title: Literature-related discovery: Potential treatments and preventatives for SARS

text: Abstract Literature-related discovery (LRD) is the linking of two or more previously disjoint concepts in order to produce novel, interesting, plausible, and intelligible connections (i.e., potential discovery). LRD has been used to identify potential treatments or preventative actions for challenging medical problems, among myriad other applications. Severe acute respiratory syndrome (SARS) was the first pandemic of the 21st century. SARS was eventually controlled through increased hygienic measures (e.g., face mask protection, frequent hand washing, living quarter disinfection), travel restrictions, and quarantine. According to recent reviews of SARS, none of the drugs that were used during the pandemic worked. For the present paper, SARS was selected as the first application of LRD to an infectious disease. The main goal of this research was to identify non-drug non-surgical treatments that would 1) prevent the occurrence, or 2) reduce the progression rate, or 3) stop/reverse the progression of SARS. The MeSH taxonomy of Medline was used to restrict potential discoveries to selected semantic classes, and to identify potential discoveries efficiently. To enhance the volume of potential discovery, databases were used in addition to Medline. These included the Science Citation Index (SCI) and, in contrast to previous work, a full text database. Because of the richness of the full text, ‘surgical’ queries were developed that targeted the exact types of potential discovery of interest while eliminating clutter more efficiently.


Geographical overlap between alpha-1 antitrypsin deficiency and COVID-19 infection in Italy: casual or causal?


title: Isolation and identification of a variant subtype G 2b porcine epidemic diarrhea virus and S gene sequence characteristic

text: Abstract Porcine epidemic diarrhea (PED) which is caused by porcine epidemic diarrhea virus (PEDV), is an intestinal communicable disease. In recent years, though pigs have been immunized with the vaccines in pig farms, PED still broke out and caused severe economic losses to the swine industry in the northeast China. In this study, the sample was positive for PEDV variant strains via the nano-nest PCR. The strain was successfully isolated from positive samples and was serially passaged in Vero-E6 cells. In addition, the strain was identified via electron microscopy observation, indirect immunofluorescence assay and infection experiment in newborn piglets and named PEDV CH/JLDH/2016 strain (Accession No. MF346935). Phylogenetic analysis of the S gene showed that the CH/JLDH/2016 strain was clustered into G2b subgroup. Comparing with the CV777 vaccine strain, amino acid sequence analysis of CH/JLDH/2016 strain showed that 15 nucleotides were inserted and 9 were absent in S gene, whose amino acid sequence it educed insertions of 5 amino acids(58NQGX61 and 145N) and absences of 3 amino acids(164RD165 and 1204Y). Our strain, in the SS2 epitope have no amino acid, variant while in SS6 epitope, Y changed into S in 776th amino acid. The results indicated that PEDV G2b variant strains have been emerged in Jilin province. The identification of new types of PEDV variant strains would stimulate the development of effective vaccines for the prevention and control of PED. The novel vaccines that based on these newly identified PEDV variant strains may contribute to the control of PED outbreaks in China.


title: Protein Kinase C subtype δ interacts with Venezuelan equine encephalitis virus capsid protein and regulates viral RNA binding through modulation of capsid phosphorylation

text: Protein phosphorylation plays an important role during the life cycle of many viruses. Venezuelan equine encephalitis virus (VEEV) capsid protein has recently been shown to be phosphorylated at four residues. Here those studies are extended to determine the kinase responsible for phosphorylation and the importance of capsid phosphorylation during the viral life cycle. Phosphorylation site prediction software suggests that Protein Kinase C (PKC) is responsible for phosphorylation of VEEV capsid. VEEV capsid co-immunoprecipitated with PKCδ, but not other PKC isoforms and siRNA knockdown of PKCδ caused a decrease in viral replication. Furthermore, knockdown of PKCδ by siRNA decreased capsid phosphorylation. A virus with capsid phosphorylation sites mutated to alanine (VEEV CPD) displayed a lower genomic copy to pfu ratio than the parental virus; suggesting more efficient viral assembly and more infectious particles being released. RNA:capsid binding was significantly increased in the mutant virus, confirming these results. Finally, VEEV CPD is attenuated in a mouse model of infection, with mice showing increased survival and decreased clinical signs as compared to mice infected with the parental virus. Collectively our data support a model in which PKCδ mediated capsid phosphorylation regulates viral RNA binding and assembly, significantly impacting viral pathogenesis.


title: Health risks to air travelers

text: With focused pretravel counseling and intervention, travelers can be prepared to avoid many risks of in-flight problems. Travel medicine practitioners can include appropriate guidance for in-flight health and safety in discussions during pretravel visits.


title: Chapter 9. Educational process

text: PURPOSE: To provide recommendations and standard operating procedures (SOPs) for intensive care unit (ICU) and hospital preparations for an influenza pandemic or mass disaster with focus on education of all stakeholders, specifically the emergency executive control groups, ICU staff and staff co-opted to assist with patient management. METHODS: Based on a literature review and expert opinion, a Delphi process was used to define the essential topics, including staff education. RESULTS: Key recommendations include: (1) define functional roles and responsibilities of the internal personnel and interface agencies or sectors; (2) determine logistic support and requirements necessary for the effective implementation of the SOPs; (3) determine what is required to maintain the SOPs; (4) recommended training and activities include: (a) personal protection techniques; (b) environmental contamination; (c) medical management; (d) laboratory specimens; (e) alert lists; (f) training of recruited staff; (g) ethical issues; (h) psychosocial issues; (i) dealing with the deceased; (j) policies for restricting visitors; (k) mechanisms for enforcing policies; (5) Training should begin as soon as possible with daily demonstrations followed by supervised practice; (6) identify the staff to participate in training programs, verify that they have participated and evaluate their knowledge subsequently. CONCLUSIONS: Judicious planning and adoption of protocols for staff education are necessary to optimize outcomes during a pandemic.


Prior Evidence of Putative Novel Rhinovirus Species, Australia


title: Leven na covid-19

text: Besmetting met het coronavirus kan leiden tot de ziekte covid-19. Zodra de patiënt aan de beterende hand is, dringt de vraag zich op wanneer hij coronavrij is en welke klachten hij kan overhouden aan covid-19.


title: Evaluation of the effects of oral colostrum supplementation during the first fourteen days on the health and performance of preweaned calves

text: Abstract Increasing concerns about antimicrobial resistance have led to the development and implementation of alternatives to antimicrobial use in animal production. The objective of this clinical trial was to determine the effect of colostrum supplementation of the milk replacer ration on morbidity, mortality, feed intake, and weight gain of preweaned calves. Ninety 1-d-old calves on each of 3 commercial calf ranches were randomly allocated to 1 of 3 groups. Treatment-group calves received 10g of supplemental immunoglobulin G (IgG) in the form of 70g of colostrum powder in the milk replacer twice daily for 14 d. The placebo-group calves received a nutritionally equivalent supplement lacking IgG in the milk replacer twice daily for 14 d. Control calves received milk replacer without supplements twice daily. Calves were housed in individual hutches and were weighed on d 1, 28, and 60. Serum was collected on d 2 for serum IgG determination. Daily health evaluations for the first 28 d of life were performed by study personnel blinded to treatment group assignment. Observed illness was treated based on health assessment, rectal temperature, and specific calf ranch protocols. Feed consumption (milk and grain) was recorded. Calves receiving supplemental colostrum had less diarrhea and received fewer antimicrobial treatments than control and placebo calves. The results indicated that calf diarrhea was associated with low serum IgG levels and low-weight calves. Grain consumption and weight gain over the first 28 d of life were significantly greater in colostrum-supplemented calves compared with control calves. No differences in mortality or respiratory disease incidence among groups were detected. Supplemental colostrum during the first 2 wk of life can reduce diarrheal disease in preweaned calves on calf ranches and thereby reduce the amount of antimicrobial treatments needed.


title: Life in Epidemics: Infections Change, Front-Line Docs Remain the Same

text: Physicians working in the era of coronavirus 2019 (COVID-19) have proven as heroic as those who faced acquired immunodeficiency syndrome (AIDS) a generation ago.


title: Thousands of New York MH professionals volunteer for service

text: Considered the U.S. epicenter of the COVID‐19 pandemic with more than 67,000 cases reported last month and increasing steadily, New York state is embracing the more than 6,000 mental health professionals who have heeded the call to volunteer to help residents in emotional stress from COVID‐19.


title: Twenty years of cell-penetrating peptides: from molecular mechanisms to therapeutics

text: The recent discovery of new potent therapeutic molecules that do not reach the clinic due to poor delivery and low bioavailability have made of delivery a key stone in therapeutic development. Several technologies have been designed to improve cellular uptake of therapeutic molecules, including cell-penetrating peptides (CPPs). CPPs were first discovered based on the potency of several proteins to enter cells. Numerous CPPs have been described so far, which can be grouped into two major classes, the first requiring chemical linkage with the drug for cellular internalization and the second involving formation of stable, non-covalent complexes with drugs. Nowadays, CPPs constitute very promising tools for non-invasive cellular import of cargo and have been successfully applied for in vitro and in vivo delivery of therapeutic molecules varying from small chemical molecule, nucleic acids, proteins, peptides, liposomes and particles. This review will focus on the structure/function and cellular uptake mechanism of CPPs in the general context of drug delivery. We will also highlight the application of peptide carriers for the delivery of therapeutic molecules and provide an update of their clinical evaluation. This article is part of a themed section on Vector Design and Drug Delivery. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009


title: The Impact of Infection on Population Health: Results of the Ontario Burden of Infectious Diseases Study

text: BACKGROUND: Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting. METHODOLOGY/PRINCIPAL FINDINGS: We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005–2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization. CONCLUSIONS/SIGNIFICANCE: Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.


title: Complete genome sequence analysis of a predominant infectious bronchitis virus (IBV) strain in China

text: Infectious bronchitis (IB) is one of the major diseases in poultry flocks all over the world caused by infectious bronchitis virus (IBV). In the study, the complete genome sequence of strain A2 was sequenced and analyzed, which was a predominant IBV strain in China. The results indicated that there were mutations, insertions, and deletions distributed in the whole genome. The A2 virus had the highest identity to S14 and BJ in terms of full genome, whereas had a further distance to Massachusetts strains. Phylogenetic analysis showed that A2 isolate clustered together with most Chinese strains. The results of this study suggest that strain A2 may play an important role in IBV’s evolution and A2-like IBVs are predominant strains in China.


title: Low viral loads and lymphoid organ spheroids are associated with yellow head virus (YHV) tolerance in whiteleg shrimp Penaeus vannamei

text: Summary Yellow head virus (YHV) is an invertebrate nidovirus that has caused mass mortality in penaeid shrimp since 1990. Several YHV types are known, but only the original type (YHV-type 1 or YHV-1) is highly virulent. Most studies have focused on acute YHV-1 infections and there is limited work on YHV-1 survivors. We compared moribund and surviving (14%) whiteleg shrimp Penaeus (Litopenaeus) vannamei from an experimental challenge with YHV-1. Although grossly normal, all survivors were positive for YHV-1 by specific, reverse transcriptase polymerase chain reaction (RT-PCR) assays, histological analysis or transmission electron microscopy (TEM), indicating that they were not resistant but tolerant to YHV-1. On the other hand, real-time PCR analysis revealed that mean YHV-1 copies/ng total RNA for survivors (2.8×104±6.9×104) were approximately 40 times lower (P<0.05) than those in moribund shrimp (1.2×106±6.7×105 copies/ng total RNA). This was confirmed by strong positive immunohistochemical and in situ hybridization (ISH) reactions for YHV-1 in lymphoid organ tubules (LOT) of moribund shrimp and weak positive reaction only in lymphoid organ spheroids (LOS) of survivors. TEM revealed morphologically complete YHV virions in both groups. Furthermore, immuno-TEM and Western blot analysis revealed that YHV-1 structural proteins gp116 and p20 were present at comparable reactive levels in each group. Thus, YHV-1 tolerance was not associated with absence of gp116 as previously reported for palaemonid shrimp. Instead, it was associated with the presence of YHV-positive LOS and a relatively low viral load.


Globe to globe: whither (local) public health?


COVID-19 and the gastrointestinal tract: emerging clinical data


Cellular Superspreaders: An Epidemiological Perspective on HIV Infection inside the Body


title: COVID‐19‐associated immune thrombocytopenia

text: Thrombocytopenia is a risk factor for increased morbidity and mortality in patients with the new severe acute respiratory syndrome corona virus, SARS‐CoV‐2 infection (COVID‐19 infection).(1) Thrombocytopenia in COVID‐19 patients may be caused by disseminated intravascular coagulation (DIC), sepsis or drug‐induced. Recently a single case report suggested immune thrombocytopenia (ITP) may be associated with COVID‐19 infection.(2) ITP is a rare autoimmune disease characterized by a platelet count < 100x10(9)/L, leading to an increased bleeding risk.(3) Several risk factors have been described for ITP including environmental (e.g. infection, malignancy and drugs) and genetic predisposition.(4) We report here the first case series of three patients with ITP associated with COVID‐19 infection.


title: COVID-19 and heme oxygenase: novel insight into the disease and potential therapies

text: The COVID-19 pandemic needs therapies that are presently available and safe. We propose that subjects with metabolic syndrome, old age, and male gender have the greatest morbidity and mortality and have low stress proteins, in particular, low intracellular heme oxygenase (HO-1), making them particularly vulnerable to the disease. Additionally, COVID-19’s heme reduction may contribute to even lower HO-1. Low-grade inflammation associated with these risk factors contributes to triggering a cytokine storm that spreads to multi-organ failure and near death. The high mortality of those treated with ventilator assistance may partially be explained by ventilator-induced inflammation. The cytoprotective and anti-inflammatory properties of HO-1 can limit the infection’s damage. A paradox of COVID-19 hospital admissions data suggests that fewer cigarette-smokers are admitted compared with non-smokers in the general population. This unexpected observation may result from smoke induction of HO-1. Therapies with anti-viral properties that raise HO-1 include certain anesthetics (sevoflurane or isoflurane), hemin, estrogen, statins, curcumin, resveratrol, and melatonin. Controlled trials of these HO-1 inducers should be done in order to prevent or treat COVID-19 disease.


SARS: The First Pandemic of the 21(st) Century


In Reply to ‘Is SARS-CoV-2 Serology Relevant for Hemodialysis Patients With COVID-19?’


title: Infection on a chip: a microscale platform for simple and sensitive cell-based virus assays

text: The plaque assay has long served as the “gold standard” to measure virus infectivity and test antiviral drugs, but the assay is labor-intensive, lacks sensitivity, uses excessive reagents, and is hard to automate. Recent modification of the assay to exploit flow-enhanced virus spread with quantitative imaging has increased its sensitivity. Here we performed flow-enhanced infection assays in microscale channels, employing passive fluid pumping to inoculate cell monolayers with virus and drive infection spread. Our test of an antiviral drug (5-fluorouracil) against vesicular stomatitis virus infections of BHK cell monolayers yielded a two-fold improvement in sensitivity, relative to the standard assay based on plaque counting. The reduction in scale, simplified fluid handling, image-based quantification, and higher assay sensitivity will enable infection measurements for high-throughput drug screening, sero-conversion testing, and patient-specific diagnosis of viral infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10544-008-9263-7) contains supplementary material, which is available to authorized users.


title: Human rhinoviruses in Chinese adults with acute respiratory tract infection

text: Summary Objective To evaluate the roles of human rhinoviruses (HRVs) in acute respiratory tract infections (ARTIs) in Chinese adults and determine the association between species of HRV and clinical presentations. Methods RT-PCR methods were used to detect HRVs in throat and nasal swabs collected from 6104 adult patients with ARTIs from December 2005 to April 2008 in Beijing, China. Results HRV strains were detected in 271 ARTIs cases, 65% of which tested positive for HRV-A, 25% for HRV-B, and 10% for HRV-C. Aside from fever, pharyngeal congestion and headache were the most common clinical symptoms observed in the HRVs infected patients. HRV-A infected patients had a higher percentage of upper respiratory symptoms than patients infected by the two other HRV species. Systemic symptoms such as chilliness and myalgia were more frequent in people infected by HRV-B. The three HRV species exhibited unique infection timing when analyzed monthly. Conclusion HRV-C can be detected in adult patients with acute upper respiratory tract infections, but is not the predominant species in this population.


title: Query Based Intelligent Web Interaction with Real World Knowledge

text: This paper describes an integrated system based on open-domain and domain-specific knowledge for the purpose of providing query-based intelligent web interaction. It is understood that general purpose conversational agents are not able to answer questions on specific domain subject. On the other hand, domain specific systems lack the flexibility to handle common sense questions. To overcome the above limitations, this paper proposed an integrated system comprises of an artificial intelligent conversation software robot or chatterbot, called Artificial Intelligence Natural-language Identity (hereafter, AINI), and an Automated Knowledge Extraction Agent (AKEA) for the acquisition of real world knowledge from the Internet. The objective of AKEA is to retrieve real world knowledge or information from trustworthy websites. AINI is the mechanism used to manage the knowledge and to provide appropriate answer to the user. In this paper, we compare the performance of the proposed system against two popular search engines, two question answering systems and two other conversational systems.


title: IFITM3 restricts the morbidity and mortality associated with influenza

text: The 2009 H1N1 influenza pandemic showed the speed with which a novel respiratory virus can spread and the ability of a generally mild infection to induce severe morbidity and mortality in a subset of the population. Recent in vitro studies show that the interferon-inducible transmembrane (IFITM) protein family members potently restrict the replication of multiple pathogenic viruses. Both the magnitude and breadth of the IFITM proteins' in vitro effects suggest that they are critical for intrinsic resistance to such viruses, including influenza viruses. Using a knockout mouse model, we now test this hypothesis directly and find that IFITM3 is essential for defending the host against influenza A virus in vivo. Mice lacking Ifitm3 display fulminant viral pneumonia when challenged with a normally low-pathogenicity influenza virus, mirroring the destruction inflicted by the highly pathogenic 1918 'Spanish' influenza. Similar increased viral replication is seen in vitro, with protection rescued by the re-introduction of Ifitm3. To test the role of IFITM3 in human influenza virus infection, we assessed the IFITM3 alleles of individuals hospitalized with seasonal or pandemic influenza H1N1/09 viruses. We find that a statistically significant number of hospitalized subjects show enrichment for a minor IFITM3 allele (SNP rs12252-C) that alters a splice acceptor site, and functional assays show the minor CC genotype IFITM3 has reduced influenza virus restriction in vitro. Together these data reveal that the action of a single intrinsic immune effector, IFITM3, profoundly alters the course of influenza virus infection in mouse and humans.


title: Chapter 2 Syndromic surveillance using web data: a systematic review

text: Abstract During the recent years, a lot of debate is taken place about the evolution of Smart Healthcare systems. Particularly, how these systems can help people improve human conditions of health, by taking advantages of the new Information and Communication Technologies (ICT), regarding early prediction and efficient treatment. The purpose of this study is to provide a systematic review of the current literature available that focuses on information systems on syndromic surveillance using web data. All published items concern articles, books, reviews, reports, conference announcements, and dissertations. We used a variation of PRISMA Statements methodology to conduct a systematic review. The review identifies the relevant published papers from the year 2004 to 2018, systematically includes and explores them to extract similarities, gaps, and conclusions on the research that has been done so far. The results presented concern the year, the examined disease, the web data source, the geographic location/country, and the data analysis method used. The results show that influenza is the most examined infectious disease. The internet tools most used are Twitter and Google. Regarding the geographical areas explored in the published papers, the most examined country is the United States, since many scientists come from this country. There is a significant growth of articles since 2009. There are also various statistical methods used to correlate the data retrieved from the internet to the data from national authorities. The conclusion of all researches is that the Web can be a useful tool for the detection of serious epidemics and for a creation of a syndromic surveillance system using the Web, since we can predict epidemics from web data before they are officially detected in population. With the advance of ICT, Smart Healthcare can benefit from the monitoring of epidemics and the early prediction of such a system, improving national or international health strategies and policy decision. This can be achieved through the provision of new technology tools to enhance health monitoring systems toward the new innovations of Smart Health or eHealth, even with the emerging technologies of Internet of Things. The challenges and impacts of an electronic system based on internet data include the social, medical, and technological disciplines. These can be further extended to Smart Healthcare, as the data streaming can provide with real-time information, awareness on epidemics and alerts for both patients or medical scientists. Finally, these new systems can help improve the standards of human life.


title: Receptor tyrosine kinase inhibitors block proliferation of TGEV mainly through p38 mitogen-activated protein kinase pathways

text: Abstract Emerging coronaviruses (CoVs) primarily cause severe gastroenteric or respiratory diseases in humans and animals, and no approved therapeutics are currently available. Here, A9, a receptor tyrosine kinase inhibitor (RTKI) of the tyrphostin class, is identified as a robust inhibitor of transmissible gastroenteritis virus (TGEV) infection in cell-based assays. Moreover, A9 exhibited potent antiviral activity against the replication of various CoVs, including murine hepatitis virus (MHV), porcine epidemic diarrhea virus (PEDV) and feline infectious peritonitis virus (FIPV). We further performed a comparative phosphoproteomic analysis to investigate the mechanism of action of A9 against TGEV infection in vitro. We specifically identified p38 and JNK1, which are the downstream molecules of receptor tyrosine kinases (RTKs) required for efficient TGEV replication, as A9 targets through plaque assays, qRT-PCR and Western blotting assays. p38 and JNK1 inhibitors and RNA interference further showed that the inhibitory activity of A9 against TGEV infection was mainly mediated by the p38 mitogen-activated protein kinase (MAPK) signaling pathway. All these findings indicated that the RTKI A9 directly inhibits TGEV replication and that its inhibitory activity against TGEV replication mainly occurs by targeting p38, which provides vital clues to the design of novel drugs against CoVs.


title: Detection of human bocavirus from children and adults with acute respiratory tract illness in Guangzhou, southern China

text: BACKGROUND: Human bocavirus (HBoV) is a newly discovered parvovirus associated with acute respiratory tract illness (ARTI) and gastrointestinal illness. Our study is the first to analyze the characteristics of HBoV-positive samples from ARTI patients with a wide age distribution from Guangzhou, southern China. METHODS: Throat swabs (n=2811) were collected and analyzed from children and adults with ARTI over a 13-month period. The HBoV complete genome from a 60 year-old female patient isolate was also determined. RESULTS: HBoV DNA was detected in 65/2811 (2.3%) samples, of which 61/1797 were from children (<18 years old) and 4/1014 from adults (≥18 years old). Seasonal peaks of 4.8% and 7.7% were detected in May and June, respectively. 28 of 65 (43.1%) HBoV-positive samples were co-detected with 11/16 other potential pathogens. Mycoplasma pneumoniae had the highest frequency of 16.9% (11/65). Upper and lower respiratory tract illness were common symptoms, with 19/65 (29.2%) patients diagnosed with pneumonia by chest radiography. All four adult patients had systemic influenza-like symptoms. Phylogenetic analysis of the complete genome revealed a close relationship with other HBoVs, and a more distant relationship with HBoV2 and HBoV3. CONCLUSIONS: HBoV was detected from children and adults with ARTI from Guangzhou, southern China. Elderly people were also susceptive to HBoV. A single lineage of HBoV was detected among a wide age distribution of patients with ARTI.


COVID-19 and the General Surgical Department – Measures to Reduce Spread of SARS-COV-2 Among Surgeons


title: Peptide reagent design based on physical and chemical properties of amino acid residues

text: It has tremendous values for both drug discovery and basic research to develop a solid bioinformatical tool for guiding peptide reagent design. Based on the physical and chemical properties of amino acids, a new strategy for peptide reagent design, the so‐called AABPD (amino acid based‐peptide design), is proposed. The peptide samples in a training dataset are described by a series of HMLP (heuristic molecular lipophilicity potential) parameters and other physicochemical properties of amino acid residues that form a three‐dimensional data matrix where each component is defined by three indexes: the first index refers to the peptide samples, the second to the amino acid positions, and the third to the amino acid parameters. The binding free energy between a peptide ligand and its protein receptor is calculated by a linear free energy equation through the physicochemical parameters, resulting in a set of simultaneous linear equations between the bioactivity of the peptides and the physicochemical properties of amino acids. An iterative double least square technique is developed for the solution of the three‐dimensional simultaneous linear equation set to determine the amino acid position coefficients of peptide sequence and the physicochemical parameter coefficients of amino acid residues alternately. The two sets of coefficients thus obtained are used for predicting the bioactivity of other query peptide reagents. Two calculation examples, the peptide substrate specificity of the SARS coronavirus 3C‐like proteinase and the affinity prediction for epitope‐peptides with Class I MHC molecules are studied by using the peptide reagent design strategy. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007


How is the cardiovascular patient managed during Covid‐19 pandemic? A report from the frontline


The Italian war-like measures to fight coronavirus spreading: Re-open closed hospitals now


title: Differential Host Cell Gene Expression and Regulation of Cell Cycle Progression by Nonstructural Protein 11 of Porcine Reproductive and Respiratory Syndrome Virus

text: Nonstructural protein 11 (nsp11) of porcine reproductive and respiratory syndrome virus (PRRSV) is a viral endoribonuclease with an unknown function. The regulation of cellular gene expression by nsp11 was examined by RNA microarrays using MARC-nsp11 cells constitutively expressing nsp11. In these cells, the interferon-β, interferon regulatory factor 3, and nuclear factor-κB activities were suppressed compared to those of parental cells, suggesting that nsp11 might serve as a viral interferon antagonist. Differential cellular transcriptome was examined using Affymetrix exon chips representing 28,536 transcripts, and after statistical analyses 66 cellular genes were shown to be upregulated and 104 genes were downregulated by nsp11. These genes were grouped into 5 major signaling pathways according to their functional relations: histone-related, cell cycle and DNA replication, mitogen activated protein kinase signaling, complement, and ubiquitin-proteasome pathways. Of these, the modulation of cell cycle by nsp11 was further investigated since many of the regulated genes fell in this particular pathway. Flow cytometry showed that nsp11 caused the delay of cell cycle progression at the S phase and the BrdU staining confirmed the cell cycle arrest in nsp11-expressing cells. The study provides insights into the understanding of specific cellular responses to nsp11 during PRRSV infection.


title: Risk factors for calf mortality in large Swedish dairy herds

text: Abstract The aim of this study was to identify possible risk factors for 1–90 day calf mortality in large Swedish dairy herds. Sixty herds with a herd size of ≥160 cows were visited once between December 2005 and March 2006. Thirty herds were known to have low mortality (LM) and 30 were known high mortality herds (HM). Upon the visit, data about housing and management was collected from interviews with personnel responsible for the calves. The herd status regarding the calves’ passive transfer (total protein), levels of α-tocopherol, β-carotene and retinol, and excretion of faecal pathogens (Cryptosporidium spp., Escherichia coli F5, rota and corona virus) was evaluated based on targeted sampling of high risk calf groups; in each herd, blood and faecal samples were collected from calves 1–7 and 1–14 days old, respectively. Similarly, the herd status regarding clinical respiratory disease in calves and history of respiratory virus exposure was evaluated based on lung auscultations and blood samplings of calves 60–90 days old. The median calf mortality risk (in calves 1–90 days of age) among HM herds was 9% (Range: 6–24%) and among LM herds 1% (Range: 0–2%). LM and HM herds were compared using five logistic regression models, covering potential risk factors within different areas: “Disease susceptibility”, “Factors affecting the gastrointestinal tract”, “Factors related to transmission of infectious disease”, “Hygiene” and “Labour management”. The percentage of calves, 1–7 days old, with inadequate serum concentrations of α-tocopherol and β-carotene were significantly higher in HM herds compared to LM herds and also associated with higher odds of being a HM herd (OR=1.02; p =0.023 and OR=1.05; p =0.0028, respectively). The variable “Average number of faecal pathogens in the sampled target group” was significantly associated with higher odds of being a HM herd (OR=4.65; p =0.015), with a higher average in HM herds. The percentage of calves with diarrhoea treated with antibiotics was significantly higher in HM herds and was associated with higher odds of being a HM herd (OR=1.08; p =0.021). The median age at death of calves in the age interval 1–90 days that died during a one-year period was significantly lower among HM herds (13 days) than in LM herds (24 days) (p =0.0013) The results indicate that gastrointestinal disorders may be an important cause of calf mortality in large Swedish dairy herds. Furthermore, our study provides additional indications that fat soluble vitamins might play an important role for calf health.


title: Eosinophil Responses During COVID-19 Infections and Coronavirus Vaccination

text: Abstract Eosinophils are circulating and tissue-resident leukocytes that have potent pro-inflammatory effects in a number of diseases. Recently, eosinophils have been shown to have a variety of other functions, including immunoregulation and antiviral activity. Eosinophil levels vary dramatically in a number of clinical settings, especially following eosinophil-targeted therapy, which is now available to selectively deplete these cells. There are key COVID-19–related questions concerning eosinophils whose answers affect recommended prevention and care. First, do patients with eosinophilia-associated diseases have an altered course of COVID-19? Second, do patients with eosinopenia (now intentionally induced by biological drugs) have unique COVID-19 susceptibility and/or disease course? This is a particularly relevant question as eosinopenia is associated with acute respiratory deterioration during infection with the Severe Acute Respiratory Syndrome (SARS)-Corona Virus (CoV)-2, the causative agent of COVID-19. Third, do eosinophils contribute to the lung pathology induced during COVID-19 and will they contribute to immunopotentiation potentially associated with emerging COVID-19 vaccines? Herein, we address these timely questions and project considerations during the emerging COVID-19 pandemic.


title: Identification and Typing of Human Enterovirus: A Genomic Barcode Approach

text: Identification and typing of human enterovirus (HEVs) are important to pathogen detection and therapy. Previous phylogeny-based typing methods are mainly based on multiple sequence alignments of specific genes in the HEVs, but the results are not stable with respect to different choices of genes. Here we report a novel method for identification and typing of HEVs based on information derived from their whole genomes. Specifically, we calculate the k-mer based barcode image for each genome, HEV or other human viruses, for a fixed k, 1<k<7, where a genome barcode is defined in terms of the k-mer frequency distribution across the whole genome for all combinations of k-mers. A phylogenetic tree is constructed using a barcode-based distance and a neighbor-joining method among a set of 443 representative non-HEV human viruses and 395 HEV sequences. The tree shows a clear separation of the HEV viruses from all the non-HEV viruses with 100% accuracy and a separation of the HEVs into four distinct clads with 93.4% consistency with a multiple sequence alignment-based phylogeny. Our detailed analyses of the HEVs having different typing results by the two methods indicate that our results are in better agreement with known information about the HEVs.


title: In the South, if you give us lemons, we will make you lemonade

text: • COVID-19 has necessitated a quick pivot from in-person to virtual cystic fibrosis (CF) care; • Virtual care for CF, especially implemented with a rural population, has multiple considerations; • Here, we share pearls and pitfalls of our early experience, as well as important considerations for the future of CF virtual care.


title: Causes of variability in prevalence rates of communicable diseases among secondary school Students in Kisumu County, Kenya

text: PURPOSE: To determine causes of variability in communicable disease prevalence rates among students in secondary schools to inform policy formulation in the public health sector. METHODS: A representative cluster sample size for students was estimated using Fisher et al.’s formula while schools, sub-counties and education zones were clustered and sample size was calculated based on coefficient of variation by school type. Data were collected by questionnaire, medical examination using standard procedures, and focus group discussion, and descriptive analysis was performed on the completed questions. Comparisons between risk factors were made by chi-square and ANOVA analysis using SPSS for Windows (version 15.2; Chicago, IL) software. A p value of < 0.05 was considered statistically significant. RESULTS: There was significant variation between communicable disease prevalence rates and age (X(2) (4, 0.05) = 2.458), school size (X(2) (12, 0.05) = 18.636), gender (X(2) (4, 0.05) = 5.723) and class of students (X(2) (12, 0.05) = 15.202), and bed and desk spacing (p < 0.05 at 95% CI). However, there was no significant association in prevalence rates between both locality and type of school. There was strong evidence that student age has an effect on prevalence rates. The prevalence rate of malaria was higher in male (14.02%) than female students (6.68%) compared to prevalence of diarrhea, which was higher in female (7.96%) than male students. CONCLUSION: This study has revealed that the prevalences of diarrhea, tuberculosis, pneumonia and other respiratory tract infections are lower among female secondary school students than males and that the prevalence of malaria is higher in males than females. Age of secondary school students is a significant vulnerability factor for malaria, diarrhea, tuberculosis and pneumonia, which were the important communicable diseases most prevalent among secondary school students in Kisumu County, Kenya.


title: Short-term effects of meteorological factors, air pollution, and sunspot on childhood hand, foot, and mouth disease in Tianjin, China: a new time series regression, 2014–2018

text: This study is aimed at defining the relationship between a set of environmental factors and childhood HFMD and then at estimating the related effect. The 16 environmental factors included meteorological, air pollution, and sunspot. A traditional TSR modified by using susceptible-infectious-recovery models and distribution lag nonlinear model was applied to estimate the short-term effects of daily environmental factors on children HFMD occurrence in 2014–2018 with adjustment of potential confounding factors. A total of 70,027 children aged 0–15 years with HFMD were enrolled. No significant effect was observed for daily sunspot numbers and average visibility. We found positive effects of the ambient average temperature, with an approximately m-shaped curve of the overall cumulative relationship, peaking at 25.6 °C with a relative risk (RR) of 1.45 (95% confidence intervals 1.21–1.73). The largest RR value of hot effect was achieved on the current day and then decreased by 2 days (total group, male group, and scatter group) or 1 day (female group and nursery group), and the effect lasted about 6 to 8 days from the lag 4 or lag 6 day. A greater association of temperature with HFMD for the female group and the scattered group was observed. This study suggests that ambient average temperature might be a risk factor for children HFMD in Tianjin. Further studies are warranted to confirm these findings.


An overview of the Sino–German symposium on new developments in surgical and basic pathology


title: Recombinant viral proteins for use in diagnostic ELISAs to detect virus infection

text: ELISAs provide a valuable tool in the detection and diagnosis of virus infection. The ability to produce recombinant viral proteins will ensure that future ELISAs are safe, specific and rapid. This latter point being the most crucial advantage in that even if a virus cannot be cultured, provided gene sequence is available, it is possible to rapidly respond to emerging viruses and new viral strains of existing pathogens. Indeed, ELISAs based on peptides (corresponding to epitopes) also hold great promise, as in this case no cloning or expression of a recombinant protein is required. Both recombinant protein and peptide based systems lend themselves to large scale production and purification. These approaches can also be used to distinguish recombinant vaccines from parental or wild type viruses.


title: Cholesterol-rich lipid rafts play an important role in the Cyprinid herpesvirus 3 replication cycle

text: Abstract The Cyprinus herpesvirus 3 (CyHV-3) is a member of the new Alloherpesviridae virus family in the Herpesvirales order. CyHV-3 has been implicated in a large number of disease outbreaks in carp populations causing up to 100% mortality. The aim of this study was to investigate the requirement of cholesterol-rich lipid rafts in CyHV-3 entry and replication in carp cells. Plasma membrane cholesterol was depleted from common carp brain (CCB) cells with methyl-β-cyclodextrin (MβCD). Treated and non-treated cells were infected with CyHV-3 and virus binding and infection parameters were assessed using RT-qPCR, immunocytochemistry and virus titration. The effect of cholesterol reduction severely stunted virus entry in vitro, however after cholesterol replenishment virus entry and subsequent replication rates were similar to the control infection. Furthermore, cholesterol depletion did not significantly influence virus binding and the subsequent post-entry replication stage, however had an impact on virus egress. Comparative analysis of the lipid compositions of CyHV-3 and CCB membrane fractions revealed strong similarities between the lipid composition of the CyHV-3 and CCB lipid rafts. The results presented here show that cholesterol-rich lipid rafts are important for the CyHV-3 replication cycle especially during entry and egress.


title: Vaccinia Virus LC16m8∆ as a Vaccine Vector for Clinical Applications

text: The LC16m8 strain of vaccinia virus, the active ingredient in the Japanese smallpox vaccine, was derived from the Lister/Elstree strain. LC16m8 is replication-competent and has been administered to over 100,000 infants and 3,000 adults with no serious adverse reactions. Despite this outstanding safety profile, the occurrence of spontaneously-generated large plaque-forming virulent LC16m8 revertants following passage in cell culture is a major drawback. We identified the gene responsible for the reversion and deleted the gene (B5R) from LC16m8 to derive LC16m8Δ. LC16m8∆ is non-pathogenic in immunodeficient severe combined immunodeficiency (SCID) mice, genetically-stable and does not reverse to a large-plaque phenotype upon passage in cell culture, even under conditions in which most LC16m8 populations are replaced by revertants. Moreover, LC16m8∆ is >500-fold more effective than the non-replicating vaccinia virus (VV), Modified Vaccinia Ankara (MVA), at inducing murine immune responses against pathogenic VV. LC16m8∆, which expresses the SIV gag gene, also induced anti-Gag CD8(+) T-cells more efficiently than MVA and another non-replicating VV, Dairen I minute-pock variants (DIs). Moreover, LC16m8∆ expressing HIV-1 Env in combination with a Sendai virus vector induced the production of anti-Env antibodies and CD8(+) T-cells. Thus, the safety and efficacy of LC16m8∆ mean that it represents an outstanding platform for the development of human vaccine vectors.


title: Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection

text: Severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-like coronavirus are a potential threat to global health. However, reviews of the long-term effects of clinical treatments in SARS patients are lacking. Here a total of 25 recovered SARS patients were recruited 12 years after infection. Clinical questionnaire responses and examination findings indicated that the patients had experienced various diseases, including lung susceptibility to infections, tumors, cardiovascular disorders, and abnormal glucose metabolism. As compared to healthy controls, metabolomic analyses identified significant differences in the serum metabolomes of SARS survivors. The most significant metabolic disruptions were the comprehensive increase of phosphatidylinositol and lysophospha tidylinositol levels in recovered SARS patients, which coincided with the effect of methylprednisolone administration investigated further in the steroid treated non-SARS patients with severe pneumonia. These results suggested that high-dose pulses of methylprednisolone might cause long-term systemic damage associated with serum metabolic alterations. The present study provided information for an improved understanding of coronavirus-associated pathologies, which might permit further optimization of clinical treatments.


title: Renin-angiotensin system inhibition in COVID-19 patients

text: Angiotensin-converting enzyme (ACE) inhibitors (ACEIs) and angiotensin II type‑1 receptor blockers (ARBs) are among the most widely prescribed drugs for the treatment of arterial hypertension, heart failure and chronic kidney disease. A number of studies, mainly in animals and not involving the lungs, have indicated that these drugs can increase expression of angiotensin-converting enzyme 2 (ACE2). ACE2 is the cell entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) that is currently battering the globe. This has led to the hypothesis that use of ACEIs and ARBs may increase the risk of developing severe COVID-19. In this point of view paper, possible scenarios regarding the impact of ACEI/ARB pharmacotherapy on COVID-19 are discussed in relation to the currently available evidence. Although further research on the influence of blood-pressure-lowering drugs, including those not targeting the renin-angiotensin system, is warranted, there are presently no compelling clinical data showing that ACEIs and ARBs increase the likelihood of contracting COVID-19 or worsen the outcome of SARS-CoV‑2 infections. Thus, unless contraindicated, use of ACEIs/ARBs in COVID-19 patients should be continued in line with the recent recommendations of medical societies.


title: Autophagic machinery activated by dengue virus enhances virus replication

text: Abstract Autophagy is a cellular response against stresses which include the infection of viruses and bacteria. We unravel that Dengue virus-2 (DV2) can trigger autophagic process in various infected cell lines demonstrated by GFP-LC3 dot formation and increased LC3-II formation. Autophagosome formation was also observed under the transmission electron microscope. DV2-induced autophagy further enhances the titers of extracellular and intracellular viruses indicating that autophagy can promote viral replication in the infected cells. Moreover, our data show that ATG5 protein is required to execute DV2-induced autophagy. All together, we are the first to demonstrate that DV can activate autophagic machinery that is favorable for viral replication.


title: Synthesis and Evaluation of Non-peptidic Cysteine Protease Inhibitors of P. falciparum Derived from Etacrynic Acid

text: A series of etacrynic acid derivatives was synthesized and screened for their in vitro activity against Plasmodium falciparum, as well as their activity against recombinantly expressed falcipain-2 and -3. The two most active compounds of the series displayed IC(50) values of 9.0 and 18.8 μM against Plasmodia.


title: Rapid Identification Viruses from Nasal Pharyngeal Aspirates in Acute Viral Respiratory Infections by RT-PCR and Electrospray Ionization Mass Spectrometry

text: Diagnosis of the etiologic agent of respiratory viral infection relies traditionally on culture or antigen detection. This pilot was conducted evaluation comparing performance characteristics of the RT-PCR and Electrospray Ionization Mass Spectrometry (RT-PCR/ESI-MS) platform to conventional virological methods for identifying multiple clinically relevant respiratory viruses in nasopharyngeal aspirates. The RT-PCR/ESI-MS respiratory virus surveillance kit was designed to detect respiratory syncytial virus, influenza A and B, parainfluenza types 1-4, adenoviridae types A-F, coronaviridae, human bocavirus, and human metapneumovirus. Patients (N=192) attending an emergency department during the 2007-8 respiratory season consented, and “excess” frozen archived nasopharyngeal aspirates were analysed; 46 were positive by conventional virology and 69 by RT-PCR/ESI-MS, among which there were six samples with multiple viral pathogens detected. The sensitivity and specificity of the assay were 89.1% and 80.3%, respectively. Additional viruses that were not identified by conventional virology assays were detected (4 human bocaviruses and 7 coronaviruses). Samples in which the RT-PCR/ESI-MS results disagreed with conventional virology were sent for analysis by a third method using a commercial RT-PCR-based assay, which can identify viruses not detectable by conventional virologic procedures. Time to first result of RT-PCR/ESI-MS was 8 hours. RT-PCR/ESI-MS demonstrated capacity to detect respiratory viruses identifiable and unidentifiable by conventional methods rapidly.


title: Porvair adapts manufacturing to fight Covid-19

text: Porvair has adapted its manufacturing to produce ventilators and contribute towards medical testing and pharmaceutical production.


title: Cell-Type-Specific Effects of RNase L on Viral Induction of Beta Interferon

text: The interferon (IFN)-inducible antiviral state is mediated in part by the 2′,5′-oligoadenylate (2-5A) synthetase (OAS)/RNase L system. 2-5A, produced from ATP by OAS proteins in response to viral double-stranded RNA, binds to and activates RNase L. RNase L restricts viral infections by degrading viral and cellular RNA, inducing autophagy and apoptosis, and producing RNA degradation products that amplify production of type I interferons (IFNs) through RIG-I-like receptors. However, the effects of the OAS/RNase L pathway on IFN induction in different cell types that vary in basal levels of these proteins have not been previously reported. Here we report higher basal expression of both RNase L and OAS in mouse macrophages in comparison to mouse embryonic fibroblasts (MEFs). In MEFs, RNase L gene knockout decreased induction of IFN-β by encephalomyocarditis virus infection or poly(rI):poly(rC) (pIC) transfection. In contrast, in macrophages, RNase L deletion increased (rather than decreased) induction of IFN-β by virus or pIC. RNA damage from RNase L in virus-infected macrophages is likely responsible for reducing IFN-β production. Similarly, direct activation of RNase L by transfection with 2-5A induced IFN-β in MEFs but not in macrophages. Also, viral infection or pIC transfection caused RNase L-dependent apoptosis of macrophages but not of MEFs. Our results suggest that cell-type-specific differences in basal levels of OAS and RNase L are determinants of IFN-β induction that could affect tissue protection and survival during viral infections.


title: Structural requirements for initiation of cross‐reactivity and CNS autoimmunity with a PLP(139–151) mimic peptide derived from murine hepatitis virus

text: MS is an autoimmune CNS demyelinating disease in which infection appears to be an important pathogenic factor. Molecular mimicry, the cross‐activation of autoreactive T cells by mimic peptides from infectious agents, is a possible explanation for infection‐induced autoimmunity. Infection of mice with a non‐pathogenic strain of Theiler's murine encephalomyelitis virus (TMEV) engineered to express an epitope from Haemophilus influenzae (HI) sharing 6/13 amino acids with the dominant proteolipid protein (PLP) epitope, PLP(139–151), can induce CNS autoimmune disease. Here we demonstrate that another PLP(139–151) mimic sequence derived from murine hepatitis virus (MHV) which shares only 3/13 amino acids with PLP(139–151) can also induce CNS autoimmune disease, but only when delivered by genetically engineered TMEV, not by immunization with the MHV peptide. Further, we demonstrate the importance of proline at the secondary MHC class II contact residue for effective cross‐reactivity, as addition of this amino acid to the native MHV sequence increases its ability to cross‐activate PLP(139–151)‐specific autoreactive T cells, while substitution of proline in the HI mimic peptide has the opposite effect. This study describes a structural requirement for potential PLP(139–151) mimic peptides, and provides further evidence for infection‐induced molecular mimicry in the pathogenesis of autoimmune disease.


Coronavirus: lessons from Xinjiang


CT-Verlauf einer Coronavirus(2019-nCoV)-Pneumonie


title: SARS Transmission, Risk Factors, and Prevention in Hong Kong

text: We analyzed information obtained from 1,192 patients with probable severe acute respiratory syndrome (SARS) reported in Hong Kong. Among them, 26.6% were hospital workers, 16.1% were household members of SARS patients and had probable secondary infections, 14.3% were Amoy Garden residents, 4.9% were inpatients, and 20.1% were contacts of SARS patients who were not family members. The remaining 347 case-patients (29.1%) did not have “known” sources of infection. Excluding those <16 years of age, 330 patients with cases from “undefined” sources were used in a 1:2 matched case-control study. Multivariate analysis of this case-control study showed that having visited mainland China, hospitals, or the Amoy Gardens were risk factors (odds ratio [OR] 1.95 to 7.63). In addition, frequent mask use in public venues, frequent hand washing, and disinfecting the living quarters were significant protective factors (OR 0.36 to 0.58). In Hong Kong, therefore, community-acquired infection did not make up most transmissions, and public health measures have contributed substantially to the control of the SARS epidemic.


title: Virtual screening and repurposing of FDA approved drugs against COVID-19 main protease

text: Abstract Aims In December 2019, the Coronavirus disease-2019 (COVID-19) virus has emerged in Wuhan, China. In this research, the first resolved COVID-19 crystal structure (main protease) was targeted in a virtual screening study by of FDA approved drugs dataset. In addition, a knowledge gap in relations of COVID-19 with the previously known fatal Coronaviruses (CoVs) epidemics, SARS and MERS CoVs, was covered by investigation of sequence statistics and phylogenetics. Materials and methods Molecular modeling, virtual screening, docking, sequence comparison statistics and phylogenetics of the COVID-19 main protease were investigated. Key findings COVID-19 Mpro formed a phylogenetic group with SARS CoV that was distant from MERS CoV. The identity% was 96.061 and 51.61 for COVID-19/SARS and COVID-19/MERS CoV sequence comparisons, respectively. The top 20 drugs in the virtual screening studies comprised a broad-spectrum antiviral (ribavirin), anti-hepatitis B virus (telbivudine), two vitamins (vitamin B12 and nicotinamide) and other miscellaneous systemically acting drugs. Of special interest, ribavirin had been used in treating cases of SARS CoV. Significance The present study provided a comprehensive targeting of the first resolved COVID+19 structure of Mpro and found a suitable save drugs for repurposing against the viral Mpro. Ribavirin, telbivudine, vitamin B12 and nicotinamide can be combined and used for COVID treatment. This initiative relocates already marketed and approved safe drugs for potential use in COVID-treatment.


title: An intelligent system for predicting and preventing MERS-CoV infection outbreak

text: MERS-CoV is an airborne disease which spreads easily and has high death rate. To predict and prevent MERS-CoV, real-time analysis of user’s health data and his/her geographic location are fundamental. Development of healthcare systems using cloud computing is emerging as an effective solution having benefits of better quality of service, reduced cost, scalability, and flexibility. In this paper, an effective cloud computing system is proposed which predicts MERS-CoV-infected patients using Bayesian belief network and provides geographic-based risk assessment to control its outbreak. The proposed system is tested on synthetic data generated for 0.2 million users. System provided high accuracy for classification and appropriate geographic-based risk assessment. The key point of this paper is the use of geographic positioning system to represent each MERS-CoV users on Google maps so that possibly infected users can be quarantined as early as possible. It will help uninfected citizens to avoid regional exposure and the government agencies to manage the problem more effectively.


title: Transmission risk of patients with COVID-19 meeting discharge criteria should be interpreted with caution

text: 目前全球新型冠状病毒流行形势仍严峻且持续恶化. 评估符合出院标准的 2019 冠状病毒病 (COVID-19) 患者的传染性对于疾病控制至关重要. 本研究报告两例核酸检测结果与临床表现及影像学表现不相符的患者, 以此来呼吁临床工作者谨慎考虑符合出院标准的 COVID-19 患者的传染性.


title: Facing the COVID‐19 outbreak: What should we know and what could we do?

text: A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, Hubei Province in China in December 2019 and caused a serious type of pneumonia called coronavirus disease 2019 or COVID-19. This epidemic quickly spread across China and extended to more than 20 other countries. This commentary discusses the reasons for the fast spread of SARS-CoV-2 in three aspects: the infectious sources, including the biological nature of the virus; the susceptible population; and the transmission routes. The current situations and suggestions regarding the control of the disease are summarized. This article is protected by copyright. All rights reserved.


title: The antiviral activity of antibodies in vitro and in vivo

text: Publisher Summary This chapter discusses in vitro and in vivo antiviral activities of antibody. Since experimentation is far easier in vitro, researchers have been sought to develop in vitro assays that are expected to predict activity in vivo. This could be important in both vaccine design and in passive antibody administration. The proposed mechanisms of in vitro neutralization range from those requiring binding of a single antibody molecule to virus to those requiring substantially complete antibody coating of virus. In vitro, antiviral activity can be separated into activity against virions and activity against infected cells. The activity against virions most often considered is neutralization that can be defined as the loss of infectivity, which ensues when antibody molecule(s) bind to a virus particle, and occurs without the involvement of any other agency. In vivo, it is conventional to distinguish phenomenologically between two types of antibody antiviral activity. One of them is the ability of antibody to protect against infection when it is present before or immediately following infection. Evidence for a number of viruses in vitro indicates that lower antibody concentrations are required to inhibit infection propagated by free virus than are required to inhibit infection propagated by cell-to-cell spread.


title: A Machine Learning Model to Identify Early Stage Symptoms of SARS-Cov-2 Infected Patients

text: The recent outbreak of the respiratory ailment COVID-19 caused by novel coronavirus SARS-Cov2 is a severe and urgent global concern. In the absence of effective treatments, the main containment strategy is to reduce the contagion by the isolation of infected individuals; however, isolation of unaffected individuals is highly undesirable. To help make rapid decisions on treatment and isolation needs, it would be useful to determine which features presented by suspected infection cases are the best predictors of a positive diagnosis. This can be done by analyzing patient characteristics, case trajectory, comorbidities, symptoms, diagnosis, and outcomes. We developed a model that employed supervised machine learning algorithms to identify the presentation features predicting COVID-19 disease diagnoses with high accuracy. Features examined included details of the individuals concerned, e.g., age, gender, observation of fever, history of travel, and clinical details such as the severity of cough and incidence of lung infection. We implemented and applied several machine learning algorithms to our collected data and found that the XGBoost algorithm performed with the highest accuracy (>85%) to predict and select features that correctly indicate COVID-19 status for all age groups. Statistical analyses revealed that the most frequent and significant predictive symptoms are fever (41.1%), cough (30.3%), lung infection (13.1%) and runny nose (8.43%). While 54.4% of people examined did not develop any symptoms that could be used for diagnosis, our work indicates that for the remainder, our predictive model could significantly improve the prediction of COVID-19 status, including at early stages of infection.


title: RSV hospitalisation and healthcare utilisation in moderately prematurely born infants

text: Respiratory syncytial virus (RSV) infection is associated with chronic respiratory morbidity in infants born very prematurely. Our aims were to determine if infants born moderately prematurely (32–35 weeks of gestation) who had had an RSV hospitalisation, compared to those who had not, had greater healthcare utilisation and related cost of care in the first 2 years. Two thousand and sixty-six eligible infants’ records were examined to identify three groups: 20 infants admitted for an RSV lower respiratory tract infection (RSV), 30 admitted for another respiratory problem (other respiratory) and 108 admitted for a non-respiratory problem/never admitted (non-respiratory). Healthcare utilisation was assessed by examining hospital and general practitioner records and cost of care calculated using the National Scheme of Reference costs and the British National Formulary prices. The mean cost of care in the RSV group (£12,505) was greater than the non-respiratory (£1,178) (95% CI for difference £5,015 to £17,639, p = 0.002) and the other respiratory (£3,356) groups (95% CI for difference £2,963 to £15,606, p < 0.001). The adjusted mean differences in the cost of care were £11,186 between the RSV and non-respiratory groups (95% CI £4,763 to £17,609) and £9,076 (95% CI £2,515 to £15,637) between the RSV and the other respiratory groups. Forty-two of 2,066 eligible infants had an RSV hospitalisation (2%); thus, assuming prophylaxis would reduce the hospitalisation rate by 50%, the number needed to treat was 98. In conclusion, RSV hospitalisation in moderately prematurely born infants is associated with increased health-related cost of care. Nevertheless, if RSV prophylaxis is to be cost-effective, a high risk group of moderately prematurely born infants needs to be identified.


title: Evaluation of novel multiplex qPCR assays for diagnosis of pathogens associated with the bovine respiratory disease complex

text: Abstract Bovine respiratory disease complex is the most common disease requiring the use of antimicrobials in industrial calf production worldwide. Pathogenic bacteria (Mannheimia haemolytica (Mh), Pasteurella multocida (Pm), Histophilus somni (Hs), and Mycoplasma bovis) and a range of viruses (bovine respiratory syncytial virus, bovine coronavirus, bovine parainfluenza virus type 3, bovine viral diarrhea virus and bovine herpesvirus type 1) are associated with this complex. As most of these pathogens can be present in healthy and diseased calves, simple detection of their presence in diseased calves carries low predictive value. In other multi-agent diseases of livestock, quantification of pathogens has added substantially to the predictive value of microbiological diagnosis. The aim of this study was to evaluate the ability of two recently developed quantitative PCR (qPCR) kits (Pneumo4B and Pneumo4V) to detect and quantify these bacterial and viral pathogens, respectively. Test efficiencies of the qPCR assays, based on nucleic acid dilution series of target bacteria and viruses, were 93–106% and 91–104%, respectively, with assay detection limits of 10–50 copies of nucleic acids. All 44 strains of target bacteria were correctly identified, with no false positive reactions in 135strains of non-target bacterial species. Based on standard curves of log10 CFU versus cycle threshold (Ct) values, quantification was possible over a 5-log range of bacteria. In 92 tracheal aspirate samples, the kappa values for agreement between Pneumo4B and bacterial culture were 0.64-0.84 for Mh, Pm and Hs. In an additional 84 tracheal aspirates, agreement between Pneumo4B or Pneumo 4V and certified diagnostic qPCR assays was moderate (0.57) for M. bovis and high (0.71–0.90) for viral pathogens. Thus Pneumo4 kits specifically detected and quantified the relevant pathogens.


title: Chapter 22. Non-HIV antiviral agents

text: Publisher Summary This chapter focuses on non-HIV antiviral agents. The development of antiviral agents to treat non-HIV infections is largely focused on therapies for the treatment of chronic hepatitis infections B and C. Nucleoside analog continue to be the mainstay of Hepatitis B Virus (HBV) therapeutics. The first small molecule inhibitor of Hepatitis C Virus (HCV), the NS3 protease inhibitor BILN-2061, entered phase 2 clinical trials, producing a striking reduction in viral load in treated individuals. The development of the HCV replicon system and its application to screening for antiviral agents provided tangible benefit with the disclosure of mechanistically and structurally diverse HCV inhibitors. Adefovir dipivoxil has been approved in the United States and the European Union for the treatment of HBV, providing a second small molecule antiviral to add to lamivudine (3TC) and the injectable protein IFNα as the only approved agents for treating HBV infection. The chapter also provides details of the inhibitors of hepatitis B and C virus, the inhibitors of simplex virus and human cytomegalovirus, the inhibitors of respiratory viruses and the inhibitors of West Nile virus and Papilloma virus.


Coronavirus Disease 2019: Understanding Immunopathogenesis Is the “Holy Grail” to Explain Why Children Have Less Severe Acute Disease


title: Viral rewiring of cellular lipid metabolism to create membranous replication compartments

text: Positive-strand RNA (+RNA) viruses (e.g. poliovirus, hepatitis C virus, dengue virus, SARS-coronavirus) remodel cellular membranes to form so-called viral replication compartments (VRCs), which are the sites where viral RNA genome replication takes place. To induce VRC formation, these viruses extensively rewire lipid metabolism. Disparate viruses have many commonalities as well as disparities in their interactions with the host lipidome and accumulate specific sets of lipids (sterols, glycerophospholipids, sphingolipids) at their VRCs. Recent years have seen an upsurge in studies investigating the role of lipids in +RNA virus replication, in particular of sterols, and uncovered that membrane contact sites and lipid transfer proteins are hijacked by viruses and play pivotal roles in VRC formation.


title: A three-generation family cluster with COVID-19 infection: Should quarantine be prolonged?

text: Abstract Objectives Families are a transmission route for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) because of the close contact. Monitoring of the viral load will be a valuable method to reduce the optimal number of quarantine days, especially in presymptomatic and symptomatic carriers of their households. The traditional three-generation families living together are seen frequently in East Asia, including in Taiwan. Study Design We report on a family cluster with six individuals infected with coronavirus disease in Taiwan. Methods The current public policy in Taiwan is quarantine for at least 14 days, based on the incubation period, or until the patient has tested negative three days in a row using the SARS-CoV-2 reverse transcription-polymerase chain reaction. Details on the onset date of clinical symptoms, throat swab conversion, and course of disease were collected from medical records retrospectively. Results In the household of this three-generation Taiwanese family, the infection rate was 60%. The ratio of males to females was 4:2, and the age range was 11–85 years. The prevalence of asymptomatic disease was 33.3% (2/6). The longest throat swab conversion time was 37 days, and the estimated course of disease from symptoms to first conversion of throat swab was 59 days. Conclusions Large families, including three-generation families in a single dwelling, should be monitored when the index case is found. Presymptomatic and symptomatic family members could be quarantined for an appropriate duration which, in our experience, is 2 months.


Letter to the Editor: The Effects of Force-Feeding Sick Dairy Calves: A Comment on Quigley et al. (2006)


title: Post COVID-19: Planning strategies to resume orthopaedic surgery –challenges and considerations

text: Abstract The Coronavirus SARS-CoV-2 (COVID-19) pandemic has had a substantial effect on the health care systems around the world. As the disease has spread, many developed and developing countries have been stretched on their resources such as personnel as well as adequate equipment. As a result of resource disparity, in a populous country like India, the elective orthopaedic surgeries stand cancelled whilst trauma and emergency services have been reorganised following Indian Orthopaedic Association and recent urgent British Orthopaedic association guidelines. Though these guidelines provide strategies to deal with trauma and orthopaedic surgery management in the present scenario, once the COVID-19 pandemic stabilizes, restarting elective orthopaedic surgery and managing delayed trauma conditions in evolving health care systems is going to be a profound task. We look at the future challenges and considerations of re-establishing trauma and orthopaedic flow during the post-COVID-19 phase and suggest an algorithm to follow (Fig. 1).


title: A Novel Negative Pressure Isolation Device for Aerosol Transmissible COVID-19

text: The coronavirus disease 2019 (COVID-19) pandemic creates a need to protect health care workers (HCWs) from patients undergoing aerosol-generating procedures which may transmit the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Existing personal containment devices (PCDs) may protect HCWs from respiratory droplets but not from potentially dangerous respiratory-generated aerosols. We describe a new PCD and its aerosol containment capabilities. The device ships flat and folds into a chamber. With its torso drape and protective arm sleeves mounted, it provides contact, droplet, and aerosol isolation during intubation and cardiopulmonary resuscitation (CPR). Significantly improved ergonomics, single-use workflow, and ease of removal distinguish this device from previously published designs.


title: Immune responses to porcine epidemic diarrhea virus (PEDV) in swine and protection against subsequent infection

text: Understanding the immune responses against Porcine epidemic diarrhea virus (PEDV) is important to prevent infection and to design control strategies. We evaluated both systemic and mucosal immune responses to PEDV in pigs and assessed if prior exposure to virus protects against re-infection. Three-week-old pigs were infected with PEDV and immune response in blood, intestine, and mesenteric lymph node (MLN) was evaluated. At 30 dpi, virus exposed pigs were challenged with a field isolate of PEDV and immune response at 5 d post challenge was evaluated. We found that PEDV RNA persists in the intestine even after fecal shedding of the virus was stopped at 28 dpi and pigs previously exposed to PEDV are protected from virus shedding after re-infection. PEDV infection induced both humoral and cell mediated immune response with an increase in PEDV specific IgA and IgG antibodies in intestine and serum. Flow cytometry analysis showed a significantly higher frequency of B cells and lower frequency of T cells at 4 dpi. The frequency of CD4/CD8 double positive (DP) memory T cells was significantly increased in the MLN of challenged animals. These studies may provide further insights into understanding the mucosal immune response to PEDV and its role in protection against disease.


title: Fast type I interferon response protects astrocytes from flavivirus infection and virus-induced cytopathic effects

text: BACKGROUND: Neurotropic flaviviruses such as tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV), West Nile virus (WNV), and Zika virus (ZIKV) are causative agents of severe brain-related diseases including meningitis, encephalitis, and microcephaly. We have previously shown that local type I interferon response within the central nervous system (CNS) is involved in the protection of mice against tick-borne flavivirus infection. However, the cells responsible for mounting this protective response are not defined. METHODS: Primary astrocytes were isolated from wild-type (WT) and interferon alpha receptor knock out (IFNAR(−/−)) mice and infected with neurotropic flaviviruses. Viral replication and spread, IFN induction and response, and cellular viability were analyzed. Transcriptional levels in primary astrocytes treated with interferon or supernatant from virus-infected cells were analyzed by RNA sequencing and evaluated by different bioinformatics tools. RESULTS: Here, we show that astrocytes control viral replication of different TBEV strains, JEV, WNV, and ZIKV. In contrast to fibroblast, astrocytes mount a rapid interferon response and restrict viral spread. Furthermore, basal expression levels of key interferon-stimulated genes are high in astrocytes compared to mouse embryonic fibroblasts. Bioinformatic analysis of RNA-sequencing data reveals that astrocytes have established a basal antiviral state which contributes to the rapid viral recognition and upregulation of interferons. The most highly upregulated pathways in neighboring cells were linked to type I interferon response and innate immunity. The restriction in viral growth was dependent on interferon signaling, since loss of the interferon receptor, or its blockade in wild-type cells, resulted in high viral replication and virus-induced cytopathic effects. Astrocyte supernatant from TBEV-infected cells can restrict TBEV growth in astrocytes already 6 h post infection, the effect on neurons is highly reinforced, and astrocyte supernatant from 3 h post infection is already protective. CONCLUSIONS: These findings suggest that the combination of an intrinsic constitutive antiviral response and the fast induction of type I IFN production by astrocytes play an important role in self-protection of astrocytes and suppression of flavivirus replication in the CNS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-016-0748-7) contains supplementary material, which is available to authorized users.


title: Recombinant lentogenic Newcastle disease virus expressing Ebola virus GP infects cells independently of exogenous trypsin and uses macropinocytosis as the major pathway for cell entry

text: BACKGROUND: Using reverse genetics, we generated a recombinant low-pathogenic LaSota strain Newcastle disease virus (NDV) expressing the glycoprotein (GP) of Ebola virus (EBOV), designated rLa-EBOVGP, and evaluated its biological characteristic in vivo and in vitro. RESULTS: The introduction and expression of the EBOV GP gene did not increase the virulence of the NDV vector in poultry or mice. EBOV GP was incorporated into the particle of the vector virus and the recombinant virus rLa-EBOVGP infected cells and spread within them independently of exogenous trypsin. rLa-EBOVGP is more resistant to NDV antiserum than the vector NDV and is moderately sensitive to EBOV GP antiserum. More importantly, infection with rLa-EBOVGP was markedly inhibited by IPA3, indicating that rLa-EBOVGP uses macropinocytosis as the major internalization pathway for cell entry. CONCLUSIONS: The results demonstrate that EBOV GP in recombinant NDV particles functions independently to mediate the viral infection of the host cells and alters the cell-entry pathway.


title: Operation of mitochondrial machinery in viral infection-induced immune responses

text: Abstract Mitochondria have been recognized as ancient bacteria that contain evolutionary endosymbionts. Metabolic pathways and inflammatory signals interact within mitochondria in response to different stresses, such as viral infections. In this commentary, we address several interesting questions, including (1) how do mitochondrial machineries participate in immune responses; (2) how do mitochondria mediate antiviral immunity; (3) what mechanisms involved in mitochondrial machinery, including the downregulation of mitochondrial DNA (mtDNA), disturbances of mitochondrial dynamics, and the induction of mitophagy and regulation of apoptosis, have been adopted by viruses to evade antiviral immunity; (4) what mechanisms involve the regulation of mitochondrial machineries in antiviral therapeutics; and (5) what are the potential challenges and perspectives in developing mitochondria-targeting antiviral treatments? This commentary provides a comprehensive review of the roles and mechanisms of mitochondrial machineries in immunity, viral infections and related antiviral therapeutics.


title: How should be the Surgical Treatment Approach during the COVID-19 Pandemic in Patients with Gastrointestinal Cancer?

text: COVID-19 was first seen in China at the end of December 2019. COVID-19 is a novel type of coronavirus that is defined as SARS-CoV-2, which can be mild or severe in the lungs, causing acute respiratory infection. The disease was first presented in the literature as Coronavirus Disease 2019 (COVID-19) in February 2020. The disease spread rapidly and was declared as a pandemic by the World Health Organization (WHO) on March 11, 2020. There have been approximately 7734185 reported cases, and 412369 reported deaths to date (09/June/2020). As COVID-19 spread in the world and our country, hospitals struggling with this disease have also become risky areas for transmitting the disease. Health workers also have a high risk of viral contamination from direct contact of droplets and surfaces. Personal protective equipment (PPE), such as masks, coveralls, gloves, face shields and/or goggles, are mandatory. The aim is to spread the flow of cases requiring hospitalization over time, thereby preventing possible accumulation in hospitals. All non-urgent procedures, such as elective surgeries and diagnostic interventions, were significantly affected. The hospitalization procedures were mostly allocated to patients with COVID-19 infection, and surgical operations were postponed. Only urgent surgical cases and oncological surgeries that cannot be postponed were performed during this pandemic process. Patients followed by oncology are immunosuppressed both because of the disease itself and the side effects of chemotherapy and/or radiotherapy taken. This makes patients more susceptible to infections, and the prognosis of infections in these patients is worse and more destructive. Cancer patients are almost twice as likely to catch COVID-19 compared to the general population. The choice of surgical procedures and perioperative management of the patients with malignancy has become even more important in the COVID-19 pandemic. In this study, we analyzed the treatment processes of our patients with malignancy that underwent a surgical oncological procedure during this pandemic.


title: An updated review of the association of host genetic factors with susceptibility and resistance to COVID‐19

text: The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in human populations sparked a global pandemic of the coronavirus disease 2019 (COVID‐19). According to preliminary data, about 14% of cases are considered severe and 5% of cases result in critical illness and, reported case fatality rates vary from 1% to more than 7%. However, the symptoms of the disease and the clinical outcome are very different in infected people. In view of these differences, it is clearly apparent that to gain insight into the biology of the SARS‐CoV‐2, it is important to study not just the infectious particle in itself but also to investigate the virus‐host cell interactions that occur during infection. This review seeks to consider the various aspects of genetic factors in determining the susceptibility and host resistance to SARS‐CoV‐2 throughout the recently published literature.


title: A multi-centre pilot proficiency programme to assess the quality of molecular detection of respiratory viruses

text: Abstract Objectives To assess the quality of molecular detection of respiratory viruses in clinical diagnostic laboratories. Study design Respiratory virus proficiency panels were produced from diluted stocks of respiratory viruses provided and tested by four reference laboratories. The panels consisted of strong positive, positive, low positive and negative samples for influenza viruses A and B, respiratory syncytial virus, parainfluenza viruses 1 and 3, adenovirus serotypes 4 and 7, human rhinovirus serotypes 16, 72 and 90, human coronaviruses OC43 and 229E. The panels were sent to 17 participants; results and information on methodology was collected. Results All laboratories returned results, of which five submitted complete data sets. So, for analysis all results were combined. Samples were correctly identified by participants in 93.75%, 76.75% and 47.03% for the high positive, positive and low positive samples, respectively. One false positive was reported for all data sets (1.1%). The overall score for all assays using different methodologies was 78.8%. Laboratory performance was not dependant on methodology as all in-house methodologies could achieve optimal results, but dependant on careful optimisation and procedures specific to the laboratory. Conclusions The first proficiency panel showed that in general all participants performed well. Although, it also highlights areas for improvement for all participants in order to generate robust results for use in clinical diagnostics.


title: The Impact of Human Mobility on HIV Transmission in Kenya

text: Disease spreads as a result of people moving and coming in contact with each other. Thus the mobility patterns of individuals are crucial in understanding disease dynamics. Here we study the impact of human mobility on HIV transmission in different parts of Kenya. We build an SIR metapopulation model that incorporates the different regions within the country. We parameterise the model using census data, HIV data and mobile phone data adopted to track human mobility. We found that movement between different regions appears to have a relatively small overall effect on the total increase in HIV cases in Kenya. However, the most important consequence of movement patterns was transmission of the disease from high infection to low prevalence areas. Mobility slightly increases HIV incidence rates in regions with initially low HIV prevalences and slightly decreases incidences in regions with initially high HIV prevalence. We discuss how regional HIV models could be used in public-health planning. This paper is a first attempt to model spread of HIV using mobile phone data, and we also discuss limitations to the approach.


Upsurge of deep venous thrombosis in patients affected by COVID-19: preliminary data and possible explanations


The added value of long-lasting preparedness for the management of a patient with Ebola


title: The impact of the COVID-19 pandemic on patients with OCD: effects of contamination symptoms and remission state before the quarantine in a preliminary naturalistic study

text: The containment measures implemented to reduce the progression of the COVID-19 pandemic can increase the risk of serious mental disorders, including obsessive-compulsive disorder (OCD). The general fear of getting infected and the importance given to personal hygiene, may have a negative impact on this clinical population. In a group of patients with OCD who had completed an evidence-based therapeutic path for OCD before the quarantine, this study evaluated the changes on OCD symptoms during the quarantine and investigated the effects of contamination symptoms and remission state before the quarantine on OCD symptom worsening during the quarantine. The Yale-Brown Obsessive Compulsive (Y-BOCS) Severity score, administered before the quarantine, was re-administered after six weeks since the beginning of the complete lockdown. A significant increase in obsession and compulsion severity emerged. Remission status on OCD symptoms and having contamination symptoms before the quarantine were significantly associated with more elevated OCD symptom worsening during the quarantine. To our knowledge, this is the first study which assessed OCD symptoms at the COVID-19 time. Our results support the need to improve relapse prevention during the period of social restrictions and develop alternative strategies such as online consultations and digital psychiatric management.


title: Subcutaneous administration of Interferon beta-1a for COVID-19: A non-controlled prospective trial

text: BACKGROUND: Recently, a new coronavirus spreads rapidly throughout the countries and resulted in a worldwide epidemic. Interferons have direct antiviral and immunomodulatory effects. Antiviral effects may include inhibition of viral replication, protein synthesis, virus maturation, or virus release from infected cells. Previous studies have shown that some coronaviruses are susceptible to interferons. The aim of this study was to evaluate the therapeutic effects of IFN-β-1a administration in COVID-19. METHODS: In this prospective non-controlled trial, 20 patients included. They received IFN-β-1a at a dose of 44 µg subcutaneously every other day up to 10 days. All patients received conventional therapy including Hydroxychloroquine, and lopinavir/ritonavir. Demographic data, clinical symptoms, virological clearance, and imaging findings recorded during the study. RESULTS: The mean age of the patients was 58.55 ± 13.43 years. Fever resolved in all patients during first seven days. Although other symptoms decreased gradually. Virological clearance results showed a significant decrease within 10 days. Imaging studies showed significant recovery after 14-day period in all patients. The mean time of hospitalization was 16.8 ± 3.4 days. There were no deaths or significant adverse drug reactions in the 14-day period. CONCLUSIONS: Our findings support the use of IFN-β-1a in combination with hydroxychloroquine and lopinavir/ritonavir in the management of COVID-19. Clinical trial registration number: IRCT20151227025726N12


Potential implications of COVID-19 pandemic on the homeless population


title: Glycoproteome in silkworm Bombyx mori and alteration by BmCPV infection

text: Abstract The biological functions of protein glycosylation have been increasingly recognized but not yet been very well understood, especially in lower organisms. Silkworm as a model lepidopteran insect and important economic insect, has been widely studied in life science, however, the current knowledge on the glycosylation status of its proteome is not satisfactory, and little is known about how pathogenic infections could affect the glycosylation status. This study performed large scale glycosite mapping for the silkworm Bombyx mori P50 strain, and quantitatively compared with that infected with the Bombyx mori cytoplasmic polyhedrosis virus (BmCPV). Some 400 glycoproteins were mapped in the silkworm, including N- and O-glycoproteins. Upon virus infection, the glycosylation levels of 41 N-glycopeptides were significantly changed, some of them belonging to transmembrane glycoproteins. The O-glycosylation profiles were also affected. In addition, 4 BmCPV-encoded viral proteins were found to be glycosylated for the first time, including polyhedrin, P101, VP3, and the NS protein. This study drafted a silkworm protein glycosylation map and underlined the potential impact of virus infection on glycosylation. Significance This study reveals the characteristics of the glycoproteome in the silkworm strain P50, and quantitatively compared to that infected by the virus BmCPV, which underlines the impact of virus infection on the alteration of protein glycosylation in invertebrate species. Our findings add to the knowledge of the post translational modifications of this model organism, and also uncovered for the first time the glycosylation status of the viral proteins expressed by BmCPV.


title: Dynamic changes of D-dimer and neutrophil-lymphocyte count ratio as prognostic biomarkers in COVID-19

text: BACKGROUND: Since December 2019, the outbreak of COVID-19 caused a large number of hospital admissions in China. Many patients with COVID-19 have symptoms of acute respiratory distress syndrome, even are in danger of death. This is the first study to evaluate dynamic changes of D-Dimer and Neutrophil-Lymphocyte Count Ratio (NLR) as a prognostic utility in patients with COVID-19 for clinical use. METHODS: In a retrospective study, we collected data from 349 hospitalized patients who diagnosed as the infection of the COVID-19 in Wuhan Pulmonary Hospital. We used ROC curves and Cox regression analysis to explore critical value (optimal cut-off point associated with Youden index) and prognostic role of dynamic changes of D-Dimer and NLR. RESULTS: Three hundred forty-nine participants were enrolled in this study and the mortality rate of the patients with laboratory diagnosed COVID-19 was 14.9%. The initial and peak value of D-Dimer and NLR in deceased patients were higher statistically compared with survivors (P < 0.001). There was a more significant upward trend of D-Dimer and NLR during hospitalization in the deceased patients, initial D-Dimer and NLR were lower than the peak tests (MD) -25.23, 95% CI: − 31.81- -18.64, P < 0.001; (MD) -43.73, 95% CI:-59.28- -31.17, P < 0.001. The test showed a stronger correlation between hospitalization days, PCT and peak D-Dimer than initial D-Dimer. The areas under the ROC curves of peak D-Dimer and peak NLR tests were higher than the initial tests (0.94(95%CI: 0.90–0.98) vs. 0.80 (95% CI: 0.73–0.87); 0.93 (95%CI:0.90–0.96) vs. 0.86 (95%CI:0.82–0.91). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR was 0.73 mg/L, 3.78 mg/L,7.13 and 14.31 respectively. 35 (10.03%) patients were intubated. In the intubated patients, initial and peak D-Dimer and NLR were much higher than non-intubated patients (P < 0.001). The critical value of initial D-Dimer, peak D-Dimer, initial NLR and peak NLR in prognosticate of intubation was 0.73 mg/L, 12.75 mg/L,7.28 and 27.55. The multivariable Cox regression analysis showed that age (HR 1.04, 95% CI 1.00–1.07, P = 0.01), the peak D-Dimer (HR 1.03, 95% CI 1.01–1.04, P < 0.001) were prognostic factors for COVID-19 patients’ death. CONCLUSIONS: To dynamically observe the ratio of D-Dimer and NLR was more valuable during the prognosis of COVID-19. The rising trend in D-Dimer and NLR, or the test results higher than the critical values may indicate a risk of death for participants with COVID-19.


title: A Conceptual Discussion about R(0) of SARS-COV-2 in Healthcare Settings

text: To date, no specific estimate of R(0) for SARS-CoV-2 is available for healthcare settings. Using inter-individual contact data, we highlight that R(0) estimates from the community cannot translate directly to healthcare settings, with pre-pandemic R(0) values ranging 1.3-7.7 in three illustrative healthcare institutions. This has implications for nosocomial Covid-19 control.


title: Detection and quantification of human metapneumovirus in pediatric specimens by real-time RT-PCR

text: Abstract Background: Human metapneumovirus (hMPV), a recently identified virus, causes respiratory illness in children. Objectives: A real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was developed and used to detect and quantify hMPV in respiratory specimens. Study design: The quantitative RT-PCR assay amplified an approximately 70 base pair fragment from the hMPV fusion protein gene. The assay was validated and used to test respiratory specimens obtained from children seen at a hospital in Seattle, Washington, from December 2002 through May 2003. Results: The assay detected 1000hMPV copies/mL of specimen, did not detect 19 other respiratory viruses, and was able to detect and accurately quantify isolates from the four known hMPV genetic lineages in a proficiency panel of 20 previously tested samples. hMPV was detected in 52 (7.2%) of 719 pediatric respiratory specimens. The mean log10copies/mL of hMPV in the 52 positive specimens was 7.67 (range=4.59–10.60). Children aged 7–12 months had a significantly higher hMPV prevalence (12.4%) than did children younger than 7 months (4.7%) (P <0.005). Children in this age group also had significantly higher levels of hMPV in their respiratory specimens (mean log8.43 copies/mL) than did the younger children (mean log6.93copies/mL) (P =0.0025). Conclusions: The rapid real-time RT-PCR assay described here is a sensitive test for clarifying the epidemiology of and diseases associated with hMPV.


title: The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro

text: Abstract Although several clinical trials are now underway to test possible therapies, the worldwide response to the COVID-19 outbreak has been largely limited to monitoring/containment. We report here that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum anti-viral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 h post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants further investigation for possible benefits in humans.


title: Canine and Feline Blood Donor Screening for Infectious Disease

text: Consensus Statements of the American College of Veterinary Internal Medicine (ACVIM) provide veterinarians with guidelines regarding the pathophysiology, diagnosis, or treatment of animal diseases. The foundation of the Consensus Statement is evidence‐based medicine, but if such evidence is conflicting or lacking, the panel provides interpretive recommendations on the basis of their collective expertise. The Consensus Statement is intended to be a guide for veterinarians, but it is not a statement of standard of care or a substitute for clinical judgment. Topics of statements and panel members to draft the statements are selected by the Board of Regents with input from the general membership. A draft prepared and input from Diplomates is solicited at the Forum and via the ACVIM Web site and incorporated in a final version. This Consensus Statement was approved by the Board of Regents of the ACVIM before publication.