and management of convalescent plasma therapy, providing emotional counselling and psychological support, and providing scientific information about COVID-19 vaccines. Conclusion The need of pharmaceutical care services in COVID-19 hospitalized patients during this pandemic was quite distinguished from the past. Hospital pharmacists shall join the collaborative multidisciplinary team to improve COVID-19 patients’ outcome and reduce mortality, and to facilitate the pandemic control.


title: An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice

text: Coronaviruses (CoVs) traffic frequently between species resulting in novel disease outbreaks, most recently exemplified by the newly emerged SARS-CoV-2, the causative agent of COVID-19. Herein, we show that the ribonucleoside analog β-D-N(4)-hydroxycytidine (NHC, EIDD-1931) has broad spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to the nucleoside analog inhibitor remdesivir. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (β-D-N(4)-hydroxycytidine-5′-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. The potency of NHC/EIDD-2801 against multiple coronaviruses and oral bioavailability highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses.


title: RIG-I-like receptor regulation in virus infection and immunity

text: Mammalian cells have the intrinsic capacity to detect viral pathogens and to initiate an antiviral response that is characterized by the induction of interferons (IFNs) and proinflammatory cytokines. A delicate regulation of the signaling pathways that lead to cytokine production is needed to ensure effective clearance of the virus, while preventing tissue damage caused by excessive cytokine release. Here, we focus on the mechanisms that modulate the signal transduction triggered by RIG-I-like receptors (RLRs) and their adaptor protein MAVS, key components of the host machinery for sensing foreign RNA. Specifically, we summarize recent advances in understanding how RLR signaling is regulated by posttranslational and posttranscriptional mechanisms, microRNAs (miRNAs) and autophagy. We further discuss how viruses target these regulatory mechanisms for immune evasion.


title: Evaluation of attenuated VSVs with mutated M or/and G proteins as vaccine vectors

text: Vesicular stomatitis virus (VSV) is a promising vector for vaccine and oncolysis, but it can also produce acute diseases in cattle, horses, and swine characterized by vesiculation and ulceration of the tongue, oral tissues, feet, and teats. In experimental animals (primates, rats, and mice), VSV has been shown to lead to neurotoxicities, such as hind limb paralysis. The virus matrix protein (M) and glycoprotein (G) are both major pathogenic determinants of wild-type VSV and have been the major targets for the production of attenuated strains. Existing strategies for attenuation included: (1) deletion or M51R substitution in the M protein (VSVΔM51 or VSVM51R, respectively); (2) truncation of the C-terminus of the G protein (GΔ28). Despite these mutations, recombinant VSV with mutated M protein is only moderately attenuated in animals, whereas there are no detailed reports to determine the pathogenicity of recombinant VSV with truncated G protein at high dose. Thus, a novel recombinant VSV (VSVΔM51-GΔ28) as well as other attenuated VSVs (VSVΔM51, VSV-GΔ28) were produced to determine their efficacy as vaccine vectors with low pathogenicity. In vitro studies indicated that truncated G protein (GΔ28) could play a more important role than deletion of M51 (ΔM51) for attenuation of recombinant VSV. VSVΔM51-GΔ28 was determined to be the most attenuated virus with low pathogenicity in mice, with VSV-GΔ28 also showing relatively reduced pathogenicity. Further, neutralizing antibodies stimulated by VSV-GΔ28 proved to be significantly higher than in mice treated with VSVΔM51-GΔ28. In conclusion, among different attenuated VSVs with mutated M and/or G proteins, recombinant VSV with only truncated G protein (VSV-GΔ28) demonstrated ideal balance between pathogenesis and stimulating a protective immune response. These properties make VSV-GΔ28 a promising vaccine vector and vaccine candidate for preventing vesicular stomatitis disease.


title: COVID-19 Pandemic: An Insult Over Injury for Lebanon

text: The outbreak of the novel coronavirus disease in 2019 (COVID-19) caused a plethora of challenges worldwide and tested healthcare systems across the six continents. Lebanon had recently faced harsh political and economic crises. We aim to describe the effect of COVID-19 on an already crisis-stricken country. A descriptive analysis of the burden of COVID-19 pandemic on Lebanon was performed. Relevant data on COVID-19 was retrieved from the Lebanese Ministry of Public Health from February 21 till June 13th, 2020. Results obtained were analyzed and a literature review was performed. 1422 confirmed COVID-19 cases were identified and reported in Lebanon by June 13th, 2020, comprising an incidence rate of 208/million persons. There has been a total of 31 deaths thus far, with a reported death rate of 5/million persons. The age group with the highest number of cases was 20–29 years. Beirut was the district with the highest number of cases (18%). The COVID-19 crisis has impacted the country on a multifactorial level. COVID-19 could not have come at a worse time for Lebanon. The country is on brink of bankruptcy, the healthcare system is struggling for survival and the government is striving to regain the trust of the population.


title: The global challenge of infectious diseases: the evolving role of the National Institutes of Health in basic and clinical research

text: The US has entered a new period of fiscal restraint. What does this mean for basic research? Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, discusses the way forward for research scientists in the US.


title: Anti-infective immunoadhesins from plants

text: Immunoadhesins are recombinant proteins that combine the ligand-binding region of a receptor or adhesion molecule with immunoglobulin constant domains. All FDA-approved immunoadhesins are designed to modulate the interaction of a human receptor with its normal ligand, such as Etanercept (Enbrel(®)), which interferes with the binding of tumour necrosis factor (TNF) to the TNF-alpha receptor and is used to treat inflammatory diseases such as rheumatoid arthritis. Like antibodies, immunoadhesins have long circulating half-lives, are readily purified by affinity-based methods and have the avidity advantages conferred by bivalency. Immunoadhesins that incorporate normal cellular receptors for viruses or bacterial toxins hold great, but as yet unrealized, potential for treating infectious disease. As decoy receptors, immunoadhesins have potential advantages over pathogen-targeted monoclonal antibodies. Planet Biotechnology has specialized in developing anti-infective immunoadhesins using plant expression systems. An immunoadhesin incorporating the cellular receptor for anthrax toxin, CMG2, potently blocks toxin activity in vitro and protects animals against inhalational anthrax. An immunoadhesin based on the receptor for human rhinovirus, ICAM-1, potently blocks infection of human cells by one of the major causes of the common cold. An immunoadhesin targeting the MERS coronavirus is in an early stage of development. We describe here the unique challenges involved in designing and developing immunoadhesins targeting infectious diseases in the hope of inspiring further research into this promising class of drugs.


title: Prevalence of avian infectious bronchitis virus in broiler chicken farms in south of Iraq, 2014 – 2015

text: Avian infectious bronchitis (IB), caused by a gammacoronavirus, is an OIE-listed (List B) disease and characterized by respiratory and renal involvements, causing high mortality, and economic loss in both layers and broilers. In comparison with other diagnostic methods, real-time polymerase chain reaction (RT-PCR) and conventional RT-PCR are potent, more sensitive and faster techniques for infectious bronchitis virus (IBV) detection. This research was conducted to detect IBV using specific primers of IB in three governorates (Basra, Thi-Qar and Muthana) in the south of Iraq. Tracheal specimens were collected from 46 IB suspected commercial broiler flocks. XCE2+ and XCE2- Primers, which amplify all IBV serotypes, were used. Primers MCE1+, BCE1+ and DCE1+ were used to amplify the specific nucleotide sequences of Massachusetts, 793/B and D274 genotypes, respectively. The results of real-time RT-PCR of this study showed that 34 (74.00%) out of 46 infected flocks were positive to IBV. The results of nested PCR showed that 50.00% and 5.89% of positive samples were belonged to genotypes 793/B and Massachusetts, respectively, and the remaining positive (44.11%) were unknown. The results indicate presence of Massachusetts and 793/B IBV strains in commercial broilers in southern Iraq.


title: Laboratory data analysis of novel coronavirus (COVID-19) screening in 2510 patients

text: Abstract Background Novel coronavirus (COVID-19) is highly infectious and requires early detection, isolation, and treatment. We tried to find some useful information by analyzing the covid-19 screening data, so as to provide help for clinical practice. Method We collected nucleic acid and hematology data from 2510 patients for COVID-19 infection for retrospective analysis. Result COVID-19 and influenza A and B infection rates were 1.3%, 3%, and 3%, respectively. COVID-19 nucleic acid was detected in stool but not in tear samples from 8 positive patients. Among the 32 patients with COVID-19, 15 (47%) and 16 (50%) patients showed decreased lymphocyte count and lymphocyte ratio, 21(66%) and 24(75%) patients showed decreased eosinophil count and eosinophil ratio, and 18 (56%) patients showed increased C-reactive protein. Ten hematological indicators significantly differed in the blood of patients with COVID-19 and those with influenza A and B (P < 0.05). Eighteen hematological indicators significantly differed between patients with COVID-19 and negative patients (P < 0.05). Conclusion The positive rate of influenza A and B infection was higher than that of COVID-19. When pharyngeal swab collection may cause infection, fecal samples can be examined. Evaluation of pharyngeal swab and fecal samples can improve the positive rate of nucleic acid detection. The COVID-19 can cause some hematological indices changes.


title: Perceptions of Occupational Risk and Changes in Clinical Practice of U.S. Vitreoretinal Surgery Fellows during the COVID-19 Pandemic

text: Abstract Purpose To assess perceptions of occupational risk and changes to clinical practice of ophthalmology trainees in the United States during the COVID-19 pandemic. Design An anonymous, non-validated, cross-sectional survey was conducted online. Data was collected from April 7-16, 2020. Participants 2019-2020 second year U.S. vitreoretinal surgery fellows in two-year vitreoretinal surgery training programs were invited to participate. Intervention Online survey. Main outcome measures Survey questions assessed policies guiding COVID-19 response, known or suspected exposure to SARS-CoV-2, changes in clinical duties and volume, and methods to reduce occupational risk including availability of personal protective equipment. Results Completed responses were obtained from 62 of 87 eligible recipients (71.2% response rate). Training settings included academic (58.1%), hybrid academic/private practice (35.5%), and private practice only settings (6.5%). Overall, 19.4% of respondents reported an exposure to a COVID-19 positive patient, 14.5% reported self-quarantining due to possible exposure, and 11.3% reported being tested for COVID-19. In regards to PPE, N95 masks were available in the emergency room (n=40, 64.5%), office (n=35, 56.5%), and operating room settings (n=35, 56.5%). Perceived comfort level with PPE recommendations was significantly associated with availability of an N95 respirator mask in the clinic (p<0.001), emergency room (p<0.001) or operating room (p=0.002) settings. Additional risk mitigation methods outside of PPE were: reduction in patient volume (n=62, 100%), limiting patient companions (n=59, 95.2%), use of a screening process (n=59, 95.2%), use of a slit lamp face shield (n=57, 91.9%), temperature screening of all persons entering clinical space (n=34, 54.84%), and placement of face mask on patients (n=33, 53.2%). Overall, 16.1% reported additional clinical duties within the scope of ophthalmology, and 3.2% reported being re-deployed to non-ophthalmology services. 98.4% of respondents expected a reduction in surgical case volume. No respondents reported loss of employment or reduction in pay or benefits due to COVID-19. Conclusion and Relevance: Suspected or confirmed clinical exposure to COVID-19 positive patients occurred in approximately one-fifth of trainee respondents. Perceived comfort level with PPE standards was significantly associated with N95 respirator mask availability. As surgical training programs grapple with the COVID-19 pandemic, analysis of trainees’ concerns may inform development of mitigation strategies.


title: Use of Bayesian Belief Network techniques to explore the interaction of biosecurity practices on the probability of porcine disease occurrence in Canada

text: Abstract Identification and quantification of pathogen threats need to be a priority for the Canadian swine industry so that resources can be focused where they will be most effective. Here we create a tool based on a Bayesian Belief Network (BBN) to model the interaction between biosecurity practices and the probability of occurrence of four different diseases on Canadian swine farms. The benefits of using this novel approach, in comparison to other methods, is that it enables us to explore both the complex interaction and the relative importance of biosecurity practices on the probability of disease occurrence. In order to build the BBN we used two datasets. The first dataset detailed biosecurity practices employed on 218 commercial swine farms across Canada in 2010. The second dataset detailed animal health status and disease occurrence on 90 of those farms between 2010 and 2012. We used expert judgement to identify 15 biosecurity practices that were considered the most important in mitigating disease occurrence on farms. These included: proximity to other livestock holdings, the health status of purchased stock, manure disposal methods, as well as the procedures for admitting vehicles and staff. Four diseases were included in the BBN: Porcine reproductive and respiratory syndrome (PRRS), (a prevalent endemic aerosol pathogen), Swine influenza (SI) (a viral respiratory aerosol pathogen), Mycoplasma pneumonia (MP) (an endemic respiratory disease spread by close contact and aerosol) and Swine dysentery (SD) (an enteric disease which is re-emerging in North America). This model indicated that the probability of disease occurrence was influenced by a number of manageable biosecurity practices. Increased probability of PRRS and of MP were associated with spilt feed (feed that did not fall directly in a feeding trough), not being disposed of immediately and with manure being brought onto the farm premises and spread on land adjacent to the pigs. Increased probabilities of SI and SD were associated with the farm allowing access to visiting vehicles without cleaning or disinfection. SD was also more likely to occur when the health status of purchased stock was not known. Finally, we discuss how such a model can be used by the Canadian swine industry to quantify disease risks and to determine practices that may reduce the probability of disease occurrence.


title: Canine distemper virus-induced depletion of uninfected lymphocytes is associated with apoptosis

text: Abstract Canine distemper virus (CDV), a negative stranded RNA morbillivirus, causes a multisystemic disease in dogs, which is associated with a severe immune suppression. The aim of the study was to examine the influence of early CDV infection on leukocyte depletion, lymphopenia and virus-induced cell death in dogs infected with a virulent CDV strain. From 10 infected dogs, peripheral blood leukocytes were harvested periodically, phenotyped and analyzed for CDV antigen content and apoptosis using Annexin V-FITC and propidium iodide labeling. CDV infection induced a severe CD3+ T cell and CD21+ B cell depletion in all animals at 3 days post-infection (d.p.i.). For dogs with severe distemper, developing virus persistence in the lymphoid tissue and central nervous system, this lymphopenia lasted until the end of the experiment. Increased levels of lymphocyte apoptosis were found at 3 d.p.i., and monocyte apoptosis at 6 d.p.i. This was more prominent in the group of animals with severe distemper. At 3 d.p.i. no leukocyte infection was detectable indicating that the early lymphocyte depletion and apoptosis was not a direct consequence of virus infection. Taken together, our results demonstrate that CDV-induced lymphopenia is an early event and that the degree of lymphocyte depletion correlates with the severity of disease and virus persistence in the lymphoid tissue and central nervous system.


title: Papel del rinovirus en las infecciones respiratorias en niños hospitalizados

text: Antecedentes El rinovirus se considera un agente causal de cuadros catarrales banales, sin embargo se ha descrito como un agente inductor de exacerbaciones asmáticas en adultos y niños mayores. En nuestro medio no se ha descrito el papel del rinovirus en infecciones respiratorias de niños hospitalizados. Objetivos Describir las infecciones confirmadas por rinovirus en niños hospitalizados por infección respiratoria en un hospital de segundo nivel. Pacientes y métodos Estudio descriptivo prospectivo de las infecciones confirmadas por rinovirus en niños hospitalizados por fiebre o infección respiratoria en la temporada 2004-2005. Para el diagnóstico virológico se realizó inmunofluorescencia y reacción en cadena de la polimerasa (PCR) en aspirado nasofaríngeo. Se describen las características clínicas de los pacientes. Resultados Se describen un total de 76 niños hospitalizados con infección por rinovirus, lo que supuso el 25 % de los pacientes hospitalizados por procesos respiratorios o fiebre. El rinovirus fue el segundo agente viral identificado tras el virus respiratorio sincitial (29,9% de los hospitalizados). El 71,1 % de los pacientes fueron menores de 2 años. Los diagnósticos más frecuentes fueron sibilancias recurrentes en el 60,5 %, bronquiolitis en 23,7 %, neumonía en el 7,9 % e infección respiratoria de vías altas en el 5,3%. Presentaron fiebre de más de 38 °C el 57,9 % de los niños e infiltrado radiológico el 23,7%. Presentaron hipoxia el 43,4% de los niños. En niños mayores de 2 años el diagnóstico fue crisis asmática en 21 de los 22 casos. Conclusiones Los rinovirus se detectaron en un importante porcentaje de los niños hospitalizados a consecuencia de infección respiratoria, siendo precedidos en frecuencia sólo por el virus respiratorio sincitial. En nuestra serie es el agente viral más frecuentemente asociado con episodios de sibilancias recurrentes en niños mayores de 2 años, y el segundo en los más pequeños. Background Rhinovirus is a recognized cause of common cold and has been shown to cause asthma exacerbations in adults and children. The burden of rhinovirus infections in hospitalized children has not been described in Spain. Objective To describe confirmed rhinovirus infections in children hospitalized for respiratory tract infection in a secondary public hospital. Patients and methods We performed a prospective descriptive study in children admitted to hospital with fever or respiratory tract infection and with a positive isolation of rhinovirus in nasopharyngeal washings between September 2004 and July 2005. Virological diagnosis was made with direct immunofluorescent assay and/or reverse transcription-polymerase chain reaction in specimens obtained from nasopharyngeal washings. The clinical characteristics of the patients were analyzed. Results There were 76 children with rhinovirus infection, representing 25 % of admissions in 304 children with fever or respiratory tract infection. Rhinovirus was the second most frequent viral agent identified after respiratory syncytial virus (RSV) (29.9 % of admissions). Fifty-four children (71.1%) were under 2 years of age. The most frequent clinical diagnoses were recurrent wheezing in 60.5 %, bronchiolitis in 23.7%, pneumonia in 7.9%, and upper respiratory tract infection in 5.3 %. Fever > 38 °C was present in 57.9% of the patients and radiologic infiltrate was found in 23.7%. Oxygen saturation less than 95% was found in 43.4% of the patients. Of 22 children aged more than 2 years, a diagnosis of asthmatic crisis was made in 21. Conclusions Rhinoviruses were frequently identified in hospitalized children with respiratory tract disease and were the second most common viruses after RSV. In our series, it was the most frequent cause of recurrent wheezing in hospitalized children and the second most common cause in infants.


title: Clinical and Molecular Epidemiology of Human Rhinovirus Infections in Patients with Hematologic Malignancy

text: BACKGROUND: Human rhinoviruses (HRVs) are common causes of upper respiratory tract infection (URTI) in hematologic malignancy (HM) patients. Predictors of lower respiratory tract infection (LRTI) including the impact of HRV species and types are poorly understood. OBJECTIVES: This study aims to describe the clinical and molecular epidemiology of HRV infections among HM patients. STUDY DESIGN: From April 2012–March 2013, HRV-positive respiratory specimens from symptomatic HM patients were molecularly characterized by analysis of partial viral protein 1 (VP1) or VP4 gene sequence. HRV LRTI risk-factors and outcomes were analyzed using multivariable logistic regression. RESULTS: One hundred and ten HM patients presented with HRV URTI (n=78) and HRV LRTI (n=32). Hypoalbuminemia (OR 3.0; 95% CI, 1.0 – 9.2; p=0.05) was independently associated with LRTI, but other clinical and laboratory markers of host immunity did not differ between patients with URTI versus LRTI. Detection of bacterial co-pathogens was common in LRTI cases (25%). Among 92 typeable respiratory specimens, there were 58 (64%) HRV-As, 12 (13%) HRV-Bs, and 21 (23%) HRV-Cs, and one Enterovirus 68. LRTI rates among HRV-A (29%), HRV-B (17%), and HRV-C (29%) were similar. HRV-A infections occurred year-round while HRV-B and HRV-C infections clustered in the late fall and winter. CONCLUSIONS: HRVs are associated with LRTI in HM patients. Illness severity is not attributable to specific HRV species or types. The frequent detection of bacterial co-pathogens in HRV LRTIs further substantiates the hypothesis that HRVs predispose to bacterial superinfection of the lower airways, similar to that of other community-acquired respiratory viruses.


Hydroxychloroquine- and azithromycin-related heart disorders


title: Testing for viral contaminants of veterinary vaccines in Hungary

text: Abstract The safety of veterinary vaccines is of paramount importance and it is significantly jeopardised by extraneous agents such as bacteria, mycoplasma, Chlamydia and viruses. Several critical steps of vaccine manufacture involve a potential risk of viral contamination. Viruses, as extraneous, agents can be divided into two main groups. Group 1 agents, such as Pestivirus, chicken anaemia virus (CAV), and egg drop syndrome virus (EDSV) are well-known to manufacturers and authorities. Compendial detection methods, clear guidelines and legislation have been established to minimise the risk of contamination with these agents. Contrary to group 1, group 2 agents like Torque Teno virus (TTV) or RD114, a replication-competent feline γ-retrovirus, have only recently been recognised and their role as contaminants needs further investigation. Randomly selected veterinary vaccines used between 1992 and 2009 were tested by nucleic acid amplification for CAV, EDSV, and TTV. Pestivirus contamination was examined in 33 vaccines used between 1996 and 2006 and a further 27 vaccines used between 2007 and 2009 based on random selection of these vaccines. In addition to random tests done on vaccines used from 2007 on, 12 batches of live Aujeszky's disease vaccines submitted to our laboratory for Official Control Authority Batch Release (OCABR) were also tested for Pestivirus.


title: Modified Bhramari Pranayama in Covid 19 Infection

text: The Coronavirus (2019-Cov-2) infection Covid-19 is highly contagious caused by single stranded RNA virus (+ssRNA) with nucleocapsid and spreading widely all across the world and responsible for more than 3.6 million morbidity and 0.25 million mortality No specific treatment is available till date. The clinical symptoms are mainly upper respiratory leading to diffuse viral pneumonia and multiple organ failure involving. Kidney, Liver and Heart along with coagulopathies. During 2004 (SARS-CoV) pandemic role of nitric oxide in its management is well demonstrated. Nitric Oxide (NO) reversed pulmonary hypertension. Improved severe hypoxia and shortened the stay in ICU and ventilatory support. Nitric Oxide increased the survival rate. The genetic composition of Corona Virus (SARS-CoV) is almost similar to Covid-19, thus indicates good chances of effectiveness or enhancement in results by Nitric Oxide along with other modes in treatment of Covid-19. It has been proved by studies by serendipity humming increases NO Expression dramatically.It is estimated that humming increases the endogenous generation of nitric oxide level by 15-fold. Hypoxia in ARD Syndrome leads to blood coagulation by depression of body defence anticoagulatory and fibrolytic properties along with metabolic acidosis. If we go into hypoxic hypercapnic state no hyper coagulation takes place. Hence Bhramari by enhancing the expression of Nitric Oxide and increased Carbon dioxide by extended exhalation and alkaline pH prevents coagulopathies and morbidity due to Covid-19.


Maladie de Kawasaki (MK) de l'adulte chronique et létale, compliquée d'une spondylarthropathie (SpA), sensibles aux immunoglobulines intraveineuses (Ig-IV)


title: Hypercytokinemia and Pathogen–Host Interaction in COVID-19

text: Severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 (SARS-CoV-2) is a novel coronavirus identified as the cause of coronavirus disease-2019 (COVID-19) that began in Wuhan, China in late 2019 and spread now in 210 countries and territories around the world. Many people are asymptomatic or with mild symptoms. However, in some cases (usually the elderly and those with comorbidities) the disease may progress to pneumonia, acute respiratory distress syndrome and multi-organ dysfunction that can lead to death. Such wide interindividual differences in response to SARS-CoV-2 infection may relate to several pathogen- and host-related factors. These include the different levels of the ubiquitously present human angiotensin I converting enzyme 2 (ACE2) receptors gene expression and its variant alleles, the different binding affinities of ACE2 to the virus spike (S) protein given its L- and S-subtypes and the subsequent extent of innate immunity-related hypercytokinemia. The extensive synthesis of cytokines and chemokines in coronavirus diseases was suggested as a major factor in exacerbating lung damage and other fatal complications. The polymorphisms in genes coding for pro-inflammatory cytokines and chemokines have been associated with mediating the response and susceptibility to a wide range of infections and their severe outcomes. Understanding the nature of pathogen–host interaction in COVID-19 symptomatology together with the role of hypercytokinemia in disease severity may permit developing new avenues of approach for prevention and treatment and can delineate public health measures to control the spread of the disease.


title: A nonstructural and antigenic glycoprotein is encoded by ORF3 of the IAF-Klop strain of porcine reproductive and respiratory syndrome virus

text: Open reading frame 3 (ORF3) of the genome of porcine reproductive and respiratory syndrome virus (PRRSV), Quebec strain IAF-Klop, was reverse-transcribed and cloned into the procaryotic expression vector pGEX-4T-1, then subcloned into the eucaryotic expression vector pAdCMV5 which was used as a shuttle vector to generate a replication-defective recombinant adenovirus. The procaryotic GST-ORF3 recombinant fusion protein was used to raise a monospecific antiserum in rabbits. By Western-immunoblotting with PRRSV-infected cell extracts, the ORF3 encoded protein had an estimated molecular mass (M(r)) of 42 kDa, similar to that of the protein expressed by the adenovirus vector. Endoglycosidase F digestion showed that the ORF3 encoded protein occurs in an highly glycosylated form (GP(3)) in the infected MARC-145 cells. Pulse-chase and radioimmunoprecipitation experiments revealed that the GP(3) protein was present in amounts equivalent to those of the N, M, and GP(5) proteins in the infected cells, whereas no GP(3) could be detected in purified virions. During the first 30 min of chase, the GP(3) undergoes a gradual downward shift of its apparent M(r), thought to result from trimming of the mannose-rich glycan structures. Tested convalescent pig sera that were found to be seropositive to PRRSV by indirect immunofluorescence reacted positively with the recombinant GST-ORF3 fusion protein by immunoblotting. Data indicated that the ORF3 protein of the Quebec reference strain of PRRSV is a highly glycosylated and antigenic protein, which is nonstructural.


title: The path towards effective antivirals against rabies

text: Abstract Rabies virus remains an important burden of disease claiming an estimated 60,000 lives each year, mainly children, and having a huge economical and societal cost. Post-exposure prophylaxis (PEP) is highly effective, however in patients that present with neurological symptoms the case-fatality ratio is extremely high (>99%). During the last decades several attempts to identify potent and effective antivirals were made. Only a few of these demonstrated improvement in clinical signs in animal studies and none of the trials in humans showed significant efficacy. Here we explore novel opportunities to identify more potent anti-rabies molecules. In particular important progress has been made on antivirals against other Mononegavirales (paramyxoviruses, filoviruses) which should be an impetus to test and optimize these molecules towards anti-rabies virus therapies. Effective rabies antivirals for therapeutic use need to be molecules that can be dosed into the cerebrospinal fluid and that rapidly and potently block ongoing virus replication and as such stop the further spread of the virus. Antivirals for prophylactic use can also be envisaged and these should be able to prevent infection of peripheral nerve cells and should have the potential to replace the current anti-rabies immunoglobulins that are used in PEP.


title: Características de las infecciones respiratorias agudas causadas por los coronavirus OC43, NL63 y 229E

text: Resumen Antecedentes y objetivos Las infecciones respiratorias agudas son una entidad muy frecuente en la población general. La mayoría de ellas son debidas a infecciones víricas. Este estudio pretende precisar las características clínicas y epidemiológicas de los pacientes adultos con infección respiratoria por los coronavirus OC43, NL63 y 229E. Pacientes y métodos Entre enero del 2013 y febrero del 2014 se estudió prospectivamente a todos los pacientes con sospecha clínica de infección respiratoria mediante la toma de un frotis faríngeo y la realización de una reacción en cadena de la polimerasa en transcripción reversa en tiempo real en búsqueda de coronavirus. Resultados En 48 casos (7,0% de los 686 pacientes incluidos; 12,6% de los 381 en los que se detectó algún virus) se pudo demostrar la presencia de algún coronavirus. En 24 casos se trataba del OC43 (50%), en 14 del NL63 (29%) y en 10 del 229E (21%). La edad media fue de 54,5 años, con un ligero predominio de varones. Las presentaciones clínicas más frecuentes fueron el cuadro gripal inespecífico (43,7%), la neumonía (29,2%) y la agudización de enfermedad pulmonar obstructiva crónica (8,3%). El 52% de los pacientes precisaron ingreso hospitalario, en 2 ocasiones en cuidados intensivos. No se produjo ningún fallecimiento. Conclusión Las infecciones respiratorias agudas causadas por coronavirus inciden preferentemente en varones fumadores en la edad media de la vida, frecuentemente afectados de enfermedades previas. La sintomatología clínica mas frecuente ha sido el cuadro gripal inespecífico. Abstract Background and objectives Acute respiratory infection is a very common condition in the general population. The majority of these infections are due to viruses. This study attempted to determine the clinical and epidemiological characteristics of adult patients with respiratory infection by the coronavirus OC43, NL63 and 229E. Patients and methods Between January 2013 and February 2014, we prospectively studied all patients with suspected clinical respiratory infection by taking throat swabs and performing a reverse transcription polymerase chain reaction in search of coronavirus. Results In 48 cases (7.0% of the 686 enrolled patients; 12.6% of the 381 in whom a virus was detected) the presence of a coronavirus demonstrated. In 24 cases, the virus was OC43 (50%); in 14 cases, the virus was NL63 (29%); and in 10 cases, the virus was 229E (21%). The mean age was 54.5 years, with a slight predominance of men. The most common clinical presentations were nonspecific influenza symptoms (43.7%), pneumonia (29.2%) and chronic obstructive pulmonary disease exacerbation (8.3%). Fifty-two percent of the patients required hospitalization, and 2 patients required intensive care. There were no deaths. Conclusion Acute respiratory infections caused by coronavirus mainly affect middle-aged male smokers, who are often affected by previous diseases. The most common clinical picture has been nonspecific influenza symptoms.


title: Clinical aspects of influenza A (H1N1) in HIV-infected individuals in São Paulo during the pandemic of 2009

text: Abstract Objective To describe the clinical aspects of H1N1 among HIV coinfected patients seen at a reference center for AIDS treatment in São Paulo, Brazil. Design Observational and prospective cohort study. Methods Descriptive study of clinical and laboratory investigation of HIV-infected patients with confirmed diagnosis of influenza A (H1N1) in 2009. We analyzed patients monitored in CRT/DST/AIDS, a specialized service for people living with HIV, located in São Paulo, Brazil. Results 108 individuals presented with symptoms of H1N1 infection at the CRT DST/AIDS in 2009. Eighteen patients (16.7%) had confirmation of the diagnosis of influenza A. Among the confirmed cases, ten (55.6%) were hospitalized and eight (44.4%) were outpatients. Dyspnea was present in nine patients (50%), hemoptysis in three (16%). Six patients (60%) required therapy with supplemental oxygen. All patients had good clinical outcomes and none died. Conclusions In our hospital, the symptoms that led patients to seek medical care were similar to the common flu. Hospital admission and the early introduction of antibiotics associated with oseltamivir may have been the cause of the favorable outcome of our cases.


title: Isolation and characterization of a novel mesonivirus from Culex mosquitoes in China

text: Abstract A new insect nidovirus (named Yichang virus) from the family Mesoniviridae was isolated, identified, and characterized from Culex mosquitoes in Hubei, China. Results showed a high number of viral RNA copies (up to 1011 copies/ml) within 48h in C6/36 cells. In addition, the titers of the Yichang virus reached maximal levels of 107 PFU/mL at 6 d post-infection (dpi). The virus produced moderate cytopathic effects when the multiplicity of infection ranged from 0.001–0.1 at 6 dpi, but did not replicate in mammalian cells. Under electron microscopy, the virion of the Yichang virus appeared as spherical particles with diameters of ∼80nm and large club-shaped projections. Although subsequent genomic sequence analysis revealed that the Yichang virus had similar protein patterns as those of other mesoniviruses, the nucleotide acids shared less than 20% BLAST query coverage with known viruses in the family Mesoniviridae, and showed a maximum sequence identity of 67% for RNA-dependent RNA polymerase (RdRp). The putative protein sequences showed slightly higher identity (28%–68%), and the most conserved domain was RdRp. Based on the phylogenetic and pairwise evolutionary distance analyses, the Yichang virus should be considered a new species belonging to a currently unassigned genus within the family Mesoniviridae.


title: Vaccine-preventable disease control in the People’s Republic of China: 1949–2016

text: Abstract Background China's immunization program is one of the oldest and largest in the world. Rates of vaccine-preventable diseases (VPD) are comparable to those in high-income countries. The program's evolution has been characterized by ambitious target setting and innovative strategies that have not been widely described. Methods We reviewed national and provincial health department archives; analyzed disease surveillance, vaccination coverage, and serosurvey data from 1950 through 2016; and, conducted in-depth interviews with senior Chinese experts involved early VPD control efforts. Results Widespread immunization began in the 1950s with smallpox, diphtheria, and Bacillus-Calmette Guerin vaccines, and in the 1960s with pertussis, tetanus, polio, measles, and Japanese encephalitis (JE) vaccines. The largest drops in absolute VPD burden occurred in the 1970s with establishment of the Rural Cooperative Medical System and a cadre of trained peasant health workers whose responsibilities included vaccinations. From 1970 to 1979, incidence per 100,000 population dropped 48% from 3.3 to 1.75 for diphtheria, 50% from 152.2 to 49.4 for pertussis, 77% from 2.5 to 0.6 for polio, 60% from 450.5 to 178.3 for measles, and 72% from 18.0 to 5.1 for JE, averting an average of 4 million VPD cases each year. Until the early 1980s, vaccines were delivered through annual winter campaigns using a coordinated ‘rush-relay’ system to expedite transport while leveraging vaccine thermostability. Establishment of the cold chain system during in the 1980s allowed bi-monthly vaccination rounds and more timely vaccination resulting in rates of diphtheria, pertussis, measles and meningitis falling over 90% from 1980 to 1989, while polio and JE rates fell 40–50%. In the 1990s, progress stalled as financing for public health was weakened by broad market reforms. Large investments in public health and immunizations by the central government since 2004 has led to further declines in VPD burden and increased equity. During 2011–2016, the incidence per 100,000 population was <2.0 for measles and <0.2 for pertussis, JE, meningococcal meningitis, and hepatitis A. From 1992 to 2014, the prevalence of chronic hepatitis B infection in children <5 years fell from 9.7% to 0.3%, a 97% decline. China was certified polio-free in 2000 and diphtheria was last reported in 2006. Conclusions Long-term political commitment to immunizations as a basic right, ambitious targets, use of disease incidence as the primary metric to assess program performance, and nationwide scale-up of successful locally developed strategies that optimized use of available limited resources have been critical to China's success in controlling vaccine-preventable diseases.


The Role of Phylogenetic Analysis in Clarifying the Infection Source of a COVID-19 Patient


title: Middle East Respiratory Syndrome Coronavirus and the One Health concept

text: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is one of the major threats to the healthcare systems in some countries, especially in the Arabian Peninsula. MERS-CoV is considered an ideal example of the One Health concept. This is due to the animals, especially dromedary camels, play important roles in the transmission and sustainability of the virus, and the virus can be transmitted through aerosols of infected patients into the environment. However, there is some debate regarding the origin of MERS-CoV either from bats or other unknown reservoirs. The dromedary camel is the only identified animal reservoir to date. These animals play important roles in sustaining the virus in certain communities and may act as an amplifier of the virus by secreting it in their body fluids, especially in nasal and rectal discharges. MERS-CoV has been detected in the nasal and rectal secretions of infected camels, and MERS-CoV of this origin has full capacity to infect human airway epithelium in both in vitro and in vivo models. Other evidence confirms the direct transmission of MERS-CoV from camels to humans, though the role of camel meat and milk products has yet to be well studied. Human-to-human transmission is well documented through contact with an active infected patient or some silently infected persons. Furthermore, there are some significant risk factors of individuals in close contact with a positive MERS-CoV patient, including sleeping in the same patient room, removing patient waste (urine, stool, and sputum), and touching respiratory secretions from the index case. Outbreaks within family clusters have been reported, whereby some blood relative patients were infected through their wives in the same house were not infected. Some predisposing genetic factors favor MERS-CoV infection in some patients, which is worth investigating in the near future. The presence of other comorbidities may be another factor. Overall, there are many unknown/confirmed aspects of the virus/human/animal network. Here, the most recent advances in this context are discussed, and the possible reasons behind the emergence and sustainability of MERS-CoV in certain regions are presented. Identification of the exact mechanism of transmission of MERS-CoV from camels to humans and searching for new reservoir/s are of high priority. This will reduce the shedding of the virus into the environment, and thus the risk of human infection can be mitigated.


title: The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality

text: Abstract Since December 2019, a viral pneumonia (COVID-19) from Wuhan, China has swept the world. Although the case fatality rate is not high, the number of people infected is large, and there are still a large number of patients dying. With the collation and publication of more and more clinical data, a large number of data suggest that there are mild or severe cytokine storms in severe patients, which is also an important cause of death. Therefore, the treatment of cytokine storm has become an important part of rescuing severe patients. Interleukin-6 (IL-6) plays an important role in cytokine release syndrome (CRS). If it can block the signal transduction pathway of IL-6, it is expected to become a new method for the treatment of severe patients. Tocilizumab is a blocker of IL-6R, which can effectively block IL-6 signal transduction pathway. So, tocilizumab is likely to become an effective drug for patients with severe COVID-19.


title: Comparative Pathogenesis of Three Human and Zoonotic SARS-CoV Strains in Cynomolgus Macaques

text: The severe acute respiratory syndrome (SARS) epidemic was characterized by increased pathogenicity in the elderly due to an early exacerbated innate host response. SARS-CoV is a zoonotic pathogen that entered the human population through an intermediate host like the palm civet. To prevent future introductions of zoonotic SARS-CoV strains and subsequent transmission into the human population, heterologous disease models are needed to test the efficacy of vaccines and therapeutics against both late human and zoonotic isolates. Here we show that both human and zoonotic SARS-CoV strains can infect cynomolgus macaques and resulted in radiological as well as histopathological changes similar to those seen in mild human cases. Viral replication was higher in animals infected with a late human phase isolate compared to a zoonotic isolate. While there were significant differences in the number of host genes differentially regulated during the host responses between the three SARS-CoV strains, the top pathways and functions were similar and only apparent early during infection with the majority of genes associated with interferon signaling pathways. This study characterizes critical disease models in the evaluation and licensure of therapeutic strategies against SARS-CoV for human use.


title: Human bocavirus commonly involved in multiple viral airway infections

text: Abstract Background Human bocavirus (HBoV) was recently discovered in children with acute respiratory tract infections. We have included a PCR for HBoV in a study on airway infections in children. Objectives To study the occurrence of HBoV in Norwegian children, and to evaluate the results of a semiquantitive PCR. Study design During a 4-month period in the winter season 2006/2007 we collected nasopharyngeal aspirations from children who were admitted to the Department of Pediatrics. All samples were examined for 17 agents with real-time PCR. Results HBoV was detected in 45 of 376 samples (12%). The occurrence of HBoV was stable during the study period. Multiple viral infections were present in 78% of the samples (42% double, 20% triple and 16% quadruple infections). RS-virus, enterovirus and human metapneumovirus were the most frequently codetected agents. In samples with a high load for HBoV, significantly fewer multiple infections were found than in the other samples. Eighty-eight percent of the 25 patients with HBoV recorded as either the only or the dominating virus, and 50% of the other patients, had lower respiratory tract infection. The difference was statistically significant. Conclusions HBoV was frequently detected in nasopharyngeal aspirates from children with airway infections in Norway. Multiple viral infections were common among the HBoV-infected patients. Semiquantitive PCR results may be useful for interpretation of clinical relevance.


NK cells in asthma exacerbation


title: Characterization of the glycoproteins of bat-derived influenza viruses

text: Abstract Recently found bat-derived influenza viruses (BatIVs) have hemagglutinin (HA) and neuraminidase (NA) gene segments distinct from those of previously known influenza A viruses. However, pathogenicities of these BatIVs remain unknown since infectious virus strains have not been isolated yet. To gain insight into the biological properties of BatIVs, we generated vesicular stomatitis viruses (VSVs) pseudotyped with the BatIV HA and NA. We found that VSVs pseudotyped with BatIV HAs and NAs efficiently infected particular bat cell lines but not those derived from primates, and that proteolytic cleavage with a trypsin-like protease was necessary for HA-mediated virus entry. Treatment of the susceptible bat cells with some enzymes and inhibitors revealed that BatIV HAs might recognize some cellular glycoproteins as receptors rather than the sialic acids used for the other known influenza viruses. These data provide fundamental information on the mechanisms underlying the cellular entry and host restriction of BatIVs.


title: The global spread of 2019-nCoV: a molecular evolutionary analysis

text: The global spread of the 2019-nCoV is continuing and is fast moving, as indicated by the WHO raising the risk assessment to high. In this article, we provide a preliminary phylodynamic and phylogeographic analysis of this new virus. A Maximum Clade Credibility tree has been built using the 29 available whole genome sequences of 2019-nCoV and two whole genome sequences that are highly similar sequences from Bat SARS-like Coronavirus available in GeneBank. We are able to clarify the mechanism of transmission among the countries which have provided the 2019-nCoV sequence isolates from their patients. The Bayesian phylogeographic reconstruction shows that the 2019–2020 nCoV most probably originated from the Bat SARS-like Coronavirus circulating in the Rhinolophus bat family. In agreement with epidemiological observations, the most likely geographic origin of the new outbreak was the city of Wuhan, China, where 2019-nCoV time of the most recent common ancestor emerged, according to molecular clock analysis, around November 25(th), 2019. These results, together with previously recorded epidemics, suggest a recurring pattern of periodical epizootic outbreaks due to Betacoronavirus. Moreover, our study describes the same population genetic dynamic underlying the SARS 2003 epidemic, and suggests the urgent need for the development of effective molecular surveillance strategies of Betacoronavirus among animals and Rhinolophus of the bat family.


title: Prior treatment with immunosuppressants among COVID‐19 inpatients at one hospital in Spain

text: Vulnerability to coronavirus disease 2019 (COVID‐19) in patients with cardiovascular risk factors is well known. However, the prognostic influence of immunosuppressive drugs or their ability to counteract the cytokine storm involving critically‐ill patients are uncertain. The scarce related literature mainly involves transplantation.


title: How bad is it? Suicidality in the middle of the COVID‐19 pandemic

text: OBJECTIVE: The current paper examines the intersection between social vulnerability, individual risk, and social/psychological resources with adult suicidality during the COVID‐19 pandemic. METHOD: Data come from a national sample (n = 10,368) of U.S. adults. Using an online platform, information was gathered during the third week of March 2020, and post‐stratification weighted to proportionally represent the U.S. population in terms of age, gender, race/ethnicity, income, and geography. RESULTS: Nearly 15 percent of sampled respondents were categorized as high risk, scoring 7+ on the Suicide Behaviors Questionnaire‐Revised (SBQ‐R). This level of risk varied across social vulnerability groupings: Blacks, Native Americans, Hispanics, families with children, unmarried, and younger respondents reported higher SBQ‐R scores than their counterparts (p < .000). Regression results confirm these bivariate differences and also reveal that risk factors (food insecurity, physical symptoms, and CES‐D symptomatology) are positive and significantly related to suicidality (p < .000). Additionally, resource measures are significant and negatively related to suicidality (p < .000). CONCLUSIONS: These results provide some insight on the impact COVID‐19 is having on the general U.S. population. Practitioners should be prepared for what will likely be a significant mental health fall‐out in the months and years ahead.


title: GESTIÓN Y LIDERAZGO DE LOS SERVICIOS DE ENFERMERÍA EN EL PLAN DE EMERGENCIA DE LA PANDEMIA COVID-19: LA EXPERIENCIA DEL HOSPITAL CLÍNIC DE BARCELONA

text: Resumen A nivel internacional, la enorme demanda para gestionar la pandemia del COVID-19 ha supuesto un reto tanto en la provisión de personal cómo en suministros y material sanitario. No existe precedente ni publicaciones relacionadas con la gestión y liderazgo de los servicios de enfermería en España dentro del plan de emergencia de la pandemia COVID-19. En este artículo se describe la experiencia del Hospital Clínico de Barcelona en las circunstancias extraordinarias actuales que constituyen, sin duda, una gestión enfermera de enorme magnitud y sin precedentes debido al elevado número de personas afectadas y el extraordinario riesgo del personal sanitario. Siguiendo las orientaciones nacionales e internacionales para paliar la pandemia, proteger la salud y prevenir la propagación del brote. La capacidad de trabajo en equipo, la gestión emocional y el respeto a las decisiones organizativas han hecho posible que se hayan podido afrontar los retos que la pandemia ha puesto por delante y que desde la Dirección de Enfermería se pueda liderar de forma serena y ordenada las diferentes acciones a realizar. Por último, será necesario continuar con un profundo análisis de la situación y de las acciones desarrolladas para poder identificar las áreas de mejora, así como evaluar la globalidad del proceso. Abstract At the international level, the enormous demand to manage the COVID-19 pandemic has posed a challenge both in the provision of personnel and in supplies and sanitary material. There is no precedent or publication related to the management and leadership of nursing services in Spain within the emergency plan for the COVID-19 pandemic. This article describes the experience of the Hospital Clinico de Barcelona in the current extraordinary circumstances that undoubtedly constitute a nursing management of enormous magnitude and unprecedented due to the high number of people affected and the extraordinary risk of healthcare personnel. Following national and international guidelines to alleviate the pandemic, protect health and prevent the spread of the outbreak. The ability to work as a team, emotional management and respect for organizational decisions have made it possible to face the challenges that the pandemic has put in place and that the Nursing Department can lead in a calm and orderly manner the different actions to perform. Lastly, it will be necessary to continue with an in-depth analysis of the situation and of the actions carried out in order to identify the areas for improvement as well as to evaluate the overall nature of the process


title: Diagnostic approaches for viruses and prions in stem cell banks

text: Abstract Some stem cell lines may contain an endogenous virus or can be contaminated with exogenous viruses (even of animal origin) and may secrete viral particles or express viral antigens on their surface. Moreover, certain biotechnological products (e.g. bovine fetal serum, murine feeder cells) may contain prion particles. Viral and prion contamination of cell cultures and “feeder” cells, which is a common risk in all biotechnological products derived from the cell lines, is the most challenging and potentially serious outcome to address, due to the difficulty involved in virus and prion detection and the potential to cause serious disease in recipients of these cell products. Stem cell banks should introduce adequate quality assurance programs like the microbiological control program and can provide researchers with valuable support in the standardization and safety of procedures and protocols used for the viral and prion testing and in validation programs to assure the quality and safety of the cells.


The Case for Masks – Health Care Workers Can Benefit, Too


title: Ebola hemorrhagic fever: Properties of the pathogen and development of vaccines and chemotherapeutic agents

text: Ebola hemorrhagic fever (EHF) epidemic currently ongoing in West Africa is not the first among numerous epidemics in the continent. Yet it seems to be the worst EHF epidemic outbreak caused by Ebola virus Zaire since 1976 as regards its extremely large scale and rapid spread in the population. Experiments to study the agent have continued for more than 20 years. The EHF virus has a relatively simple genome with seven genes and additional reading frame resulting from RNA editing. While being of a relatively low genetic capacity, the virus can be ranked as a standard for pathogenicity with the ability to evade the host immune response in uttermost perfection. The EHF virus has similarities with retroviruses, but belongs to (–)RNA viruses of a nonretroviral origin. Genetic elements of the virus, NIRV, were detected in animal and human genomes. EHF virus glycoprotein (GP) is a class I fusion protein and shows more similarities than distinctions in tertiary structure with SIV and HIV gp41 proteins and even influenza virus hemagglutinin. EHF is an unusual infectious disease, and studying the molecular basis of its pathogenesis may contribute to new findings in therapy of severe conditions leading to a fatal outcome.


title: Recomendaciones prácticas para el manejo perioperatorio del paciente con sospecha o infección grave por coronavirus SARS-CoV-2

text: Resumen En diciembre del 2019, la Comisión Municipal de Salud y Sanidad de Wuhan (provincia de Hubei, China) informó de una serie de casos de neumonía de etiología desconocida. El 7 de enero del 2020, las autoridades chinas identificaron como agente causante del brote un nuevo tipo de virus de la familia Coronaviridae, denominado SARS-CoV-2. Desde entonces, se han notificado miles de casos con una diseminación global. Las infecciones en humanos provocan un amplio espectro clínico que va desde infección leve del tracto respiratorio superior, hasta síndrome de distrés respiratorio agudo grave y sepsis. No existe un tratamiento específico para SARS-CoV-2, motivo por lo que los aspectos fundamentales son establecer medidas adecuadas de prevención y el tratamiento de soporte y manejo de las complicaciones. Abstract In December 2019, the Wuhan Municipal Health and health Commission (Hubei Province, China) reported a series of cases of pneumonia of unknown etiology. On January 7, 2020, the Chinese authorities identified as a causative agent of the outbreak a new type of virus of the Coronaviridiae family, called SARS-CoV-2. Since then, thounsands of cases have been reported with global dissemination. Infections in humans cause a broad clinical spectrum ranging from mild upper respiratory tract infection, to severe acute respiratory distress syndrome and sepsis. There is not specific treatment for SARS-CoV-2, which is why the fundamental aspects are to establish adequate prevention measures and support treatment and management of complications.


title: Cross-sectional investigation and risk factor analysis of community-acquired and hospital-associated canine viral infectious respiratory disease complex

text: Canine infectious respiratory disease complex (CIRDC) is associated with multiple factors. The possible transmission source can be via community-acquired infection (CAI) or hospital-associated infection (HAI), but the variable factors within these two routes are not well described. This study aimed to (i) investigate a cross-sectional incidence of canine respiratory viruses, including influenza (CIV), parainfluenza, distemper (CDV), respiratory coronavirus (CRCoV), adenovirus-2, and herpesvirus, in respiratory-diseased dogs, and (ii) analyze the possibly related risk factors. In total 209 dogs with respiratory illness, consisting of 133 CAI and 76 HAI dogs, were studied. Both nasal and oropharyngeal swabs were sampled from each dog and subjected for CIRDC virus detection using multiplex PCRs. Common six viruses associated with CIRDC were detected in both groups with CIV and CRCoV being predominantly found. Only CDV was significantly more prevalent in CAI than HAI dogs. Multiple virus detections were found in 81.2% and 78.9% of CAI and HAI dogs, respectively. Co-detection of CIV and CRCoV was represented the highest proportion and most often found with other CIRD viruses. Moreover, the clinical severity level was notably related to the age of infected dogs, but not to the vaccination status, sex and transmission route. Since healthy or control dogs were not included in this study, the prevalence of the CIRD virus infections could not be assessed.


title: Differential gene modulation of pattern-recognition receptor TLR and RIG-I-like and downstream mediators on intestinal mucosa of pigs infected with PEDV non S-INDEL and PEDV S-INDEL strains

text: Abstract Porcine epidemic diarrhea virus (PEDV) strains can be divided into non-S-INDEL and S-INDEL strains. PEDV pathogenesis is strain-specific, and studies in neonatal pigs have demonstrated that the PEDV non-S-INDEL strains are more pathogenic than the PEDV S-INDEL strains. RNA viruses, including PEDV, can interact with a large number of pattern recognition receptors (PRRs) in the intestinal mucosa, including toll-like receptors (TLRs) and RIG-I-like receptors (RLRs). We investigated the differential gene modulation of TLRs, RIG-I, and downstream mediators on the intestinal mucosa of neonatal pigs infected with PEDV S-INDEL and non-S-INDEL strains. Ten five-day-old piglets were inoculated orally with 10ml of 104 TCDI50/ml of either PEDV non-S-INDEL or S-INDEL strains. PEDV S-INDEL infection induced pro-inflammatory cytokines through the non-canonical NF-κB signaling pathway by activating RIG-I. In contrast, PEDV non-S-INDEL infection suppressed the induction of pro-inflammatory cytokines and type 1 interferon production by down-regulation of TLRs and downstream signaling molecules.


title: Regenerative Medicine in COVID-19 Treatment: Real Opportunities and Range of Promises

text: Novel coronavirus disease (COVID-19) has attracted much attention around the world due to its rapid transmission among humans and relatively high mortality rate. Studies are increasing to find the best therapeutic approach for the disease and its management. Regenerative medicine offers various cell-tissue therapeutics and related products, such as stem cell therapy, natural killer (NK) cell therapy, Chimeric antigen receptor (CAR) T cell therapy, exosomes, and tissue products. Interestingly, mesenchymal stem cells (MSCs) can reduce inflammatory symptoms and protect against cytokine storm, which critically contributes to the COVID-19 progression. Notably, having the potentials to exert cytotoxic effects on infected cells and induce interferon production probably make NK cells a candidate for COVID-19 cell therapy. Besides, exosomes are one of the crucial products of cells that can exert therapeutic effects through the induction of immune responses and neutralizing antibody titers. The paper aims to briefly consider current options for COVID-19 therapy to show that there is no specific cure for COVID-19, and then assess the real opportunities and range of promises regenerative medicine can provide for specific treatment of COVID-19. [Figure: see text]


title: Identification of non-essential regions in nucleocapsid protein of porcine reproductive and respiratory syndrome virus for replication in cell culture

text: Abstract Nucleocapsid (N) protein of porcine reproductive and respiratory syndrome virus (PRRSV) plays a central role in virus replication. In this study, serial N- and C-terminal truncations of N protein were performed in the context of type 2 PRRSV infectious cDNA clone, and our results revealed that a stretch of inter-genotypic variable N terminal residues aa 5–13 (5NGKQQKKK13K) and the last four inter-genotypic variable aa residues (120SPS123A) at the C terminus of N protein were dispensable for type 2 PRRSV infectivity. All the recovered deletion mutant viruses had spontaneous mutations in the N coding region, including substitution, deletion and insertion. We re-engineered the additional internal deletion with or without the original C-terminal deletion back into wild-type APRRS and found that the internal domain spanning the inter-genotypic variable residues 39–42 (39KGP42G) and conserved residues 48–52 (48KNPE52K), respectively, were dispensable for type 2 PRRSV viability. These results demonstrated that N protein contains non-essential regions for virus viability in cell culture. Such dispensable regions could be utilized as insertion site for foreign tag expression and the rescued viruses could be the candidates for marker vaccine.


title: Poliovirus infection induces the co-localization of cellular protein SRp20 with TIA-1, a cytoplasmic stress granule protein

text: Different types of environmental stress cause mammalian cells to form cytoplasmic foci, termed stress granules, which contain mRNPs that are translationally silenced. These foci are transient and dynamic, and contain components of the cellular translation machinery as well as certain mRNAs and RNA binding proteins. Stress granules are known to be induced by conditions such as hypoxia, nutrient deprivation, and oxidative stress, and a number of cellular factors have been identified that are commonly associated with these foci. More recently it was discovered that poliovirus infection also induces the formation of stress granules, although these cytoplasmic foci appear to be somewhat compositionally unique. Work described here examined the punctate pattern of SRp20 (a host cell mRNA splicing protein) localization in the cytoplasm of poliovirus-infected cells, demonstrating the partial co-localization of SRp20 with the stress granule marker protein TIA-1. We determined that SRp20 does not co-localize with TIA-1, however, under conditions of oxidative stress, indicating that the close association of these two proteins during poliovirus infection is not representative of a general response to cellular stress. We confirmed that the expression of a dominant negative version of TIA-1 (TIA-1-PRD) results in the dissociation of stress granules. Finally, we demonstrated that expression of wild type TIA-1 or dominant negative TIA-1-PRD in cells during poliovirus infection does not dramatically affect viral translation. Taken together, these studies provide a new example of the unique cytoplasmic foci that form during poliovirus infection.


title: Prednisolone for the first rhinovirus‐induced wheezing and 4‐year asthma risk: A randomized trial

text: BACKGROUND: Previous findings show that corticosteroid treatment during the first acute wheezing episode may reduce recurrent wheezing in children with high rhinovirus genome load at 12‐month follow‐up. Longer‐term effects have not been investigated prospectively. METHODS: After PCR confirmation of rhinovirus from nasopharyngeal aspirate, 79 children with the first acute wheezing episode were randomized to receive orally prednisolone or placebo for 3 days. The initiation of asthma control medication before the age of 5 years was confirmed from medical record and/or from parental interview. The outcome was the time to initiation of regular asthma control medication. Interaction analysis examined rhinovirus genome load. RESULTS: Fifty‐nine (75%) children completed the follow‐up. Asthma control medication was initiated in 40 (68%) children at the median age of 20 months. Overall, prednisolone did not affect the time to initiation of asthma control medication when compared to placebo (P=.99). Rhinovirus load modified the effect of prednisolone regarding the time to initiation of asthma control medication (P‐value for interaction=.04). In children with high rhinovirus load (>7000 copies/mL; n=23), the risk for initiation of medication was lower in the prednisolone group compared to the placebo group (P=.05). In the placebo group, asthma medication was initiated to all children with high rhinovirus load (n=9) during the 14 months after the first wheezing episode. CONCLUSIONS: Overall, prednisolone did not affect the time to initiation of asthma control medication when compared to placebo. However, prednisolone may be beneficial in first‐time wheezing children whose episode was severe and associated with high rhinovirus load. (ClinicalTrials.gov, NCT00731575).


title: In vivo and in vitro models of demyelinating disease X. A Schwannoma-L-2 somatic cell hybrid persistently yielding high titres of mouse hepatitis virus strain JHM

text: Abstract Following infection of RN2 rat Schwannoma cells with unfiltered JHMV inocula, a cell line with an altered phenotype evolved, which was shown to be a somatic cell hybrid of RN2 and mouse L-2 cells. This cell line, EJ, persistently yields JHMV at titres greater than 106 pfu/ml and does not show the suppression of virus production at 39.5 °C that is characteristic of a persistently infected RN2 line. Intracellular viral nucleocapsids are demonstrated. Cloning of EJ hybrids yields cell lines that show a variety of responses to infection by JHMV or MHV3.


Comment on “Should anti-diabetic medications be reconsidered amid COVID-19 pandemic?”


title: Haemophilus influenzae Type a Meningitis in Immunocompetent Child, Oman, 2015

text: Meningitis caused by Haemophilus influenzae type b (Hib) was eliminated in Oman after the introduction of Hib vaccine in 2001. However, a case of H. influenzae type a meningitis was diagnosed in a child from Oman in 2015, which highlights the need to monitor the incidence of invasive non-Hib H. influenzae disease.


title: COVID-19 infections and outcomes in patients with multiple myeloma in New York City: a cohort study from five academic centers

text: IMPORTANCE: New York City is a global epicenter for the SARS-CoV-2 outbreak with a significant number of individuals infected by the virus. Patients with multiple myeloma have a compromised immune system, due to both the disease and anti-myeloma therapies, and may therefore be particularly susceptible to coronavirus disease 2019 (COVID-19); however, there is limited information to guide clinical management. OBJECTIVE: To assess risk factors and outcomes of COVID-19 in patients with multiple myeloma. DESIGN: Case-series. SETTING: Five large academic centers in New York City. PARTICIPANTS: Patients with multiple myeloma and related plasma cell disorders who were diagnosed with COVID-19 between March 10(th), 2020 and April 30(th,) 2020. EXPOSURES: Clinical features and risk factors were analyzed in relation to severity of COVID-19. MAIN OUTCOMES AND MEASURES: Descriptive statistics as well as logistic regression were used to estimate disease severity reflected in hospital admissions, intensive care unit (ICU) admission, need for mechanical ventilation, or death. RESULTS: Of 100 multiple myeloma patients (male 58%; median age 68, range 41–91) diagnosed with COVID-19, 74 (74%) were admitted; of these 13 (18%) patients were placed on mechanical ventilation, and 18 patients (24%) expired. None of the studied risk factors were significantly associated (P>0.05) with adverse outcomes (ICU-admission, mechanical ventilation, or death): hypertension (N=56) odds ratio (OR) 2.3 (95% confidence interval [CI] 0.9–5.9); diabetes (N=18) OR 1.1 (95% CI 0.3–3.2); age >65 years (N=63) OR 2.0 (95% CI 0.8–5.3); high dose melphalan with autologous stem cell transplant <12 months (N=7) OR 1.2 (95% CI 0.2–7.4), IgG<650 mg/dL (N=42) OR=1.2 (95% CI 0.4–3.1). In the entire series of 127 patients with plasma cell disorders, hypertension was significantly associated with the combined end-point (OR 3.4, 95% CI 1.5–8.1). CONCLUSIONS AND RELEVANCE: Although multiple myeloma patients have a compromised immune system due to both the disease and therapy; in this largest disease specific cohort to date of patients with multiple myeloma and COVID-19, compared to the general population, we found risk factors for adverse outcome to be shared and mortality rates to be within the higher range of officially reported mortality rates.


title: Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study

text: BACKGROUND: Since Dec 31, 2019, the Chinese city of Wuhan has reported an outbreak of atypical pneumonia caused by the 2019 novel coronavirus (2019-nCoV). Cases have been exported to other Chinese cities, as well as internationally, threatening to trigger a global outbreak. Here, we provide an estimate of the size of the epidemic in Wuhan on the basis of the number of cases exported from Wuhan to cities outside mainland China and forecast the extent of the domestic and global public health risks of epidemics, accounting for social and non-pharmaceutical prevention interventions. METHODS: We used data from Dec 31, 2019, to Jan 28, 2020, on the number of cases exported from Wuhan internationally (known days of symptom onset from Dec 25, 2019, to Jan 19, 2020) to infer the number of infections in Wuhan from Dec 1, 2019, to Jan 25, 2020. Cases exported domestically were then estimated. We forecasted the national and global spread of 2019-nCoV, accounting for the effect of the metropolitan-wide quarantine of Wuhan and surrounding cities, which began Jan 23–24, 2020. We used data on monthly flight bookings from the Official Aviation Guide and data on human mobility across more than 300 prefecture-level cities in mainland China from the Tencent database. Data on confirmed cases were obtained from the reports published by the Chinese Center for Disease Control and Prevention. Serial interval estimates were based on previous studies of severe acute respiratory syndrome coronavirus (SARS-CoV). A susceptible-exposed-infectious-recovered metapopulation model was used to simulate the epidemics across all major cities in China. The basic reproductive number was estimated using Markov Chain Monte Carlo methods and presented using the resulting posterior mean and 95% credibile interval (CrI). FINDINGS: In our baseline scenario, we estimated that the basic reproductive number for 2019-nCoV was 2·68 (95% CrI 2·47–2·86) and that 75 815 individuals (95% CrI 37 304–130 330) have been infected in Wuhan as of Jan 25, 2020. The epidemic doubling time was 6·4 days (95% CrI 5·8–7·1). We estimated that in the baseline scenario, Chongqing, Beijing, Shanghai, Guangzhou, and Shenzhen had imported 461 (95% CrI 227–805), 113 (57–193), 98 (49–168), 111 (56–191), and 80 (40–139) infections from Wuhan, respectively. If the transmissibility of 2019-nCoV were similar everywhere domestically and over time, we inferred that epidemics are already growing exponentially in multiple major cities of China with a lag time behind the Wuhan outbreak of about 1–2 weeks. INTERPRETATION: Given that 2019-nCoV is no longer contained within Wuhan, other major Chinese cities are probably sustaining localised outbreaks. Large cities overseas with close transport links to China could also become outbreak epicentres, unless substantial public health interventions at both the population and personal levels are implemented immediately. Independent self-sustaining outbreaks in major cities globally could become inevitable because of substantial exportation of presymptomatic cases and in the absence of large-scale public health interventions. Preparedness plans and mitigation interventions should be readied for quick deployment globally. FUNDING: Health and Medical Research Fund (Hong Kong, China).


title: Seasonal variation of window opening behaviors in two naturally ventilated hospital wards

text: Abstract Natural ventilation enables personal control, and occupant behaviors in window opening play a decisive role on natural ventilation performance, indoor air quality (IAQ), and/or airborne infection risk in a hospital setting. The occupant behaviors differ significantly from different building types with different functions and living habits. Based on a one-year field measurement in two general hospital wards in Nanjing, China, the effects of air quality (i.e. indoor CO2 concentration and outdoor PM2.5 concentration) and the climatic parameters (i.e. indoor/outdoor temperature, relative humidity, and outdoor wind speed, wind direction and rainfall) on window opening/closing behaviors are analyzed. Indoor air temperature or relative humidity is found to be a dominant factor for window opening behaviors. Seasonal differences are observed for the different influences of physical factors. The outdoor temperature is found to be associated with the window opening probability negatively during the cooling season, but positively during the transition and heating seasons. The indoor relative humidity positively affects the window opening probability during the transition season while a negative impact appears during the cooling and heating seasons. Based on the seasonal variation of window opening behaviors, Logistic regression models in different seasons (cooling, transition and heating seasons) are developed to predict the window opening/closing state and are verified to be promisingly adaptable with results of accuracy bigger than 70%.


title: The antiviral activity of poly-γ-glutamic acid, a polypeptide secreted by Bacillus sp., through induction of CD14-dependent type I interferon responses

text: Abstract Poly-γ-glutamic acid (γ-PGA) is an anionic polypeptide secreted by Bacillus sp. that has been shown to activate immune cells through interactions with toll-like receptor 4 (TLR4). However, its ability to induce the type I interferon (IFN) response has not yet been characterized. Here, we demonstrate that γ-PGA induces type I IFN signaling pathway via the TLR4 signaling pathway. The induction required both myeloid differentiation factor 2 (MD2) and the pattern-recognition receptor CD14, which are two TLR4-associated accessory proteins. The γ-PGA with high molecular weights (2000 and 5000 kDa) was able to activate the subsequent signals through TLR4/MD2 to result in dimerization of IRF-3, a transcription factor required for IFN gene expression, leading to increases in mRNA levels of the type I IFN-response genes, 2′–5′ OAS and ISG56. Moreover, γ-PGA (2000 kDa) displayed an antiviral activity against SARS coronavirus and hepatitis C virus. Our results identify high-molecular weight γ-PGA as a TLR4 ligand and demonstrate that γ-PGA requires both CD14 and MD2 for the activation of type I IFN responses. Our results suggest that the microbial biopolymer γ-PGA may have therapeutic potential against a broad range of viruses sensitive to type I IFNs.


title: Sequence analysis of the 3′-end of feline calicivirus genome

text: Abstract The nucleotide sequence of the 3′-end of the Japanese F4 strain of feline calicivirus (FCV) RNA was determined from a cloned cDNA of 3.5 kbp. We found three open reading frames (ORFs). The largest ORF encoded a 668-amino acid protein of 73,588 Da, which was presumably the capsid precursor protein of FCV and had significant amino acid sequence homology with the VP3 of picornaviruses. A small ORF at the extreme 3′-end was compared with that of the F9 strain of FCV, a vaccine strain originally from the U.S. Highly conserved amino acid sequences were shown, suggesting that this ORF might be functional and encode a putative 106-amino acid protein of 12,153 Da. The other ORF in the 5′-flanking region of the cDNA had consensus amino acid sequences conserved among the RNA-dependent RNA polymerases.


title: 13 Strengthening the role of the IBC in the 21st century

text: Abstract The US government (USG) has not fully implemented a robust system to evaluate dual-use research (DUR). In particular, the USG has failed to effectively fund, support, and expand the role of the local Institutional Biosafety Committee in the oversight of DUR and in the changing scientific landscape; a comprehensive education program for all in life sciences research with regard to the dual-use dilemma has not been forthcoming; and finally, there has been no systematic evaluation of the impact of USG policy, regulations, and guidance on an institution’s cost structure and on scientific discovery. We detail our judgments on current USG DUR policy and provide recommendations for future oversight of DUR from our perspective as senior administrators and laboratory scientists charged with the responsibility of conducting life-sciences research in an era of increasing regulatory requirements and decreasing federal support.