title: The More the Better? A Comparison of the Information Sources Used by the Public during Two Infectious Disease Outbreaks

text: Recent infectious disease outbreaks have resulted in renewed recognition of the importance of risk communication planning and execution to public health control strategies. Key to these efforts is public access to information that is understandable, reliable and meets their needs for informed decision-making on protective health behaviours. Learning from the trends in sources used in previous outbreaks will enable improvements in information access in future outbreaks. Two separate random-digit dialled telephone surveys were conducted in Alberta, Canada, to explore information sources used by the public, together with their perceived usefulness and credibility, during the 2003 Severe Acute Respiratory Syndrome (SARS) epidemic (n = 1209) and 2009–2010 H1N1 pandemic (n = 1206). Traditional mass media were the most used information sources in both surveys. Although use of the Internet increased from 25% during SARS to 56% during H1N1, overall use of social media was not as high as anticipated. Friends and relatives were commonly used as an information source, but were not deemed very useful or credible. Conversely, doctors and health professionals were considered credible, but not consulted as frequently. The use of five or more information sources increased by almost 60% between the SARS and H1N1 surveys. There was a shift to older, more educated and more affluent respondents between the surveys, most likely caused by a decrease in the use of landlines amongst younger Canadians. It was concluded that people are increasingly using multiple sources of health risk information, presumably in a complementary manner. Subsequently, although using online media is important, this should be used to augment rather than replace more traditional information channels. Efforts should be made to improve knowledge transfer to health care professionals and doctors and provide them with opportunities to be more accessible as information sources. Finally, the future use of telephone surveys needs to account for the changing demographics of the respondents accessed through such surveys.


title: Zygote injection of CRISPR/Cas9 RNA successfully modifies the target gene without delaying blastocyst development or altering the sex ratio in pigs

text: The CRISPR/Cas9 genome editing tool has increased the efficiency of creating genetically modified pigs for use as biomedical or agricultural models. The objectives were to determine if DNA editing resulted in a delay in development to the blastocyst stage or in a skewing of the sex ratio. Six DNA templates (gBlocks) that were designed to express guide RNAs that target the transmembrane protease, serine S1, member 2 (TMPRSS2) gene were in vitro transcribed. Pairs of CRISPR guide RNAs that flanked the start codon and polyadenylated Cas9 were co-injected into the cytoplasm of zygotes and cultured in vitro to the blastocyst stage. Blastocysts were collected as they formed on days 5, 6 or 7. PCR was performed to determine genotype and sex of each embryo. Separately, embryos were surgically transferred into recipient gilts on day 4 of estrus. The rate of blastocyst development was not significantly different between CRISPR injection embryos or the non-injected controls at day 5, 6 or 7 (p = 0.36, 0.09, 0.63, respectively). Injection of three CRISPR sets of guides resulted in a detectable INDEL in 92–100 % of the embryos analyzed. There was not a difference in the number of edits or sex ratio of male to female embryos when compared between days 5, 6 and 7 to the controls (p > 0.22, >0.85). There were 12 resulting piglets and all 12 had biallelic edits of TMRPSS2. Zygote injection with CRISPR/Cas9 continues to be a highly efficient tool to genetically modify pig embryos. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11248-016-9989-6) contains supplementary material, which is available to authorized users.


title: Cytokine cascade and networks among MSM HIV seroconverters: implications for early immunotherapy

text: The timing, intensity and duration of the cytokine cascade and reorganized interrelations in cytokine networks are not fully understood during acute HIV-1 infection (AHI). Using sequential plasma samples collected over three years post-infection in a cohort of MSM HIV-1 seroconvertors, we determined the early kinetics of cytokine levels during FiebigI-IV stages using Luminex-based multiplex assays. Cytokines were quantified and relationships between cytokines were assessed by Spearman correlation. Compared with HIV-negative MSM, HIV-infected individuals had significantly increased multiple plasma cytokines, including GM-CSF, IFN-α2, IL-12p70, IP-10 and VEGF, during both acute and chronic stages of infection. Furthermore, rapid disease progressors (RDPs) had earlier and more robust cytokine storms, compared with slow disease progressors (SDPs) (49.6 days vs. 74.9 days, respectively; 6.7-fold vs. 3.7-fold change of cytokines, respectively), suggesting the faster and stronger cytokine storm during AHI could promote disease progression. On the other hand, HIV-1 infection induced more interlocked cytokines network, establishing new strong correlations and imposing a higher rigidity. There were, respectively, 146 (44.9%) statistically significant correlations of cytokines in RDPs and 241 (74.2%) in SDPs (p < 0.001). This study suggests that immunomodulatory interventions aimed at controlling cytokine storm in AHI may be beneficial to slow eventual disease progression.


title: Predominance of G3B and G14 equine group A rotaviruses of a single VP4 serotype in Japan

text: A total of 65 equine group A rotaviruses (GAR) isolated from diarrheal foals at 48 farms in Hokkaido, Japan, between 1996 (29 isolates) and 1997 (36 isolates) were characterized for their VP7 and VP4 serotypes by PCR, nucleotide sequencing, and virus neutralization (VN) tests. By PCR VP7 typing, all isolates were classified as G3 or G14, and the predominant serotype in each year was G3 (86%) in 1996 and G14 (53%) in 1997. VN tests with these 20 isolates randomly selected confirmed the specificity of PCR on the bases of complete agreement of the results in these methods (9 G3 and 11 G14), and revealed that all 9 G3 isolates were subtype G3B. There were five differing amino acid residues in three VP7 antigenic regions between subtypes G3A and G3B. Antiserum to a baculovirus recombinant that expressed P[12] VP4 neutralized all isolates and P[12] reference strains. These results suggest that genotype P[12] GAR belong to a single VP4 serotype, and that one VP4 and two VP7 serotypes (G3B and G14) of GAR were predominant in the equine population in Japan.


title: Influenza in long‐term care facilities

text: Long‐term care facility environments and the vulnerability of their residents provide a setting conducive to the rapid spread of influenza virus and other respiratory pathogens. Infections may be introduced by staff, visitors or new or transferred residents, and outbreaks of influenza in such settings can have devastating consequences for individuals, as well as placing extra strain on health services. As the population ages over the coming decades, increased provision of such facilities seems likely. The need for robust infection prevention and control practices will therefore remain of paramount importance if the impact of outbreaks is to be minimised. In this review, we discuss the nature of the problem of influenza in long‐term care facilities, and approaches to preventive and control measures, including vaccination of residents and staff, and the use of antiviral drugs for treatment and prophylaxis, based on currently available evidence.


Human Bocavirus: A New Viral Pathogen


title: Stability of infectious human coronavirus NL63

text: Abstract The human coronavirus NL63 was identified in 2004 and subsequent studies showed its worldwide distribution. Infection with this pathogen is associated with upper and lower respiratory tract diseases of mild to moderate severity. Furthermore, HCoV-NL63 is the main cause of croup in children. Within this study an optimal protocol for freeze-drying that allows safe and effective preservation of HCoV-NL63 infectious material was developed. Lyophilized virus preparations can be stored either at ambient temperature or at +4°C. In the latter case samples may be stored for at least two months. Surprisingly, conducted analysis showed that HCoV-NL63 virions are exquisitely stable in liquid media and can be stored also without preservatives at ambient temperature for up to 14 days.


title: Pathophysiology of Diarrhea in Calves

text: Infectious diarrhea in calves is most commonly associated with enterotoxigenic Escherichia coli, Cryptosporidium parvum, rotavirus, coronavirus, or some combination of these pathogens. Each of these agents leads to diarrhea through either secretion or malabsorption/maldigestion, though the specific mechanisms and pathways may differ. Specific pharmacologic control and treatment are dependent on gaining a greater understanding of the pathophysiology of these organisms.


title: Lentivirus Display: Stable Expression of Human Antibodies on the Surface of Human Cells and Virus Particles

text: BACKGROUND: Isolation of human antibodies using current display technologies can be limited by constraints on protein expression, folding and post-translational modifications. Here we describe a discovery platform that utilizes self-inactivating (SIN) lentiviral vectors for the surface display of high-affinity single-chain variable region (scFv) antibody fragments on human cells and lentivirus particles. METHODOLOGY/PRINCIPAL FINDINGS: Bivalent scFvFc human antibodies were fused in frame with different transmembrane (TM) anchoring moieties to allow efficient high-level expression on human cells and the optimal TM was identified. The addition of an eight amino acid HIV-1 gp41 envelope incorporation motif further increased scFvFc expression on human cells and incorporation into lentiviral particles. Both antibody-displaying human cells and virus particles bound antigen specifically. Sulfation of CDR tyrosine residues, a property recently shown to broaden antibody binding affinity and antigen recognition was also demonstrated. High level scFvFc expression and stable integration was achieved in human cells following transduction with IRES containing bicistronic SIN lentivectors encoding ZsGreen when scFvFc fusion proteins were expressed from the first cassette. Up to 10(6)-fold enrichment of antibody expressing cells was achieved with one round of antigen coupled magnetic bead pre-selection followed by FACS sorting. Finally, the scFvFc displaying human cells could be used directly in functional biological screens with remarkable sensitivity. CONCLUSIONS/SIGNIFICANCE: This antibody display platform will complement existing technologies by virtue of providing properties unique to lentiviruses and antibody expression in human cells, which, in turn, may aid the discovery of novel therapeutic human mAbs.


title: Evaluation of antiviral and cytotoxic activities of methanolic extract of S. grandiflora (Fabaceae) flowers

text: Abstract Objective To investigate the cytotoxicity and antiviral activity of methanolic extract of S. grandiflora flowers using different cell lines and viruses. Methods The methanolic flower extracts were prepared and evaluated for their antiviral and cytotoxic activities using viruses like herpes simplex-1 and 2, vaccinia, vesicular stomatitis, cox sackie, respiratory syncytical, feline corona, feline herpes, para influenza, reo-1, sindbis and punta toro viruses in different cell lines, like Hel, HeLa, Crandell Reus feline kidney and Vero cell cultures. Results Among the viruses used the extract possessed strongest antiviral activity against herpes simplex 1 and 2, repiratory syncytical, para influenza, reo, sindbis, cox sackie and punta toro viruses that was (EC50=20 μg/mL and 45 μg/mL) and moderate activity for remaining viruses (EC50= 100 μg/mL). The antiviral activities assessed by calculating the selectivity index may be due to the presence of flavonoids in the extracts there by inhibit the virus cell fusion in the early and replication stages. The cytotoxicity effect was evaluated using MTT assay and the results revealed that the extracts exhibited cytotoxicity from the range of 20 to 100 μg/mL. Conclusions Present results confirmed that the S. grandiflora used as a good antimicrobial agent in future.


title: Binding site‐based classification of coronaviral papain‐like proteases

text: The coronavirus replicase gene encodes one or two papain‐like proteases (termed PL1pro and PL2pro) implicated in the N‐terminal processing of the replicase polyprotein and thus contributing to the formation of the viral replicase complex that mediates genome replication. Using consensus fold recognition with the 3D‐JURY meta‐predictor followed by model building and refinement, we developed a structural model for the single PLpro present in the severe acute respiratory syndrome coronavirus (SCoV) genome, based on significant structural relationships to the catalytic core domain of HAUSP, a ubiquitin‐specific protease (USP). By combining the SCoV PLpro model with comparative sequence analyses we show that all currently known coronaviral PLpros can be classified into two groups according to their binding site architectures. One group includes all PL2pros and some of the PL1pros, which are characterized by a restricted USP‐like binding site. This group is designated the R‐group. The remaining PL1pros from some of the coronaviruses form the other group, featuring a more open papain‐like binding site, and is referred to as the O‐group. This two‐group, binding site‐based classification is consistent with experimental data accumulated to date for the specificity of PLpro‐mediated polyprotein processing and PLpro inhibition. It also provides an independent evaluation of the similarity‐based annotation of PLpro‐mediated cleavage sites, as well as a basis for comparison with previous groupings based on phylogenetic analyses. Proteins 2006.


COVID 19 and the Patient with Obesity – The Editors Speak Out


title: Survey of Clinical Laboratory Practices for 2015 Middle East Respiratory Syndrome Coronavirus Outbreak in the Republic of Korea

text: BACKGROUND: It is crucial to understand the current status of clinical laboratory practices for the largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infections in the Republic of Korea to be well prepared for future emerging infectious diseases. METHODS: We conducted a survey of 49 clinical laboratories in medical institutions and referral medical laboratories. A short questionnaire to survey clinical laboratory practices relating to MERS-CoV diagnostic testing was sent by email to the directors and clinical pathologists in charge of the clinical laboratories performing MERS-CoV testing. The survey focused on testing volume, reporting of results, resources, and laboratory safety. RESULTS: A total of 40 clinical laboratories responded to the survey. A total of 27,009 MERS-CoV real-time reverse transcription PCR (rRT-PCR) tests were performed. Most of the specimens were sputum (73.5%). The median turnaround time (TAT) was 5.29 hr (first and third quartile, 4.11 and 7.48 hr) in 26 medical institutions. The median TAT of more than a half of the laboratories (57.7%) was less than 6 hr. Many laboratories were able to perform tests throughout the whole week. Laboratory biosafety preparedness included class II biosafety cabinets (100%); separated pre-PCR, PCR, and post-PCR rooms (88.6%); negative pressure pretreatment rooms (48.6%); and negative pressure sputum collection rooms (20.0%). CONCLUSIONS: Clinical laboratories were able to quickly expand their diagnostic capacity in response to the 2015 MERS-CoV outbreak. Our results show that clinical laboratories play an important role in the maintenance and enhancement of laboratory response in preparation for future emerging infections.


Point of view of the Dutch Society for Gynaecological Endoscopy (WGE) on surgery during the COVID-19 crisis


title: In Silico Evaluation of the Effectivity of Approved Protease Inhibitors against the Main Protease of the Novel SARS-CoV-2 Virus

text: The coronavirus disease, COVID-19, caused by the novel coronavirus SARS-CoV-2, which first emerged in Wuhan, China and was made known to the World in December 2019 turned into a pandemic causing more than 126,124 deaths worldwide up to April 16th, 2020. It has 79.5% sequence identity with SARS-CoV-1 and the same strategy for host cell invasion through the ACE-2 surface protein. Since the development of novel drugs is a long-lasting process, researchers look for effective substances among drugs already approved or developed for other purposes. The 3D structure of the SARS-CoV-2 main protease was compared with the 3D structures of seven proteases, which are drug targets, and docking analysis to the SARS-CoV-2 protease structure of thirty four approved and on-trial protease inhibitors was performed. Increased 3D structural similarity between the SARS-CoV-2 main protease, the HCV protease and α-thrombin was found. According to docking analysis the most promising results were found for HCV protease, DPP-4, α-thrombin and coagulation Factor Xa known inhibitors, with several of them exhibiting estimated free binding energy lower than −8.00 kcal/mol and better prediction results than reference compounds. Since some of the compounds are well-tolerated drugs, the promising in silico results may warrant further evaluation for viral anticipation. DPP-4 inhibitors with anti-viral action may be more useful for infected patients with diabetes, while anti-coagulant treatment is proposed in severe SARS-CoV-2 induced pneumonia.


title: Influenza and respiratory syncytial virus in infants study (IRIS) of hospitalized and non-ill infants aged <1 year in four countries: study design and methods

text: BACKGROUND: This multi-country prospective study of infants aged <1 year aims to assess the frequency of influenza virus and respiratory syncytial virus (RSV) infections associated with hospitalizations, to describe clinical features and antibody response to infection, and to examine predictors of very severe disease requiring intensive care. METHODS/DESIGN: We are enrolling a hospital-based cohort and a sample of non-ill infants in four countries (Albania, Jordan, Nicaragua, and the Philippines) using a common protocol. We are currently starting year 2 of a 2- to 3-year study and will enroll approximately 3,000 infants hospitalized for any acute illness (respiratory or non-respiratory) during periods of local influenza and/or RSV circulation. After informed consent and within 24 h of admission, we collect blood and respiratory specimens and conduct an interview to assess socio-demographic characteristics, medical history, and symptoms of acute illness (onset ≤10 days). Vital signs, interventions, and medications are documented daily through medical record abstraction. A follow-up health assessment and collection of convalescent blood occurs 3-5 weeks after enrollment. Influenza and RSV infection is confirmed by singleplex real time reverse transcriptase polymerase chain reaction (rRT-PCR) assays. Serologic conversion will be assessed comparing acute and convalescent sera using hemagglutination inhibition assay for influenza antibodies and enzyme-linked immunosorbent assay (ELISA) for RSV. Concurrent with hospital-based enrollment, respiratory specimens are also being collected (and tested by rRT-PCR) from approximately 1,400 non-ill infants aged <1 year during routine medical or preventive care. DISCUSSION: The Influenza and RSV in Infants Study (IRIS) promises to expand our knowledge of the frequency, clinical features, and antibody profiles of serious influenza and RSV disease among infants aged <1 year, quantify the proportion of infections that may be missed by traditional surveillance, and inform decisions about the potential value of existing and new vaccines and other prevention and treatment strategies.


title: Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts’ consensus statement

text: Since the outbreak of 2019 novel coronavirus infection (2019-nCoV) in Wuhan City, China, by January 30, 2020, a total of 9692 confirmed cases and 15,238 suspected cases have been reported around 31 provinces or cities in China. Among the confirmed cases, 1527 were severe cases, 171 had recovered and been discharged at home, and 213 died. And among these cases, a total of 28 children aged from 1 month to 17 years have been reported in China. For standardizing prevention and management of 2019-nCoV infections in children, we called up an experts’ committee to formulate this experts’ consensus statement. This statement is based on the Novel Coronavirus Infection Pneumonia Diagnosis and Treatment Standards (the fourth edition) (National Health Committee) and other previous diagnosis and treatment strategies for pediatric virus infections. The present consensus statement summarizes current strategies on diagnosis, treatment, and prevention of 2019-nCoV infection in children.


title: A Truncated Receptor-Binding Domain of MERS-CoV Spike Protein Potently Inhibits MERS-CoV Infection and Induces Strong Neutralizing Antibody Responses: Implication for Developing Therapeutics and Vaccines

text: An emerging respiratory infectious disease with high mortality, Middle East respiratory syndrome (MERS), is caused by a novel coronavirus (MERS-CoV). It was first reported in 2012 in Saudi Arabia and has now spread to eight countries. Development of effective therapeutics and vaccines is crucial to save lives and halt the spread of MERS-CoV. Here, we show that a recombinant protein containing a 212-amino acid fragment (residues 377-588) in the truncated receptor-binding domain (RBD: residues 367–606) of MERS-CoV spike (S) protein fused with human IgG Fc fragment (S377-588-Fc) is highly expressed in the culture supernatant of transfected 293T cells. The purified S377-588-Fc protein efficiently binds to dipeptidyl peptidase 4 (DPP4), the receptor of MERS-CoV, and potently inhibited MERS-CoV infection, suggesting its potential to be further developed as a therapeutic modality for treating MERS-CoV infection and saving the patients’ lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4 receptor and effectively neutralizes MERS-CoV infection. These findings indicate that this truncated RBD protein shows promise for further development as an effective and safe vaccine for the prevention of MERS-CoV infection.


title: Crystal structure of the post-fusion core of the Human coronavirus 229E spike protein at 1.86 Å resolution

text: Human coronavirus 229E (HCoV-229E) usually causes mild upper respiratory infections in heathy adults, but may lead to severe complications or mortality in individuals with weakened immune systems. Virus entry of HCoV-229E is mediated by its spike (S) protein, where the S1 domain facilitates attachment to host cells and the S2 domain is involved in subsequent fusion of the virus and host membranes. During the fusion process, two heptad repeats, HR1 and HR2, in the S2 domain assemble into a six-helix membrane-fusion structure termed the fusion core. Here, the complete fusion-core structure of HCoV-229E has been determined at 1.86 Å resolution, representing the most complete post-fusion conformation thus far among published human alphacoronavirus (α-HCoV) fusion-core structures. The overall structure of the HCoV-229E fusion core is similar to those of SARS, MERS and HCoV-NL63, but the packing of its 3HR1 core differs from those of SARS and MERS in that it contains more noncanonical ‘x’ and ‘da’ layers. Side-by-side electrostatic surface comparisons reveal that the electrostatic surface potentials are opposite in α-HCoVs and β-HCoVs at certain positions and that the HCoV-229E surface also appears to be the most hydrophobic among the various HCoVs. In addition to the highly conserved hydrophobic interactions between HR1 and HR2, some polar and electrostatic interactions are also well preserved across different HCoVs. This study adds to the structural profiling of HCoVs to aid in the structure-based design of pan-coronavirus small molecules or peptides to inhibit viral fusion.


title: Preparation of a cell line persistently infected with maedi/visna virus and production of viral antigens

text: We attempted to prepare a cell line that produces maedi/visna virus (MVV) and is free of contamination by other viruses and mycoplasmas. Three cell lines, which originated from a sheep, goat and bat, were infected with MVV and passaged approximately every 5 days. The cultured cells were then subjected to polymerase chain reaction analysis for MVV provirus. As a result, a cell line persistently infected with MVV was established from ZZ-R cells, which originated from the fetal goat tongue. The 50-fold concentrated culture fluid formed a precipitation line against reference antiserum.


title: Middle East respiratory syndrome coronavirus (MERS-CoV) neutralising antibodies in a high-risk human population, Morocco, November 2017 to January 2018

text: BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) remains a major concern for global public health. Dromedaries are the source of human zoonotic infection. MERS-CoV is enzootic among dromedaries on the Arabian Peninsula, the Middle East and in Africa. Over 70% of infected dromedaries are found in Africa. However, all known zoonotic cases of MERS have occurred in the Arabian Peninsula with none being reported in Africa. AIM: We aimed to investigate serological evidence of MERS-CoV infection in humans living in camel-herding areas in Morocco to provide insights on whether zoonotic transmission is taking place. METHODS: We carried out a cross sectional seroprevalence study from November 2017 through January 2018. We adapted a generic World Health Organization MERS-CoV questionnaire and protocol to assess demographic and risk factors of infection among a presumed high-risk population. ELISA, MERS-CoV spike pseudoparticle neutralisation tests (ppNT) and plaque neutralisation tests (PRNT) were used to assess MERS-CoV seropositivity. RESULTS: Serum samples were collected from camel slaughterhouse workers (n = 137), camel herders (n = 156) and individuals of the general population without occupational contact with camels but living in camel herding areas (n = 186). MERS-CoV neutralising antibodies with ≥ 90% reduction of plaque numbers were detected in two (1.5%) slaughterhouse workers, none of the camel herders and one individual from the general population (0.5%). CONCLUSIONS: This study provides evidence of zoonotic transmission of MERS-CoV in Morocco in people who have direct or indirect exposure to dromedary camels.


title: Inflammasomes in antiviral immunity: clues for influenza vaccine development

text: Inflammasomes are cytosolic multiprotein complexes that sense microbial motifs or cellular stress and stimulate caspase-1-dependent cytokine secretion and cell death. Recently, it has become increasingly evident that both DNA and RNA viruses activate inflammasomes, which control innate and adaptive immune responses against viral infections. In addition, recent studies suggest that certain microbiota induce inflammasomes-dependent adaptive immunity against influenza virus infections. Here, we review recent advances in research into the role of inflammasomes in antiviral immunity.


title: Epidemiological status of the Middle East respiratory syndrome coronavirus in 2019: an update from January 1 to March 31, 2019

text: PURPOSE: This study represents the current epidemiological status of Middle East respiratory syndrome coronavirus (MERS-CoV) worldwide in the first three months of 2019. PATIENTS AND METHODS: Full details of the MERS-CoV cases available and published in the disease outbreak news on the WHO website were retrieved. Related details of laboratory-confirmed MERS-CoV were extracted and analyzed by standard statistical methods. RESULTS: A total of 107 cases of MERS-CoV, including 18 deaths (overall case fatality rate (CFR), 16.8%; male-specific CFR was 17.5% [14/80] and female-specific CFR was 14.8% [4/27]) were reported to WHO from the National International Health Regulation Focal Points of Saudi Arabia and Oman. The overall mean age was 50±17 years and 80 patients (74.8%) were male. The average time from the onset of the symptoms to the first hospitalization was 3±3.3 days; from the first hospitalization to laboratory confirmation was 3.6±6.5 days; from the onset of symptom to death was 17.5±11.7 days; and the mean length of hospitalization for patients with MERS-CoV was 3.5±3.9 days. Males in comparison to females had a 1.5-fold increased chance (adjusted OR =1.5 [95% CI: 1.3–1.8]) of death related to MERS-CoV infection; 1.05 [95% CI: 1.1–3.3], 1.05 [95% CI: 1.2–2.8] and 1.06 [95% CI: 1.2–2.0] for those who had exposure to camels, camel milk consumption, and close contact with MERS-CoV cases, respectively. Health care workers had 2.4 fold [95% CI: 1.2–3.1] greater odds of death compared to other people. CONCLUSION: The knowledge obtained from this study can contribute to the development of a prevention program and early system warning against MERS-CoV infection.


title: A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection.

text: Abstract The SARS-CoV-2 epidemic is pressuring health care systems worldwide. Disease outcomes in certain subgroups of patients are still scarce, and data are needed. Therefore, we describe here the experience of four dialysis centers of the Brescia Renal COVID task force. During March 2020, within an overall population of 643 hemodialysis patients, SARS-CoV-2 RNA positivity was detected in 94 (15%). At disease diagnosis, 37 of the 94 (39%) patients (group 1) were managed on an outpatient basis whereas the remaining 57 (61%) (group 2) required hospitalization. Choices regarding management strategy were made based on disease severity. In group 1, 41% received antivirals and 76% hydroxychloroquine. Eight percent died and 5% developed acute respiratory distress syndrome (ARDS). In group 2, 79% received antivirals and 77% hydroxychloroquine. Forty two percent died and 79% developed ARDS. Overall mortality rate for the entire cohort was 29%. History of ischemic cardiac disease, fever, older age (over age 70) and dyspnea at presentation were associated with the risk of developing ARDS whereas fever, cough and a C-reactive protein higher than 50 mg/l at disease presentation were associated with the risk of death. Thus, in our population of hemodialysis patients with SARS-CoV-2 infection, we documented a wide range of disease severity. The risk of ARDS and death is significant for patients requiring hospital admission at disease diagnosis.


title: Harnessing host–virus evolution in antiviral therapy and immunotherapy

text: Pathogen resistance and development costs are major challenges in current approaches to antiviral therapy. The high error rate of RNA synthesis and reverse‐transcription confers genome plasticity, enabling the remarkable adaptability of RNA viruses to antiviral intervention. However, this property is coupled to fundamental constraints including limits on the size of information available to manipulate complex hosts into supporting viral replication. Accordingly, RNA viruses employ various means to extract maximum utility from their informationally limited genomes that, correspondingly, may be leveraged for effective host‐oriented therapies. Host‐oriented approaches are becoming increasingly feasible because of increased availability of bioactive compounds and recent advances in immunotherapy and precision medicine, particularly genome editing, targeted delivery methods and RNAi. In turn, one driving force behind these innovations is the increasingly detailed understanding of evolutionarily diverse host–virus interactions, which is the key concern of an emerging field, neo‐virology. This review examines biotechnological solutions to disease and other sustainability issues of our time that leverage the properties of RNA and DNA viruses as developed through co‐evolution with their hosts.


title: Cimiside E arrests cell cycle and induces cell apoptosis in gastric cancer cells

text: Cimiside E was isolated from the Cimicifuga heracleifolia Komarov extract, which has been previously demonstrated to possess apoptotic action on gastric cancer cells. The IC(50) value of cimiside E on gastric cancer cells for 24 h was 14.58 µM. The mechanism of apoptosis was further elucidated through western blot, RT-PCR, morphology, Annexin V-FITC/PI staining and cell cycle analysis. Cell cycle arrest was induced by cimiside E in S phase at a lower concentration (30 µM) and G2/M phase at higher concentrations (60 and 90 µM). Cimiside E mediated apoptosis through the induction of the caspase cascade for both the extrinsic and intrinsic pathways. These findings suggest that cimiside E may be an effective chemopreventive agent against cancer.


title: Antibody responses against SARS coronavirus are correlated with disease outcome of infected individuals

text: Most of the SARS‐CoV‐infected patients spontaneously recovered without clinical intervention while a small percentage succumbed to the disease. Here, we characterized temporal changes in N protein‐specific and S glycoprotein‐specific neutralizing antibody (Nab) responses in infected patients who have either recovered from or succumbed to SARS‐CoV infection. Recovered patients were found to have higher and sustainable levels of both N protein‐specific and S glycoprotein‐specific Nab responses, suggesting that antibody responses likely play an important role in determining the ultimate disease outcome of SARS‐CoV‐infected patients. J. Med. Virol. 78:1–8, 2006. © 2005 Wiley‐Liss, inc.


title: Coping with COVID‐19: ventilator splitting with differential driving pressures using standard hospital equipment

text: The global COVID‐19 pandemic has led to a worldwide shortage of ventilators. This shortage has initiated discussions on how to support multiple patients with a single ventilator (ventilator splitting). Ventilator splitting is incompletely tested, experimental and the effects have not been fully characterised. This study investigated the effect of ventilator splitting on system variables (inspiratory pressure, flow and volume) and the possibility of different ventilation targets for each limb using only standard hospital equipment. Experiments were conducted on two test lungs with different compliances (0.02 l.cmH(2)O(−1) and 0.04 l.cmH(2)O(−1)). The ventilator was used in both pressure and volume control modes and was set to ventilate the low compliance lungs at end‐tidal volumes of 500 ± 20 ml. A flow restrictor apparatus consisting of a Hoffman clamp and tracheal tube was connected in series to the inspiratory limb of the high compliance test lungs and the resistance modified to achieve end‐tidal volumes of 500 ± 20 ml. The restriction apparatus successfully modified the inspiratory pressure, minute ventilation and volume delivered to the high compliance test lungs in both pressure control (27.3–17.8 cmH(2)O, 15.2–8.0 l.min(−1) and 980–499 ml, respectively) and volume control (21.0–16.7 cmH(2)O, 10.7–7.9 l.min(−1) and 659–498 ml, respectively) ventilation modes. Ventilator splitting is not condoned by the authors. However, these experiments demonstrate the capacity to simultaneously ventilate two test lungs of different compliances, and using only standard hospital equipment, modify the delivered pressure, flow and volume in each test lung.


title: Dideoxy fluoro-ketopyranosyl nucleosides as potent antiviral agents: Synthesis and biological evaluation of 2,3- and 3,4-dideoxy-3-fluoro-4- and -2-keto-β-d-glucopyranosyl derivatives of N(4)-benzoyl cytosine

text: The synthesis of the dideoxy fluoro ketopyranonucleoside analogues, 1-(2,3-dideoxy-3-fluoro-6-O-trityl-β-d-glycero-hexopyranosyl-4-ulose)-N(4)-benzoyl cytosine (7a), 1-(3,4-dideoxy-3-fluoro-6-O-trityl-β-d-glycero-hexopyranosyl-2-ulose)-N(4)-benzoyl cytosine (13a) and their detritylated analogues 8a and 14a, respectively, is described. Condensation of peracetylated 3-deoxy-3-fluoro-d-glucopyranose (1) with silylated N(4)-benzoyl cytosine, followed by selective deprotection and isopropylidenation afforded compound 2. Routine deoxygenation at position 2′, followed by a deprotection-selective reprotection sequence afforded the partially tritylated dideoxy nucleoside of cytosine 6, which upon oxidation of the free hydroxyl group at the 4′-position, furnished the desired tritylated 2,3-dideoxy-3-fluoro ketonucleoside 7a in equilibrium with its hydrated form 7b. Compound 2 was the starting material for the synthesis of the dideoxy fluoro ketopyranonucleoside 13a. Similarly, several subsequent protection and deprotection steps as well as routine deoxygenation at position 4′, followed by oxidation of the free hydroxyl group at the 2′-position of the partially tritylated dideoxy nucleoside 12, yielded the desired carbonyl compound 13a in equilibrium with its hydrated form 13b. Finally, trityl removal from 7a/b and 13a/b provided the unprotected 2,3-dideoxy-3-fluoro-4-keto and 3,4-dideoxy-3-fluoro-2-ketopyranonucleoside analogues 8a and 14a, in equilibrium with their gem-diol forms 8b and 14b. None of the compounds showed inhibitory activity against a wide variety of DNA and RNA viruses at subtoxic concentrations, except 7a/b that was highly efficient against rotavirus infection. Nucleoside 7a/b also exhibited cytostatic activity against cells of various cancers. BrdU-cell cycle analysis revealed that the mechanism of cytostatic activity may be related to a delay in G1/S phase and initiation of programmed cell death.


title: A global agenda for older adult immunization in the COVID-19 era: a roadmap for action

text: Abstract Given our global interconnectedness, the COVID-19 pandemic highlights the urgency of building a global system that can support both routine and pandemic/epidemic adult immunization. As such, a framework to recommend vaccines and build robust platforms to deliver them to protect the rapidly expanding demographic of older adults is needed. Adult immunization as a strategy has the broad potential to preserve and improve medical, social, and economic outcomes, including maintaining functional ability that benefits older adults, their families, communities, and countries. While we will soon have multiple vaccines against COVID-19, we must recognize that we already have a variety of vaccines against other pathogens. These that can prevent simultaneous co-infection with COVID-19, and can help keep adults healthier, favorably impacting the outcome of a COVID-19 illness. Further, administering a vaccine against COVID-19 requires planning now to determine how older adults will be immunized and how current delivery strategies will occur in a timely manner. A group of international experts with various backgrounds from health and aging disciplines met to discuss the evidence case for adult immunization and crucial knowledge gaps that must be filled in order to implement effective policies and programs for older adult immunization. This group, coming together as the International Council on Adult Immunization (ICAI), outlined a high-level roadmap to catalyze action, provide policy guidance, and envision a global adult immunization platform that can be adapted by countries to fit their local contexts. Further meetings centered around the value of adult immunization, particularly in the context of COVID-19. There was agreement that programs to deliver existing influenza, pneumococcal, herpes zoster vaccines, and future COVID-19 vaccines to over a billion older adults who are at substantially higher risk of death and disability due to vaccine-preventable diseases are more urgent than ever before. Here we present a proposed framework for delivering routine and pandemic vaccines. We call upon the global community and governments to prioritize action for integrating robust adult immunization programs into the public health agenda.


title: Recomendaciones en el manejo de la pandemia por coronavirus SARS-CoV-2 (Covid-19) en pacientes con trasplante renal

text: The SARS-CoV-2 (Covid-19) coronavirus pandemic is evolving very quickly and means a special risk for both immunosuppressed and comorbid patients. Knowledge about this growing infection is also increasing although many uncertainties remain, especially in the kidney transplant population. This manuscript presents a proposal for action with general and specific recommendations to protect and prevent infection in this vulnerable population such as kidney transplant recipients.


title: A Cluster of Health Care Workers with COVID-19 Pneumonia Caused by SARS-CoV-2

text: Abstract Background The current outbreak of coronavirus disease 2019 (COVID-19) caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, Hubei, China, spreads across national and international borders. Methods We prospectively collected medical records of 14 health care workers (HCWs) who were infected with SARS-CoV-2, in neurosurgery department of Wuhan Union Hospital, China. Results Among the 14 HCWs, 12 were conformed cases, the other 2 were suspected cases. Most of them were either exposed to the two index patients or infected coworkers, without knowing they were COVID-19 patients. There were 4 male and 10 female infected HCWs in this cohort, whose mean age was 36 years (SD, 6 years). The main symptoms included myalgia or fatigue (100%), fever (86%) and dry cough (71%). On admission, 79% of infected HCWs showed leucopenia and 43% lymphopenia. Reduced complement C3 could be seen in 57% of the infected HCWs and IL-6 was significently elevated in 86% of them. The proportion of lymphocytes subsets, concentrations of immunoglobulins, complement C4, IL-2, IL-4, IL-10, TNF-α and IFN-γ were within normal range in these 14 infected HCWs. The most frequent findings on pulmonary computed tomographic images were bilateral multifocal ground-glass opacifications (86%). Conclusions Human-to-human transmission of COVID-19 pneumonia has occurred among HCWs, and most of these infected HCWs with confirmed COVID-19 are mild cases. Our data suggest that in the epidemic area of COVID-19, stringent and urgent surveillance and infection-control measures should be implemented to protect doctors and nurses from COVID-19 infection.


title: Monoclonal Antibody Combinations that Present Synergistic Neutralizing Activity: A Platform for Next-Generation Anti-Toxin Drugs

text: Monoclonal antibodies (MAbs) are among the fastest-growing therapeutics and are being developed for a broad range of indications, including the neutralization of toxins, bacteria and viruses. Nevertheless, MAbs potency is still relatively low when compared to conventional polyclonal Ab preparations. Moreover, the efficacy of an individual neutralizing MAb may significantly be hampered by the potential absence or modification of its target epitope in a mutant or subtype of the infectious agent. These limitations of individual neutralizing MAbs can be overcome by using oligoclonal combinations of several MAbs with different specificities to the target antigen. Studies conducted in our lab and by others show that such combined MAb preparation may present substantial synergy in its potency over the calculated additive potency of its individual MAb components. Moreover, oligoclonal preparation is expected to be better suited to compensating for reduced efficacy due to epitope variation. In this review, the synergistic neutralization properties of combined oligoclonal Ab preparations are described. The effect of Ab affinity, autologous Fc fraction, and targeting a critical number of epitopes, as well as the unexpected contribution of non-neutralizing clones to the synergistic neutralizing effect are presented and discussed.


title: Severe acute respiratory syndrome coronavirus 3C-like protease-induced apoptosis

text: The pathogenesis of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is an important issue for the treatment and prevention of severe acute respiratory syndrome. Recently, SARS-CoV has been demonstrated to induce cell apoptosis in Vero-E6 cells. The possible role of SARS-CoV 3C-like protease (3CL(pro)) in virus-induced apoptosis is characterized in this study. Growth arrest and apoptosis via caspase-3 and caspase-9 activities were demonstrated in SARS-CoV 3CL(pro)-expressing human promonocyte cells. The fluorescence intensity of dihydrorhodamine 123 staining indicated that cellular reactive oxygen species were markedly increased in SARS-CoV 3CL(pro)-expressing cells. Moreover, in vivo signalling pathway assay indicated that 3CL(pro) increased the activation of the nuclear factor-kappa B-dependent reporter, but inhibited activator protein-1-dependent transcription. This finding is likely to be responsible for virus-induced apoptotic signalling.


title: CFTR Delivery to 25% of Surface Epithelial Cells Restores Normal Rates of Mucus Transport to Human Cystic Fibrosis Airway Epithelium

text: Dysfunction of CFTR in cystic fibrosis (CF) airway epithelium perturbs the normal regulation of ion transport, leading to a reduced volume of airway surface liquid (ASL), mucus dehydration, decreased mucus transport, and mucus plugging of the airways. CFTR is normally expressed in ciliated epithelial cells of the surface and submucosal gland ductal epithelium and submucosal gland acinar cells. Critical questions for the development of gene transfer strategies for CF airway disease are what airway regions require CFTR function and how many epithelial cells require CFTR expression to restore normal ASL volume regulation and mucus transport to CF airway epithelium? An in vitro model of human CF ciliated surface airway epithelium (CF HAE) was used to test whether a human parainfluenza virus (PIV) vector engineered to express CFTR (PIVCFTR) could deliver sufficient CFTR to CF HAE to restore mucus transport, thus correcting the CF phenotype. PIVCFTR delivered CFTR to >60% of airway surface epithelial cells and expressed CFTR protein in CF HAE approximately 100-fold over endogenous levels in non-CF HAE. This efficiency of CFTR delivery fully corrected the basic bioelectric defects of Cl(−) and Na(+) epithelial ion transport and restored ASL volume regulation and mucus transport to levels approaching those of non-CF HAE. To determine the numbers of CF HAE surface epithelial cells required to express CFTR for restoration of mucus transport to normal levels, different amounts of PIVCFTR were used to express CFTR in 3%–65% of the surface epithelial cells of CF HAE and correlated to increasing ASL volumes and mucus transport rates. These data demonstrate for the first time, to our knowledge, that restoration of normal mucus transport rates in CF HAE was achieved after CFTR delivery to 25% of surface epithelial cells. In vivo experimentation in appropriate models will be required to determine what level of mucus transport will afford clinical benefit to CF patients, but we predict that a future goal for corrective gene transfer to the CF human airways in vivo would attempt to target at least 25% of surface epithelial cells to achieve mucus transport rates comparable to those in non-CF airways.


docid: qylpzgfu

title: Mechanisms of enveloped virus entry into animal cells

text: Abstract The ability of viruses to transfer macromolecules between cells makes them attractive starting points for the design of biological delivery vehicles. Virus-based vectors and sub-viral systems are already finding biotechnological and medical applications for gene, peptide, vaccine and drug delivery. Progress has been made in understanding the cellular and molecular mechanisms underlying virus entry, particularly in identifying virus receptors. However, receptor binding is only a first step and we now have to understand how these molecules facilitate entry, how enveloped viruses fuse with cells or non-enveloped viruses penetrate the cell membrane, and what happens following penetration. Only through these detailed analyses will the full potential of viruses as vectors and delivery vehicles be realised. Here we discuss aspects of the entry mechanisms for several well-characterised viral systems. We do not attempt to provide a fully comprehensive review of virus entry but focus primarily on enveloped viruses.


title: Coordinated Destruction of Cellular Messages in Translation Complexes by the Gammaherpesvirus Host Shutoff Factor and the Mammalian Exonuclease Xrn1

text: Several viruses encode factors that promote host mRNA degradation to silence gene expression. It is unclear, however, whether cellular mRNA turnover pathways are engaged to assist in this process. In Kaposi's sarcoma-associated herpesvirus this phenotype is enacted by the host shutoff factor SOX. Here we show that SOX-induced mRNA turnover is a two-step process, in which mRNAs are first cleaved internally by SOX itself then degraded by the cellular exonuclease Xrn1. SOX therefore bypasses the regulatory steps of deadenylation and decapping normally required for Xrn1 activation. SOX is likely recruited to translating mRNAs, as it cosediments with translation initiation complexes and depletes polysomes. Cleaved mRNA intermediates accumulate in the 40S fraction, indicating that recognition occurs at an early stage of translation. This is the first example of a viral protein commandeering cellular mRNA turnover pathways to destroy host mRNAs, and suggests that Xrn1 is poised to deplete messages undergoing translation in mammalian cells.


title: A novel neutralizing monoclonal antibody targeting the N-terminal domain of the MERS-CoV spike protein

text: Middle East respiratory syndrome coronavirus (MERS-CoV) has caused fatal infections, some through hospital-acquired transmission, in affected regions since its emergence in 2012. Although the virus is not pandemic among humans, it poses a great threat to public health due to its zoonotic origin. Thus, both preventative and therapeutic countermeasures are urgently needed. In this study, we discovered a panel of neutralizing monoclonal antibodies (mAbs) against MERS-CoV, which mapped to a wide range of regions on the spike (S) protein of the virus. In addition to mAbs with neutralizing epitopes located on the receptor-binding domain, one mAb, 5F9, which binds to the N-terminal domain (NTD) of the MERS-CoV S1 subunit, showed efficient neutralizing activity against the wild-type MERS-CoV strain EMC/2012, with a half maximal inhibitory concentration of 0.2 μg/mL. We concluded that a novel neutralizing epitope for MERS-CoV also resides on the NTD of the S protein, indicating that the NTD might be important during the viral infection process. Our findings have significant implications for further vaccine design and for the development of prophylactic and therapeutic monoclonal immunotherapies against MERS-CoV infection.


title: Examining the Complex Relationship Between Tuberculosis and Other Infectious Diseases in Children

text: Millions of children are exposed to tuberculosis (TB) each year, many of which become infected with Mycobacterium tuberculosis. Most children can immunologically contain or eradicate the organism without pathology developing. However, in a minority, the organism overcomes the immunological constraints, proliferates and causes TB disease. Each year a million children develop TB disease, with a quarter dying. While it is known that young children and those with immunodeficiencies are at increased risk of progression from TB infection to TB disease, our understanding of risk factors for this transition is limited. The most immunologically disruptive process that can happen during childhood is infection with another pathogen and yet the impact of co-infections on TB risk is poorly investigated. Many diseases have overlapping geographical distributions to TB and affect similar patient populations. It is therefore likely that infection with viruses, bacteria, fungi and protozoa may impact on the risk of developing TB disease following exposure and infection, although disentangling correlation and causation is challenging. As vaccinations also disrupt immunological pathways, these may also impact on TB risk. In this article we describe the pediatric immune response to M. tuberculosis and then review the existing evidence of the impact of co-infection with other pathogens, as well as vaccination, on the host response to M. tuberculosis. We focus on the impact of other organisms on the risk of TB disease in children, in particularly evaluating if co-infections drive host immune responses in an age-dependent way. We finally propose priorities for future research in this field. An improved understanding of the impact of co-infections on TB could assist in TB control strategies, vaccine development (for TB vaccines or vaccines for other organisms), TB treatment approaches and TB diagnostics.


Management of the airway and lung isolation for thoracic surgery during the COVID‐19 pandemic


Mise au point: évolutions des indications de la coloscopie chez l’enfant en 2012


title: Betrachtung der Pandemie Phase 3 – „mitigation“ – vom Endpunkt Hospitalisation her

text: BACKGROUND: The phase 3—“mitigation”—of the current pandemic by SARS-CoV‑2 is now imminent also in Germany. Given the high complexity many issues have to be taken into account. Simplification is urgently warranted not to loose focus of the important things to be done. METHODS: To look at phase 3 from the endpoint—in this case hospital admission—should facilitate the focus on key variables upstream. Based on a simplified model of approximated and plausible parameters for the overall attack rate (AR), the AR(hospitalization) and the AR(ICU admission), the resources needed are compared with the available resources i.e. number of beds available in general and beds in ICU in particular. The calculations are carried out population-based for Ploen County as well as regionally together with the Kiel metropolitan area. RESULTS: Since the ARs in the up do date available cohorts are overestimated, considerably lower AR(hospitalization) and AR(ICU) should be expected. An AR(hospitalization) of 10% could not be materialized in Ploen County; one with 5% could. In the regional analysis together with the University Hospital Kiel (UKSH) an AR(hospitalization) of up to 10% is feasible, as also an AR(ICU) of 3%. The kinetics of hospital admissions is, however, dependent from countermeasures in public health as well as admission habits of the family physicians. The available number of beds is determined by beds made available and by the mean duration of hospitalization. The latter depends from the age and underlying conditions of the patients. CONCLUSIONS: System failure has to be averted by clarity in regard to the key parameters and their independent variables. The regional management is crucial and should be coordinated by a so-called bed-coordinator. Close cooperation allover the health care system is needed in alliance with the local health departments.


title: Placental transfer and safety in pregnancy of medications under investigation to treat COVID-19

text: Abstract Background Treatment of COVID-19 is mostly symptomatic, but a wide range of medications are under investigation against SARS-CoV-2. Although pregnant women are excluded from clinical trials, they will inevitably receive therapies whenever they appear effective in non-pregnant patients and even under compassionate use. Method We conducted a review of the literature on placental transfer and pregnancy safety data of drugs under current investigation for COVID-19. Results Regarding remdesivir, there are no data in pregnant women. Several other candidates already have safety data in pregnant women, since they are repurposed drugs already used for their established indications. They may thus be used in pregnancy, although their safety in the context of COVID-19 may differ from conventional use. These include the HIV protease inhibitors such as lopinavir/ritonavir which have low placental transfer; interferon which does not cross the placental barrier, and (hydroxy) chloroquine, which have high placental transfer. There are also pregnancy safety and placental transfer data for colchicine, steroids, oseltamivir and azithromycin, as well as some monoclonals. However, some drugs are strictly prohibited in pregnancy due to known teratogenicity (thalidomide) or fetal toxicities (renin-angiotensin system blockers). Other candidates including tocilizumab and other IL-6 inhibitors, umifenovir and favipiravir have insufficient data on pregnancy outcomes. Conclusion In life-threatening cases of COVID-19, the potential risks of therapy to the fetus may be more than offset by the benefit of curing the mother. While preclinical and placental transfer studies are required for a number of potential anti-SARS CoV2 drugs, several medications can already be used in pregnant women.


title: Characteristics of COVID-19 Near China's Epidemic Center

text: Background: This study described and analyzed the age, gender, infection sources, and timing characteristics of the 416 confirmed cases in two cities near the center of China's COVID-19 outbreak. Methods: This study used publicly available data to examine gender, age, source of infection, date returned from Hubei, date of disease onset, date of first medical visit, date of final diagnosis, and date of recovery of COVID-19 cases. Results: Public-use data revealed similar risks of infection by age and that the numbers of new and final diagnoses of confirmed cases first increased, peaked at about two weeks, and then gradually decreased. The main sources of infection were firsthand or secondhand exposure in Hubei Province and contact with confirmed cases, which mostly involved contact with infected household members. The mean periods from disease onset to first medical visit, first visit to final diagnosis, and final diagnosis to recovery were 4.44, 3.18, and 13.42 days, respectively. Conclusions: The results suggest that the measures taken to control the rate of infection were effective. Prevention and control efforts should respond as quickly as possible, isolate and control activities of individuals leaving infected areas, and restrict household contact transmission.


title: Outbreak of Marburg Hemorrhagic Fever in Angola: A Review of the History of the Disease and its Biological Aspects

text: Transmission of a dangerous infectious disease threatens not merely a local population but the world at large as the result of immigration and increased and faster travel. Any outbreak elicits considerable concern and demands that various precautionary methods be instituted and that the disease be contained as quickly as possible. Recently, an old disease, one that may have been present for centuries and was identified decades ago, reared its ugly head, killing more than 200 people before it was contained. Fortunately, the disease, Marburg hemorrhagic fever, was limited to a small geographic area, but the devastation of lives was much greater than that of many epidemics and was a warning of the numerous factors, including fear, lack of understanding, and deception, that can exacerbate the spread of disease and hinder implementation of restraints. This article reviews the history of the disease caused by Marburg virus and its biological components.


title: Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development

text: Stress proteins (SPs) including heat-shock proteins (HSPs), RNA chaperones, and ER associated stress proteins are molecular chaperones essential for cellular homeostasis. The major functions of HSPs include chaperoning misfolded or unfolded polypeptides, protecting cells from toxic stress, and presenting immune and inflammatory cytokines. Regarded as a double-edged sword, HSPs also cooperate with numerous viruses and cancer cells to promote their survival. RNA chaperones are a group of heterogeneous nuclear ribonucleoproteins (hnRNPs), which are essential factors for manipulating both the functions and metabolisms of pre-mRNAs/hnRNAs transcribed by RNA polymerase II. hnRNPs involve in a large number of cellular processes, including chromatin remodelling, transcription regulation, RNP assembly and stabilization, RNA export, virus replication, histone-like nucleoid structuring, and even intracellular immunity. Dysregulation of stress proteins is associated with many human diseases including human cancer, cardiovascular diseases, neurodegenerative diseases (e.g., Parkinson’s diseases, Alzheimer disease), stroke and infectious diseases. In this review, we summarized the biologic function of stress proteins, and current progress on their mechanisms related to virus reproduction and diseases caused by virus infections. As SPs also attract a great interest as potential antiviral targets (e.g., COVID-19), we also discuss the present progress and challenges in this area of HSP-based drug development, as well as with compounds already under clinical evaluation.


title: IL-10 Mediated Regulation of Liver Inflammation during Acute Murine Cytomegalovirus Infection

text: Various cell types in both lymphoid and non-lymphoid tissues produce the anti-inflammatory cytokine interleukin (IL)-10 during murine cytomegalovirus (MCMV) infection. The functions of IL-10 in the liver during acute infection and the cells that generate this cytokine at this site have not been extensively investigated. In this study, we demonstrate that the production of IL-10 in the liver is elevated in C57BL/6 mice during late acute MCMV infection. Using IL-10 green fluorescence protein (GFP) reporter knock-in mice, designated IL-10-internal ribosomal entry site (IRES)-GFP-enhanced reporter (tiger), NK cells are identified as major IL-10 expressing cells in the liver after infection, along with T cells and other leukocytes. In the absence of IL-10, mice exhibit marked elevations in proinflammatory cytokines and in the numbers of mononuclear cells and lymphocytes infiltrating the liver during this infection. IL-10-deficiency also enhances liver injury without improving viral clearance from this site. Collectively, the results indicate that IL-10-producing cells in the liver provide protection from collateral injury by modulating the inflammatory response associated with MCMV infection.


title: Immunoinformatics and Structural Analysis for Identification of Immunodominant Epitopes in SARS-CoV-2 as Potential Vaccine Targets.

text: A new coronavirus infection, COVID-19, has recently emerged, and has caused a global pandemic along with an international public health emergency. Currently, no licensed vaccines are available for COVID-19. The identification of immunodominant epitopes for both B- and T-cells that induce protective responses in the host is crucial for effective vaccine design. Computational prediction of potential epitopes might significantly reduce the time required to screen peptide libraries as part of emergent vaccine design. In our present study, we used an extensive immunoinformatics-based approach to predict conserved immunodominant epitopes from the proteome of SARS-CoV-2. Regions from SARS-CoV-2 protein sequences were defined as immunodominant, based on the following three criteria regarding B- and T-cell epitopes: (i) they were both mapped, (ii) they predicted protective antigens, and (iii) they were completely identical to experimentally validated epitopes of SARS-CoV. Further, structural and molecular docking analyses were performed in order to understand the binding interactions of the identified immunodominant epitopes with human major histocompatibility complexes (MHC). Our study provides a set of potential immunodominant epitopes that could enable the generation of both antibody- and cell-mediated immunity. This could contribute to developing peptide vaccine-based adaptive immunotherapy against SARS-CoV-2 infections and prevent future pandemic outbreaks.


Why are oseltamivir and zanamivir effective against the newly emerged influenza A virus (A/H1N1)?


title: Synthesis and antiviral activity evaluation of acyclic 2′-azanucleosides bearing a phosphonomethoxy function in the side chain

text: Abstract Acyclic 2′-azanucleosides with a phosphonomethoxy function in the side chain were obtained by coupling of diethyl {2-[N-(pivaloyloxymethyl)-N-(p-toluenesulfonyl)amino]ethoxymethyl}phosphonate with the pyrimidine nucleobases via the Vorbrüggen-type protocol. The compounds were evaluated in vitro for activity against a broad variety of RNA and DNA viruses.


title: Butyrate‐producing gut bacteria and viral infections in kidney transplant recipients: A pilot study

text: BACKGROUND: The gut microbiome is being associated increasingly with development of infections besides Clostridium difficile infection. A recent study found an association between butyrate‐producing gut (BPG) bacteria and less frequent development of lower respiratory viral infections in allogeneic hematopoietic stem cell transplant recipients (Haak et al, Blood 131(26): 2978, 2018). In this investigation, we examine the relationship between the abundance of BPG bacteria and the development of viral infections in a cohort of kidney transplant recipients. METHODS: We recruited 168 kidney transplant recipients who provided 510 fecal specimens in the first 3 months after transplantation and profiled the gut microbiota using 16S rRNA gene sequencing of the V4‐V5 hypervariable region. We classified the kidney transplant recipients into higher BPG Bacteria Group and lower BPG Bacteria Group using the same criteria of 1% relative gut abundance of BPG bacteria as the Haak et al study. RESULTS: Administration of antibiotics against anaerobes was associated with a significant decrease in the relative gut abundance of BPG bacteria. The higher BPG Bacteria Group was associated with less development of respiratory viral infections (Hazard Ratio [HR]: 0.28, P = .01) but not with less development of CMV viremia (HR: 0.38, P = .13) or BK viremia (HR: 1.02, P = .98) at 2 years post transplantation. CONCLUSION: Our pilot investigation supports future validation of the relationship between high relative gut abundance of BPG bacteria and decreased risk for development of respiratory viral infections.


title: Currently used nucleic acid amplification tests for the detection of viruses and atypicals in acute respiratory infections

text: Abstract For the detection of respiratory viruses conventional culture techniques are still considered as the gold standard. However, results are mostly available too late to have an impact on patient management. The latest developments include appropriate DNA- and RNA-based amplification techniques (both NASBA and PCR) for the detection of an extended number of agents responsible for LRTI. Real time amplification, the latest technical progress, produces, within a considerable shorter time, results with a lower risk of false positives. As results can be obtained within the same day, patient management with appropriate therapy or reduction of unnecessary antibiotic therapy in LRTI will be possible. A number of technical aspects of these amplification assays, and their advantages are discussed. The availability and use of these new diagnostic tools in virology has contributed to a better understanding of the role of respiratory viruses in LRTI. The increasing importance of the viral agents, Mycoplasma pneumoniae and Chlamydophila pneumoniae in ARI is illustrated. A great proportion of ARI are caused by viruses, but their relative importance depends on the spectrum of agents covered by the diagnostic techniques and on the populations studied, the geographical location and the season. The discovery of new viruses is ongoing; examples are the hMPV and the increasing number of coronaviruses. Indications for the use of these rapid techniques in different clinical situations are discussed. Depending on the possibilities, the laboratory could optimize its diagnostic strategy by applying a combination of immunofluorescence for the detection of RSV an IFL, and a combination of real-time amplification tests for other respiratory viruses and the atypical agents. When implementing a strategy, a compromise between sensitivity, clinical utility, turn around time and cost will have to be found.


title: Miller‐Fisher syndrome after SARS‐CoV‐2 infection

text: On March 11th, 2020, the WHO declared the SARS‐Cov‐2 pandemic. Syndromes have been detected in relation to COVID‐19 such as encephalitis, acute necrotizing hemorrhagic encephalopathy and cerebrovascular complications. There are also cases of peripheral nervous system involvement. Our case would be the 3rd patient with MFS associated with COVID‐19 as far as we know. We present a 51 years old female diagnosed with MFS two weeks after COVID‐19. RT‐PCR to SARS‐CoV‐2 was negative but IgG was positive. Most of the cases were mild or moderate with typical signs and symptoms. All were treated with IV immunoglobulin with good response in most cases. Despite the short evolution time of the cases surviving the current pandemic, the description of cases of post‐infectious neurological syndromes suggests that this is probably not an infrequent complication in the subacute stage of Covid‐19 disease.


docid: hzpbujye

title: Quantifying what could have been – the impact of the Australian and New Zealand governments’ response to COVID-19

text: The Australian and New Zealand governments both initiated strict social distancing measures in response to the COVID-19 pandemic in late March. It remains difficult to quantify the impact this had in reducing the spread of the virus. Bayesian structural time series model provide a model to quantify the scenario in which these government-level interventions were not placed. Our models predict these strict social distancing measures caused a 79% and 61% reduction in the daily cases of COVID-19 across Australia and New Zealand respectively. This provides both evidence and impetus for governments considering similar measures in response to COVID-19 and other pandemics.


title: Immune Characteristics of Patients with Coronavirus Disease 2019 (COVID-19)

text: Up to now, little is known about the detailed immune profiles of COVID-19 patients from admission to discharge. In this study we retrospectively reviewed the clinical and laboratory characteristics of 18 COVID-19 patients from January 30, 2020 to February 21, 2020. These patients were divided into two groups; group 1 had a severe acute respiratory syndrome coronavirus 2 nucleic acid-positive duration for more than 15 days (n = 6) and group 2 had a nucleic acid-positive duration for less than 15 days (n = 12). Group 1 patients had lower level of peripheral blood lymphocytes (0.40 vs. 0.78 ×10(9)/L, p = 0.024) and serum potassium (3.36 vs. 3.79 mmol/L, p = 0.043) on admission but longer hospitalization days (23.17 vs. 15.75 days, p < 0.001) compared to Group 2 patients. Moreover, baseline level of lymphocytes (r = -0.62, p = 0.006) was negatively correlated with the nucleic acid-positive duration. Additionally, lymphocytes (420.83 vs. 1100.56 /μL), T cells (232.50 vs. 706.78 /μL), CD4(+) T cells (114.67 vs. 410.44 /μL), and CD8(+) T cells (94.83 vs. 257.44 /μL) in the peripheral blood analyzed by flow cytometry were significantly different between Group 1and Group 2. Furthermore, there was also a negative correlation between lymphocytes (r = -0.54, p = 0.038) or T cells (r = -0.55, p = 0.034) at diagnosis and the nucleic acid-positive duration, separately. In conclusion, the patients with nucleic acid-positive ≥ 15 days had significantly decreased lymphocytes, T cell and its subsets compared to those who remained positive for less than 15 days.


title: Emerging and re-emerging infectious diseases in Iran

text: Despite development of preventive and controlling strategies regarding infectious diseases, they are still considered as one of the most significant leading causes of morbidity and mortality, worldwide. Changes in humans’ demographics and behaviors, microbial and ecological alterations, agricultural development, international travels and susceptibility to infectious diseases have resulted in increased reports of emerging infectious diseases (EIDs) and reemerging infectious diseases (RIDs) in various geographical areas. Because of the various types of geographic properties in Iran, substantial climatic variability, as well as unstable political situations and poor public health conditions in some of neighboring countries, EIDs and RIDs are serious public health problems; among them, zoonotic and drug resistant diseases are the most significant. Hence, this review provides an overview of the significant bacterial, viral and fungal EIDs and RIDs in Iran regarding their epidemiological aspects.


title: A retrospective review of memantine use and COVID‐19‐associated mortality from a national database

text: We read with interest the recent papers by Brenner and Cimolai regarding the therapeutic potential of memantine for coronavirus disease (COVID-19). In this retrospective, we investigated the relationship between treatment with memantine and COVID-19-associated mortality in 5,726 patients with COVID-19, of whom 140 had died. Our analysis revealed no association between memantine treatment and mortality in patients with COVID-19. However, we must explore all feasible options for preventing and treating COVID-19 due to the current lack of licensed vaccines or therapeutics for the disease. This article is protected by copyright. All rights reserved.


docid: cdzgfsik

title: Rapid-response vaccines—does DNA offer a solution?

text: In responding to future influenza pandemics and other infectious agents, plasmid DNA overcomes many of the limitations of conventional vaccine production approaches.


title: Comparison of forced‐air warming and electric heating pad for maintenance of body temperature during total knee replacement

text: We conducted a randomised controlled trial to compare the efficacy of forced‐air warming (Bair Hugger(™), Augustine Medical model 500/OR, Prairie, MN) with that of an electric heating pad (Operatherm 202, KanMed, Sweden) for maintenance of intra‐operative body temperature in 60 patients undergoing total knee replacement under combined spinal‐epidural anaesthesia. Intra‐operative tympanic and rectal temperatures and verbal analogue score for thermal comfort were recorded. There were no differences in any measurements between the two groups, with mean (SD) final rectal temperatures of 36.8 (0.4) °C with forced‐air warming and 36.9 (0.4) °C with the electric pad. The heating pad is as effective as forced‐air warming for maintenance of intra‐operative body temperature.


title: Distinct transcriptional modules in the peripheral blood mononuclear cells response to human respiratory syncytial virus or to human rhinovirus in hospitalized infants with bronchiolitis

text: Human respiratory syncytial virus (HRSV) is the main cause of bronchiolitis during the first year of life, when infections by other viruses, such as rhinovirus, also occur and are clinically indistinguishable from those caused by HRSV. In hospitalized infants with bronchiolitis, the analysis of gene expression profiles from peripheral blood mononuclear cells (PBMC) may be useful for the rapid identification of etiological factors, as well as for developing diagnostic tests, and elucidating pathogenic mechanisms triggered by different viral agents. In this study we conducted a comparative global gene expression analysis of PBMC obtained from two groups of infants with acute viral bronchiolitis who were infected by HRSV (HRSV group) or by HRV (HRV group). We employed a weighted gene co-expression network analysis (WGCNA) which allows the identification of transcriptional modules and their correlations with HRSV or HRV groups. This approach permitted the identification of distinct transcription modules for the HRSV and HRV groups. According to these data, the immune response to HRSV infection—comparatively to HRV infection—was more associated to the activation of the interferon gamma signaling pathways and less related to neutrophil activation mechanisms. Moreover, we also identified host-response molecular markers that could be used for etiopathogenic diagnosis. These results may contribute to the development of new tests for respiratory virus identification. The finding that distinct transcriptional profiles are associated to specific host responses to HRSV or to HRV may also contribute to the elucidation of the pathogenic mechanisms triggered by different respiratory viruses, paving the way for new therapeutic strategies.


COVID-19 in Bangladesh: Public Awareness and Insufficient Health Facility Remain Key Challenges


title: Should RT‐PCR be considered a gold standard in the diagnosis of COVID‐19?

text: In reference to the comments by Dramé M., et al., 2020, that question the possibility of whether the reverse-transcriptase-polymerase-chain-reaction (RT-PCR) for viral load should be considered a gold standard in the diagnosis of Covid-19. They justify this doubt due to its sensitivity, which only reaches 38%, and is certainly no better than luck. However, in the cited publication by Liu K., et al., 2020, Hainan, China, it does not specify RT-PCR sensitivity. This article is protected by copyright. All rights reserved.


title: Covid19: minimising risk to healthcare workers during aerosol producing respiratory therapy using an innovative constant flow canopy

text: An innovative constant flow canopy enable non invasive respiratory support with minimal risk of HCW infection.


title: Antiviral effect of lithium chloride on feline calicivirus in vitro

text: Feline calicivirus (FCV) is a highly contagious pathogen that causes oral and upper respiratory tract disease in cats. Despite widespread vaccination, the prevalence of FCV remains high. Furthermore, a high gene mutation rate has led to the emergence of variants, and some infections are lethal. To date, there is no effective antiviral drug available for treating FCV infection. Here, we show that lithium chloride (LiCl) effectively suppresses the replication of FCV strain F9 in Crandell-Reese feline kidney (CRFK) cells. The antiviral activity of LiCl occurred primarily during the early stage of infection and in a dose-dependent manner. LiCl treatment also inhibited the cytopathic effect. LiCl treatment exhibited a strong inhibitory effect against a panel of other two reference strains and two recent FCV isolates from China. These results demonstrate that LiCl might be an effective anti-FCV drug for controlling FCV disease. Further studies are required to explore the antiviral activity of LiCl against FCV replication in vivo.


Immunology: SARS vaccine tests well in mouse model


docid: ghjzmeww

title: Location is everything: protein translocations as a viral infection strategy

text: Protein movement between different subcellular compartments is an essential aspect of biological processes, including transcriptional and metabolic regulation, and immune and stress responses. As obligate intracellular parasites, viruses are master manipulators of cellular composition and organization. Accumulating evidences have highlighted the importance of infection-induced protein translocations between organelles. Both directional and temporal, these translocation events facilitate localization-dependent protein interactions and changes in protein functions that contribute to either host defense or virus replication. The discovery and characterization of protein movement is technically challenging, given the necessity for sensitive detection and subcellular resolution. Here, we discuss infection-induced translocations of host and viral proteins, and the value of integrating quantitative proteomics with advanced microscopy for understanding the biology of human virus infections.


Emerging success against Covid-19 pandemic: Hospital surge capacity in Taiwan


title: Nested–polymerase chain reaction detection of Pneumocystis carinii f. sp. canis in a suspected immunocompromised Cavalier King Charles spaniel with multiple infections

text: A 7-month-old Cavalier King Charles Spaniel female was referred due to a chronic cough refractory to antibiotic treatments. Laboratory findings showed leukocytosis, increased serum C-reactive protein, hypogammaglobulinemia, and decreased total serum immunoglobulin G concentration. Thoracic radiographs showed a mild bronchial pattern. Cytology of the bronchoalveolar lavage fluid revealed a septic inflammation. Bordetella bronchiseptica, Mycoplasma spp., and Pneumocystis carinii were identified by polymerase chain reaction testing, and Klebsiella pneumonia was cultured from the bronchoalveolar lavage fluid. Moreover, Escherichia coli was also cultured from urine. Pneumocystis spp. identification was done by sequencing of genetic amplicons. The dog died due to cardiopulmonary arrest secondary to a spontaneous pneumothorax on the day following the procedure. This report documents the detection of Pneumocystis carinii f. sp. canis in a suspected immunocompromised Cavalier King Charles Spaniel with concurrent pulmonary and urinary tract infections involving four different pathogens, and highlights the importance of the use of polymerase chain reaction testing to detect canine Pneumocystis spp. in cases with negative bronchoalveolar lavage cytology.


title: Coronaviruses: A patent dataset report for research and development (R&D) analysis

text: This work shows a patent database for Coronaviruses that provides an overview of the patenting activity and trends in focused antiviral therapy with the use of triazole based compounds, glycoprotein, and protease inhibitors as possible treatment. The patent data was obtained from Orbit Intelligence Software using a patent family structure to get a big database that could be used for built patent landscape report (PLR), market analysis, technical and competitive intelligence, and monitoring and survey of a new ideas for the treatment of coronavirus diseases. The raw data is reported in four databases, which were classified according to different items: legal status (alive, dead), 1(st) application year (after 2015, 2011-2015, 2006-2010, 2001-2005), and Top 5 International Patents Classifications (IPC). The main players, the investment trend, markets, geographical distribution, technology overview, technologies distribution, and patent citation are showed by this analysed data report.


title: Language and imagined Gesellschaft: Émile Durkheim’s civil-linguistic nationalism and the consequences of universal human ideals

text: When Thomas Luckmann, a pioneer of the “linguistic turn” in sociology, regarded Émile Durkheim as a source for the sociology of language, he had lifeworldly community–building in mind. However, the French sociologist himself understood language in the context of civil society–building. To Durkheim, language was a “social thing in the highest degree” that enabled general ideas and intermediated them to people. Abstract human ideals like the civil religion since the French Revolution could be shared through (a common) language. Thus, Durkheim took the exclusive use of French in the Third Republic’s laic public education for granted, ignoring the patois in the country: This “child of the Enlightenment” considered French to be a universal language of Gesellschaft and, beyond ethno-communal elements, to work as a basis for the organic solidarity of French national civil society where the social division of labor was progressing. Durkheim’s theory was predicated on civil-linguistic, not ethnolinguistic, nationalism.


title: LBSapSal-vaccinated dogs exhibit increased circulating T-lymphocyte subsets (CD4(+) and CD8(+)) as well as a reduction of parasitism after challenge with Leishmania infantum plus salivary gland of Lutzomyia longipalpis

text: BACKGROUND: The development of a protective vaccine against canine visceral leishmaniasis (CVL) is an alternative approach for interrupting the domestic cycle of Leishmania infantum. Given the importance of sand fly salivary proteins as potent immunogens obligatorily co-deposited during transmission of Leishmania parasites, their inclusion in an anti-Leishmania vaccine has been investigated in the last few decades. In this context, we previously immunized dogs with a vaccine composed of L. braziliensis antigens plus saponin as the adjuvant and sand fly salivary gland extract (LBSapSal vaccine). This vaccine elicited an increase in both anti-saliva and anti-Leishmania IgG isotypes, higher counts of specific circulating CD8(+) T cells, and high NO production. METHODS: We investigated the immunogenicity and protective effect of LBSapSal vaccination after intradermal challenge with 1 × 10(7) late-log-phase L. infantum promastigotes in the presence of sand fly saliva of Lutzomyia longipalpis. The dogs were followed for up to 885 days after challenge. RESULTS: The LBSapSal vaccine presents extensive antigenic diversity with persistent humoral and cellular immune responses, indicating resistance against CVL is triggered by high levels of total IgG and its subtypes (IgG1 and IgG2); expansion of circulating CD5(+), CD4(+), and CD8(+) T lymphocytes and is Leishmania-specific; and reduction of splenic parasite load. CONCLUSIONS: These results encourage further study of vaccine strategies addressing Leishmania antigens in combination with proteins present in the saliva of the vector.


title: Application of siRNA Against SARS in the Rhesus Macaque Model

text: Containment of the SARS coronavirus (SCV) outbreak was accompanied by the rapid characterization of this new pathogen's genome sequence in 2003, encouraging the development of anti-SCV therapeutics using short interfering RNA (siRNA) inhibitors. A pair of siRNA duplexes identified as potent SCV inhibitors in vitro was evaluated for in vivo efficacy and safety in a rhesus macaque SARS model using intranasal administration with clinical viable delivery carrier in three dosing regimens. Observations of SCV-induced SARS-like symptoms, measurements of SCV RNA presence in the respiratory tract, microscopic inspections of lung histopathology, and immunohistochemistry sections from 21 tested macaques consistently demonstrated siRNA-mediated anti-SCV activity. The prophylactic and therapeutic efficacies resulted in relief of animals from SCV infection-induced fever, diminished SCV in upper airway and lung alveoli, and milder acute diffuse alveoli damage (DAD). The dosages of siRNA used, 10 to 40 mg/kg, did not show any sign of siRNA-induced toxicity. These results support that a clinical investigation of this anti-SARS siRNA therapeutic agent is warranted. The study also illustrates the capability of siRNA to enable a massive reduction in development time for novel targeted therapeutic agents. We detail a representative example of large-mammal siRNA use.


title: A Randomized Trial of Instructor-Led Training Versus Video Lesson in Training Health Care Providers in Proper Donning and Doffing of Personal Protective Equipment

text: OBJECTIVE: This study compared live instructor-led training with video-based instruction in personal protective equipment (PPE) donning and doffing. It assessed the difference in performance between (1) attending 1 instructor-led training session in donning and doffing PPE at 1 month prior to assessment, and (2) watching training videos for 1 month. METHODS: This randomized controlled trial pilot study divided 21 medical students and junior doctors into 2 groups. Control group participants attended 1 instructor-led training session. Video group participants watched training videos demonstrating the same procedures, which they could freely watch again at home. After 1 month, a doctor performed a blind evaluation of performance using checklists. RESULTS: Nineteen participants were assessed after 1 month. The mean donning score was 84.8/100 for the instructor-led group and 88/100 for the video group; mean effect size was 3.2 (95% CI: -7.5 to 9.5). The mean doffing score was 79.1/100 for the instructor-led group and 73.9/100 for the video group; mean effect size was 5.2 (95% CI: -7.6 to 18). CONCLUSION: Our study found no significant difference in donning and doffing scores between instructor-led and video lessons. Video training could be a fast and resource-efficient method of training in PPE donning and doffing in responding to the COVID-19 pandemic.


title: Drive-Through Screening Center for COVID-19: A Safe and Efficient Screening System Against Massive Community Outbreak Kwon KT, Ko JH, Shin H, et al. J Korean Med Sci. Published online March 16, 2020. doi: https://doi.org/10.3346/jkms.2020.35.e123.

text: The current Coronavirus Disease 2019 (COVID-19) pandemic has necessitated the testing of significant numbers of patients. Modeled after those used during a previous bioterrorism disaster and influenza pandemic, the authors present a descriptive report of their drive-through screening center and processes. The authors recommend use of a large parking lot geographically removed from large population centers. Additionally, they recommend either a tent or temporary building to be used for work space and shelter from weather. They utilized a four-step process: Entrance → Registration → Examination → Specimen collection → Instructions → Exit. Patients do not leave their cars during this process. To minimize contact and preserve personal protective equipment (PPE), communication is performed either by mobile phone or electronic medical record whenever possible. Temperature is obtained with a contactless thermometer. If the physician strongly suspects COVID-19 during the examination step, the patient is transported to a designated hospital after specimen collection. Test specimens were collected with the car window opened the minimum amount necessary and car ventilation mode on internal circulation. Patients are provided with information about obtaining test results, home quarantine, and anticipatory guidance. Healthcare workers (HCWs) who had direct contact with patients wore the following PPE: N95 respirator, eye shield/face shield/goggles, hooded coverall/gown, and inner and outer gloves. To decrease viral spread and minimize the possibility of specimen contamination, HCWs wore two gowns and two pairs of gloves for patients who required testing; the external gloves/gown were removed and hands disinfected after each patient contact. The authors reported that this process took approximately ten minutes per test, allowing them to screen 100 people per day with a staff of 4-8 HCWs. This is estimated to be 1/3 the amount of time that a typical screening process would take. The authors recommended rotating staff every 1-2 hours if possible, and to ensure that no HCW wore an N95 respirator for longer than four consecutive hours. They also noted the need to be cognizant of relevant environmental issues, such as hot/cold weather, etc., and to adapt the working environment accordingly. Lastly, there must be adequate communication with the public regarding the limitations of the screening center to minimize the number of people who may attempt to use this resource inappropriately. They recommend considering a similar process for other uses such as medication distribution or vaccine administration. Comment: While not a typical research manuscript we would select for Abstracts, this article describes a non-novel approach to a novel viral pandemic. The drive-through screening process has a number of advantages as outlined above, especially as centers begin seeing higher numbers of potential COVID-19 patients. It is important to consider and plan for the unintended consequences of such a program, including how HCWs will handle unexpectedly ill patients and patients arriving by alternative transportation (bike, walking, public transportation). Healthcare leaders considering a drive-through screening option should also consider the heightened emotions and fear that are present during epidemic/pandemic conditions and plan for security accordingly.


title: Validation of Syndromic Surveillance for Respiratory Pathogen Activity

text: Syndromic surveillance is increasingly used to signal unusual illness events. To validate data-source selection, we retrospectively investigated the extent to which 6 respiratory syndromes (based on different medical registries) reflected respiratory pathogen activity. These syndromes showed higher levels in winter, which corresponded with higher laboratory counts of Streptococcus pneumoniae, respiratory syncytial virus, and influenza virus. Multiple linear regression models indicated that most syndrome variations (up to 86%) can be explained by counts of respiratory pathogens. Absenteeism and pharmacy syndromes might reflect nonrespiratory conditions as well. We also observed systematic syndrome elevations in the fall, which were unexplained by pathogen counts but likely reflected rhinovirus activity. Earliest syndrome elevations were observed in absenteeism data, followed by hospital data (+1 week), pharmacy/general practitioner consultations (+2 weeks), and deaths/laboratory submissions (test requests) (+3 weeks). We conclude that these syndromes can be used for respiratory syndromic surveillance, since they reflect patterns in respiratory pathogen activity.


New vaccine coalition targets epidemics


Characteristics of critically ill patients infected with COVID-19 in Abu Dhabi, United Arab Emirates


title: Viral nucleic acid analysis with PCR in lacrimal tissue and nasal swab samples of primary acquired nasolacrimal duct obstruction cases

text: PURPOSE: To evaluate the role of viral infections in the pathogenesis of primary acquired nasolacrimal duct obstruction. METHODS: The study included 48 patients diagnosed with primary acquired nasolacrimal duct obstruction undergoing dacryocystorhinostomy surgery. Prior to dacryocystorhinostomy surgery, nasal swab sample was taken from the inferior meatus at the same side. During dacryocystorhinostomy, tissue biopsy sample (2 × 2 mm) was taken from the junction area of the lacrimal sac and nasolacrimal duct. Following nucleic acid extraction, polymerase chain reaction was performed. RESULTS: The patients consisted of 9 (18.8%) men and 39 (81.2%) women with a mean age of 51.0 ± 14.3 years. Qualitative polymerase chain reaction showed viral genome in the nasal swabs of 10 (20.8%) patients, including coronavirus 229E (three cases), coronavirus HKU1 (two cases), respiratory syncytial virus (two cases), coronavirus OC43 (one case), coronavirus NL63 (one case), and adenovirus (one case). In the dacryocystorhinostomy samples, viral genomes were detected in four (8.3%) cases, including respiratory syncytial virus (two cases), coronavirus HKU1 (one case), and adenovirus (one case). There was a statistically significant agreement between nasal mucosal swab and dacryocystorhinostomy biopsy samples in terms of respiratory syncytial virus positivity (kappa = 1.000, p = 0.001). CONCLUSION: Although the viral genome was detected in the samples, a direct relationship between viruses and pathogenesis of primary acquired nasolacrimal duct obstruction could not be revealed because of the low number of positive results. However, considering the profibrotic characteristics of specific viruses such as respiratory syncytial virus and adenovirus, viral infections may be one of the many predisposing factors of primary acquired nasolacrimal duct obstruction.


title: Influenza Virus-Induced Robust Expression of SOCS3 Contributes to Excessive Production of IL-6

text: Influenza A virus (IAV) remains a major public health threat in the world, as indicated by the severe pneumonia caused by its infection annually. Interleukin-6 (IL-6) involved excessive inflammatory response to IAV infection profoundly contributes to the virus pathogenesis. However, the precise mechanisms underlying such a response are poorly understood. Here we found from both in vivo and in vitro studies that IAV not only induced a surge of IL-6 release, but also greatly upregulated expression of suppressor of cytokine signaling-3 (SOCS3), the potent suppressor of IL-6-associated signal transducer and activator of transcription 3 (STAT3) signaling. Interestingly, there existed a cytokine-independent mechanism of the robust induction of SOCS3 by IAV at early stages of the infection. Furthermore, we employed SOCS3-knockdown transgenic mice (TG), and surprisingly observed from virus challenge experiments using these mice that disruption of SOCS3 expression provided significant protection against IAV infection, as evidenced by attenuated acute lung injury, a higher survival rate of infected animals and lower viral load in infected tissues as compared with those of wild-type littermates under the same condition. The activity of nuclear factor-kappa B (NFκB) and the expression of its target gene IL-6 were suppressed in SOCS3-knockdown A549 cells and the TG mice after infection with IAV. Moreover, we defined that enhanced STAT3 activity caused by SOCS3 silencing was important for the regulation of NFκB and IL-6. These findings establish a critical role for IL-6-STAT3-SOCS3 axis in the pathogenesis of IAV and suggest that influenza virus may have evolved a strategy to circumvent IL-6/STAT3-mediated immune response through upregulating SOCS3.


title: Ingepakt aan het werk

text: WUHAN, CHINA - Verpleegkundigen in Wuhan hebben het niet gemakkelijk sinds de uitbraak van het nieuwe coronavirus. Deze icverpleegkundigen doen hun werk in hermetisch afgesloten pakken. Toch zijn er in China zeker 6 zorgverleners overleden en zouden er ruim 1700 artsen en verpleegkundigen besmet zijn.


title: Innate Immune Evasion Strategies of DNA and RNA viruses

text: Upon infection, both DNA and RNA viruses can be sensed by pattern recognition receptors (PRRs) in the cytoplasm or the nucleus to activate antiviral innate immunity. Sensing of viral products leads to the activation of a signaling cascade that ultimately results in transcriptional activation of Type I and III interferons, as well as other antiviral genes that mediate viral clearance and inhibit viral spread. Therefore, in order for viruses to replicate and spread efficiently, they must inhibit the host signaling pathways that induce the innate antiviral immune response. In this review, we will highlight recent advances the understanding of the mechanisms by which viruses evade PRR detection, intermediate signaling molecule activation, transcription factor activation, and the actions of antiviral proteins.