title: Characterization of the Two Overlapping Papain-like Proteinase Domains Encoded in Gene 1 of the Coronavirus Infectious Bronchitis Virus and Determination of the C-Terminal Cleavage Site of an 87-kDa Protein

text: Abstract In a previous report, we showed that proteolytic processing of an 87-kDa mature viral protein from the coronavirus infectious bronchitis virus (IBV) 1a and 1a/1b polyproteins was mediated by two putative overlapping papain-like proteinase domains (PLPDs) encoded within the region from nucleotides 4243 to 5553 of ORF 1a (Liuet al.,1995). In this study, we demonstrate that only the first domain, PLPD-1, is responsible for this cleavage, as deletion of the second domain did not affect the formation of the 87-kDa protein. Site-directed mutagenesis studies further showed that a previously predicted nucleophilic cysteine residue (Cys1274) and a histidine residue (His1437) were essential for the proteinase activity, indicating that they may be important components of the catalytic center of the proteinase. Meanwhile, expression of a series of deletion mutants revealed that the 87-kDa protein was encoded by the 5′-most 2.6 kb of ORF 1a. Deletion and amino acid substitution mutation studies demonstrated that the Gly673–Gly674dipeptide bond was most likely the cleavage site responsible for releasing the C-terminus of the 87-kDa protein from the 1a and 1a/1b polyproteins.


title: Prevalence of Sars-Cov-2 Infection in Health Workers (HWs) and Diagnostic Test Performance: The Experience of a Teaching Hospital in Central Italy

text: (1) Background: Health workers (HWs) are at high risk of acquiring SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infections. Therefore, health authorities further recommend screening strategies for SARS-CoV-2 infection in exposed or high-risk HWs. Nevertheless, to date, the best/optimal method to screen HWs for SARS-CoV-2 infection is still under debate, and data on the prevalence of SARS-CoV-2 infection in HWs are still scarce. The present study aims to assess the SARS-CoV-2 infection rate amongst HWs in a teaching hospital in Central Italy and the diagnostic performance of SARS-CoV-2 serology (index test) in comparison with the SARS-CoV-2 RNA PCR assay (reference standard). (2) Methods: A cross-sectional study on the retrospective data of HWs tested for SARS-CoV-2 by RNA-RT-PCR on nasopharyngeal swabs and by an IgM/IgG serology assay on venous blood samples, irrespective of exposure and/or symptoms, was carried out. (3) Results: A total of 2057 HWs (median age 46, 19–69 years, females 60.2%) were assessed by the RNA RT-PCR assay and 58 (2.7%) tested positive for SARS-CoV-2 infection. Compared with negative HWs, SARS-CoV-2-positives were younger (mean age 41.7 versus 45.2, p < 0.01; 50% versus 31% under or equal to 40 years old, p < 0.002) and had a shorter duration of employment (64 versus 125 months, p = 0.02). Exposure to SARS-CoV-2 was more frequent in positive HWs than in negatives (55.2% versus 27.5%, p < 0.0001). In 44.8% of positive HWs, no exposure was traced. None of the positive HWs had a fatal outcome, none of them had acute respiratory distress syndrome, and only one required hospitalization for mild/moderate pneumonia. In 1084 (51.2%) HWs, nasopharyngeal swabs and an IgM/IgG serology assay were performed. With regard to IgM serology, sensitivity was 0% at a specificity of 98.99% (positive predictive value, PPV 0%, negative predictive value, NPV 99.2%). Concerning IgG serology and irrespective of the time interval between nasopharyngeal swab and serology, sensitivity was 50% at a specificity of 99.1% (PPV 28.6%, NPV 99.6%). IgG serology showed a higher diagnostic performance when performed at least two weeks after testing SARS-CoV-2-positive at the RNA RT-PCR assay by a nasopharyngeal swab. (4) Conclusions: Our experience in Central Italy demonstrated a low prevalence of SARS-CoV-2 infection amongst HWs, but higher than in the general population. Nearly half of the positive HWs reported no previous exposure to SARS-CoV-2-infected subjects and were diagnosed thanks to the proactive screening strategy implemented. IgG serology seems useful when performed at least two weeks after an RNA RT-PCR assay. IgM serology does not seem to be a useful test for the diagnosis of active SARS-CoV-2 infection. High awareness of SARS-CoV-2 infection is mandatory for all people, but especially for HWs, irrespective of symptoms, to safeguard their health and that of patients.


title: A study of the virulence in mice of high copying fidelity variants of human enterovirus 71

text: Abstract Polioviruses with a G64S mutation in the 3D polymerase have enhanced replication fidelity and are attenuated in animal models. Here we describe the mouse virulence properties of high replication fidelity 3D polymerase variants of human enterovirus 71 (HEV71), with mutations at positions 3D-S264L, 3D-G64R or at 3D-S264L plus 3D-G64R. Mouse-adapted strains (MP-G64R, MP-S264L and MP-S264L-G64R) were constructed in order to compare the virulence of the 3D polymerase variants with that of mouse-adapted parental virus (MP-26M). MP-S264L and MP-S264L-G64R were attenuated in mice (mean survival time 7.0 and 7.5 days p.i., respectively) compared to MP-G64R and MP-26M (mean survival time 6.5 and 6.0 days p.i., respectively). MP-26M and MP-G64R infection induced early onset, severe generalised necrotising myositis, whereas MP-S264L and MP-S264L-G64R infection induced a later onset, mild and focal skeletal muscle myositis. Our findings demonstrate that only the 3D-S264L mutation attenuates HEV71 in mice, suggesting that the high replication fidelity phenotype is not essential for virulence attenuation in this model.


title: Mutation in murine coronavirus replication protein nsp4 alters assembly of double membrane vesicles

text: Abstract Coronaviruses are positive-strand RNA viruses that replicate in the cytoplasm of infected cells by generating a membrane-associated replicase complex. The replicase complex assembles on double membrane vesicles (DMVs). Here, we studied the role of a putative replicase anchor, nonstructural protein 4 (nsp4), in the assembly of murine coronavirus DMVs. We used reverse genetics to generate infectious clone viruses (icv) with an alanine substitution at nsp4 glycosylation site N176 or N237, or an asparagine to threonine substitution (nsp4-N258T), which is proposed to confer a temperature sensitive phenotype. We found that nsp4-N237A is lethal and nsp4-N258T generated a virus (designated Alb ts6 icv) that is temperature sensitive for viral replication. Analysis of Alb ts6 icv-infected cells revealed that there was a dramatic reduction in DMVs and that both nsp4 and nsp3 partially localized to mitochondria when cells were incubated at the non-permissive temperature. These results reveal a critical role of nsp4 in directing coronavirus DMV assembly.


Commentary: Changing the equation by boosting the numerator


title: Effects of severe acute respiratory syndrome (SARS) coronavirus infection on peripheral blood lymphocytes and their subsets

text: Summary Introduction Severe acute respiratory syndrome (SARS) caused large outbreaks of atypical pneumonia in 2003, with the largest localized outbreak occurring in Beijing, China. Lymphopenia was prominent amongst the laboratory abnormalities reported in acute SARS. Methods The effect of SARS on peripheral blood lymphocytes and their subsets was examined in 271 SARS coronavirus-infected individuals. Results There was a significant decrease in the CD45+, CD3+, CD4+, CD8+, CD19+ and CD16+/56+ cell counts over the five weeks of the SARS illness although CD4+/CD8+ ratios did not change significantly. The lymphopenia was prolonged, reaching a nadir during days 7–9 in the second week of illness before returning towards normal after five weeks, with the lowest mean CD4+ cell count of 317 cells×106/L at day 7, and CD8+ cell count of 239 cells×106/L at day 8. Patients with more severe clinical illness, or patients who died, had significantly more profound CD4+ and CD8+ lymphopenia. Discussion Lymphopenia is a prominent part of SARS-CoV infection and lymphocyte counts may be useful in predicting the severity and clinical outcomes. Possible reasons for the SARS-associated lymphopenia may be direct infection of lymphocytes by SARS-CoV, lymphocyte sequestration in the lung or cytokine-mediated lymphocyte trafficking. There may also be immune-mediated lymphocyte destruction, bone marrow or thymus suppression, or apoptosis.


title: Real-time PCR compared to Binax NOW and cytospin-immunofluorescence for detection of influenza in hospitalized patients

text: Abstract Background Rapid tests have had a significant impact on influenza diagnosis, but more accurate tests are needed for hospitalized patients who test negative by rapid methods. Objective We sought to determine the increased yield obtained from influenza RT-PCR in hospitalized patients compared to two rapid methods. Study design Binax NOW, cytospin-enhanced direct immunofluoroescence (DFA), and influenza A and B multiplex TaqMan RT-PCR were performed on 237 clinical samples. Results Binax NOW detected 70 (53.0%), cytospin-DFA detected 127 (96.2%), and TaqMan RT-PCR detected 132 (100%) influenza-positive samples. The difference in sensitivity was significant between RT-PCR and Binax NOW (p <0.0001), but not between RT-PCR and cytospin-DFA (p =0.0736). Two samples testing positive for influenza B by all three methods, tested falsely positive for influenza A by Binax. Eight true positive samples did not become reactive by Binax until 30min, and thus were counted as negative. Conclusions The accuracy of real-time RT-PCR should greatly improve the diagnosis of influenza in hospitals using simple rapid flu tests, but may have a more modest impact in hospitals with expertise in cytospin-DFA. Further studies are needed to determine the effect of influenza RT-PCR on patient management and costs in hospitalized patients.


title: Acute lower respiratory infections in ≥5 year -old hospitalized patients in Cambodia, a low-income tropical country: clinical characteristics and pathogenic etiology

text: BACKGROUND: Few data exist on viral and bacterial etiology of acute lower respiratory infections (ALRI) in ≥5 year –old persons in the tropics. METHODS: We conducted active surveillance of community-acquired ALRI in two hospitals in Cambodia, a low-income tropical country. Patients were tested for acid-fast bacilli (AFB) by direct sputum examination, other bacteria by blood and/or sputum cultures, and respiratory viruses using molecular techniques on nasopharyngeal/throat swabs. Pulmonologists reviewed clinical/laboratory data and interpreted chest X-rays (CXR) to confirm ALRI. RESULTS: Between April 2007 - December 2009, 1,904 patients aged ≥5 years were admitted with acute pneumonia (50.4%), lung sequelae-associated ALRI (24.3%), isolated pleural effusions (8.9%) or normal CXR-related ALRI (17.1%); 61 (3.2%) died during hospitalization. The two former diagnoses were predominantly due to bacterial etiologies while viral detection was more frequent in the two latter diagnoses. AFB-positive accounted for 25.6% of acute pneumonia. Of the positive cultures (16.8%), abscess-prone Gram-negative bacteria (39.6%) and Haemophilus influenzae (38.0%) were most frequent, followed by Streptococcus pneumoniae (17.7%). Of the identified viruses, the three most common viruses included rhinoviruses (49.5%), respiratory syncytial virus (17.7%) and influenza viruses (12.1%) regardless of the diagnostic groups. Wheezing was associated with viral identification (31.9% vs. 13.8%, p < 0.001) independent of age and time-to-admission. CONCLUSIONS: High frequency of H. influenzae and S. pneumoniae infections support the need for introduction of the respective vaccines in the national immunization program. Tuberculosis was frequent in patients with acute pneumonia, requiring further investigation. The relationship between respiratory viruses and wheezing merits further studies.


title: Detection of new genetic variants of Betacoronaviruses in Endemic Frugivorous Bats of Madagascar

text: BACKGROUND: Bats are amongst the natural reservoirs of many coronaviruses (CoVs) of which some can lead to severe infection in human. African bats are known to harbor a range of pathogens (e.g., Ebola and Marburg viruses) that can infect humans and cause disease outbreaks. A recent study in South Africa isolated a genetic variant closely related to MERS-CoV from an insectivorous bat. Though Madagascar is home to 44 bat species (41 insectivorous and 3 frugivorous) of which 34 are endemic, no data exists concerning the circulation of CoVs in the island’s chiropteran fauna. Certain Malagasy bats can be frequently found in close contact with humans and frugivorous bats feed in the same trees where people collect and consume fruits and are hunted and consumed as bush meat. The purpose of our study is to detect and identify CoVs from frugivorous bats in Madagascar to evaluate the risk of human infection from infected bats. METHODS: Frugivorous bats belonging to three species were captured in four different regions of Madagascar. We analyzed fecal and throat swabs to detect the presence of virus through amplification of the RNA-dependent RNA polymerase (RdRp) gene, which is highly conserved in all known coronaviruses. Phylogenetic analyses were performed from positive specimens. RESULTS: From 351 frugivorous bats, we detected 14 coronaviruses from two endemic bats species, of which 13 viruses were identified from Pteropus rufus and one from Eidolon dupreanum, giving an overall prevalence of 4.5%. Phylogenetic analysis revealed that the Malagasy strains belong to the genus Betacoronavirus but form three distinct clusters, which seem to represent previously undescribed genetic lineages. CONCLUSIONS: Our findings suggest that CoVs circulate in frugivorous bats of Madagascar, demonstrating the needs to evaluate spillover risk to human populations especially for individuals that hunt and consume infected bats. Possible dispersal mechanisms as to how coronaviruses arrived on Madagascar are discussed.


title: Reducing transmission of COVID-19 using a continuous negative pressure operative field barrier during oral maxillofacial surgery

text: Oral and maxillofacial surgery in patients with suspected or confirmed COVID-19, presents a high risk of exposure and cross contamination to the operative room personnel. We designed, simulated and implemented a continue negative pressure operative field barrier to provide an additional layer of protection, using standard equipment readily available in most operative rooms during oral and maxillofacial procedures.


Religious tourism and mass religious gatherings — The potential link in the spread of COVID-19. Current perspective and future implications


title: Human Monocyte Subset Distinctions and Function: Insights From Gene Expression Analysis

text: Monocytes are a highly plastic innate immune cell population that displays significant heterogeneity within the circulation. Distinct patterns of surface marker expression have become accepted as a basis for distinguishing three monocyte subsets in humans. These phenotypic subsets, termed classical, intermediate and nonclassical, have also been demonstrated to differ in regard to their functional properties and disease associations when studied in vitro and in vivo. Nonetheless, for the intermediate monocyte subset in particular, functional experiments have yielded conflicting results and some studies point to further levels of heterogeneity. Developments in genetic sequencing technology have provided opportunities to more comprehensively explore the phenotypic and functional differences among conventionally-recognized immune cell subtypes as well as the potential to identify novel subpopulations. In this review, we summarize the transcriptomic evidence in support of the existence of three separate monocyte subsets. We also critically evaluate the insights into subset functional distinctions that have been garnered from monocyte gene expression analysis and the potential utility of such studies to unravel subset-specific functional changes which arise in disease states.


title: Pushing the limits of the scanning mechanism for initiation of translation

text: Abstract Selection of the translational initiation site in most eukaryotic mRNAs appears to occur via a scanning mechanism which predicts that proximity to the 5′ end plays a dominant role in identifying the start codon. This ‘position effect’ is seen in cases where a mutation creates an AUG codon upstream from the normal start site and translation shifts to the upstream site. The position effect is evident also in cases where a silent internal AUG codon is activated upon being relocated closer to the 5′ end. Two mechanisms for escaping the first-AUG rule – reinitiation and context-dependent leaky scanning – enable downstream AUG codons to be accessed in some mRNAs. Although these mechanisms are not new, many new examples of their use have emerged. Via these escape pathways, the scanning mechanism operates even in extreme cases, such as a plant virus mRNA in which translation initiates from three start sites over a distance of 900 nt. This depends on careful structural arrangements, however, which are rarely present in cellular mRNAs. Understanding the rules for initiation of translation enables understanding of human diseases in which the expression of a critical gene is reduced by mutations that add upstream AUG codons or change the context around the AUGSTART codon. The opposite problem occurs in the case of hereditary thrombocythemia: translational efficiency is increased by mutations that remove or restructure a small upstream open reading frame in thrombopoietin mRNA, and the resulting overproduction of the cytokine causes the disease. This and other examples support the idea that 5′ leader sequences are sometimes structured deliberately in a way that constrains scanning in order to prevent harmful overproduction of potent regulatory proteins. The accumulated evidence reveals how the scanning mechanism dictates the pattern of transcription – forcing production of monocistronic mRNAs – and the pattern of translation of eukaryotic cellular and viral genes.


title: Assessment of the Angolan (CHERRT) Mobile Laboratory Curriculum for Disaster and Pandemic Response

text: INTRODUCTION: As of April 5, 2020, the World Health Organization reported over one million confirmed cases and more than 62,000 confirmed coronavirus (COVID-19) deaths affecting 204 countries/regions. The lack of COVID-19 testing capacity threatens the ability of both the United States (US) and low middle income countries (LMIC) to respond to this growing threat, The purpose of this study was to assess the effectiveness through participant self-assessment of a rapid response team (RRT) mobile laboratory curriculum METHODS: We conducted a pre and post survey for the purpose of a process improvement assessment in Angola, involving 32 individuals. The survey was performed before and after a 14-day training workshop held in Luanda, Angola, in December 2019. A paired t-test was used to identify any significant change on six 7-point Likert scale questions with α< 0.05 (95% confidence interval). RESULTS: All six of the questions – 1) “I feel confident managing a real laboratory sample test for Ebola or other highly contagious sample;” 2) “I feel safe working in the lab environment during a real scenario;” 3) “I feel as if I can appropriately manage a potentially highly contagious laboratory sample;” 4)“I feel that I can interpret a positive or negative sample during a suspected contagious outbreak;” 5) “I understand basic Biobubble/mobile laboratory concepts and procedures;” and 6) “I understand polymerase chain reaction (PCR) principles” – showed statistical significant change pre and post training. Additionally, the final two questions – “I can more effectively perform my role/position because of the training I received during this course;” and “This training was valuable” – received high scores on the Likert scale. CONCLUSION: This Angolan RRT mobile laboratory training curriculum provides the nation of Angola with the confidence to rapidly respond and test at the national level a highly infectious contagion in the region and perform on-scene diagnostics. This mobile RRT laboratory provides a mobile and rapid diagnostic resource when epidemic/pandemic resource allocation may need to be prioritized based on confirmed disease prevalence.


title: High-throughput sequencing for the aetiologic identification of viral encephalitis, meningoencephalitis, and meningitis. A narrative review and clinical appraisal

text: Abstract Background Viral aetiologies are the most common cause of central nervous system (CNS) infections. Approximately one-half of CNS infections remain of undetermined origin. High-throughput sequencing (HTS) brought new perspectives to CNS infection investigations, allowing investigation of viral aetiologies with an unbiased approach. HTS use is still limited to specific clinical situations. Objectives The aim of this review was to evaluate the contribution and pitfalls of HTS for the aetiologic identification of viral encephalitis, meningoencephalitis, and meningitis in CNS patient samples. Sources PubMed was searched from 1 January 2008 to 2 August 2018 to retrieve available studies on the topic. Additional publications were included from a review of full-text sources. Content Among 366 studies retrieved, 29 used HTS as a diagnostic technique. HTS was performed in cerebrospinal fluid and brain biopsy samples of 307 patients, including immunocompromised, immunocompetent paediatric, and adult cases. HTS was performed retrospectively in 18 studies and prospectively in 11. HTS led to the identification of a potential causal virus in 41 patients, with 11 viruses known and ten not expected to cause CNS infections. Various HTS protocols were used. Implications The additional value of HTS is difficult to quantify because of various biases. Nevertheless, HTS led to the identification of a viral cause in 13% of encephalitis, meningoencephalitis, and meningitis cases in which various assays failed to identify the cause. HTS should be considered early in clinical management as a complement to routine assays. Standardized strategies and systematic studies are needed for the integration of HTS in clinical management.


title: COVID‐19 and the Canadian cattle/beef sector: Some preliminary analysis

text: Canada's cattle/beef sector has already weathered a shock after a 2003 case of BSE resulted in closed borders and industry restructuring. Now the sector has to adjust to similar shocks due to COVID‐19. This paper examines the supply chain from the consumer up to the cow‐calf producer by considering consumer reactions, labour market constraints, and supply response. A quarterly market model of North American cattle and beef markets is used to examine price and revenue impacts associated with the market disruptions. Depending on the scenario, there is considerable price and revenue suppression at all levels of the market. This article is protected by copyright. All rights reserved


title: Simultaneous quantitation of two orchid viruses by the TaqMan® real-time RT-PCR

text: Abstract Simultaneous quantitation of two orchid viruses, cymbidium mosaic potexvirus (CymMV) and odontoglossum ringspot tobamovirus (ORSV), were carried out using the TaqMan® real-time RT-PCR, a novel detection technique that combines RT-PCR with the power of fluorescent detection. Four TaqMan® probes were synthesized, targeting at the RNA-dependent RNA polymerase (RdRp) and coat protein (CP) genes of both viruses. The reporter dye FAM (6-carboxyfluorescein) was used to label the 5′ terminus of probes specific to CymMV, while TET (tetrachloro-6-carboxyfluorescein) was used for the ORSV probes. TAMRA (6-carboxy-tetramethyl-rhodamine), which was attached at the 3′ terminus of each probe, was used as the universal quencher. With increasing amounts of standard RNA templates, the respective threshold cycle (C T) values were determined and a linear relationship was established between these C T values and the logarithm of initial template amounts. The amounts of starting templates in mixed-infected Oncidium flowers and leaves were estimated from the standard curves. As little as 104 copies or 5 fg each of CymMV and ORSV could be detected simultaneously with either the RdRp or CP gene as the target. This system offers a sensitive, high throughput and rapid method for plant virus detection.


title: Implementation of an Elastomeric Mask Program as a Strategy to Eliminate Disposable N95 Mask Use and Resterilization: Results from a Large Academic Medical Center

text: BACKGROUND: The COVD-19 global pandemic has placed a large demand on personal protective equipment for healthcare workers. N-95 respirators, required to perform aerosolizing procedures, are in short supply and have increased significantly in cost. The lack of a clear end to the pandemic requires that hospitals need to create a long-term, cost effective solution to the N95 shortage. We initially used previously described methods to reuse and resterilize N95 masks however we found they did not solve the issues related to just in time fit-testing and cost. METHODS: We initiated a program with the aim to reduce our dependence on N95 masks by initiating a phased program to acquire industrial style elastomeric P100 masks as a substitute for reuse and resterilization of disposable N95s. We created an allocation strategy based on availability of the masks, as well as an operational plan to fit test, educate, and disinfect the masks. RESULTS: Within 1 month we were able to reduce the number of N95s needed by our network by 95%. We also found due that the cost was conservatively 10 times less per month than purchasing disposable N95s and the cost benefit increases the longer that they are needed. CONCLUSION: Establishing an elastomeric mask program is feasible and less expensive than programs focused on reusing and disinfecting disposable N95 masks. A well thought out elastomeric distribution and disinfection program does not pose greater operational challenges than an N95 reuse and resterilization program. In addition, elastomeric masks can be stored for future surges and should be considered an essential part of all healthcare facilities’ supply of personal protective equipment. Implementation of the program has eliminated our dependence on disposable N95s to maintain normal operations during the global pandemic.


title: Novel Corona Virus 2019 pneumonia in a kidney transplant recipient

text: COVID 19 pandemic is spreading worldwide and the impact of the disease in transplant patients is evolving. In this case report, we presented a 63 years old female kidney transplant recipient who presented with dyspnea and cough and diagnosed with COVID 19 pneumonia. On the 4(th) day of admission, the patient’s condition worsened. Therefore, the immunosuppressive medications were discontinued, and hydrocortisone started. The patient died on the 5(th) day.


title: Synthesis and biological evaluation of 2-oxonicotinonitriles and 2-oxonicotinonitrile based nucleoside analogues

text: Drug resistance and emergence of new pathogens highlight the need for developing new therapeutic agents. We focused on 2-oxonicotinonitrile (2-ONN) as derivative of the natural product 2-pyridinone. Herein, we describe the synthesis of 2-ONNs bearing two aryl groups, which we coupled with organohalides, including three glycosyl bromides, to prepare the nucleoside analogues. Coupling occurred mostly at the 2-ONN ring nitrogen to give the aimed targets, and in a few cases, it happened at the 2-oxo position giving O-alkylation products. Free 2-ONNs and their acetylated nucleosides were tested against a number of viruses. The nucleoside analogue 2a(Ac) showed good anti SARS-CoV and anti influenza A (H(5)N(1)) activities. Additionally, 7b had good activity against Gram positive bacterium, Bacillis subtilis.


title: Epidemic and molecular evolution of human bocavirus in hospitalized children with acute respiratory tract infection

text: Human bocavirus (HBoV) is a novel parvovirus, often associated with respiratory tract diseases in children. This study explored the epidemiological characteristics and molecular evolution of HBoV-1 in southeastern China. Nasopharyngeal aspirates were collected from children admitted to hospital with acute respiratory tract infections. HBoV-1 was detected using real-time reverse transcription polymerase chain reaction and further characterized by complete genome sequences analysis. Among the 3,022 recruited children, 386 (12.77 %) were HBoV-1-positive and 300 (77.72 %) had co-detection with other respiratory viruses. Seasonal prevalence peaked in summer. HBoV-1 presence was significantly associated with asthma attack [odds ratio = 1.74; 95 % confidence interval: 1.30, 2.31; p < 0.001]. Similar results were obtained when either single detection or co-detection of HBoV-1 was considered, demonstrating the minor impact of co-detection on the clinical characteristics or epidemic pattern. Phylogenetic analysis based on the complete genome sequences showed that all the HBoV-1 sequences clustered together and no branch was formed that was supported by bootstrap value ≥750. The overall evolutionary rate of the complete genome of HBoV-1 was estimated at 1.08 × 10(−4) nucleotide substitutions per site per year (s/s/y) [95 % highest probability density: (0.40–1.86) × 10(−4) s/s/y]. Selective pressure analysis showed that all the ω-values were less than 1, suggesting that HBoV-1 was under negative selective pressure. Site-by-site analysis identified the codon site 40 of the VP1 gene under positive selection. In conclusion, our study disclosed the epidemiological and genetic dynamics of HBoV-1 epidemics in southeastern China in the most recent 3 years, the information of which might help to further improve our understanding of HBoV-1 infection and guide better surveillance and control strategies in the future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10096-014-2215-7) contains supplementary material, which is available to authorized users.


title: Effect of the Wet Market on the coronavirus disease (COVID-19) transmission dynamics in China, 2019-2020

text: Abstract Objectives The novel coronavirus (SARS-CoV-2) originating from Wuhan rapidly spread throughout China. While its origin remains uncertain, accumulating evidence links a wet market for the early SARS-CoV-2 spread in Wuhan. Similarly, the influence of the marketplace on the early transmission dynamics is yet to be investigated. Methods Using the daily series of COVID-19 incidence stratified according to contact history with the market, we have conducted quantitative modeling analyses to estimate the reproduction numbers (R) for the market-to-human and human-to-human transmission, the reporting probability and the early effects of public health interventions. Results We estimated R at 0.24 (95%CrI: 0.01-1.38) for market-to-human transmission, and 2.37 (95%CrI: 2.08-2.71) for human-to-human transmission during the early spread in China (2019-2020). Moreover, we estimated that the reporting rate for cases stemming from market-to-human transmission was 2-34 fold higher than that for cases stemming from human-to-human transmission, suggesting that contact history with the wet market played a key role in identifying COVID-19 cases. Conclusions Our R estimate tied to market-to-human transmission has substantial uncertainty, but it was significantly lower compared to the reproduction number driving human-to-human transmission. Our results also suggest that asymptomatic and subclinical infections constitute a substantial component of the COVID-19 morbidity burden.


title: Influence of infection on exacerbations of multiple sclerosis

text: Exacerbations of multiple sclerosis (MS) are triggered by exogenous events, the best documented being viral upper respiratory infections (URIs), which can stimulate secretion of cytokines such as interferon‐γ (IFN‐γ) by immune cells. In conjunction with a recent clinical trial of systemic interferon‐β (IFN‐β) in relapsing–remitting MS, we studied the occurrence of viral infections and their correlation with MS attacks. Thirty patients kept daily logs, noting URI symptoms in themselves, family members, and co‐workers. Patients were examined every 3 months, or whenever an attack of MS occurred, and were tested for antibodies to common upper respiratory pathogens. A strong correlation was found between MS attacks and URIs. There were 168 URIs in 2,792 patient‐weeks, including 996 weeks at risk (the interval beginning 1 week before and ending 5 weeks after onset of URI symptoms) and 1,796 weeks not at risk. Nearly two‐thirds of attacks occurred in periods at risk. Attack rates were 2.92 per year in weeks at risk compared to 1.16 per year in weeks not at risk, a significant difference (p ≤ 0.001). High‐dose interferon reduced the frequency of MS attacks, but had no effect on the number of URIs. Although a specific virus could not be incriminated, we concluded that URIs of presumed viral origin are an important trigger of MS attacks, and that treatment with IFN‐β reduces the attack rate, but not by preventing URIs. Rather, it may modulate responses to viral infection that would otherwise lead to immune activation and clinical symptoms.


title: Impact of the first month of Covid 19 lockdown on oncologic surgical activity in the Ile de France region university hospital otorhinolaryngology departments

text: Abstract Objective: To evaluate the impact of the first month of lockdown related to the Covid 19 epidemic on the oncologic surgical activity in the Ile de France region university hospital otorhinolaryngology departments. Material and Methods: A multicenter prospective observational assessment was conducted in 6 university hospital otorhinolaryngology departments (Paris Centre, Nord, Est and Sorbonne) during the 1-month periods before (Month A) and after (Month B) lockdown on March 17, 2020. The main goal was to evaluate lockdown impact on oncologic surgical activity in the departments. Secondary goals were to report population characteristics, surgery conditions, postoperative course, progression of Covid status in patients and surgeons, and adverse events. Results: 224 procedures were performed. There was 10.9 % reduction in overall activity, without significant difference between departments. Squamous cell carcinoma and larynx, hypopharynx, oropharynx, oral cavity and nasal cavity and sinus locations were predominant, at 79% and 75.8 % of cases respectively, with no significant differences between months. T3/4 and N2/3 tumors were more frequent in Month B (p = .002 and .0004). There was no significant difference between months regarding surgical approach, type of reconstruction, postoperative course, tracheotomy and nasogastric feeding-tube time, intensive care stay or hospital stay. None of the Month A patients were Covid-19-positive, versus 3 in Month B, without adverse events. None of the otorhinolaryngologists involved in the procedures developed symptoms suggesting Covid-19 infestation. Conclusion: The present study underscored the limited impact of the Covid-19 epidemic and lockdown on surgical diagnosis and cancer surgery in the Ile de France university otorhinolaryngology departments, maintaining chances for optimal survival without spreading the virus.


title: A Review of Pediatric Critical Care in Resource-Limited Settings: A Look at Past, Present, and Future Directions

text: Fifteen years ago, United Nations world leaders defined millenium development goal 4 (MDG 4): to reduce under-5-year mortality rates by two-thirds by the year 2015. Unfortunately, only 27 of 138 developing countries are expected to achieve MDG 4. The majority of childhood deaths in these settings result from reversible causes, and developing effective pediatric emergency and critical care services could substantially reduce this mortality. The Ebola outbreak highlighted the fragility of health care systems in resource-limited settings and emphasized the urgent need for a paradigm shift in the global approach to healthcare delivery related to critical illness. This review provides an overview of pediatric critical care in resource-limited settings and outlines strategies to address challenges specific to these areas. Implementation of these tools has the potential to move us toward delivery of an adequate standard of critical care for all children globally, and ultimately decrease global child mortality in resource-limited settings.


title: Temperature in Nursing Home Residents Systematically Tested for SARS-CoV-2

text: Abstract Objectives Many nursing home residents infected with SARS-CoV-2 fail to be identified with standard screening for the associated COVID-19 syndrome. Current nursing home COVID-19 screening guidance includes assessment for fever defined as a temperature of at least 38.0°C. The objective of this study is to describe the temperature changes before and after universal testing for SARS-CoV-2 in nursing home residents. Design Cohort study Setting and Participants: The Veterans Administration (VA) operates 134 Community Living Centers (CLC), similar to nursing homes, that house residents who cannot live independently. VA guidance to CLCs directed daily clinical screening for COVID-19 that included temperature assessment. Measures All CLC residents (n=7325) underwent SARS-CoV-2 testing. We report the temperature in window of the 14 days before and after universal SARS-CoV-2 testing among CLC residents. Baseline temperature was calculated for 5 days prior to the study window. Results SARS-CoV-2 was identified in 443 (6.0%) residents. The average maximum temperature in SARS-CoV-2 positive residents was 37.66 (0.69) compared to 37.11 (0.36) (p=0.001) in SARS-CoV-2 negative residents. Temperatures in those with SARS-CoV-2 began rising 7 days prior to testing and remained elevated during the 14-day follow up. Among SARS-CoV-2 positive residents, only 26.6% (n=118) met the fever threshold of 38.0°C during the survey period. Most residents (62.5%, n=277) with confirmed SARS-CoV-2 did experience two or more 0.5°C elevations above their baseline values. One cohort of SARS-CoV-2 residents’ (20.3%, n=90) temperatures never deviated >0.5°C from baseline. Conclusions and Implications A single screening for temperature is unlikely to detect nursing home residents with SARS-CoV-2. Repeated temperature measurement with a patient-derived baseline can increase sensitivity. The current fever threshold as a screening criteria for SARS-CoV-2 infection should be reconsidered.


title: High-throughput Detection of Respiratory Pathogens in Animal Specimens by Nanoscale PCR

text: Nanoliter scale real-time PCR uses spatial multiplexing to allow multiple assays to be run in parallel on a single plate without the typical drawbacks of combining reactions together. We designed and evaluated a panel based on this principle to rapidly identify the presence of common disease agents in dogs and horses with acute respiratory illness. This manuscript describes a nanoscale diagnostic PCR workflow for sample preparation, amplification, and analysis of target pathogen sequences, focusing on procedures that are different from microliter scale reactions. In the respiratory panel presented, 18 assays were each set up in triplicate, accommodating up to 48 samples per plate. A universal extraction and pre-amplification workflow was optimized for high-throughput sample preparation to accommodate multiple matrices and DNA and RNA based pathogens. Representative data are presented for one RNA target (influenza A matrix) and one DNA target (equine herpesvirus 1). The ability to quickly and accurately test for a comprehensive, syndrome-based group of pathogens is a valuable tool for improving efficiency and ergonomics of diagnostic testing and for acute respiratory disease diagnosis and management.


title: Cytomegalovirus Pneumonia: Community-Acquired Pneumonia in Immunocompetent Hosts

text: Cytomegaloviruses (CMVs) are DNA viruses and are members of the Herpesviridae family. Morphologically, CMV resembles other herpes viruses, particularly herpes simplex viruses, with important cytopathic differences. CMVs are recognized pathogens that cause community-acquired pneumonia (CAP) in compromised hosts, such as, those who undergo transplants and those on immunosuppressive drugs or steroids. This article discusses the clinical presentation, diagnosis, and therapy for this viral CAP.


title: Applying Theory of Planned Behavior to Predict Nurses' Intention and Volunteering to Care for Sars Patients in Southern Taiwan

text: Severe acute respiratory syndrome (SARS) spread worldwide after an outbreak in Guangdong Province, China, in mid-November 2002. Health care workers were at highest risk of infection. The purpose of this study, which was based on Ajzen's theory of planned behavior (TPB), was to determine the extent to which personal attitudes, subjective norms, and perceived control influence nurses' intention and volunteering to care for SARS patients. After the SARS outbreak, a total of 750 staff nurses (response rate 90%) at one hospital completed a questionnaire assessing their intention to provide care to SARS patients. Overall, 42.7% of nurses had a positive intention to provide care to SARS patients, and 25.4% of nurses would volunteer to care for SARS patients. Four factors explaining 35% of the variance in nurses' intention to care for SARS patients were self-efficacy (β = 0.39, p < 0.001), attitude (β = 0.25, p < 0.001), years of working in the study hospital (β = −0.15, p < 0.001), and receiving resources from the hospital (β = 0.13, p < 0.001). Two factors explaining 15% of the variance in nurses' volunteering to care for SARS patients were intention (β = 0.31, p < 0.001) and attitude (β = 0.15, p < 0.001). The final model shows that the variables of the TPB contributed significantly to the explanation of a portion of variance in nurses' intention and volunteering to care for SARS patients. The results are helpful for human resources managers facing a new contagious disease.


COVID‑19: Current Knowledge and Best Practices for Orthopaedic Surgeons


title: Viral RNA in Blood as Indicator of Severe Outcome in Middle East Respiratory Syndrome Coronavirus Infection

text: We evaluated the diagnostic and clinical usefulness of blood specimens to detect Middle East respiratory syndrome coronavirus infection in 21 patients from the 2015 outbreak in South Korea. Viral RNA was detected in blood from 33% of patients at initial diagnosis, and the detection preceded a worse clinical course.


title: Clinical evaluation of an immunochromatographic IgM/IgG antibody assay and chest computed tomography for the diagnosis of COVID-19

text: Abstract Background We evaluated the clinical performance of an immunochromatographic (IC) IgM/IgG antibody assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and chest computed tomography (CT) for the diagnosis of Coronavirus disease 2019 (COVID-19). Methods We examined 139 serum specimens collected from 112 patients with COVID-19 and 48 serum specimens collected from 48 non-COVID-19 patients. The presence of IgM/IgG antibody for SARS-CoV2 was determined using the One Step Novel Coronavirus (COVID-19) IgM/IgG Antibody Test. Chest CT was performed in COVID-19 patients on admission. Findings Of the139 COVID-19 serum specimens, IgM was detected in 27.8%, 48.0%, and 95.8% of the specimens collected within 1 week, 1-2 weeks, and >2 weeks after symptom onset and IgG was detected in 3.3%, 8.0%, and 62.5%, respectively. Among the 48 non-COVID-19 serum specimens, 1 generated a false-positive result for IgM. Thirty-eight of the 112 COVID-19 patients were asymptomatic, of whom 15 were positive for IgM, and 74 were symptomatic, of whom 22 were positive for IgM and 7 were positive for IgG. The diagnostic sensitivity of CT scan alone and in combination with the IC assay was 57.9 % (22/38) and 68.4% (26/38) for the asymptomatic patients and 74.3% (55/74) and 82.4% (61/74) for the symptomatic patients, respectively. Conclusion The IC assay had low sensitivity during the early phase of infection, and thus IC assay alone is not recommended for initial diagnostic testing for COVID-19. If RT-qPCR is not available, the combination of chest CT and IC assay may be useful for diagnosing COVID-19.


title: Autonomous Tetramerization Domains in the Glycan-binding Receptors DC-SIGN and DC-SIGNR

text: Multivalent binding of glycans on pathogens and on mammalian cells by the receptors DC-SIGN (CD209) and DC-SIGNR (L-SIGN, CD299) is dependent on correct disposition of the C-type carbohydrate-recognition domains projected at the C-terminal ends of necks at the cell surface. In the work reported here, neck domains of DC-SIGN and DC-SIGNR expressed in isolation are shown to form tetramers in the absence of the CRDs. Stability analysis indicates that interactions between the neck domains account fully for the stability of the tetrameric extracellular portions of the receptors. The neck domains are approximately 40% α-helical based on circular dichroism analysis. However, in contrast to other glycan-binding receptors in which fully helical neck regions are intimately associated with C-terminal C-type CRDs, the neck domains in DC-SIGN and DC-SIGNR act as autonomous tetramerization domains and the neck domains and CRDs are organized independently. Neck domains from polymorphic forms of DC-SIGNR that lack some of the repeat sequences show modestly reduced stability, but differences near the C-terminal end of the neck domains lead to significantly enhanced stability of DC-SIGNR tetramers compared to DC-SIGN.


title: Paediatric ethical issues during the COVID‐19 pandemic are not just about ventilator triage

text: Administrators and providers worry about an overwhelming shortage in critical life-saving ventilators for adults during the COVID-19 pandemic. Attention has focused on developing algorithms for ventilator allocation using several factors, including: pre-existing illness, likelihood to return to baseline health, and length of ventilation (a negative factor in adults) (1). These factors, however, do not easily translate to pediatric medicine nor does ventilator allocation represent an urgent crisis for pediatric medicine.


title: ROLE OF REHABILITATION DEPARTMENT FOR ADULT COVID-19 PATIENTS: THE EXPERIENCE OF THE SAN RAFFAELE HOSPITAL OF MILAN

text: Abstract The rapid evolution of the health emergency linked to the spread of SARS-CoV-2 requires specifications for the rehabilitative management of COVID-19 patients. The symptomatic evolution of COVID-19 patients is characterized by two phases: an acute phase in which respiratory symptoms prevail, and a post-acute phase in which patients can show symptoms related to prolonged immobilization, to previous and current respiratory dysfunctions as well as cognitive and emotional disorders. There is thus the need for specialized rehabilitative care for these patients. This communication reports the experience of the San Raffaele Hospital of Milan (Italy) and recommends the set-up of specialized clinical pathways for the rehabilitation of COVID-19 patients. In this hospital, between February 1st and March 2nd 2020, about 50 patients were admitted every day with COVID-19 symptoms. In those days, about 400 acute care beds were created (Intensive Care/Infectious Diseases). In the following 30 days, from March 2nd to mid-April, despite the presence of 60 daily arrivals to the ER, the organization of patient flow between different wards was modified and several different units were created based on a more accurate integration of patients’ needs. According to this new organization, patients were admitted first to acute care COVID-19 units, and then to COVID-19 rehabilitation units, post-COVID-19 rehabilitation units and/or quarantine/observation units. After hospital discharge, telemedicine was used to follow-up with patients at home. Such clinical pathways should each involve dedicated multidisciplinary teams composed of pulmonologists, physiatrists, neurologists, cardiologists, physiotherapists, neuropsychologists, occupational therapists, speech therapists and nutritionists.


title: MMWR summary: COVID‐19 reports

text: This month’s MMWR selections summarize several recent observations related to COVID‐19 infection.


title: Comparing early outbreak detection algorithms based on their optimized parameter values

text: Abstract Background Many researchers have evaluated the performance of outbreak detection algorithms with recommended parameter values. However, the influence of parameter values on algorithm performance is often ignored. Methods Based on reported case counts of bacillary dysentery from 2005 to 2007 in Beijing, semi-synthetic datasets containing outbreak signals were simulated to evaluate the performance of five outbreak detection algorithms. Parameters’ values were optimized prior to the evaluation. Results Differences in performances were observed as parameter values changed. Of the five algorithms, space–time permutation scan statistics had a specificity of 99.9% and a detection time of less than half a day. The exponential weighted moving average exhibited the shortest detection time of 0.1 day, while the modified C1, C2 and C3 exhibited a detection time of close to one day. Conclusion The performance of these algorithms has a correlation to their parameter values, which may affect the performance evaluation.


Making brochure of Coronavirus disease (COVID‐19) for children with autism spectrum disorder and their family members


title: Estimation of transmission parameters of a fluoroquinolone-resistant Escherichia coli strain between pigs in experimental conditions

text: Antimicrobial resistance is of primary importance regarding public and animal health issues. Persistence and spread of resistant strains within a population contribute to the maintenance of a reservoir and lead to treatment failure. An experimental trial was carried out to study the horizontal transmission of a fluoroquinolone-resistant Escherichia coli strain from inoculated to naïve pigs. All naïve contact pigs had positive counts of fluoroquinolone-resistant E. coli after only two days of contact. Moreover, re-infections of inoculated pigs caused by newly contaminated animals were suspected. A maximum likelihood method, based on a susceptible-infectious-susceptible (SIS) model, was used to determine the transmission parameters. Two transmission levels were identified depending on the quantity of bacteria shed by infected individuals: (i) low-shedders with bacterial counts of resistant E. coli in the faeces between 5*10(3 )and 10(6 )CFU/g (β(L )= 0.41 [0.27; 0.62]), (ii) high shedders with bacterial counts above 10(6 )CFU/g (β(H )= 0.98 [0.59; 1.62]). Hence, transmission between animals could be pivotal in explaining the persistence of resistant bacteria within pig herds.


title: RNA interference inhibits hepatitis E virus mRNA accumulation and protein synthesis in vitro

text: Abstract Hepatitis E virus (HEV) is a zoonotic pathogen to which several species, including human beings, pigs and rodents, are reported to be susceptible. To date, vaccines developed against HEV still need to be improved and a structural gene (ORF2), which encodes a capsid protein with high sequence conservation found across HEV genotypes, is a potential candidate. To exploit the possibility of using RNA interference (RNAi) as a strategy against HEV infection, four small interference RNA (siRNA) duplex targeting ORF2 gene were constructed. A challenge against HEV infection by RNAi was performed in A549 cells. Real-Time quantitative polymerase chain reaction (Real-Time qPCR) and Western blot assay demonstrated that four HEV specific siRNAs (si-ORF2-1, si-ORF2-2, si-ORF2-3 and si-ORF2-4) were capable of protecting cells against HEV infection with very high specificity and efficiency. The results suggest that RNAi is a potent anti-HEV infection prophylaxis strategy.


title: Molecular Pathogenesis Lessons from the World of Infectious Diseases Research

text: This Guest Editorial introduces this month's special Infectious Disease Theme Issue, a series of reviews focusing on the molecular pathogenic processes of four representative pathogens, including two bacteria (brucellae and Staphylococcus aureus), a virus (influenza), and a parasite (Trypanosoma cruzi).


title: Interleukin-6 induction in vitro in mouse brain endothelial cells and astrocytes by exposure to mouse hepatitis virus (MHV-4, JHM)

text: Abstract Interleukin-6 (IL-6) induction, as detected by bioassay and Northern analysis, was examined in vitro in endothelial cells or astrocytes derived from BALB/c (susceptible) or SJL (resistant) mice following exposure to mouse hepatitis virus (MHV-4) or UV inactivated MHV-4 (UV-MHV-4). In BALB/c endothelial cells, up to 16-fold more IL-6 (> 640 U/ml) was induced, compared to SJL cells which showed a minimal response (40 U/ml), relative to basal levels (< 20 U/ml). In contrast, both BALB/c and SJL astrocytes showed a substantial IL-6 response to MHV-4 and UV-MHV-4 exposure, although a strain difference persisted. Despite strain and cell specific differences in released IL-6, equivalent levels of IL-6 mRNA were induced in all cell types following exposure to MHV-4 or UV-MHV-4.


title: The Benefits and Costs of Using Social Distancing to Flatten the Curve for COVID-19

text: We examine the net benefits of social distancing to slow the spread of COVID-19 in USA. Social distancing saves lives but imposes large costs on society due to reduced economic activity. We use epidemiological and economic forecasting to perform a rapid benefit–cost analysis of controlling the COVID-19 outbreak. Assuming that social distancing measures can substantially reduce contacts among individuals, we find net benefits of about $5.2 trillion in our benchmark case. We examine the magnitude of the critical parameters that might imply negative net benefits, including the value of statistical life and the discount rate. A key unknown factor is the speed of economic recovery with and without social distancing measures in place. A series of robustness checks also highlight the key role of the value of mortality risk reductions and discounting in the analysis and point to a need for effective economic stimulus when the outbreak has passed.


title: The Role of Chest Imaging in Patient Management during the COVID-19 Pandemic: A Multinational Consensus Statement from the Fleischner Society

text: Abstract With more than 900,000 confirmed cases worldwide and nearly 50,000 deaths during the first three months of 2020, the COVID-19 pandemic has emerged as an unprecedented healthcare crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, healthcare delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and healthcare workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. While mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography (CXR) and computed tomography (CT) are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pre-test probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing COVID-19 patients across a spectrum of healthcare environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based upon the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of CXR and CT in the management of COVID-19.


title: Primate lentiviruses are differentially inhibited by interferon-induced transmembrane proteins

text: Abstract Interferon-induced transmembrane (IFITM) proteins inhibit the entry of a large number of viruses. Not surprisingly, many viruses are refractory to this inhibition. In this study, we report that different strains of HIV and SIV are inhibited by human IFITM proteins to various degrees, with SIV of African green monkeys (SIVAGM) being mostly restricted by human IFITM2. Interestingly, SIVAGM is as much inhibited by human IFITM2 as by IFITM3 of its own host African green monkeys. Our data further demonstrate that the entry of SIVAGM is impaired by human IFITM2 and that this inhibition is overcome by the cholesterol-binding compound amphotericin B that also overcomes IFITM inhibition of influenza A viruses. These results suggest that IFITM proteins exploit similar mechanisms to inhibit the entry of both pH-independent primate lentiviruses and the pH-dependent influenza A viruses.


title: Infecciones virales graves en pacientes inmunocompetentes

text: Viruses play a significant role in serious infections in adults and sometimes lead to the need for hospitalization and admission to intensive care units, especially in cases of severe respiratory distress or encephalopathy. Influenza and parainfluenza viruses, syncytial respiratory virus, herpes viruses and adenovirures are the most frequent causes of these severe infections. A review of the literature has been performed in order to update the epidemiology, pathogenesis and therapeutic approach of viral infections affecting immunocompetent patients. Furthermore, ventilator-associated pneumonia (VAP) is the most frequent nosocomial infection in intensive care units and has a high morbidity and mortality rate. It is mainly a bacterial disease, although the potential role of viruses as pathogens or copathogens in VAP is under discussion. Therefore, a brief review of the potential pathogenic role of viruses in VAP has also been performed.


title: Structure-based screening of novel lichen compounds against SARS Coronavirus main protease (Mpro) as potentials inhibitors of COVID-19

text: ABSTRACT: The outbreak of SARS-CoV-2 and deaths caused by it all over the world have imposed great concern on the scientific community to develop potential drugs to combat Coronavirus disease-19 (COVID-19). In this regard, lichen metabolites may offer a vast reservoir for the discovery of antiviral drug candidates. Therefore, to find novel compounds against COVID-19, we created a library of 412 lichen compounds and subjected to virtual screening against the SARS-CoV-2 Main protease (Mpro). All the ligands were virtually screened, and 27 compounds were found to have high affinity with Mpro. These compounds were assessed for drug-likeness analysis where two compounds were found to fit well for redocking studies. Molecular docking, drug-likeness, X-Score, and toxicity analysis resulting in two lichen compounds, Calycin and Rhizocarpic acid with Mpro-inhibiting activity. These compounds were finally subjected to molecular dynamics simulation to compare the dynamics behavior and stability of the Mpro after ligand binding. The binding energy was calculated by MM-PBSA method to determine the intermolecular protein–ligand interactions. Our results showed that two compounds; Calycin and Rhizocarpic acid had the binding free energy of − 42.42 kJ mol/1 and − 57.85 kJ mol/1 respectively as compared to reference X77 (− 91.78 kJ mol/1). We concluded that Calycin and Rhizocarpic acid show considerable structural and pharmacological properties and they can be used as hit compounds to develop potential antiviral agents against SARS-CoV-2. These lichen compounds may be a suitable candidate for further experimental analysis. GRAPHIC ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11030-020-10118-x) contains supplementary material, which is available to authorized users.


title: Knowledge and attitude towards the Middle East respiratory syndrome coronavirus among healthcare personnel in the southern region of Saudi Arabia

text: Abstract Introduction Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to the family Coronaviridae, and is named for the crown-like spikes on its surface. The clinical presentation of MERS-CoV infection ranges from asymptomatic to very severe disease, and the classical presentation includes fever, cough chills, sore throat, myalgia, and arthralgia. Methods A cross-sectional study of 339 healthcare personnel was conducted over an 8-month period in the Aseer region of Saudi Arabia using a structured survey that included demographic information and questions testing participant’s knowledge. Results Approximately two-thirds of the respondents properly identified the causative agent of MERS-CoV as an RNA virus (66.4%, n=225) that is enveloped (68.1%, n=231). On the other hand, few respondents identified the proper number of strains or the genus (16.5% and 17.4%, respectively). More than half of the study sample identified the disease as zoonotic (57.2%, n=194). Similarly, 89.1% (n=302) identified that camels and bats are prone to infection with coronaviruses. Only 23.9% (n=81) properly identified March through May as the season with the highest transmission rate. There was a massive lack of adequate knowledge regarding prevalence of antibodies. Only 18.3% (n=62) of respondents identified PCR as the proper diagnostic confirmatory test for MERS-CoV infection. Regarding MERS-CoV clinical features, 76.4% (n=259) recognized the presence of sub-clinical infection, 64.7% (n=218) indicated that cases should be immediately isolated, and 46.9% (n=159) identified the main cause of mortality as respiratory failure. Conclusions There is limited microbiological and virological knowledge of MERS-CoV infection among healthcare personnel in the southern region of Saudi Arabia, although the clinical aspects are known.


Research and Funding in the Time of COVID‐19: Conversations with Gary Pierzynski of The Ohio State University and Scott Angle of USDA‐NIFA


title: Importance of respiratory airway management as well as psychological and rehabilitative treatments to COVID-19 patients

text: Abstract The clinical therapy for severe 2019 coronavirus disease (i.e., COVID-19) sufferers is relatively challenging. Herein, the processes involving salvage of a critical COVID-19 patient were retrospectively analyzed. The condition of an obese female critical COVID-19 sufferer progressively worsened in the initial period after admission. According to her symptoms and examination reports, endotracheal intubation and mechanical ventilation were timely conducted and meanwhile high-dose sedatives and analgesics were administrated. In the later therapeutic phase, however, sedative and analgesic dosages were gradually reduced, and psychological and rehabilitative therapies were conducted, concomitantly with enhancement of airway care to facilitate sputum expectoration. Eventually, the endotracheal tube was feasibly removed after intubation for 18 days and subsequently replaced with noninvasive ventilation and a high-flow nasal cannula oxygen therapy. Intensive airway care alongside psychological and rehabilitative therapies can shorten the mechanical ventilation time and improve the prognosis of COVID-19 sufferers.


title: Feline calicivirus and other respiratory pathogens in cats with Feline calicivirus-related symptoms and in clinically healthy cats in Switzerland

text: BACKGROUND: Cats with feline calicivirus (FCV)-related symptoms are commonly presented to veterinary practitioners. Various clinical manifestations have been attributed to FCV, i.e. upper respiratory tract disease (URTD), oral ulcerations, gingivostomatitis, limping syndrome and virulent systemic disease. Additionally, healthy cats can shed FCV. The aims of this study were 1) to investigate the frequency of FCV in cats with FCV-related symptoms and in healthy cats in Switzerland, 2) to assess risk and protective factors for infection, such as signalment, housing conditions, vaccination, and co-infection with URTD-associated pathogens, and 3) to address the association between clinical symptoms and FCV infection. RESULTS: Oropharyngeal, nasal and conjunctival swabs were collected in 24 veterinary practices from 200 FCV-suspect and 100 healthy cats originating from 19 cantons of Switzerland. The samples were tested for FCV using virus isolation and reverse-transcription real-time quantitative polymerase chain reaction (qPCR) and for feline herpesvirus-1 (FHV-1), Mycoplasma felis, Chlamydophila felis, Bordetella bronchiseptica using real-time qPCR. Within the two populations (FCV-suspect/healthy), the observed PCR prevalences were: FCV 45 %/8 %, FHV-1 20 %/9 %, C. felis 8 %/1 %, B. bronchiseptica 4 %/2 %, M. felis 47 %/31 % and any co-infections thereof 40 %/14 %. Based on multivariable regression models amongst FCV-suspect cats (odds ratio [95 % confidence interval]), co-infection with M. felis (1.75 [0.97; 3.14]), group housing (2.11 [1.02; 4.34]) and intact reproductive status (1.80 [0.99; 3.28]) were found to be risk factors for FCV infection. In healthy cats, intact reproductive status (22.2 [1.85; 266.7]) and group housing (46.4 [5.70; 377.7]) were found to be associated with FCV infection. Based on an univariable approach, FCV-suspect cats were found to be significantly less often FCV-positive when vaccinated (0.48 [0.24; 0.94]). Oral ulcerations, salivation, gingivitis and stomatitis, but not classical signs of URTD were significantly associated with FCV infection (all p < 0.001). CONCLUSIONS: FCV was detected in less than half of the cats that were judged FCV-suspect by veterinary practitioners. For a clinical diagnosis, FCV-related symptoms should be revisited. FCV infection was present in some healthy cats, underlining the importance of asymptomatic carriers in FCV epidemiology. To reduce FCV-related problems in multi-cat environments, reduction of group size in addition to the generally recommended vaccination are advocated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0595-2) contains supplementary material, which is available to authorized users.


title: Development and evaluation of an enzyme-linked immunosorbent assay for detection of antibodies against the spike protein of SARS-coronavirus

text: Abstract Background: Severe acute respiratory syndrome (SARS) is caused by infection with SARS-associated coronavirus (CoV). Amino acid residues 450–650 of the spike (S) glycoprotein of SARS-CoV (S450-650) contains dominant epitopes for anti-viral antibodies (Abs) in patient sera. Objectives: To develop and evaluate an ELISA system for detection of anti-S Abs in patient sera. Study design: Express recombinant S450-650 in E. Coli and evaluate the sensitivity and specificity of an ELISA system based on the S450-650 polypeptide. Results: The S450-650-based ELISA detected IgG Abs in 41 out of 51 serum samples from 22 hospitalized patients with probable SARS, a result closely correlated with that obtained with a virus-based ELISA (r =0.75, k =0.8). Differential anti-S IgG responses were observed amongst SARS patients. Some of them produced anti-S Abs early during their infection, while others failed to make IgG Abs against the S450-650 polypeptide. None of the serum samples from 100 healthy blood donors was positive in the S450-650-based assay. Conclusion: The S450-650-based ELISA can detect anti-S IgG Abs with high sensitivity and specificity.


title: Rhinovirus-Infected Epithelial Cells Produce More IL-8 and RANTES Compared With Other Respiratory Viruses

text: PURPOSE: The environmental factors human rhinoviruses (HRVs) and house dust mites (HDMs) are the most common causes of acute exacerbations of asthma. The aim of this study was to compare the chemokine production induced by HRVs in airway epithelial cells with that induced by other respiratory viruses, and to investigate synergistic interactions between HRVs and HDMs on the induction of inflammatory chemokines in vitro. METHODS: A549 human airway epithelial cells were infected with either rhinovirus serotype 7, respiratory syncytial virus (RSV)-A2 strain, or adenovirus serotype 3 and analyzed for interleukin (IL)-8 and regulated on activation, normal T-cell expressed and secreted (RANTES) release and mRNA expression. Additionally, activation of nuclear factor (NF)-κB and activator protein (AP)-1 were evaluated. The release of IL-8 and RANTES was also measured in cells stimulated simultaneously with a virus and the HDM allergen, Der f1. RESULTS: HRV caused greater IL-8 and RANTES release and mRNA expression compared with either RSV or adenovirus. NF-κB and AP-1 were activated in these processes. Cells incubated with a virus and Der f1 showed an increased IL-8 release. However, compared with cells incubated with virus alone as the stimulator, only HRV with Der f1 showed a statistically significant increase. CONCLUSIONS: IL-8 and RANTES were induced to a greater extent by HRV compared with other viruses, and only HRV with Der f1 acted synergistically to induce bronchial epithelial IL-8 release. These findings may correspond with the fact that rhinoviruses are identified more frequently than other viruses in cases of acute exacerbation of asthma.


title: Passively acquired challenge immunity to enterotropic coronavirus in mice

text: Maternally-derived passive immunity of infant mice to challenge infection with enterotropic coronavirus mouse hepatitis virus strain Y (MHV-Y) was studied. Pups born to both naive and immune dams, but nursed by naive foster dams, were susceptible to infection, while naive or immune pups nursed by immune foster dams were protected. The MHV infectious dose was identical among naive pups inoculated at 1, 2, 3, or 4 weeks of age. Pups nursing immune dams resisted infection when inoculated at 1, 2, or 3 weeks of age. Three week old pups were protected only if they were allowed access to their immune dams. Pups born to MHV immune dams 4 in consecutive litters acquired equal MHV IgG titers in serum and whey and were all protected against challenge infection. Only pups actively ingesting immune whey at the time of or within two hours after virus inoculation were effectively protected. Pups born to dams immunized by oral inoculation with live MHV acquired both MHV-specific IgA and IgG in their whey, while pups born to dams immunized with killed virus acquired only IgG. Both IgA and IgG, but not IgG alone, were required for complete protection.


title: COVID-19 pandemic: Impacts on the air quality during the partial lockdown in São Paulo state, Brazil

text: Abstract In early March 2020, the World Health Organization declared the COVID-19 as a pandemic, and in late March 2020 partial lockdown was ordered by the São Paulo State government. The aim of this study was to assess impacts on air quality in São Paulo – Brazil, during the partial lockdown implemented to provide social distancing required due to the COVID-19 pandemic. We have analyzed data from four air quality stations in São Paulo, Brazil to assess air pollutant concentration variations during the partial lockdown. Data were compared to the five-year monthly mean and to the four-week before the partial lockdown. Overall, drastic reductions on NO (up to −77.3%), NO2 (up to −54.3%), and CO (up to −64.8%) concentrations were observed in the urban area during partial lockdown compared to the five-year monthly mean. By contrast, an increase of approximately 30% in ozone concentrations was observed in urban areas highly influenced by vehicle traffic, probably related to nitrogen monoxide decreases. Although the partial lockdown has contributed to a positive impact on air quality, it is important to take into account the negative impacts on social aspects, considering the deaths caused by COVID-19 and also the dramatic economic effects.


title: Sustained meticillin-resistant Staphylococcus aureus control in a hyper-endemic tertiary acute care hospital with infrastructure challenges in Singapore

text: Summary Background Meticillin-resistant Staphylococcus aureus (MRSA) has been entrenched in Singapore hospitals since the 1980s, with an excess of 600 non-duplicate cases of infections (120 bacteraemia episodes) each year in our 995-bed university hospital. Approximately 5% of our hospital beds are used as isolation facilities. Aim To study the impact of an MRSA control bundle that was implemented via gradual geographic extension across hospital wards. Methods The bundle included active surveillance on admission and transfer/discharge to identify ward-based acquisition of MRSA, isolation and cohorting of MRSA-infected patients, enhanced hand hygiene initiatives, and publicly displayed feedback of MRSA acquisition and hand hygiene compliance rates. Implementation was between October 2006 and June 2010 in order to provide lead-time for the incremental development of infrastructural capacity, and to develop an ethic of infection prevention among staff. Results were analysed via interrupted time-series analysis. Findings MRSA infections fell midway through the implementation, with MRSA bacteraemia declining from 0.26 [95% confidence interval (CI): 0.18–0.34] cases per 1000 inpatient-days in the first quarter of 2004 to 0.11 (95% CI: 0.07–0.19) cases per 1000 inpatient-days in the first quarter of 2012. MRSA acquisition rates fell a year after the programme had been fully implemented, whereas hand hygiene compliance rose significantly from 47% (95% CI: 44–49) in the first quarter of 2009 to 69% (95% CI: 68–71) in the first quarter of 2012. Conclusion Successful staged implementation of an MRSA bundle in a hyper-endemic setting is sustainable and represents a model that may be adapted for similar settings.


title: Treatment with convalescent plasma for critically ill patients with SARS-CoV-2 infection

text: Abstract As of March 24, 2020, novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for 379,661 infection cases with 16,428 deaths globally and the number is still increasing rapidly. Herein, we presented four critically ill patients with SARS-CoV-2 infection who received supportive care and convalescent plasma. Although all the four patients (including a pregnant woman) recovered from SARS-CoV-2 infection eventually, randomized trials are needed to eliminate the effect of other treatments and investigate the safety and efficacy of convalescent plasma therapy.


title: COVID-19 – the role of mass gatherings

text: Abstract Mass gathering (MG) medicine emerged against the backdrop of the 2009 pandemic H1N1 Public Health Emergency of International Concern (PHEIC) when the Kingdom of Saudi Arabia (KSA) hosted the largest annual mass gathering of over 3 million pilgrims from 180 plus countries. However, the events surrounding the latest threat to global health, the PHEIC COVID-19, may be sufficient to highlight the role of mass gatherings, mass migration, and other forms of dense gatherings of people on the emergence, sustenance, and transmission of novel pathogens. The COVID-19 spread illustrates the role of MGs in exacerbation of the scope of pandemics. Cancellation or suspension of MGs would be critical to pandemic mitigation. It is unlikely that medical countermeasures are available during the early phase of pandemics. Therefore, mitigation of its impact, rather than containment and control becomes a priority during pandemics. As the most systematically studied MG-related respiratory disease data come from KSA, the cancellation of Umrah by the KSA authorities, prior to emergence of cases, provide the best opportunity to develop mathematical models to quantify event cancellations related mitigation of COVID-19 transmission in KSA and to the home countries of pilgrims. COVID-19 has already provided examples of both clearly planned event cancellations such as the Umrah suspension in KSA, and where outbreaks and events were continued.


title: COVID-19 and routine childhood immunization in Africa: leveraging systems thinking and implementation science to improve immunization system performance

text: Abstract One of the routine health services that is being disrupted by coronavirus disease 2019 (COVID-19) in Africa is childhood immunization. This is because the immunization system relies on functioning health facilities and stable communities to be effective. Its disruption increases the risk of epidemics of vaccine-preventable diseases which can increase child mortality. Therefore, policymakers must quickly identify robust and context-specific strategies to rapidly scale-up routine immunization in order to mitigate the impact of COVID-19 on their national immunization performance. To achieve this, we propose a paradigm shift towards systems thinking and use of implementation science in immunization decision making. Systems thinking can inform a more nuanced and holistic understanding of the interrelationship that between COVID-19, its control strategies and childhood immunization. Tools like causal loop diagrams can be used to explicitly illustrate the systems structure by identifying the feedback loops. Once mapped and leverage points for interventions have been identified, implementation science can be used to guide the rapid uptake and utilization of multifaceted evidence-based innovations in complex practice settings. As Africa re-strategize for the post-2020 era, these emerging fields can contribute significantly in accelerating progress towards universal access to vaccines for all children on the continent despite COVID-19.


Management of acute ischemic stroke in patients with COVID-19 infection: Insights from an international panel


title: The impact of news exposure on collective attention in the United States during the 2016 Zika epidemic

text: In recent years, many studies have drawn attention to the important role of collective awareness and human behaviour during epidemic outbreaks. A number of modelling efforts have investigated the interaction between the disease transmission dynamics and human behaviour change mediated by news coverage and by information spreading in the population. Yet, given the scarcity of data on public awareness during an epidemic, few studies have relied on empirical data. Here, we use fine-grained, geo-referenced data from three online sources – Wikipedia, the GDELT Project and the Internet Archive – to quantify population-scale information seeking about the 2016 Zika virus epidemic in the U.S., explicitly linking such behavioural signal to epidemiological data. Geolocalized Wikipedia pageview data reveal that visiting patterns of Zika-related pages in Wikipedia were highly synchronized across the United States and largely explained by exposure to national television broadcast. Contrary to the assumption of some theoretical models, news volume and Wikipedia visiting patterns were not significantly correlated with the magnitude or the extent of the epidemic. Attention to Zika, in terms of Zika-related Wikipedia pageviews, was high at the beginning of the outbreak, when public health agencies raised an international alert and triggered media coverage, but subsequently exhibited an activity profile that suggests nonlinear dependencies and memory effects in the relation between information seeking, media pressure, and disease dynamics. This calls for a new and more general modelling framework to describe the interaction between media exposure, public awareness and disease dynamics during epidemic outbreaks.


title: Sequence analysis of malacoherpesvirus proteins: Pan-herpesvirus capsid module and replication enzymes with an ancient connection to “Megavirales”

text: Abstract The order Herpesvirales includes animal viruses with large double-strand DNA genomes replicating in the nucleus. The main capsid protein in the best-studied family Herpesviridae contains a domain with HK97-like fold related to bacteriophage head proteins, and several virion maturation factors are also homologous between phages and herpesviruses. The origin of herpesvirus DNA replication proteins is less well understood. While analyzing the genomes of herpesviruses in the family Malacohepresviridae, we identified nearly 30 families of proteins conserved in other herpesviruses, including several phage-related domains in morphogenetic proteins. Herpesvirus DNA replication factors have complex evolutionary history: some are related to cellular proteins, but others are closer to homologs from large nucleocytoplasmic DNA viruses. Phylogenetic analyses suggest that the core replication machinery of herpesviruses may have been recruited from the same pool as in the case of other large DNA viruses of eukaryotes.


title: The epidemiology and severity of respiratory viral infections in a tropical country: Ecuador, 2009–2016

text: Abstract Background Respiratory viral infections (RVI) are a leading cause of mortality worldwide. We compared the epidemiology and severity of RVI in Ecuador during 2009–2016. Methods Respiratory specimens collected within the national surveillance system were tested for influenza viruses, respiratory syncytial virus (RSV), adenovirus, parainfluenza virus, and human metapneumovirus. Overall and virus-specific positive detection rate (PDR) were calculated and compared the timing of epidemics caused by the different viruses. Logistic regression models were used to compare the age distribution and risk of death across respiratory viruses. Results A total of 41,172 specimens were analyzed: influenza (PDR=14.3%) and respiratory syncytial virus (RSV) (PDR=9.5%) were the most frequently detected viruses. Influenza epidemics typically peaked in December–January and RSV epidemics in March; seasonality was less evident for the other viruses. Compared to adults, children were more frequently infected with RSV, adenovirus, parainfluenza, and influenza B, while the elderly were less frequently infected with influenza A(H1N1)p. The age-adjusted risk of death was highest for A(H1N1)p (odds ratio [OR] 1.73, 95% confidence intervals [CI] 1.38–2.17), and lowest for RSV (OR 0.75, 95%CI 0.57–0.98). Conclusions Whilst influenza and RSV were the most frequently detected pathogens, the risk of death differed by RVI, being highest for pandemic influenza and lowest for RSV.


title: Role of the C-type lectins DC-SIGN and L-SIGN in Leishmania interaction with host phagocytes

text: Abstract Leishmaniasis is a parasitic disease that courses with cutaneous or visceral clinical manifestations. The amastigote stage of the parasite infects phagocytes and modulates the effector function of the host cells. Our group has described that the interaction between Leishmania and immature monocyte-derived dendritic cells (DCs) takes place through dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN), a C-type lectin that specifically recognizes fungal, viral and bacterial pathogens. The DC-SIGN-mediated recognition of Leishmania amastigotes does not induce DC maturation, and the DC-SIGN ligand/s on Leishmania parasites is/are still unknown. We have also found that the DC-SIGN-related molecule L-SIGN, specifically expressed in lymph node and liver sinusoidal endothelial cells, acts as a receptor for L. infantum, the parasite responsible for visceral leishmaniasis, but does not recognize L. pifanoi, which causes the cutaneous form of the disease. Therefore, DC-SIGN and L-SIGN differ in their ability to interact with Leishmania species responsible for either visceral or cutaneous leishmaniasis. A deeper knowledge of the parasite-C-type lectin interaction may be helpful for the design of new DC-based therapeutic vaccines against Leishmania infections.


title: Infectious bronchitis virus variants: a review of the history, current situation and control measures

text: The history, current situation and control measures for infectious bronchitis virus (IBV) variants are reviewed. A large number of IBV variants exist worldwide; some being unique to a particular area, others having a more general distribution. The possible reasons why some strains spread readily over major parts of the world, whereas other strains stay more localized are discussed. The advantages and disadvantages of strain classification by protectotyping, serotyping and genotyping are discussed in relation to in vivo protection. The different vaccination strategies are also considered.


Low ambient temperatures are associated with more rapid spread of COVID-19 in the early phase of the endemic


title: Prediction of guilt and shame proneness based on disruption to psychological contract: A new light for corruption prevention

text: Amid controversy over plurality and contestation of the meanings of corruption, previous reviews and studies showed that proneness to moral emotions, i.e. shame and guilt, can predict one's corruption behavior. To give a theoretical basis for the efforts of preventing corruption that is thick with emotional nuance, this present study employs disruption to psychological contract, i.e. psychological contract breach (PCB), as a predictor of moral emotions proneness. The study involving 265 employees (169 males, 96 females; M(age) = 32.32 years old; SD(age) = 7.28 years) of four big private banks in Jakarta, the capital city of Indonesia, shows that PCB—with noting that, in this study, its scale operational scoring represents, reversely, the contract fulfillment—can predict Guilt-negative behavior evaluation (Guilt-NBE), Guilt-repair (Guilt-REP), and Shame-negative self-evaluation (Shame-NSE); all in negative directions, proved via simple linear regression analyses. Further analysis showed a more dynamic relationship between PCB and Guilt-NBE that fits to a cubic regression model. This study contributes to the axiological aspect of business psychology, especially in the ethical psychology of banking industry.


title: Simulation‐based estimation of the early spread of COVID‐19 in Iran: actual versus confirmed cases

text: Understanding the state of the COVID‐19 pandemic relies on infection and mortality data. Yet official data may underestimate the actual cases due to limited symptoms and testing capacity. We offer a simulation‐based approach which combines various sources of data to estimate the magnitude of outbreak. Early in the epidemic we applied the method to Iran's case, an epicenter of the pandemic in winter 2020. Estimates using data up to March 20th, 2020, point to 916,000 (90% UI: 508 K, 1.5 M) cumulative cases and 15,485 (90% UI: 8.4 K, 25.8 K) total deaths, numbers an order of magnitude higher than official statistics. Our projections suggest that absent strong sustaining of contact reductions the epidemic may resurface. We also use data and studies from the succeeding months to reflect on the quality of original estimates. Our proposed approach can be used for similar cases elsewhere to provide a more accurate, early, estimate of outbreak state. © 2020 System Dynamics Society


title: Virus-like particles: The new frontier of vaccines for animal viral infections

text: Abstract Vaccination continues to be the main approach to protect animals from infectious diseases. Until recently, all licensed vaccines were developed using conventional technologies. Subunit vaccines are, however, gaining attention from researchers in the field of veterinary vaccinology, and among these, virus-like particles (VLPs) represent one of the most appealing approaches. VLPs are robust protein cages in the nanometer range that mimic the overall structure of the native virions but lack the viral genome. They are often antigenically indistinguishable from the virus from which they were derived and present important advantages in terms of safety. VLPs can stimulate strong humoral and cellular immune responses and have been shown to exhibit self-adjuvanting abilities. In addition to their suitability as a vaccine for the homologous virus from which they are derived, VLPs can also be used as vectors for the multimeric presentation of foreign antigens. VLPs have therefore shown dramatic effectiveness as candidate vaccines. Here, we review the current status of VLPs as a vaccine technology in the veterinary field, and discuss the potential advantages and challenges of this technology.


title: Role of mechanical ventilation in the airborne transmission of infectious agents in buildings

text: Infectious disease outbreaks and epidemics such as those due to SARS, influenza, measles, tuberculosis, and Middle East respiratory syndrome coronavirus have raised concern about the airborne transmission of pathogens in indoor environments. Significant gaps in knowledge still exist regarding the role of mechanical ventilation in airborne pathogen transmission. This review, prepared by a multidisciplinary group of researchers, focuses on summarizing the strengths and limitations of epidemiologic studies that specifically addressed the association of at least one heating, ventilating and/or air‐conditioning (HVAC) system‐related parameter with airborne disease transmission in buildings. The purpose of this literature review was to assess the quality and quantity of available data and to identify research needs. This review suggests that there is a need for well‐designed observational and intervention studies in buildings with better HVAC system characterization and measurements of both airborne exposures and disease outcomes. Studies should also be designed so that they may be used in future quantitative meta‐analyses.


Immune mechanisms and the gut


title: A short review of bioaerosol emissions from gas bioreactors: Health threats, influencing factors and control technologies

text: Abstract Bioaerosols have widely been a concern due to their potential harm to human health caused by the carrying and spreading of harmful microorganisms. Biofiltration has been generally used as a green and effective technology for processing VOCs. However, bioaerosols can be emitted into the atmosphere as secondary pollutants from the biofiltration process. This review presents an overview of bioaerosol emissions from gas bioreactors. The mechanism of bioaerosols production and the effect of biofiltration on bioaerosol emissions were analyzed. The results showed that the bioaerosol emission concentrations were generally exceeded 104 CFU m−3, which would damage to human health. Biomass, inlet gas velocity, moisture content, temperature, and some other factors have significant influences on bioaerosol emissions. Moreover, as a result of the analysis done herein, different inactivation technologies and microbial immobilization of bioaerosols were proposed and evaluated as a potential solution for reducing bioaerosols emissions. The purpose of this paper is to make more people realize the importance of controlling the emissions of bioaerosols in the biofiltration process and to make the treatment of VOCs by biotechnology more environmentally friendly. Additionally, the present work intends to increase people’s awareness in regards to the control of bioaerosols, including microbial fragment present in bioaerosols.


title: Low serum 25‐hydroxyvitamin D (25[OH]D) levels in patients hospitalised with COVID‐19 are associated with greater disease severity

text: OBJECTIVES: Vitamin D deficiency (VDD) has been proposed to play a role in Coronavirus Disease 2019 (COVID‐19) pathophysiology. We aim to evaluate our implementation of a local protocol for treatment of VDD among patients hospitalized for COVID‐19; to assess the prevalence of VDD among COVID‐19 inpatients, and examine potential associations with disease severity and fatality. DESIGN AND PARTICIPANTS: We conducted a retrospective interim audit of a local clinical care pathway for 134 inpatients with COVID‐19. Prevalence of VDD, compliance with local treatment protocol and relationship of baseline serum 25(OH)D with markers of COVID‐19 severity and fatality were analysed. RESULTS: 55.8% of eligible patients received Colecalciferol replacement, albeit not all according to the suggested protocol. Patients admitted to ITU were younger than those managed on medical wards (61.1 years ± 11.8 vs. 76.4 years ± 14.9, respectively, p<0.001), with greater prevalence of hypertension, higher baseline respiratory rate, National Early Warning Score‐2 and C‐Reactive protein level. While mean serum 25(OH)D levels were comparable (p=0.3), only 19% of ITU patients had 25(OH)D levels greater than 50 nmol/L vs. 39.1% of non‐ITU patients (p=0.02). However, there was no association with fatality, potentially due to small sample size and prompt diagnosis and treatment of VDD. CONCLUSIONS: Higher prevalence of VDD was observed in patients requiring ITU admission compared to patients managed on medical wards. Larger prospective studies and/or clinical trials are needed to validate and extend our observations.


title: Non-tuberculous Mycobacteria can Cause Disseminated Mycobacteriosis in Cats

text: Summary Mycobacteriosis caused by non-tuberculous mycobacteria (NTM) is a rising concern in human medicine both in immunocompromised and immunocompetent patients. In cats, mycobacteriosis caused by NTM is considered mostly to be a focal or dermal infection, with disseminated disease mostly caused by Mycobacterium avium. We describe three cases of disseminated mycobacteriosis in cats, caused by Mycobacterium malmoense, Mycobacterium branderi/shimoidei and M. avium, with no identified underlying immunosuppression. In all cases, extracellular mycobacteria were seen in the pulmonary epithelium, intestinal lumen and glomerular tufts, which could affect the shedding of the organism. The present study highlights the importance of mycobacteriosis as a differential even in immunocompetent animals. Considering the close relationship of owners and pets and the potential presence of free mycobacteria in secretions, cats should be considered as a possible environmental reservoir for mycobacteria.


title: Synthesis and antiviral evaluation of acyclic azanucleosides developed from sulfanilamide as a lead structure

text: Abstract The acyclic azanucleosides with 2-, 3-, or 4-aminobenzenesulfonyl function at the nitrogen atom of the sugar mimic were prepared by coupling of 2-, 3-, or 4-nitro-N-(2-pivaloyloxyethyl)-N-(pivaloyloxymethyl)benzenesulfonamide with the silylated pyrimidine nucleobases followed by the reduction of the nitro group with sodium dithionite in aqueous solution or the palladium-catalysed transfer hydrogenation. The azanucleosides were evaluated for, but found to be devoid of, activity against several RNA- and DNA-viruses in vitro.


title: Quality control implementation for universal characterization of DNA and RNA viruses in clinical respiratory samples using single metagenomic next-generation sequencing workflow

text: In recent years, metagenomic Next-Generation Sequencing (mNGS) has increasingly been used for an accurate assumption-free virological diagnosis. However, the systematic workflow evaluation on clinical respiratory samples and implementation of quality controls (QCs) is still lacking. A total of 3 QCs were implemented and processed through the whole mNGS workflow: a notemplate-control to evaluate contamination issues during the process; an internal and an external QC to check the integrity of the reagents, equipment, the presence of inhibitors, and to allow the validation of results for each sample. The workflow was then evaluated on 37 clinical respiratory samples from patients with acute respiratory infections previously tested for a broad panel of viruses using semi-quantitative real-time PCR assays (28 positive samples including 6 multiple viral infections; 9 negative samples). Selected specimens included nasopharyngeal swabs (n = 20), aspirates (n = 10), or sputums (n = 7). The optimal spiking level of the internal QC was first determined in order to be sufficiently detected without overconsumption of sequencing reads. According to QC validation criteria, mNGS results were validated for 34/37 selected samples. For valid samples, viral genotypes were accurately determined for 36/36 viruses detected with PCR (viral genome coverage ranged from 0.6% to 100%, median = 67.7%). This mNGS workflow allowed the detection of DNA and RNA viruses up to a semi-quantitative PCR Ct value of 36. The six multiple viral infections involving 2 to 4 viruses were also fully characterized. A strong correlation between results of mNGS and real-time PCR was obtained for each type of viral genome (R2 ranged from 0.72 for linear single-stranded (ss) RNA viruses to 0.98 for linear ssDNA viruses). Although the potential of mNGS technology is very promising, further evaluation studies are urgently needed for its routine clinical use within a reasonable timeframe. The approach described herein is crucial to bring standardization and to ensure the quality of the generated sequences in clinical setting. We provide an easy-to-use single protocol successfully evaluated for the characterization of a broad and representative panel of DNA and RNA respiratory viruses in various types of clinical samples.