title: Safety and immunogenicity of a virus-like particle pandemic influenza A (H1N1) 2009 vaccine in a blinded, randomized, placebo-controlled trial of adults in Mexico

text: Virus-like particles (VLPs) can be rapidly developed from influenza virus genetic sequences in order to supply vaccine after the onset of a pandemic. The safety and immunogenicity of one or two doses of a recombinant A (H1N1) 2009 influenza VLP vaccine was evaluated in a two-stage, Phase 2, randomized, double-blind, placebo-controlled study conducted in 4563 healthy adults, 18–64 years of age, during the H1N1 2009 pandemic in Mexico. In Part A, 1013 subjects were randomized into four treatment groups (5 μg, 15 μg, or 45 μg hemagglutinin [HA] VLP vaccine or placebo) and vaccinated 21 days apart, with sera collected on Days 1, 14 and 36 for hemagglutination inhibition (HAI) testing. After review of safety and immunogenicity data from Part A, additional subjects were immunized with a single dose of 15 μg VLP vaccine (N = 2537) or placebo (N = 1011) and assessed for safety in Part B. Results showed the H1N1 2009 VLP vaccine was safe and well-tolerated. Systemic solicited events were similar between placebo and VLP vaccinated groups with no vaccine-related serious adverse events. Dose response trends for solicited local adverse events were observed, with higher incidences of local pain, swelling, tenderness, and redness reported in the higher VLP dose groups (15 μg and 45 μg) compared to the placebo and 5 μg VLP groups following both vaccinations. Although the majority of local AEs were mild in severity, a dose trend in events of moderate or greater severity was also noted for these solicited events. The VLP vaccine groups demonstrated robust HAI immune responses after a single vaccination, with high rates of seroprotection (≥40 HAI titer) in 82–92% of all subjects and in 64–85% of subjects who were seronegative at the time of immunization. HAI geometric mean titers (GMTs), geometric mean ratios (GMRs) and seroconversion rates were also all statistically higher in the VLP groups compared to placebo for both post-baseline time points. Based on these data, additional clinical trials are in development to evaluate influenza vaccine candidate antigens manufactured using Spodoptera frugiperda (Sf9)/baculovirus-based VLP technology.


The Association of Voter Turnout with County-level COVID-19 Occurrence Early in the Pandemic


title: Rapid point-of-care testing for SARS-CoV-2 in a community screening setting shows low sensitivity

text: Abstract Objective With the current SARS-CoV2 outbreak, countless tests need to be performed on potential symptomatic individuals, contacts and travellers. The gold standard is a quantitative polymerase chain reaction (qPCR)–based system taking several hours to confirm positivity. For effective public health containment measures, this time span is too long. We therefore evaluated a rapid test in a high-prevalence community setting. Study design Thirty-nine randomly selected individuals at a COVID-19 screening centre were simultaneously tested via qPCR and a rapid test. Ten previously diagnosed individuals with known SARS-CoV-2 infection were also analysed. Methods The evaluated rapid test is an IgG/IgM–based test for SARS-CoV-2 with a time to result of 20 min. Two drops of blood are needed for the test performance. Results Of 49 individuals, 22 tested positive by repeated qPCR. In contrast, the rapid test detected only eight of those positive correctly (sensitivity: 36.4%). Of the 27 qPCR-negative individuals, 24 were detected correctly (specificity: 88.9%). Conclusion Given the low sensitivity, we recommend not to rely on an antibody-based rapid test for public health measures such as community screenings.


title: Detection and molecular characterization of caliciviruses (vesivirus and norovirus) in an outbreak of acute diarrhea in kittens from Brazil

text: Abstract Feline caliciviruses (FCVs) have occasionally been described in cats in association with enteric disease, but an etiological role for these viruses in acute gastroenteritis is still unclear. In this study, molecular characterization of FCV and feline norovirus (FNoV) was undertaken using real-time PCR (RT-PCR) and sequence analysis of the ORF1 region in fecal specimens from 29 diarrheic cats. The specimens were also screened for parvovirus, coronavirus, astrovirus and group A rotavirus. A quantitative one step RT-PCR was also performed to detect and quantitate NoV genogroup IV and the role of these animal caliciviruses in feline gastroenteritis was investigated. This is the first description of enteric FCV and FNoV in South America.


title: The influenza A virus endoribonuclease PA-X usurps host mRNA processing machinery to limit host gene expression

text: Many viruses globally shut off host gene expression to inhibit activation of cell-intrinsic antiviral responses. However, host shutoff is not indiscriminate, since viral proteins and host proteins required for viral replication are still synthesized during shutoff. The molecular determinants of target selectivity in host shutoff remain incompletely understood. Here, we report that the influenza A virus shutoff factor PA-X usurps RNA splicing to selectively target host RNAs for destruction. PA-X preferentially degrades spliced mRNAs, both transcriptome-wide and in reporter assays. Moreover, proximity-labeling proteomics revealed that PA-X interacts with cellular proteins involved in RNA splicing. The interaction with splicing contributes to target discrimination and is unique among viral host shutoff nucleases. This novel mechanism sheds light on the specificity of viral control of host gene expression and may provide opportunities for development of new host-targeted antivirals.


title: Quantifying the bat bushmeat trade in North Sulawesi, Indonesia, with suggestions for conservation action

text: Abstract The intense consumption of flying foxes in North Sulawesi, Indonesia has raised hunting pressure and extirpation is expected to spread into other regions. To assess local cultural attitudes towards bats for formulating a targeted conservation campaign, we conducted a survey of consumption practices of bats in 2013 at the eight major markets near Manado. Locals eat flying foxes at least once a month, but the frequency increases tenfold around Christian holidays. Approximately 500 metric tons of bats are imported from other provinces, with South Sulawesi as the main provider at 38%. No action has been taken to conserve the bats, as continued abundance in the market masks the effects of the bushmeat trade on wild populations. We suggest: (1) engaging churches as conduits for environmental education and quota enforcement; (2) legal regulation of interprovincial trade; (3) substituting bats with a sustainable option; (4) involving local students as campaigners to ensure higher receptiveness from local communities. Grassroots conservation initiatives combined with enforcement of existing laws aim to affect change on a local level, which has been successful in other conservation programs. These efforts would not only progress bat conservation, but conservation of other rare, endemic mammals common to the bushmeat trade.


title: WFDC1/ps20: A host factor that influences the neutrophil response to murine hepatitis virus (MHV) 1 infection

text: Abstract The whey acidic protein family member, WFDC1/ps20 is a permissivity factor in HIV infection. Herein we describe a contrasting role for ps20 in limiting MHV-1 infection. Intranasal MHV-1 infection produces a respiratory infection in mice. Using ps20 knockout mice we provide evidence that intranasal MHV-1 infection results in increased lung viral titers in ps20−/− compared to ps20+/+ mice. Accompanying MHV-1 infection we observe an increase in the number of neutrophils infiltrating the BAL and an increase in the percentage of neutrophils in the lung draining lymph nodes of ps20−/− compared with ps20+/+ mice. Gene expression levels for the neutrophil chemoattractants CXCL1 and CXCL2 are elevated in the lungs of ps20−/− mice post-MHV-1 infection. Characterization of the immune cell profile in naïve ps20−/− mice revealed an increase in circulating neutrophils compared to ps20+/+ mice. No notable differences in other immune cell profiles were observed between the ps20+/+ and ps20−/− mice. Accordingly, we examined MHV-1 infection of neutrophils and provide evidence that neutrophils isolated from ps20−/− mice are more susceptible to MHV-1 infection than neutrophils isolated from ps20+/+ mice. These data suggest roles for ps20 in regulating expression of neutrophil-specific chemotactic factors, thereby potentially modulating neutrophil migration, and in modulating neutrophil susceptibility to MHV-1 infection.


title: 33rd international mammalian genome conference: meeting highlights

text: Scientists from 12 countries met at the International Mammalian Genome Conference (IMGC) to share advances in mammalian genetics and genomics research. The event was held in Strasbourg, France and represents the city’s second time hosting the IMGC. A diverse attendance of pre-doctoral and post-doctoral trainees, young investigators, established researchers, clinicians, bioinformaticians, and computational biologists enjoyed a rich scientific program of 63 oral presentations, 65 posters, and 5 workshops in the fields of epigenetics, system genetics, developmental biology, cancer, human disease modeling, technical advances, and bioinformatics. This report presents selected highlights of this meeting which illustrate how recent advances in mammalian genetic approaches have improved our ability to decipher complex biological mechanisms.


title: A review of vaccine development and research for industry animals in Korea

text: Vaccination has proven to be the most cost-effective strategy for controlling a wide variety of infectious diseases in humans and animals. For the last decade, veterinary vaccines have been substantially developed and demonstrated their effectiveness against many diseases. Nevertheless, new vaccines are greatly demanded to effectively control newly- and re-emerging pathogens in livestock. However, development of veterinary vaccines is a challenging task, in part, due to a variety of pathogens, hosts, and the uniqueness of host-susceptibility to each pathogen. Therefore, novel concepts of vaccines should be explored to overcome the limitation of conventional vaccines. There have been greatly advanced in the completion of genomic sequencing of pathogens, the application of comparative genomic and transcriptome analysis. This would facilitate to open opportunities up to investigate a new generation of vaccines; recombinant subunit vaccine, virus-like particle, DNA vaccine, and vector-vehicle vaccine. Currently, such types of vaccines are being actively explored against various livestock diseases, affording numerous advantages over conventional vaccines, including ease of production, immunogenicity, safety, and multivalency in a single shot. In this articles, the authors present the current status of the development of veterinary vaccines at large as well as research activities conducted in Korea.


title: CXC chemokines and antimicrobial peptides in rhinovirus‐induced experimental asthma exacerbations

text: RATIONALE: Rhinoviruses (RVs) are the major triggers of asthma exacerbations. We have shown previously that lower respiratory tract symptoms, airflow obstruction, and neutrophilic airway inflammation were increased in experimental RV‐induced asthma exacerbations. OBJECTIVES: We hypothesized that neutrophil‐related CXC chemokines and antimicrobial peptides are increased and related to clinical, virologic, and pathologic outcomes in RV‐induced exacerbations of asthma. METHODS: Protein levels of antimicrobial peptides (SLPI, HNP 1–3, elafin, and LL‐37) and neutrophil chemokines (CXCL1/GRO‐α, CXCL2/GRO‐β, CXCL5/ENA‐78, CXCL6/GCP‐2, CXCL7/NAP‐2, and CXCL8/IL‐8) were determined in bronchoalveolar lavage (BAL) fluid of 10 asthmatics and 15 normal controls taken before, at day four during and 6 weeks post‐experimental infection. RESULTS: BAL HNP 1–3 and Elafin were higher, CXCL7/NAP‐2 was lower in asthmatics compared with controls at day 4 (P = 0.035, P = 0.048, and P = 0.025, respectively). BAL HNP 1–3 and CXCL8/IL‐8 were increased during infection (P = 0.003 and P = 0.011, respectively). There was a trend to increased BAL neutrophils at day 4 compared with baseline (P = 0.076). BAL HNP 1–3 was positively correlated with BAL neutrophil numbers at day 4. There were no correlations between clinical parameters and HNP1–3 or IL‐8 levels. CONCLUSIONS: We propose that RV infection in asthma leads to increased release of CXCL8/IL‐8, attracting neutrophils into the airways where they release HNP 1–3, which further enhances airway neutrophilia. Strategies to inhibit CXCL8/IL‐8 may be useful in treatment of virus‐induced asthma exacerbations.


Breast milk and infection


title: Effects of specialty proteins as alternatives to bovine or porcine spray-dried plasma in non-medicated diets fed to weaned pigs housed in an unsanitary environment

text: Two experiments were done to compare growth performance of pigs weaned at 21 ± 2 d of age that were housed in unsanitary pens and fed non-medicated diets containing alternative proteins versus spray-dried porcine (SDPP; Exp. 1) or bovine (SDBP; Exp. 2) plasma. Experiment 1 used 360 pigs fed 1 of 6 experimental diets from d 0 to 15, followed by a common diet fed to all pigs from d 15 to 28 post-weaning with 11 pens of 5 or 6 pigs/pen allotted per treatment. Experimental diets were based on 8.04% soy protein concentrate (SPC) as the control protein or a similar diet with either 2.50 or 5.00% SDPP or 0.17, 0.33, or 1.00% activated porcine plasma (APP) replacing SPC on an equal Lys basis. Experiment 2 used 300 pigs that were fed 1 of 6 experimental diets from d 0 to 14 post-weaning with 10 pens of 4 to 6 pigs/pen allotted per diet. Experiment 2 diets were based on 8.04% SPC as the control protein source or similar diets with the following specialty proteins replacing SPC on an equal Lys basis: 0.40% APP; 10.66% enzymatically hydrolyzed soy and yeast protein (EHSY); a combination (CB) of 6.36% EHSY, 0.40% APP, and 2.50% fish meal; 0.44% spray-dried whole egg from hyper-immunized hens (IEGG); or 5.00% SDBP. Results of Exp. 1 indicated pigs fed SDPP diets had greater (P < 0.05) ADG and ADFI at d 7 and 15 compared with pigs fed SPC or APP diets. Gain:feed at d 7 was higher (P < 0.05) for pigs fed diets with SDPP compared with other diets. Average BW at d 7 was greater (P < 0.05) for pigs fed diets with SDPP compared to other diets and pigs fed the 5.00% SDPP diet had greater BW at d 15 compared to diets without SDPP. At d 28 BW was greater (P < 0.05) for pigs fed the 2.50% SDPP diet compared with pigs fed diets with SPC, 0.33% APP, or 1.00% APP. Performance of pigs fed the SPC diet did not differ from APP diets at any period of the study. In Exp. 2, pigs fed the SDBP diet had greater (P < 0.05) BW, ADG, and ADFI at d 7 and 14 compared with pigs fed the other diets. Gain:feed did not differ significantly among diets. Average daily gain and ADFI of pigs did not differ among diets that did not contain SDBP. In conclusion, during the initial 2 wk post-weaning, pigs housed in unsanitary pens and fed non-medicated diets with APP in Exp. 1, or APP, EHSY, CB, or IEGG in Exp. 2 had equivalent performance to pigs fed SPC; however, performance of pigs fed diets with the alternatives was not equivalent to diets containing SDPP in Exp. 1 or SDBP in Exp. 2.


title: Novel use of home pulse oximetry monitoring in COVID‐19 patients discharged from the emergency department identifies need for hospitalization

text: OBJECTIVES: Our objective was to evaluate patient‐reported oxygen saturation (SpO(2)) using pulse oximetry as a home monitoring tool for patients with initially non‐severe COVID‐19 to identify need for hospitalization. METHODS: Patients were enrolled at the emergency department (ED) and outpatient testing centers. Each patient was given a home pulse oximeter and instructed to record their SpO(2) every eight hours. Patients were instructed to return to the ED for sustained home SpO(2) <92% or if they felt they needed emergent medical attention. Relative risk was used to assess the relation between hospitalization and home SpO(2) <92% in COVID‐19 positive patients. RESULTS: We enrolled 209 patients with suspected COVID‐19, of which 77 patients tested positive for COVID‐19 and were included. Subsequent hospitalization occurred in 22/77 (29%) patients. Resting home SpO(2) <92% was associated with an increased likelihood of hospitalization compared to SpO(2) ≥92% [RR 7.0 (95% CI 3.4 – 14.5), p‐value <0.0001]. Home SpO2 <92% was also associated with increased risk of ICU admission, ARDS and septic shock. In our cohort, 50% of patients who ended up hospitalized only returned to the ED for incidental finding of low home SpO(2) without worsening of symptoms. One‐third (33%) of non‐hospitalized patients stated they would have returned to the ED if they did not have a pulse oximeter to reassure them at home. CONCLUSIONS: This study found that home pulse oximetry monitoring identifies need for hospitalization in initially non‐severe COVID‐19 patients when a cut off of SpO(2) 92% is used. Half of patients who ended up hospitalized had SpO(2) <92% without worsening symptoms. Home SpO(2) monitoring also reduces unnecessary ED revisits.


Cancer has not gone away: A primary care perspective to support a balanced approach for timely cancer diagnosis during COVID‐19


title: Targeting SARS-CoV-2: a systematic drug repurposing approach to identify promising inhibitors against 3C-like proteinase and 2′-O-ribose methyltransferase

text: The recent pandemic associated with SARS-CoV-2, a virus of the Coronaviridae family, has resulted in an unprecedented number of infected people. The highly contagious nature of this virus makes it imperative for us to identify promising inhibitors from pre-existing antiviral drugs. Two druggable targets, namely 3C-like proteinase (3CLpro) and 2′-O-ribose methyltransferase (2′-O-MTase) were selected in this study due to their indispensable nature in the viral life cycle. 3CLpro is a cysteine protease responsible for the proteolysis of replicase polyproteins resulting in the formation of various functional proteins, whereas 2′-O-MTase methylates the ribose 2′-O position of the first and second nucleotide of viral mRNA, which sequesters it from the host immune system. The selected drug target proteins were screened against an in-house library of 123 antiviral drugs. Two promising drug molecules were identified for each protein based on their estimated free energy of binding (ΔG), the orientation of drug molecules in the active site and the interacting residues. The selected protein-drug complexes were then subjected to MD simulation, which consists of various structural parameters to equivalently reflect their physiological state. From the virtual screening results, two drug molecules were selected for each drug target protein [Paritaprevir (ΔG = −9.8 kcal/mol) & Raltegravir (ΔG = −7.8 kcal/mol) for 3CLpro and Dolutegravir (ΔG = −9.4 kcal/mol) and Bictegravir (ΔG = −8.4 kcal/mol) for 2′-OMTase]. After the extensive computational analysis, we proposed that Raltegravir, Paritaprevir, Bictegravir and Dolutegravir are excellent lead candidates for these crucial proteins and they could become potential therapeutic drugs against SARS-CoV-2. Communicated by Ramaswamy H. Sarma


title: Disability-Adjusted Life Years for Communicable Disease in the Korean Burden of Disease Study 2012

text: Globally, the incidence of communicable diseases has decreased compared to non-communicable diseases. However, chronic communicable diseases such as HIV/AIDS and tuberculosis persist worldwide. Furthermore, emerging new infections such as H1N1 influenza pose a new threat to public health. However, most studies have focused on non-communicable diseases because of their increasing incidence, with fewer studies investigating communicable diseases. Therefore, we estimated the burden of communicable diseases in Korea using national representative 2012 data. To estimate the disability-adjusted life years (DALY), we used cause of death data from the Statistics Korea to estimate the years of life lost (YLL), applied the Korean garbage code algorithm, and used national claims data from the National Health Insurance Service (NHIS) to estimate years lived with disability (YLD). In 2012, the total DALYs of communicable disease were 445 per 100,000, with 129 YLLs per 100,000 and 316 YLDs per 100,000. The total DALYs in men were 468 per 100,000, greater than the 422 per 100,000 DALYs seen in women. The DALYs of lower respiratory infections were the highest value among communicable diseases at 143/100,000 DALYs followed by tuberculosis and upper respiratory infections. The 40-49 years old age group had the largest number of total DALYs. In contrast, the over 80 years old age group had the largest number of total DALYs per 100,000 followed by the 70-79 and 0-9 years old age groups. These results enable the prioritization of interventions related to communicable diseases and can be used for evidence-based public health policies.


title: Characteristics of COVID-19 Community Practice Declines in Non-Invasive Diagnostic Imaging Professional Work

text: Purpose The operational and financial impact of the widespread COVID-19 curtailment of imaging services on radiology practices is unknown. We aimed to characterize recent COVID-19 related community practice non-invasive diagnostic imaging professional work declines. Methods Using imaging metadata from nine community radiology practices across the United States between January 2019 and May 2020, we mapped work relative value unit (wRVU) weighted stand-alone non-invasive diagnostic imaging service codes to both modality and body region. Weekly 2020 vs. 2019 wRVU changes were analyzed by modality, body region, and site of service. Practice share Chi-square testing was performed. Results Aggregate weekly wRVUs ranged from a high of 120,450 (February 2020) to a low of 55,188 (April 2020). During that -52% wRVU nadir, outpatient declines were greatest (-66%). All practices followed similar aggregate trends in the distribution of wRVUs between each 2020 vs. 2019 week (p=0.96-0.98). As a percentage of total all-practice wRVUs, declines in CT (20,046/63,992; 31%) and radiography/fluoroscopy (19,196; 30%) were greatest. By body region, declines in abdomen/pelvis (16,203; 25%) and breast (12,032; 19%) imaging were greatest. Mammography (-17%) and abdominal/pelvic CT (-14%) accounted for the largest shares of total all-practice wRVU reductions. Across modality-region groups, declines were far greatest for mammography (-92%). Conclusions Substantial COVID-19 related diagnostic imaging work declines were similar across community practices and disproportionately impacted mammography. Decline patterns could facilitate pandemic second wave planning. Overall implications for practice workflows, practice finances, patient access, and payment policy are manifold.


title: A review of vaccine research and development: Human acute respiratory infections()

text: Worldwide, acute respiratory infections (ARIs) constitute the leading cause of acute illnesses, being responsible for nearly 4 million deaths every year, mostly in young children and infants in developing countries. The main infectious agents responsible for ARIs include influenza virus, respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV-3), Streptococcus pneumoniae and Haemophilus influenzae. While effective vaccines against influenza, H. influenzae type b (Hib) and S. pneumoniae infections have been available for several years, no vaccine is available at present against illnesses caused by RSV, PIV-3, metapneumovirus or any of the three novel coronaviruses. In addition, the threat constituted by the multiple outbreaks of avian influenza during the last few years is urgently calling for the development of new influenza vaccines with broader spectrum of efficacy, which could provide immunity against an avian influenza virus pandemic. This article reviews the state of the art in vaccine R&D against ARIs and attempts to address these basic public health questions.


title: Real-world comparison of two molecular methods for detection of respiratory viruses

text: BACKGROUND: Molecular polymerase chain reaction (PCR) based assays are increasingly used to diagnose viral respiratory infections and conduct epidemiology studies. Molecular assays have generally been evaluated by comparing them to conventional direct fluorescent antibody (DFA) or viral culture techniques, with few published direct comparisons between molecular methods or between institutions. We sought to perform a real-world comparison of two molecular respiratory viral diagnostic methods between two experienced respiratory virus research laboratories. METHODS: We tested nasal and throat swab specimens obtained from 225 infants with respiratory illness for 11 common respiratory viruses using both a multiplex assay (Respiratory MultiCode-PLx Assay [RMA]) and individual real-time RT-PCR (RT-rtPCR). RESULTS: Both assays detected viruses in more than 70% of specimens, but there was discordance. The RMA assay detected significantly more human metapneumovirus (HMPV) and respiratory syncytial virus (RSV), while RT-rtPCR detected significantly more influenza A. We speculated that primer differences accounted for these discrepancies and redesigned the primers and probes for influenza A in the RMA assay, and for HMPV and RSV in the RT-rtPCR assay. The tests were then repeated and again compared. The new primers led to improved detection of HMPV and RSV by RT-rtPCR assay, but the RMA assay remained similar in terms of influenza detection. CONCLUSIONS: Given the absence of a gold standard, clinical and research laboratories should regularly correlate the results of molecular assays with other PCR based assays, other laboratories, and with standard virologic methods to ensure consistency and accuracy.


title: Therapists join national effort to help essential workers

text: Employees deemed “essential” workers (i.e., health care professionals, first responders, service industry employees, truck drivers, military and many others on the front line who are not able to work from their homes and risk exposure to COVID‐19 so that others could stay at home) can now have access to free or reduced‐fee online therapy sessions.


title: Clinical features of pediatric patients with coronavirus disease (COVID-19)

text: Abstract Background Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has spread around the world, and reports of children with COVID-19 are increasing. Objectives To assess clinical profiles of pediatric COVID-19. Study design A retrospective analysis was undertaken using clinical data of sixteen children (11 months-14 years) diagnosed with COVID-19 between January 1, 2020 and March 17, 2020 at Xiangyang Central Hospital, Hubei province, China. Results All children had positive epidemiologic histories, 12 (12/16, 75 %) involving family units. The illnesses were either mild (5/16, 31.3 %) or ordinary (11/16, 68.8 %), presenting as follows: asymptomatic (8/16, 50 %), fever and/or cough (8/16, 50 %). Four asymptomatic patients (4/16, 25 %) in ordinary cases had chest computed tomography (CT) abnormalities. Leukocyte counts were normal in 14 cases(88 %), but 2 patients (12.5 %) had leukopenia, and 1 (6.3 %) was lymphopenic. There were 11 patients with chest CT abnormalities, some nodular, others small patchy and others ground-glass opacities. In asymptomatic children, the median time to SRAS-CoV-2 nucleic acid test(NAT) positivity once exposed to a family member with confirmed infection was 15.5 days (range, 10–26 days). The median time to first NAT-negative conversion was 5.5 days (range, 1–23 days). Conclusions COVID-19 in children of Xiangyang city is often family acquired and not serious, with favorable outcomes. Asymptomatic children can be diagnosed as pneumonia because of chest CT abnormalities. It is essential to actively screen this segment of the population.


title: Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine

text: Abstract The spike (S) protein of severe acute respiratory syndrome (SARS) coronavirus (CoV), a type I transmembrane envelope glycoprotein, consists of S1 and S2 domains responsible for virus binding and fusion, respectively. The S1 contains a receptor-binding domain (RBD) that can specifically bind to angiotensin-converting enzyme 2 (ACE2), the receptor on target cells. Here we show that a recombinant fusion protein (designated RBD-Fc) containing 193-amino acid RBD (residues 318–510) and a human IgG1 Fc fragment can induce highly potent antibody responses in the immunized rabbits. The antibodies recognized RBD on S1 domain and completely inhibited SARS-CoV infection at a serum dilution of 1:10,240. Rabbit antisera effectively blocked binding of S1, which contains RBD, to ACE2. This suggests that RBD can induce highly potent neutralizing antibody responses and has potential to be developed as an effective and safe subunit vaccine for prevention of SARS.


Porcine Deltacoronavirus, Thailand, 2015


title: SARS-CoV-Encoded Small RNAs Contribute to Infection-Associated Lung Pathology

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) causes lethal disease in humans, which is characterized by exacerbated inflammatory response and extensive lung pathology. To address the relevance of small non-coding RNAs in SARS-CoV pathology, we deep sequenced RNAs from the lungs of infected mice and discovered three 18–22 nt small viral RNAs (svRNAs). The three svRNAs were derived from the nsp3 (svRNA-nsp3.1 and -nsp3.2) and N (svRNA-N) genomic regions of SARS-CoV. Biogenesis of CoV svRNAs was RNase III, cell type, and host species independent, but it was dependent on the extent of viral replication. Antagomir-mediated inhibition of svRNA-N significantly reduced in vivo lung pathology and pro-inflammatory cytokine expression. Taken together, these data indicate that svRNAs contribute to SARS-CoV pathogenesis and highlight the potential of svRNA-N antagomirs as antivirals.


title: Effects of an experimentally induced rhinovirus cold on sleep, performance, and daytime alertness

text: Abstract Study objectives: There is accumulating evidence that the common cold produces impairments in psychomotor vigilance. This has led some investigators to hypothesize that such illnesses may also have disruptive effects on sleep. While several self-report studies suggest that viral illness may influence sleep parameters, no studies have assessed polysomnographically recorded sleep following viral infections. Design: Parallel control group comparison. Setting: Sleep laboratory in a large urban medical center. Participants: Twenty-one men and women with susceptibility to the rhinovirus type 23. Interventions: Nasal inoculation with rhinovirus type 23. Measurements: Polysomnographically recorded sleep for five nights (2300–0700 h) post-viral inoculation. Twice daily (1030 and 1430 h) performance assessment during each experimental day using auditory vigilance and divided attention tasks. A multiple sleep latency test (MSLT) was performed daily for the duration of the study. Results: In symptomatic individuals, total sleep time decreased an average of 23 min, consolidated sleep decreased an average of 36 min, and sleep efficiency was reduced by an average of 5% during the active viral period (experimental days/nights 3–5) compared with the incubation period. Psychomotor performance was impaired. These changes were significantly greater than those observed in asymptomatic individuals. Conclusions: The common cold can have detrimental effects on sleep and psychomotor performance in symptomatic individuals during the initial active phase of the illness.


title: In vivo Biodistribution of a Highly Attenuated Recombinant Vesicular Stomatitis Virus Expressing HIV-1 Gag Following Intramuscular, Intranasal, or Intravenous Inoculation

text: Recombinant vesicular stomatitis viruses (rVSVs) are being developed as potential HIV-1 vaccine candidates. To characterize the in vivo replication and dissemination of rVSV vectors in mice, high doses of a highly attenuated vector expressing HIV-1 Gag, rVSV(IN)- N4CT9-Gag1, and a prototypic reference virus, rVSV(IN)-HIVGag5, were delivered intramuscularly (IM), intranasally (IN), or intravenously (IV). We used quantitative, real-time RT-PCR (Q-PCR) and standard plaque assays to measure the temporal dissemination of these viruses to various tissues. Following IM inoculation, both viruses were detected primarily at the injection site as well as in draining lymph nodes; neither virus induced significant weight loss, pathologic signs, or evidence of neuroinvasion. In contrast, following IN inoculation, the prototypic virus was detected in all tissues tested and caused significant weight loss leading to death. IN administration of rVSV(IN)- N4CT9-Gag1 resulted in detection in numerous tissues (brain, lung, nasal turbinates, and lymph nodes) albeit in significantly reduced levels, which caused little or no weight loss nor any mortality. Following IV inoculation, both prototypic and attenuated viruses were detected by Q-PCR in all tissues tested. In contrast to the prototype, rVSV(IN)-N4CT9-Gag1 viral loads were significantly lower in all organs tested, and no infectious virus was detected in the brain following IV inoculation, despite the presence of viral RNA. These studies demonstrated significant differences in the biodistribution patterns of and the associated pathogenicity engendered by the prototypic and attenuated vectors in a highly susceptible host.


title: Diagnosis of community-acquired acute respiratory illness: From conventional microbiological methods to molecular detection (multiplex)

text: Abstract Investigations of the etiologic agents of community-acquired acute respiratory illness may lead to better treatment decisions and patient outcomes. In a routine care setting, we assessed the diagnostic performance of a multiplex PCR assay with respect to conventional microbiological methods, in a continuous series of adult cases of community-acquired acute respiratory illness. We enrolled 279 adult patients hospitalised for community-acquired acute respiratory illness at Tours University Hospital during the winter of 2011–2012. Respiratory samples (mostly nasopharyngeal aspirates) were studied prospectively by indirect immunofluorescence assay and multiplex PCR, that enable detection of 8 viruses and 21 respiratory pathogens respectively. In total, 255 of the 279 (91.4%) samples had interpretable results by both methods. At least one respiratory pathogen was detected by multiplex PCR in 171 specimens (65%). Overall, 130 (76%) of the 171 positive samples were positive for only one respiratory pathogen, 37 (22%) samples were positive for two pathogens and four (2%) were positive for three pathogens. With indirect immunofluorescence assay, a respiratory virus was detected in 27 of the 255 (11%) specimens. Indirect immunofluorescence assay detected some of the influenza virus A (15/51, 29%) infections identified by multiplex PCR and some (7/15, 47%) human metapneumovirus and (5/12, 42%) respiratory syncytial virus infections, but it did not detect all the adenovirus infections. Thus, access to multiplex molecular assays improves the diagnostic spectrum and accuracy over conventional methods, increasing the frequency of identification of the respiratory pathogens involved in community-acquired acute respiratory illness.


EV71 vaccines: a milestone in the history of global vaccine development


title: Review of Issues and Challenges of Practicing Emergency Medicine Above 30,000-Feet Altitude: 2 Anonymized Cases

text: Abstract We present 2 anonymized cases to identify issues and challenges associated with long-haul in-flight medical emergencies. The first case involved a middle-aged man with a history of carditis on a systemic steroid who developed vomiting and rigor. Four physicians, including a pediatric intensivist, responded to the emergency call. In the second case, a pediatric trainee who was the only onboard medical personnel was summoned for help when a middle-aged man developed acute shortness of breath while traveling on a commercial flight. The cases illustrate the challenges and issues on the critical decisions of diagnosis, resuscitation, and whether the flight had to be returned or diverted. An extensive literature search is made to summarize the evidence available for these decisions and challenges. Epidemiology and outcomes associated with these medical emergencies are reviewed. In-flight medical emergencies are not rare. Physicians of all disciplines should be prepared to deal with these emergencies and make sensible decisions when equipment and resources are likely to be limited.


title: Evaluation of pedestrian wind comfort near ‘lift-up’ buildings with different aspect ratios and central core modifications

text: Abstract Owing to the void space at lower heights, lift-up buildings have high building permeability at ground level and subsequently improve the air circulation in congested urban areas. Despite this advantage, the lift-up design has been sparsely adopted for buildings in urban areas partly because of the lack of understanding of the combined effects of building dimensions and lift-up design on the surrounding pedestrian level wind (PLW) field. Therefore, this study aims to investigate the influence of lift-up buildings with different aspect ratios (height/width) on the surrounding PLW field and pedestrian wind comfort level. Five lift-up buildings with aspect ratios 4:1 to 0.5:1 were tested in a boundary layer wind tunnel and results were compared with those of five buildings with similar dimensions but without lift-up design. The results reveal a strong dependence of the maximum wind speed in lift-up areas with building height, which results subsequently a small area of acceptable wind conditions near tall and slender lift-up buildings. Lift-up designs adopted for short and wide buildings produce larger areas of pedestrian wind comfort. The central cores modified with corner modifications are effective in increasing the pedestrian wind comfort in the lift-up area of tall and slender buildings.


title: Las estadísticas sanitarias y la invisibilidad por sexo y de género durante la epidemia de COVID-19

text: ABSTRACT Reports on COVID-19 from the Spanish Health Ministry are valuable, but incomplete, with the perverse effect that the susceptibility to COVID-19 by sex is unclear. Prevalence of COVID-19 by sexes differs between countries. The trend in Spain shows an unequal pattern, initially more frequent in men, but women outnumbered them from March 31, after two weeks lockdown. Infections are more frequent in women than in men in close contact with probable/confirmed COVID-19 cases. Consistent with deaths in men, they are hospitalized more frequently than women: Significant gender differences in signs/symptoms can drive this pattern, already observed in other pathologies. In late April, excess mortality is the same in women (67%) than in men (66%). But, lack of exhaustive information on deaths from COVID-19 in non-hospitalized patients may contribute to lower notification of deaths in women. Invisibility of data by sex and gender is probably affecting negatively women with COVID -19 more than men.


title: Curation of viral genomes: challenges, applications and the way forward

text: BACKGROUND: Whole genome sequence data is a step towards generating the 'parts list' of life to understand the underlying principles of Biocomplexity. Genome sequencing initiatives of human and model organisms are targeted efforts towards understanding principles of evolution with an application envisaged to improve human health. These efforts culminated in the development of dedicated resources. Whereas a large number of viral genomes have been sequenced by groups or individuals with an interest to study antigenic variation amongst strains and species. These independent efforts enabled viruses to attain the status of 'best-represented taxa' with the highest number of genomes. However, due to lack of concerted efforts, viral genomic sequences merely remained as entries in the public repositories until recently. RESULTS: VirGen is a curated resource of viral genomes and their analyses. Since its first release, it has grown both in terms of coverage of viral families and development of new modules for annotation and analysis. The current release (2.0) includes data for twenty-five families with broad host range as against eight in the first release. The taxonomic description of viruses in VirGen is in accordance with the ICTV nomenclature. A well-characterised strain is identified as a 'representative entry' for every viral species. This non-redundant dataset is used for subsequent annotation and analyses using sequenced-based Bioinformatics approaches. VirGen archives precomputed data on genome and proteome comparisons. A new data module that provides structures of viral proteins available in PDB has been incorporated recently. One of the unique features of VirGen is predicted conformational and sequential epitopes of known antigenic proteins using in-house developed algorithms, a step towards reverse vaccinology. CONCLUSION: Structured organization of genomic data facilitates use of data mining tools, which provides opportunities for knowledge discovery. One of the approaches to achieve this goal is to carry out functional annotations using comparative genomics. VirGen, a comprehensive viral genome resource that serves as an annotation and analysis pipeline has been developed for the curation of public domain viral genome data . Various steps in the curation and annotation of the genomic data and applications of the value-added derived data are substantiated with case studies.


title: Comparisons of envelope through 5B sequences of infectious bronchitis coronaviruses indicates recombination occurs in the envelope and membrane genes

text: Abstract A 1.78kb sequence, including the E, M, 5a and 5b genes, and the intergenic region between the M and 5a genes, of six US strains of infectious bronchitis (corona)virus (IBV) were sequenced and compared to the published sequences for two additional strains. The overall identities as determined through pairwise analyses of nucleotide sequences of the entire 1.78kb region ranged from 90 to 99%, with the 5b open reading frame (ORF) having the greatest identity (94–99%) while the identities of the E, 5a and M ORFs ranged from 87 to 100%. Nucleotide sequencing of recent field isolates from Alabama (Ala1) and California (Cal3) revealed distinct shifts in homology in the M gene, indicating two apparent recombination events between the Holland 52/Mass41-like strain and an Ark-like strain, both origins of commonly used vaccine strains. Putative sites of recombination could also be identified in both the E and M ORFs of laboratory strains of IBV.


Missing information in animal surveillance of MERS-CoV


title: Pathogen survival in the external environment and the evolution of virulence

text: Recent studies have provided evolutionary explanations for much of the variation in mortality among human infectious diseases. One gap in this knowledge concerns respiratory tract pathogens transmitted from person to person by direct contact or through environmental contamination. The sit‐and‐wait hypothesis predicts that virulence should be positively correlated with durability in the external environment because high durability reduces the dependence of transmission on host mobility. Reviewing the epidemiological and medical literature, we confirm this prediction for respiratory tract pathogens of humans. Our results clearly distinguish a high‐virulence high‐survival group of variola (smallpox) virus, Mycobacterium tuberculosis, Corynebacterium diphtheriae, Bordetella pertussis, Streptococcus pneumoniae, and influenza virus (where all pathogens have a mean percent mortality 0.01% and mean survival time >10 days) from a low‐virulence low‐survival group containing ten other pathogens. The correlation between virulence and durability explains three to four times of magnitude of difference in mean percent mortality and mean survival time, using both across‐species and phylogenetically controlled analyses. Our findings bear on several areas of active research and public health policy: (1) many pathogens used in the biological control of insects are potential sit‐and‐wait pathogens as they combine three attributes that are advantageous for pest control: high virulence, long durability after application, and host specificity; (2) emerging pathogens such as the‘hospital superbug’methicillin‐resistant Staphylococcus aureus (MRSA) and potential bioweapons pathogens such as smallpox virus and anthrax that are particularly dangerous can be discerned by quantifying their durability; (3) hospital settings and the AIDS pandemic may provide footholds for emerging sit‐and‐wait pathogens; and (4) studies on food‐borne and insect pathogens point to future research considering the potential evolutionary trade‐offs and genetic linkages between virulence and durability.


title: Immune responses to RNA-virus infections of the CNS

text: A successful outcome for the host of virus infection of the central nervous system (CNS) requires the elimination of the virus without damage to essential non-renewable cells, such as neurons. As a result, inflammatory responses must be tightly controlled, and many unique mechanisms seem to contribute to this control. In addition to being important causes of human disease, RNA viruses that infect the CNS provide useful models in which to study immune responses in the CNS. Recent work has shown the importance of innate immune responses in the CNS in controlling virus infection. And advances have been made in assessing the relative roles of cytotoxic T cells, antibodies and cytokines in the clearance of viruses from neurons, glial cells and meningeal cells.


title: Serological detection of infection dynamics for respiratory viruses among dairy calves

text: Abstract The aim of this study is to reveal infection dynamics of bovine respiratory syncytial virus (BRSV), bovine parainfluenza virus type 3 (PI-3), bovine herpesvirus 1 (BHV-1), bovine viral diarrhea virus (BVDV), bovine adenovirus type 3 (BAV-3) and bovine coronavirus (BCoV), which are important viral pathogens of respiratory disease complex in ruminants. Through such an analysis, the regression period of maternally derived antibodies and optimum vaccination time in calves can be recommended. A total of 10 farms were grouped as large (4)-, medium (2)- and small (4)- sized enterprises according to their animal population. Newborn calves (n: 94) delivered during a calendar month on the farms were studied. Blood samples were collected from these calves during their 1st, 2nd, 3rd, 4th, 6th, 8th, 10th and 12th months of age. Blood samples were also taken from their dams during the first sampling. Neutralizing antibody titers were detected using the serum neutralization test (SN50). New PI-3 and BVDV infections at the early stages of life were determined in the calves. Maternal antibodies began to decrease in the 2nd month for BRSV, BHV-1 and BAV-3 (97.8%, 25.5% and 91.4%) and in the 3rd month for PI-3, BVDV and BCoV (85.1%, 67% and 93.6%). It was concluded that maternal antibodies begin to decrease after the 1st month and that the possible first exposure of calves to respiratory viruses is after the 2nd month. Therefore, it is recommended that the first vaccination program including prime and booster doses can be applied between 2 and 4 months of age. Furthermore, re-vaccination of animals at 6 months after the booster dose is also suggested.


title: Predictive model of diagnosing probable cases of severe acute respiratory syndrome in febrile patients with exposure risk

text: Abstract Study objective Since the World Health Organization issued a global alert about severe acute respiratory syndrome (SARS) on March 12, 2003, the illness has become a major public health challenge worldwide. The objective of this study is to identify the clinical risk factors of SARS and to develop a scoring system for early diagnosis. Methods The detailed clinical data of all patients presenting to the emergency department (ED) with a temperature higher than 38.0°C (100.3°F), documented at home or at the ED, and risks of exposure to SARS within 14 days were assessed. The diagnosis of probable SARS was made according to the definition of the Centers for Disease Control and Prevention. Items with significant differences among symptoms, signs, and laboratory tests on presentation between SARS and non-SARS groups were determined and used to develop the scoring system. Results Seventy patients were enrolled and 8 were diagnosed as probably having SARS. None of the initially discharged patients or their relatives developed SARS. Compared with the non-SARS group, the SARS group was younger (33.9±15.9 years versus 44±9.8 years; P=.02), had a higher percentage of fever prolonged more than 5 days (87.5% versus 6.5%; P<.01), myalgia (75% versus 27.4%; P=.01), and diarrhea (50% versus 9.7%; P=.02); had less occurrence of cough before or during fever (0% versus 64.5%; P=.01); and had lower absolute lymphocyte (0.9±0.3×109/L versus 1.5±1.1×109/L; P<.01) and platelet counts (144.1±36.3×109/L versus 211.6±78.8×109/L; P=.02). A 4-item symptom score based on the presence of cough before or concomitant with fever, myalgia, diarrhea, and rhinorrhea or sore throat detects SARS with 100% sensitivity and 75.9% specificity; a 6-item clinical score based on lymphopenia (<1.0×109/L), thrombocytopenia (<150×109/L) and the 4 symptom items detects SARS with 100% sensitivity and 86.3% specificity. Conclusion Certain symptoms and laboratory tests indicate higher risk of febrile probable SARS. In nonendemic areas, the febrile patients with recent contact with SARS or travel history to endemic areas could be screened for the probability of SARS by the use of clinical and symptom scores.


title: Acute promyelocytic leukaemia lying under the mask of COVID‐19‐a diagnostic and therapeutic conundrum

text: The diagnosis and management of acute promyelocytic leukaemia (APML) in the context COVID‐19 poses a challenge for clinicians. We present a case illustrating this due to the masking of the typical laboratory pattern of APML coagulopathy and the potential heightened risks of thrombosis and differentiation syndrome (DS) when the two conditions are combined.


title: Psychological crisis intervention during the outbreak period of new coronavirus pneumonia from experience in Shanghai

text: Abstract Since the middle of December 2019, human-to-human transmission of novel coronavirus pneumonia (NCP) has occurred among close contacts. At the same time, greater attention should be paid to psychological crisis intervention (PCI) among affected populations, for the timely prevention of inestimable damage from a secondary psychological crisis. PCI has been initiated via remote (telephone and internet) and onsite medical services to help medical workers, patients, and others affected to overcome any psychological difficulties. This paper outlines experiences based on the work of the Shanghai Medical Team.


title: Antibody testing for coronavirus disease 2019: not ready for prime time

text: The tests need work, and fundamental questions remain about immunity


Neurological Manifestations of COVID-19 - Continually Evolving and Perplexing


title: Sympatric speciation in parasites – what is sympatry?

text: Abstract Parasites account for a large part of known species diversity and are considered to have a high potential for sympatric speciation. However, the frequency of sympatric divergence in these organisms will depend on the definition of sympatry that one uses. Like many of our current species concepts, the typical definition of sympatry is not widely applicable to parasites. Revisiting the historically defined conditions for sympatric speciation and considering the situations in which we might regard parasites as being sympatric leads us to question the classic prediction that parasites have a greater tendency to speciate in sympatry than do free-living organisms.


title: Apelin-potential therapy for COVID-19?

text: We believe that, in parallel to the attempts for direct blockade of the SARS-CoV-2 penetration into host cell and repurposing drugs, finding new therapeutic strategies for patients with lung injury or cardiovascular complications/coagulopathies associated with COVID-19 should be paid particular attention. Apelin or its receptor agonists are of great potential treatment for COVID-19 through suppressing angiotensin-converting enzyme (ACE) and angiotensin II (Ang-II) production, as well as, down-regulating angiotensin receptor 1 (AT1R) and ACE2 up-regulation. These drugs have potential to improve acute lung injury and cardiovascular/coagulopathy complications in COVID-19 which are associated with elevated Ang-II/Ang(1–7) ratio.


Domestic Abuse during COVID-19 - What about the boys?


title: Traumatic non-missile penetrating transnasal anterior skull-base fracture and brain injury with cerebrospinal fluid leak: intraoperative leak detection and an effective reconstruction procedure for a localized skull base defect especially after COVID-19 outbreak

text: Abstract BACKGROUND Cerebrospinal fluid leakage in penetrating skull base injury is relatively rare compared to close head injury involving skull base fracture. CASE DESCRIPTION We report a case of a 65-year-old beekeeping man who presented with epistaxis and serous rhinorrhea. When he fell down on the ground near his bee boxes, a garden pole poked into his right nostril. He instantly removed the pole from his nostril by himself. Immediately after the removal of the pole, he developed some nasal bleeding and serous rhinorrhea. He then drove to our emergency room. Computed tomography showed pneumocephalus with minor cerebral contusion in the left frontal lobe, and penetrating injury in the left anterior skull base. His cerebrospinal fluid (CSF) leakage did not resolve spontaneously within one week after the injury under a strict bed rest. We repaired the CSF leakage using a fat (adipose tissue)-on-fascia autograft plug and caulked the defect in the anterior skull base with the fat-on-fascia graft (FFG) plug through the left nostril under endoscopic vision. The CSF rhinorrhea was successfully controlled. Intranasal local application of fluorescein aided in the detection of the flow direction of CSF leakage. CONCLUSIONS Endonasal endoscopic caulking of a skull base defect using FFG plug is useful for CSF leakage due to localized skull base defect, in particular for the post-COVID-19 era, because it is simple, low-cost, and timesaving: requiring no special skills or no sophisticated instruments, thus reducing infection risks during the surgery. (239 words)


title: Conventional and Specific-Pathogen Free Rats Respond Differently to Anesthesia and Surgical Trauma

text: Specific-pathogen free (SPF) animals were introduced in the 1960s to minimize disease and infection as variables in biomedical research. Our aim was to examine differences in physiological response in rat colonies bred and housed in a conventional versus SPF facility, and implications for research. Sprague-Dawley rats were anesthetized and catheterized for blood and pressure monitoring, and electrocardiogram (ECG) leads implanted. Hematology was assessed, and coagulation profile using rotational thromboelastometry. Health screening was outsourced to Cerberus Sciences. SPF rats had significantly lower pulse pressure (38% decrease), arrhythmias and prolonged QTc (27% increase) compared to conventional rats. No arrhythmias were found in conventional rats. SPF rats had significantly higher white cell, monocyte, neutrophil and lymphocyte counts, and were hyperfibrinolytic, indicated by EXTEM maximum lysis >15%. Independent assessment revealed similar pathogen exclusion between colonies, with the exception of Proteus in SPF animals. Returning to a conventional facility restored normal host physiology. We conclude that SPF animals displayed an abnormal hemodynamic, hematological and hemostatic phenotype in response to anesthesia and surgery, and provide a number of recommendations to help standardize research outcomes and translation.


title: Challenges in Drug Development Posed by the COVID‐19 Pandemic: An Opportunity for Clinical Pharmacology

text: The unprecedented challenges posed by the coronavirus disease 2019 (COVID‐19) pandemic highlight the urgency for applying clinical pharmacology and model‐informed drug development in (i) dosage optimization for COVID‐19 therapies, (ii) approaching therapeutic dilemmas in clinical trial settings, and (iii) maximizing value of information from impacted non–COVID‐19 trials. More than ever, we have a responsibility for adaptive evidence synthesis with a Totality of Evidence mindset in this race against time across biomedical research, clinical practice, drug development, and regulation.


title: A Guide to Viral Inclusions, Membrane Rearrangements, Factories, and Viroplasm Produced During Virus Replication

text: Abstract Virus replication can cause extensive rearrangement of host cell cytoskeletal and membrane compartments leading to the “cytopathic effect” that has been the hallmark of virus infection in tissue culture for many years. Recent studies are beginning to redefine these signs of viral infection in terms of specific effects of viruses on cellular processes. In this chapter, these concepts have been illustrated by describing the replication sites produced by many different viruses. In many cases, the cellular rearrangements caused during virus infection lead to the construction of sophisticated platforms in the cell that concentrate replicase proteins, virus genomes, and host proteins required for replication, and thereby increase the efficiency of replication. Interestingly, these same structures, called virus factories, virus inclusions, or virosomes, can recruit host components that are associated with cellular defences against infection and cell stress. It is possible that cellular defence pathways can be subverted by viruses to generate sites of replication. The recruitment of cellular membranes and cytoskeleton to generate virus replication sites can also benefit viruses in other ways. Disruption of cellular membranes can, for example, slow the transport of immunomodulatory proteins to the surface of infected cells and protect against innate and acquired immune responses, and rearrangements to cytoskeleton can facilitate virus release.


title: Occasional review: Influenza in COPD: pathogenesis, prevention, and treatment

text: Influenza viruses cause respiratory tract infections that in patients with underlying lung diseases such as chronic obstructive pulmonary disease (COPD) are associated with exacerbations and excess morbidity and mortality. Typically, influenza B is associated with relatively mild, local outbreaks, whereas influenza A is the cause of world-wide pandemics. Upon infection, two antigens present on the viral surface, hemagglutinin and neuraminidase result in human immunity, but since many subtypes of these antigens exist that vary over time, immunity in the population is blunted. Vaccination is advocated in high-risk groups including patients with underlying (lung) diseases and in the elderly, and needs to be repeated annually with vaccines expected to cover the expected change in viral antigenicity. When started early, antiviral drugs, especially neuraminidase-inhibitors can be prescribed in adjunct to nonspecific interventions in an attempt to shorten disease duration and to prevent complications in case of an influenza infection. Currently, the effectiveness of antiviral drugs specifically in patients with COPD has not been proven.


title: Improving preparedness for the next flu pandemic

text: Pandemic influenza remains the single greatest threat to global heath security. Efforts to increase our preparedness, by improving predictions of viral emergence, spread and disease severity, by targeting reduced transmission and improved vaccination and by mitigating health impacts in low- and middle-income countries, should receive renewed urgency.


title: Management of IBD during the COVID-19 outbreak: resetting clinical priorities

text: The coronavirus disease (COVID-19) worldwide outbreak has led to a dramatic challenge for all healthcare systems, including inflammatory bowel disease (IBD) centres. Here, we describe the fast changes and clinical issues that IBD specialists could face during this SARS-CoV-2 infection pandemic, highlighting the potential rearrangements of care and resetting of clinical priorities.


title: Exercise testing in survivors of intensive care—is there a role for cardiopulmonary exercise testing?

text: Abstract Purpose The aims of this study were to assess the feasibility of cardiopulmonary exercise testing (CPET) for the early assessment of cardiorespiratory fitness in general adult intensive care unit (ICU) survivors and to characterize the pathophysiology of exercise limitation in this population. Methods Fifty general ICU survivors (ventilated for ≥5 days) performed a maximal cycle ergometer CPET within 6 weeks of hospital discharge. Health-related quality of life was measured by the Medical Outcome Study Short Form 36 version 2.0 questionnaire. Results Fifty patients (median age, 57 years; median Acute Physiology And Chronic Health Evaluation II score, 16) completed a CPET 24 ± 14 days after hospital discharge with no adverse events. Significant exercise limitation was present with peak Vo 2 56% ± 16% predicted and anaerobic threshold (AT) 41% ± 13% of peak predicted Vo 2. Prospectively stratified subgroup comparison showed that patients ventilated for 14 days or more had a significantly lower AT and peak Vo 2 than those ventilated for 5 to 14 days (AT: 9.6 vs 11.7 mL/kg per minute O2, P = .009; peak Vo 2: 12.9 vs 15.3 mL/kg per minute O2, P = .022). At peak exercise, heart rate reserve was 25% ± 14%, breathing reserve was 47% ± 19%, and the respiratory exchange ratio was 0.96 ± 0.11. Ventilatory equivalents for CO2 (Eqco 2) were 39 ± 9. Conclusions Significant exercise limitation is evident in patients who have had critical illness. Etiology of exercise limitation appears multifactorial, with general deconditioning and muscle weakness as major contributory factors. Early CPET appears a practical method of assessing exercise capacity in ICU survivors. Cardiopulmonary exercise testing could be used to select patients who may benefit most from a targeted physical rehabilitation program, aid in exercise prescription, and help assess the response to intervention.


title: Antiviral Innate Immune Response Interferes with the Formation of Replication-Associated Membrane Structures Induced by a Positive-Strand RNA Virus

text: Infection with nidoviruses like corona- and arteriviruses induces a reticulovesicular network of interconnected endoplasmic reticulum (ER)-derived double-membrane vesicles (DMVs) and other membrane structures. This network is thought to accommodate the viral replication machinery and protect it from innate immune detection. We hypothesized that the innate immune response has tools to counteract the formation of these virus-induced replication organelles in order to inhibit virus replication. Here we have investigated the effect of type I interferon (IFN) treatment on the formation of arterivirus-induced membrane structures. Our approach involved ectopic expression of arterivirus nonstructural proteins nsp2 and nsp3, which induce DMV formation in the absence of other viral triggers of the interferon response, such as replicating viral RNA. Thus, this setup can be used to identify immune effectors that specifically target the (formation of) virus-induced membrane structures. Using large-scale electron microscopy mosaic maps, we found that IFN-β treatment significantly reduced the formation of the membrane structures. Strikingly, we also observed abundant stretches of double-membrane sheets (a proposed intermediate of DMV formation) in IFN-β-treated samples, suggesting the disruption of DMV biogenesis. Three interferon-stimulated gene products, two of which have been reported to target the hepatitis C virus replication structures, were tested for their possible involvement, but none of them affected membrane structure formation. Our study reveals the existence of a previously unknown innate immune mechanism that antagonizes the viral hijacking of host membranes. It also provides a solid basis for further research into the poorly understood interactions between the innate immune system and virus-induced replication structures.


title: Fixed-cell immunoperoxidase technique for the study of surface antigens induced by the coronavirus of transmissible gastroenteritis (TGEV)

text: Abstract An immunoperoxidase technique performed on the TGEV-infected cells was developed for detection of virus-induced antigens. The presence of M antigen of TGEV on the surface of infected cells was demonstrated by this technique. This finding is in contrast to the M protein of murine hepatitis coronavirus which migrates to the Golgi apparatus but is not transported to the plasma membrane. The time course of appearance M and S antigens on the surface of TGEV-infected cell can be studied by this technique.


title: The “biosecuritization” of healthcare delivery: Examples of post-9/11 technological imperatives

text: This paper develops the concept of “biosecuritization” to describe new instantiations of the technological imperative in healthcare. Many discourses and practices surrounding hospitals’ new investments in information and communication technologies tend to revolve around security provision. Oftentimes, however, scenarios of extreme and exceptional circumstances are used to justify the implementation of identification and tracking technologies that may be more about managerial control than patient care. Drawing upon qualitative research in 23 U.S. hospitals from 2007 to 2009, our analysis focuses on hospitals’ deployment of identification and location technologies that manage patients, track personnel, and generate data in real-time. These systems are framed as aiding in the process of managing supplies and medications for pandemic flu outbreaks, monitoring exposure patterns for infectious diseases, and helping triage or manage the location and condition of patients during mass casualty disasters. We show that in spite of the framing of security and emergency preparedness, these technologies are primarily managerial tools for hospital administrators. Just as systems can be used to track infection vectors, those same systems can be used on a daily basis to monitor the workflow of hospital personnel, including nurses, physicians, and custodial staff, and to discipline or reward according to performance. In other words, the biosecuritization modality of the technological imperative leads to the framing of medical progress as the “rationalization” of organizations through technological monitoring, which is intended to promote accountability and new forms of responsibilization of healthcare workers.


title: Withdrawing mycophenolate mofetil in treating a young kidney transplant recipient with COVID-19: A case report

text: RATIONALE: Coronavirus disease 2019 (COVID-19) is a novel infectious disease and became a global issue. Treatment of COVID-19 especially in solid organ transplant recipients is empirical and controversial, especially the adjustment of the immunosuppressants. PATIENT CONCERNS: A 29-year-old kidney transplant recipient with the symptoms of COVID-19 pneumonia. DIAGNOSES: COVID-19 pneumonia after kidney transplantation. INTERVENTIONS: He was treated with modified immunosuppressants (unchanged dose of tacrolimus and oral corticosteroids while discontinuing mycophenolate mofetil (MMF)), antibiotics, interferon α-2b inhalation and traditional Chinese medicine. OUTCOMES: He recovered from COVID-19 pneumonia after 29 days of hospitalization. And the renal function (measured as blood urea nitrogen, serum creatinine, and urine protein) returned to normal. LESSONS: In certain group of COVID-19 (e.g., mild to moderate cases, young patients without comorbidities), a reduction instead of an overall withdrawal of immunosuppressant in kidney transplant recipients is feasible.


title: Combination of multiplex reverse-transcription loop-mediated isothermal amplification with an immunochromatographic strip for subtyping influenza A virus

text: Abstract Considering the fatal human victims and economic loss by the annual epidemic influenza virus, the development of a rapid and convenient genetic analysis methodology is demanding for timely on-site pathogen detection. In this study, we utilized reverse-transcription loop-mediated isothermal amplification (RT-LAMP) for multiplex target gene amplification, and the resultant amplicons were analyzed on the immunochromatographic strip (ICS) for subtyping influenza A virus. Through the optimized primer design, reaction temperature and time, and concentration of enzymes (Bst DNA polymerase and AMV reverse transcriptase) and dNTP, the HA (H1, H3, and H5 gene) and conserved M gene were amplified. The ICS contains two test lines in addition to a control line in order to detect the presence of the HA and M gene, thereby informing us of influenza virus A type as well as its subtype (H1N1, H3N2, and H5N1). The combination of the multiplex RT-LAMP with the ICS could be complete in 40min and the pathotyping and subtyping of influenza A virus were performed even with 10 copies of viral RNA templates. Moreover, the subtyping of clinical samples, which were obtained from patients infected by influenza A virus was successfully confirmed using the multiplex RT-LAMP and ICS techniques, showing great feasibility of our methodology for real sample analysis with high speed, simplicity and sensitivity.


title: Third Tofo Advanced Study Week on Emerging and Re-emerging Viruses, 2018

text: Abstract The Third Tofo Advanced Study Week on Emerging and Re-Emerging Viruses (3rd TASW) was held in Praia do Tofo, Mozambique, from September 02 to 06, 2018. It brought together 55 participants from 10 African countries as well as from Belgium, China, Germany, Singapore, and the USA. Meeting sessions covered aspects of the epidemiology, diagnosis, molecular and structural biology, vaccine development, and antiviral drug discovery for emerging RNA viruses that are current threats in Africa and included flaviviruses (dengue and Zika), alphaviruses (chikungunya), coronaviruses, filoviruses (Ebola), influenza viruses, Crimean Congo hemorrhagic fever virus, Rift Valley fever Virus, Lassa virus, and others. Data were presented on recent flavivirus and/or chikungunyavirus outbreaks in Angola, Burkina Faso, and Mozambique. In addition, these viruses are endemic in many sub-Saharan countries. The TASW series on emerging viruses is unique in Africa and successful in promoting collaborations between researchers in Africa and other parts of the world, as well as among African scientists. This report summarizes the lectures held at the meeting and highlights advances in the field.


Effect of COVID-19 pandemic on cancer clinician decision making: Known knowns and known unknowns


title: Symptom Severity Patterns in Experimental Common Colds and Their Usefulness in Timing Onset of Illness in Natural Colds

text: Mean total symptom severity scores for subjects with experimental rhinovirus colds peak 48 h after viral inoculation. Also, total symptom scores for natural rhinovirus and nonrhinovirus colds peaked on day 2 of illness in a long-term, noncompensated epidemiology study. In contrast, the mean total symptom scores for compensated patients receiving placebo in natural cold treatment trials peaked on day 1. Comparisons by day indicated that scores for symptoms reported as occurring on day 1 in the natural cold treatment trials corresponded with experimental cold scores for symptoms reported 48 h after viral inoculation. Comparisons of frequency and cumulative distribution scores for the 2 groups indicated that natural colds in the treatment trials were of longer duration than reported. A mean total symptom severity score of ⩽7 would capture 95% of experimental colds 24 h after inoculation while excluding 30.5% of natural colds on day 1 of illness. Histories given by compensated patients in natural cold treatment trials are inaccurate.


title: Predicting Professional Quality of Life and Life Satisfaction in Spanish Nurses: A Cross-Sectional Study

text: Background: Dealing with suffering, grief, and death on a daily basis, together with the particular working conditions, may produce high levels of burnout in nurses, and hinder their well-being. The purpose of this research is to study the effect of self-care and self-compassion on nurses’ professional quality of life and well-being. Methods: The research had a cross-sectional design, used correlational methodology and a structural equation model was hypothesized. Along the study, 210 nurses from the Healthcare Public System of the Balearic Islands, participated. The study took place from June to September 2018. Results: The hypothesized model showed an overall adequate fit. Practice environment predicted both self-care and self-compassion, whereas nursing stress did not. Self-care and self-compassion predicted nurses’ professional quality of life, whereas the practice environment and nursing stress were not predictors. Finally, professional quality of life showed a positive relationship with life satisfaction. Conclusions: The study presents a comprehensive structural equation model in which self-care and self-compassion are the best predictors of nurses’ professional quality of life. A direct relation of professional quality of life and nurses’ well-being has also been found, while controlling for the effects of nurses’ practice environment and stress.


title: Evaluation of protection conferred by a vaccination program based on the H120 and CR88 commercial vaccines against a field variant of avian infectious bronchitis virus

text: Abstract Due to serotype variations among different avian infectious bronchitis viruses isolated in Tunisia since 2000, protection of chicks, especially broiler flocks, with Mass H120 vaccine often fails. Therefore, association of CR88 (793B type) with H120 vaccines was used for better response. Challenge experiments were then conducted to evaluate tracheal and renal cross-protection in chickens immunized via nasal and eye drops. Conferred protection was measured by clinical signs and macroscopic lesions observed, based on scores attributed according to their severities. The results showed a low protection conferred by H120 alone, as vaccination did not reduce tracheal and kidney lesions (70% scored as 3) after TN20/00 virus challenge, which also led to 10% mortality. Conversely, the challenge results indicated that the combination of the 2 strains (H120/CR88) allow high protection. Based on the results of the challenge experiments, a vaccination protocol coupling CR88 to H120 was applied for industrial broiler flocks. Clinical observations and serological results confirmed that association of heterologous serotypes (H120 and CR88 vaccines) increased the levels of protection against infectious bronchitis viruses compared with the H120 vaccine given alone.


Toward a clinically based classification of disease severity for paediatric COVID-19 – Authors' reply


title: Telomeres and COVID‐19

text: The medical, public health, and scientific communities are grappling with monumental imperatives to contain COVID‐19, develop effective vaccines, identify efficacious treatments for the infection and its complications, and find biomarkers that detect patients at risk of severe disease. The focus of this communication is on a potential biomarker, short telomere length (TL), that might serve to identify patients more likely to die from the SARS‐CoV‐2 infection, regardless of age. The common thread linking these patients is lymphopenia, which largely reflects a decline in the numbers of CD4/CD8 T cells but not B cells. These findings are consistent with data that lymphocyte TL dynamics impose a limit on T‐cell proliferation. They suggest that T‐cell lymphopoiesis might stall in individuals with short TL who are infected with SARS‐CoV‐2.


title: Exaptive Evolution of Target of Rapamycin Signaling in Multicellular Eukaryotes

text: Target of rapamycin (TOR) is a protein kinase that coordinates metabolism with nutrient and energy availability in eukaryotes. TOR and its primary interactors, RAPTOR and LST8, have been remarkably evolutionarily static since they arose in the unicellular last common ancestor of plants, fungi, and animals, but the upstream regulatory mechanisms and downstream effectors of TOR signaling have evolved considerable diversity in these separate lineages. Here, I focus on the roles of exaptation and adaptation in the evolution of novel signaling axes in the TOR network in multicellular eukaryotes, concentrating especially on amino acid sensing, cell-cell signaling, and cell differentiation.


title: Development and statistical validation of a guinea pig model for vaccine potency testing against Infectious Bovine Rhinothracheitis (IBR) virus

text: Infectious Bovine Rhinothracheitis (IBR) caused by bovine herpesvirus 1 (BoHV-1) infection is distributed worldwide. BoHV-1 either alone or in association with other respiratory cattle pathogens causes significant economic losses to the livestock industry. The aim of this work was to validate a guinea pig model as an alternative method to the current BoHV-1 vaccine potency testing in calves. Guinea pigs were immunized with two doses of vaccine, 21 days apart and sampled at 30 days post vaccination (dpv). BoHV-1 antibody (Ab) response to vaccination in guinea pigs, measured by ELISA and virus neutralization (VN), was statistically compared to the Ab response in cattle. The guinea pig model showed a dose–response relationship to the BoVH-1 antigen concentration in the vaccine and it was able to discriminate among vaccines containing 1 log(10) difference in its BoHV-1 concentration with very good repeatability and reproducibility (CV ≤ 20%). A regression analysis of the Ab titers obtained in guinea pigs and bovines at 30 and 60 dpv, respectively, allowed us to classify vaccines in three potency categories: “very satisfactory”, “satisfactory” and “unsatisfactory”. Bovines immunized with vaccines corresponding to each of these three categories were experimentally challenged with BoVH-1 virus, the level of protection, as measured by reduction of virus shedding and disease severity, correlated well with the vaccine category used. Data generated by 85 experiments, which included vaccination of calves and guinea pigs with 18 reference vaccines of known potency, 8 placebos and 18 commercial vaccines, was subjected to statistical analysis. Concordance analysis indicated almost perfect agreement between the model and the target species for Ab titers measured by ELISA and almost perfect to substantial agreement when Ab titers were measured by VN. Taken together these results indicate that the developed guinea pig model represents a novel and reliable tool to estimate batch-to-batch vaccine potency and to predict efficacy of killed BoHV-1 veterinary vaccines.


title: Investigation of the pharmacophore space of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) NTPase/helicase by dihydroxychromone derivatives

text: Abstract Aryl diketoacids have been identified as the first SARS-CoV NTPase/helicase inhibitors with a distinct pharmacophore featuring an arylmethyl group attached to a diketoacid. In order to search for the pharmacophore space around the diketoacid core, three classes of dihydroxychromone derivatives were prepared. Based on SAR study, an extended feature of the pharmacophore model of SARS-CoV NTPase/helicase was proposed which is constituted of a diketoacid core, a hydrophobic arylmethyl substituent, and a free catechol unit.


“COVID-19 Drive Through Testing: An Effective Strategy for Conserving Personal Protective Equipment”


title: Risk of Mycoplasma bovis transmission from contaminated sand bedding to naive dairy calves

text: Abstract The objective of this study was to evaluate the possible transmission of Mycoplasma bovis from positive sand bedding to naïve dairy calves. Twelve preweaned Holstein bull calves were blocked in pairs and randomly assigned as unexposed controls (n=6) bedded with control sand, or exposed calves (n=6) bedded with sand previously positive for M. bovis at a dairy farm. Bedding sand was cultured weekly. Nasal and ear swabs and sera were collected weekly, tracheal swabs were collected monthly, and by the end of the 105-d study, all calves were euthanized (n=10) or died (n=2). Sera were tested for M. bovis-specific antibody. Mycoplasma spp. culture was performed on nasal and ear swabs; culture and a PCR differentiating multiple Mycoplasma spp. were performed on postmortem samples of lung, retropharyngeal lymph node, and trachea from each calf. A complete necropsy also was performed. During 6 wk, mycoplasma concentration in exposed group sand was between 200 and 32,000 cfu/g. All 166 tracheal swabs, nasal and ear swabs, and postmortem tests from all calves were negative for mycoplasma. All 94 sera were negative for M. bovis-specific antibody. No gross pathology suggestive of mycoplasma disease was detected. The probability of mycoplasma detection, if an exposed calf had become infected 4 wk after exposure, ranged between 97 and 99% depending on time of exposure for individual calves. There was no evidence that sand bedding contaminated with M. bovis might serve as a source of transmission to naïve dairy calves.


title: ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection

text: Purpose Conjunctival signs and symptoms are observed in a subset of patients with COVID-19, and SARS-CoV-2 has been detected in tears, raising concerns regarding the eye both as a portal of entry and carrier of the virus. The purpose of this study was to determine whether ocular surface cells possess the key factors required for cellular susceptibility to SARS-CoV-2 entry/infection. Methods We analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2. Results Across all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the conjunctiva, limbus, and cornea, with especially prominent staining in the superficial conjunctival and corneal epithelial surface. Surgical conjunctival specimens also showed expression of ACE2 in the conjunctival epithelium, especially prominent in the superficial epithelium, as well as the substantia propria. All eye and conjunctival specimens also expressed TMPRSS2. Finally, western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and TMPRSS2. Conclusions Together, these results indicate that ocular surface cells including conjunctiva are susceptible to infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this virus. This highlights the importance of safety practices including face masks and ocular contact precautions in preventing the spread of COVID-19 disease.


Electron microscopy of SARS-CoV-2: a challenging task – Authors' reply


title: Tissue-Specific Amino Acid Transporter Partners ACE2 and Collectrin Differentially Interact With Hartnup Mutations

text: Background & Aims Hartnup amino acid transporter B0AT1 (SLC6A19) is the major luminal sodium-dependent neutral amino acid transporter of small intestine and kidney proximal tubule. The expression of B0AT1 in kidney was recently shown to depend on its association with collectrin (Tmem27), a protein homologous to the membrane-anchoring domain of angiotensin-converting enzyme (ACE) 2. Methods Because collectrin is almost absent from small intestine, we tested the hypothesis that it is ACE2 that interacts with B0AT1 in enterocytes. Furthermore, because B0AT1 expression depends on an associated protein, we tested the hypothesis that Hartnup-causing B0AT1 mutations differentially impact on B0AT1 interaction with intestinal and kidney accessory proteins. Results Immunofluorescence, coimmunoprecipitation, and functional experiments using wild-type and ace2-null mice showed that expression of B0AT1 in small intestine critically depends on ACE2. Coexpressing new and previously identified Hartnup disorder–causing missense mutations of B0AT1 with either collectrin or ACE2 in Xenopus laevis oocytes showed that the high-frequency D173N and the newly identified P265L mutant B0AT1 transporters can still be activated by ACE2 but not collectrin coexpression. In contrast, the human A69T and R240Q B0AT1 mutants cannot be activated by either of the associated proteins, although they function as wild-type B0AT1 when expressed alone. Conclusions We thus show that ACE2 is necessary for the expression of the Hartnup transporter in intestine and suggest that the differential functional association of mutant B0AT1 transporters with ACE2 and collectrin in intestine and kidney, respectively, participates in the phenotypic heterogeneity of human Hartnup disorder.


title: Síndrome respiratorio agudo grave, gripe aviar e infección por metapneumovirus humano

text: Los virus respiratorios fueron descubiertos progresivamente a partir del año 1950 gracias a la posibilidad de aislarlos en cultivos celulares. Los últimos fueron los coronavirus en la década de los años sesenta. No hubo más descubrimientos hasta 2001 con el metapneumovirus humano asociado a brotes de bronquiolitis en niños. Un año después, en noviembre de 2002, apareció el síndrome respiratorio agudo grave (SRAG) definido como una neumonía atípica, al que se asoció un nuevo virus como agente etiológico perteneciente a la familia de los coronavirus. En 2004 se descubrió otro coronavirus (CoV-NL63) y en 2005 se ha publicado el descubrimiento de un tercer coronavirus humano (CoV-HKU1). Además, varios subtipos del virus de la gripe A, que hasta ahora se pensaba que eran patógenos exclusivos de aves, se han transmitido directamente al ser humano. Si la infección respiratoria ha sido importante para el ser humano desde hace siglos, el conocimiento de nuevos virus asociados a ella se presenta en el siglo XXI como un importante campo de trabajo. Beginning in the 1950s respiratory viruses have been gradually discovered by isolation in cell cultures The last were the coronaviruses in the 1960s. No new respiratory viruses were discovered until 2001 when human metapneumovirus was found in respiratory specimens from children with bronchiolitis. A year later, in November 2002, severe acute respiratory syndrome (SARS) suddenly appeared as atypical pneumonia. A novel virus belonging to the Coronaviridae family was found to be a cause of this infection. In 2004, a second coronavirus was discovered (CoV-NL63) and in 2005 a third new coronavirus was described (CoV-HKU1). In addition, several subtypes of the influenza A virus, previously known to infect only poultry and wild birds, were recently found to have been directly transmitted to humans. Respiratory infection has been a considerable problem for humans for centuries. Now, in the 21st century, with new associated viruses continuously emerging, it remains an important field for work.


title: Impact of rotavirus vaccine on rotavirus genotypes and caliciviruses circulating in French cattle

text: Group A rotaviruses are a leading cause of neonatal calf diarrhoea worldwide and prevention of this disease includes vaccination against these viruses. In order to highlight the potential selection of rotavirus genotypes due to immune pressure driven by vaccination, the aim of this study was to compare group A rotavirus genotypes circulating in French diarrhoeic calves in rotavirus vaccinated herds (G6P[5] vaccine) with those in non-vaccinated herds during one calving season in 2010. This study showed a high prevalence of rotavirus in both groups with no significant difference between the two. No significant differences regarding G, P and G/P rotavirus genotype distribution between the two groups were observed, with G6, P[5] and G6P[5] genotypes being by far the most prevalent. Moreover, sequence analyses of the VP7 and VP4 partial coding genes of the G6P[5] strains from this study did not allow us to distinguish them according to their origin. This study also showed that other pathogens responsible for calf diarrhoea, such as genogroup III noroviruses and neboviruses, were not more frequently associated with calf diarrhoea in vaccinated herds. Altogether, these results suggest that the studied vaccine did not promote the emergence of rotavirus genotypes or variants different from those of the vaccine or other viruses responsible for calf diarrhoea, such as caliciviruses.


title: The viral innate immune antagonism and an alternative vaccine design for PRRS virus

text: Abstract Porcine reproductive and respiratory syndrome (PRRS) remains one of the most economically significant diseases in the swine industry worldwide. The current vaccines are less satisfactory to confer protections from heterologous infections and long-term persistence, and the need for better vaccines are urgent. The immunological hallmarks in PRRSV-infected pigs include the unusually poor production of type I interferons (IFNs-α/β) and the aberrant and delayed adaptive immune responses, indicating that PRRSV has the ability to suppress both innate and adaptive immune responses in the host. Type I IFNs are the potent antiviral cytokines and recent studies reveal their pleiotropic functions in the priming of expansion and maturation of adaptive immunity. Thus, IFN antagonism-negative PRRSV is hypothesized to be attenuated and to build effective and broad- spectrum innate and adaptive immune responses in pigs. Such vaccines are promising alternatives to traditional vaccines for PRRSV.


title: Household Transmission of Human Adenovirus Type 55 in Case of Fatal Acute Respiratory Disease

text: We identified a case of fatal acute respiratory disease from household transmission of human adenovirus type 55 (HAdV-55) in Anhui Province, China. Computed tomography showed severe pneumonia. Comparative genomic analysis of HAdV-55 indicated the virus possibly originated in Shanxi Province, China. More attention should be paid to highly contagious HAdV-55.


Heart failure related hospitalisation and management during COVID‐19 pandemic: are we ready to reflect? – REPLY


Role of Mask/Respirator Protection Against SARS-CoV-2


title: Enhancing Citizens Response to Out-of-Hospital Cardiac Arrest: A Systematic Review of Mobile-Phone Systems to Alert Citizens as First Responders

text: Abstract Introduction Involving laypersons in response to out-of-hospital cardiac arrest through mobile-phone technology is becoming widespread in numerous countries, and different solutions were developed. We performed a systematic review on the impact of alerting citizens as first responders and to provide an overview of different strategies and technologies used. Methods We searched electronic databases up to October 2019. Eligible studies described systems to alert citizens first responders to out-of-hospital cardiac arrest through text messages or apps. We analysed the implementation and performance of these systems and their impact on patients’ outcomes. Results We included 28 manuscripts describing 12 different systems. The first text message system was implemented in 2006 and the first app in 2010. First responders accepted to intervene in median (interquartile) 28.7% (27-29%) of alerts and reached the scene after 4.6 (4.4-5.5) minutes for performing CPR. First responders arrived before ambulance, started CPR and attached a defibrillator in 47% (34-58%), 24% (23-27%) and 9% (6-14%) of cases, respectively. Pooled analysis showed that first responders activation increased layperson-CPR rates (1463/2292 [63.8%] in the intervention group vs. 1094/1989 [55.0%] in the control group; OR=1.70; 95% CI, 1.11–2.60; p=0.01) and survival to hospital discharge or at 30 days (327/2273 [14.4%] vs. 184/1955 [9.4%]; OR=1.51; 95% CI, 1.24–1.84; p<0.001). Conclusions Alerting citizens as first responders in case of out-of-hospital cardiac arrest may reduce the intervention-free time and improve patients’ outcomes.


title: Pathogenesis of Lassa Fever

text: Lassa virus, an Old World arenavirus (family Arenaviridae), is the etiological agent of Lassa fever, a severe human disease that is reported in more than 100,000 patients annually in the endemic regions of West Africa with mortality rates for hospitalized patients varying between 5-10%. Currently, there are no approved vaccines against Lassa fever for use in humans. Here, we review the published literature on the life cycle of Lassa virus with the specific focus put on Lassa fever pathogenesis in humans and relevant animal models. Advancing knowledge significantly improves our understanding of Lassa virus biology, as well as of the mechanisms that allow the virus to evade the host’s immune system. However, further investigations are required in order to design improved diagnostic tools, an effective vaccine, and therapeutic agents.


title: Fiebre chikungunya - Una nueva amenaza global

text: Resumen Las epidemias causadas, entre otros, por los virus Ébola, Marburgo, Nipah, Lassa, coronavirus, virus del Nilo Occidental, virus de Saint Louis, virus de la inmunodeficiencia humana, dengue, fiebre amarilla y fiebre hemorrágica venezolana han puesto sobre el tapete el riesgo que estos agentes representan para la salud pública global. Entre las nuevas amenazas destaca el virus chikungunya, que ha extendido rápidamente su área endémica desde regiones remotas de África hacia la cuenca del océano Índico y el Pacífico Oriental, causando importantes epidemias en África, Asia, islas del Índico y Europa Occidental, llegando a establecerse recientemente en islas del Caribe. Debido a su comportamiento dual endémico y epidémico, a sus propiedades virológicas y a la presencia global de sus vectores, este virus entraña el riesgo de causar grandes epidemias e instalarse en el territorio continental de las Américas a partir de la introducción de casos importados y a la circulación local vista en la región caribeña. Se revisan las principales características epidemiológicas y clínicas de la fiebre chikungunya y el riesgo de introducción de esta enfermedad en las Américas, enfatizando el rol de la vigilancia y la lucha contra los mosquitos en su prevención. Abstract The recent onset of epidemics caused by viruses such as Ebola, Marburg, Nipah, Lassa, coronavirus, West-Nile encephalitis, Saint Louis encephalitis, human immunodeficiency virus, dengue, yellow fever and Venezuelan hemorrhagic fever alerts about the risk these agents represent for the global health. Chikungunya virus represents a new threat. Surged from remote African regions, this virus has become endemic in the Indic ocean basin, the Indian subcontinent and the southeast of Asia, causing serious epidemics in Africa, Indic Ocean Islands, Asia and Europe. Due to their epidemiological and biological features and the global presence of their vectors, chikungunya represents a serious menace and could become endemic in the Americas. Although chikungunya infection has a low mortality rate, its high attack ratio may collapse the health system during epidemics affecting a sensitive population. In this paper, we review the clinical and epidemiological features of chikungunya fever as well as the risk of its introduction into the Americas. We remark the importance of the epidemiological control and mosquitoes fighting in order to prevent this disease from being introduced into the Americas.


title: Electrophoretic separations on microfluidic chips

text: Abstract This review presents a brief outline and novel developments of electrophoretic separation in microfluidic chips. Distinct characteristics of microchip electrophoresis (MCE) are discussed first, in which sample injection plug, joule heat, channel turn, surface adsorption and modification are introduced, and some successful strategies and recognized conclusions are also included. Important achievements of microfluidic electrophoresis separation in small molecules, DNA and protein are then summarized. This review is aimed at researchers, who are interested in MCE and want to adopt MCE as a functional unit in their integrated microsystems.


title: Modelling can only tell us so much: politics explains the rest Adam Kucharski

text: Unknown


Intervention précoce avec un protocole d’EMDR dans un centre de dépistage du COVID-19


title: Molecular characterization of astrovirus infection in children with diarrhea in Beijing, 2005–2007

text: Human astroviruses (HAstVs) have been recognized as one of the major causes of acute gastroenteritis in children. To provide more insight into the prevalence of HAstV gastroenteritis in China, 664 fecal samples were collected from children affected with acute gastroenteritis in Beijing from March 2005 to November 2007. The samples were analyzed genetically. All eight serotypes (genotypes) of HAstVs were screened using RT‐PCR assays targeting the ORF2 region in the study. The assays detected HAstVs in 52 (7.8%) of the patients, with HAstV‐1 (50/52) being the dominant genotype during the study period. Two minor genotypes, HAstV‐6 and HAstV‐3, were also detected. Partial sequencing of the 50 HAstV‐1 strains showed that the homology of the nucleotide sequence of the ORF1a region between these strains was 88.4–100%, whereas the homology of the amino acid sequences was 95.6–100%. In the ORF2 partial region, the nucleotide identities ranged from 91.5% to 100%, and amino acid identities ranged from 97.3% to 100%. The identity of the whole genome sequence between four randomly examined HAstV‐1 strains was 91–99%. No recombination events were observed in HAstVs in this study. The findings of this study will provide baseline data for HAstVs surveillance and control. J. Med. Virol. 82:415–423, 2010. © 2010 Wiley‐Liss, Inc.