title: Study on the initial velocity distribution of exhaled air from coughing and speaking

text: Abstract Increasing concerns about the spread of airborne pathogens such as severe acute respiratory syndrome (SARS) and novel swine-origin influenza A (H1N1) have attracted public attention to bioaerosols and protection against them. The airborne pathogens are likely to be expelled from coughing or speaking, so the physical data of the exhaled particles plays a key role in analyzing the pathway of airborne viruses. The objective of this study was to analyze the initial velocity and the angle of the exhaled airflow from coughing and speaking of 17 males and 9 females using Particle Image Velocimetry (PIV) and acrylic indoor chamber. The results showed that the average initial coughing velocity was 15.3m/s for the males and 10.6m/s for the females, while the average initial speaking velocity was 4.07m/s and 2.31m/s respectively. The angle of the exhaled air from coughing was around 38° for the males and 32° for the females, while that of the exhaled air from speaking was around 49° and 78° respectively. Also, the linear relation between the tested subject’s height and their coughing and speaking velocity was shown in this study.


title: A Single Dose of Azithromycin Does Not Improve Clinical Outcomes of Children Hospitalised with Bronchiolitis: A Randomised, Placebo-Controlled Trial

text: OBJECTIVE: Bronchiolitis, one of the most common reasons for hospitalisation in young children, is particularly problematic in Indigenous children. Macrolides may be beneficial in settings where children have high rates of nasopharyngeal bacterial carriage and frequent prolonged illness. The aim of our double-blind placebo-controlled randomised trial was to determine if a large single dose of azithromycin (compared to placebo) reduced length of stay (LOS), duration of oxygen (O(2)) and respiratory readmissions within 6 months of children hospitalised with bronchiolitis. We also determined the effect of azithromycin on nasopharyngeal microbiology. METHODS: Children aged ≤18 months were randomised to receive a single large dose (30 mg/kg) of either azithromycin or placebo within 24 hrs of hospitalisation. Nasopharyngeal swabs were collected at baseline and 48hrs later. Primary endpoints (LOS, O(2)) were monitored every 12 hrs. Hospitalised respiratory readmissions 6-months post discharge was collected. RESULTS: 97 children were randomised (n = 50 azithromycin, n = 47 placebo). Median LOS was similar in both groups; azithromycin = 54 hours, placebo = 58 hours (difference between groups of 4 hours 95%CI -8, 13, p = 0.6). O(2) requirement was not significantly different between groups; Azithromycin = 35 hrs; placebo = 42 hrs (difference 7 hours, 95%CI -9, 13, p = 0.7). Number of children re-hospitalised was similar 10 per group (OR = 0.9, 95%CI 0.3, 2, p = 0.8). At least one virus was detected in 74% of children. The azithromycin group had reduced nasopharyngeal bacterial carriage (p = 0.01) but no difference in viral detection at 48 hours. CONCLUSION: Although a single dose of azithromycin reduces carriage of bacteria, it is unlikely to be beneficial in reducing LOS, duration of O(2) requirement or readmissions in children hospitalised with bronchiolitis. It remains uncertain if an earlier and/or longer duration of azithromycin improves clinical and microbiological outcomes for children. The trial was registered with the Australian and New Zealand Clinical Trials Register. Clinical trials number: ACTRN12608000150347. http://www.anzctr.org.au/TrialSearch.aspx.


Treatment with proton pump inhibitors increases the risk of secondary infections and ARDS in hospitalized patients with COVID‐19: coincidence or underestimated risk factor?


Frequency of infections in 948 MPN patients: a prospective multicenter patient-reported pilot study


title: Astroviruses in Rabbits

text: By screening rabbits with enterocolitis or enteritis complex and asymptomatic rabbits, we identified a novel astrovirus. The virus was distantly related (19.3%–23.7% aa identity) in the capsid precursor to other mammalian astroviruses within the Mamastrovirus genus. By using real-time reverse transcription PCR, with specific primers and probes and targeting a conserved stretch in open reading frame 1b, we found rabbit astrovirus in 10 (43%) of 23 samples from animals with enteric disease and in 25 (18%) of 139 samples from asymptomatic animals in Italy during 2005–2008. The mean and median titers in the positive animals were 10(2)× and 10(3)× greater, respectively, in the symptomatic animals than in the asymptomatic animals. These findings support the idea that rabbit astroviruses should be included in the diagnostic algorithm of rabbit enteric disease and animal experiments to increase information obtained about their epidemiology and potential pathogenic role.


title: Monoclonal antibodies to the matrix (El) glycoprotein of mouse hepatitis virus protect mice from encephalitis

text: Abstract Monoclonal antibodies to the matrix or El glycoprotein of mouse hepatitis virus (MHV) were tested for their ability to protect mice from a normally lethal challenge of MHV-4. Four antibodies were tested, and two of these,J.1.3 and J.3.9, were protective. Protection did not correlate with virus neutralization in vitro, antibody isotype, recognition of a unique El antigenic site, or dependence on complement in vivo. Survival from acute encephalitis was followed by subacute demyelination, as has been shown with protection mediated by neutralizing monoclonal antibodies against the major glycoprotein, E2. These results demonstrate that antibodies which are specific for a viral matrix protein are able to alter the course of disease.


title: Could Intravenous Immunoglobulin Collected from Recovered Coronavirus Patients Protect against COVID-19 and Strengthen the Immune System of New Patients?

text: The emergence of the novel coronavirus in Wuhan, China, which causes severe respiratory tract infections in humans (COVID-19), has become a global health concern. Most coronaviruses infect animals but can evolve into strains that cross the species barrier and infect humans. At the present, there is no single specific vaccine or efficient antiviral therapy against COVID-19. Recently, we showed that intravenous immunoglobulin (IVIg) treatment reduces inflammation of intestinal epithelial cells and eliminates overgrowth of the opportunistic human fungal pathogen Candida albicans in the murine gut. Immunotherapy with IVIg could be employed to neutralize COVID-19. However, the efficacy of IVIg would be better if the immune IgG antibodies were collected from patients who have recovered from COVID-19 in the same city, or the surrounding area, in order to increase the chance of neutralizing the virus. These immune IgG antibodies will be specific against COVID-19 by boosting the immune response in newly infected patients. Different procedures may be used to remove or inactivate any possible pathogens from the plasma of recovered coronavirus patient derived immune IgG, including solvent/detergent, 60 °C heat-treatment, and nanofiltration. Overall, immunotherapy with immune IgG antibodies combined with antiviral drugs may be an alternative treatment against COVID-19 until stronger options such as vaccines are available.


title: Viral Aetiology in Adults with Acute Upper Respiratory Tract Infection in Jinan, Northern China

text: Our study investigated the epidemiology of respiratory viruses in adult patients with upper respiratory tract infection (URTI) between August 2009 and September 2010 in Jinan, northern China. Nasal and throat swabs (n = 596) were collected from adult patients with URTIs. Nine respiratory-related viruses, including IFV, PIV, HRV, HMPV, HBoV, HCoV, ADV, RSV, and EV, were detected in all samples by conventional and reverse transcription polymerase chain reactions. Positive detection rate for respiratory virus was 38.76% and codetection rate was 4.70% in adults with acute respiratory tract infections. IFV (20.81%) was the dominant agent detected and IFVB had a higher incidence (12.58%) than IFVA (7.72%). Detection rates of 8.22%, 5.03%, 3.69%, and 2.52% were observed for HBoV, HRV, EV, and RSV, respectively. HCoV had the lowest detection rate of 0.50%. HBoV, HRV, EV, and ADV infection rates were higher in the 14–25-year-old group than in the 26–65-year-old group. Codetection rates were higher (7.52%) in the 14–25-year-old group than in the older age group (2.64%). The spectrum of respiratory virus infection in adult patients with URTIs was different in Jinan compared with other cities in China.


title: Structure-based drug designing for potential antiviral activity of selected natural products from Ayurveda against SARS-CoV-2 spike glycoprotein and its cellular receptor

text: The recent outbreak of COVID-19 caused by SARS-CoV-2 brought a great global public health and economic concern. SARS-CoV-2 is an enveloped RNA virus, from the genus Betacoronavirus. Although few molecules have been tested and shown some efficacy against SARS-CoV-2 in humans but a safe and cost-effective attachment inhibitors are still required for the treatment of COVID-19. Natural products are gaining attention because of the large therapeutic window and potent antiviral, immunomodulatory, anti-inflammatory, and antioxidant properties. Therefore, this study was planned to screen natural products from Ayurveda that have the potential to modulate host immune system as well as block the virus entry in host cells by interfering its interaction with cellular receptor and may be used to develop an effective and broad-spectrum strategy for the management of COVID-19 as well as other coronavirus infections in coming future. To decipher the antiviral activity of the selected natural products, molecular docking was performed. Further, the drug-likeness, pharmacokinetics and toxicity parameters of the selected natural products were determined. Docking results suggest that curcumin and nimbin exhibits highest interaction with spike glycoprotein (MolDock score − 141.36 and − 148.621 kcal/mole) and ACE2 receptor (MolDock score − 142.647 and − 140.108 kcal/mole) as compared with other selected natural products/drugs and controls. Also, the pharmacokinetics data illustrated that all selected natural products have better pharmacological properties (low molecular weight; no violation of Lipinski rule of five, good absorption profiles, oral bioavailability, good blood–brain barrier penetration, and low toxicity risk). Our study exhibited that curcumin, nimbin, withaferin A, piperine, mangiferin, thebaine, berberine, and andrographolide have significant binding affinity towards spike glycoprotein of SARS-CoV-2 and ACE2 receptor and may be useful as a therapeutic and/or prophylactic agent for restricting viral attachment to the host cells. However, few other natural products like resveratrol, quercetin, luteolin, naringenin, zingiberene, and gallic acid has the significant binding affinity towards ACE2 receptor only and therefore may be used for ACE2-mediated attachment inhibition of SARS-CoV-2.


title: Group Debriefing for People with Chronic Diseases During the SARS Pandemic: Strength-Focused and Meaning-Oriented Approach for Resilience and Transformation (SMART)

text: This study presented preliminary results on the efficacy of a novel group debriefing model called Strength-Focused and Meaning-Oriented Approach for Resilience and Transformation (SMART). The SMART debriefing (1) aimed at boosting resilience and catalyzing transformation among persons undergoing stressful events, (2) adopted a growth-oriented and holistic approach of health promotion, and (3) employed methods drawn from various indigenous sources (e.g. Asian philosophies and Traditional Chinese Medicine). Participants (N=51) were people with chronic diseases recruited about 1 month (August 2003) after the Severe Acute Respiratory Syndrome (SARS) outbreak was eventually under control, after causing widespread panic in Hong Kong. After the one-day group debriefing, participants showed significant decrease in depression level, as measured by Brief Symptom Inventory (Derogatis & Melisaratos, 1983, Psychological Medicine, 13(3), 595–605) and changes in cognitive appraisal towards SARS. Such changes were sustained in a 1-month follow-up. Clinical implications and directions for further study were discussed.


title: nCOV-19 peptides mass fingerprinting identification, binding, and blocking of inhibitors flavonoids and anthraquinone of Moringa oleifera and hydroxychloroquine

text: An rare pandemic of viral pneumonia occurs in December 2019 in Wuhan, China, which is now recognized internationally as Corona Virus Disease 2019 (COVID-19), the etiological agent classified as Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). According to the World Health Organization (WHO), it has so far expanded to more than 213 countries/territories worldwide. Our study aims to find the viral peptides of SARS-COV-2 by peptide mass fingerprinting (PMF) in order to predict its novel structure and find an inhibitor for each viral peptide. For this reason, we calculated the mass of amino acid sequences translated from the SARS-CoV2 whole genome and identify the peptides that may be a target for inhibition. Molecular peptide docking with Moringa oleifera, phytochemicals (aqueous and ethanolic) leaf extracts of flavonoids (3.56 ± 0.03), (3.83 ± 0.02), anthraquinone (11.68 ± 0.04), (10.86 ± 0.06) and hydroxychloroquine present therapy of COVID-19 in Pakistan for comparative study. Results indicate that 15 peptides of SARS-CoV2 have been identified from PMF, which is then used as a selective inhibitor. The maximum energy obtained from AutoDock Vina for hydroxychloroquine is –5.1 kcal/mol, kaempferol (flavonoid) is –6.2 kcal/mol, and for anthraquinone –6 kcal/mol. Visualization of docking complex, important effects are observed regarding the binding of peptides to drug compounds. In conclusion, it is proposed that these compounds are effective antiviral agents against COVID-19 and can be used in clinical trials. Communicated by Ramaswamy H. Sarma


title: Camel exposure and knowledge about MERS-CoV among Australian Hajj pilgrims in 2014

text: [Image: see text]


title: In vitro analysis of the oligodendrocyte lineage in mice during demyelination and remyelination

text: A demyelinating disease induced in C57B1/6N mice by intracranial injection of a coronavirus (murine hepatitis virus strain A59) is followed by functional recovery and efficient CNS myelin repair. To study the biological properties of the cells involved in this repair process, glial cells were isolated and cultured from spinal cords of these young adult mice during demyelination and remyelination. Using three-color immunofluorescence combined with [3H]thymidine autoradiography, we have analyzed the antigenic phenotype and mitotic potential of individual glial cells. We identified oligodendrocytes with an antibody to galactocerebroside, astrocytes with an antibody to glial fibrillary acidic protein, and oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells with the O4 antibody. Cultures from demyelinated tissue differed in several ways from those of age-matched controls: first, the total number of O-2A lineage cells was strikingly increased; second, the O-2A population consisted of a higher proportion of O4-positive astrocytes and cells of mixed oligodendrocyte-astrocyte phenotype; and third, all the cell types within the O-2A lineage showed enhanced proliferation. This proliferation was not further enhanced by adding PDGF, basic fibroblast growth factor (bFGF), or insulin-like growth factor I (IGF-I) to the defined medium. However, bFGF and IGF-I seemed to influence the fate of O-2A lineage cells in cultures of demyelinated tissue. Basic FGF decreased the percentage of cells expressing galactocerebroside. In contrast, IGF-I increased the relative proportion of oligodendrocytes. Thus, O-2A lineage cells from adult mice display greater phenotypic plasticity and enhanced mitotic potential in response to an episode of demyelination. These properties may be linked to the efficient remyelination achieved in this demyelinating disease.


title: A method to provide improved dose–response estimates for airborne pathogens in animals: An example using porcine reproductive and respiratory syndrome virus

text: Abstract This paper describes a method to provide improved probability estimates that exposure to a specific dose of an airborne infectious pathogen will result in animal infection. Individual animals were exposed to a specific dose of airborne pathogen. Following exposure, animals were individually housed and monitored for evidence of infection. The detection of specific antibodies and/or the pathogen in diagnostic specimens was evidence that the exposure dose resulted in infection. If replicated over a range of doses, the results can be used to derive a dose–response curve for a variety of animal species and infectious pathogens. This information is useful in estimating the likelihood of infection associated with exposure to airborne infectious microorganisms. Applications include predicting the risk of transmission associated with exposure to airborne pathogens, modeling the transmission of airborne pathogens, and determining requirements for effective exposure doses for vaccines delivered in aerosols.


title: Provision of Emergency Maxillofacial Service During the COVID-19 Pandemic : A Collaborative Five Centre UK Study

text: The global pandemic of Coronavirus disease (COVID-19) represents one of the greatest challenges to healthcare systems, and has forced medical specialties to rapidly adapt their approaches to patient care. Oral and Maxillofacial Surgery is considered particularly at risk of disease transmission due to aerosol generation during surgical interventions, patient proximity and operating environment. On day 2 (26th March, 2020) of when severe restrictions in population movement were instigated in the United Kingdom, we began a study to prospectively monitor the presentation and management of maxillofacial emergencies at five hospital trusts. Data was collected onto an online live database fed through a smartphone application. Of the total 529 patients over six weeks, 395 attended for face-to-face consultations and 134 patients received remote consultations via telephone or video link. There were 255 trauma related cases, 221 infection and 48 cases of postoperative complications. Most trauma cases were minor soft tissue injury related to slip, trip or fall at home. There were 44 cases of facial fractures with a tendency for conservative treatment. 19 cases were related to domestic violence or self-harm. Of the 211 dental related emergencies, 71% could have been managed in the primary care setting. A quarter of all emergency patients were satisfactorily managed by remote consultations. There was a significant change in the provision of emergency maxillofacial service during the pandemic lockdown. We discuss the study findings as well as the potential implications in relation to planning for possible further COVID- 19 spikes and future pandemics.


title: Screening of COVID-19-associated hypercoagulopathy using rotational thromboelastometry

text: • COVID-19 develop thrombosis. • Rotational thromboelastometry is useful for screening.


title: Antibody response to equine coronavirus in horses inoculated with a bovine coronavirus vaccine

text: A vaccine for equine coronavirus (ECoV) is so far unavailable. Bovine coronavirus (BCoV) is antigenically related to ECoV; it is therefore possible that BCoV vaccine will induce antibodies against ECoV in horses. This study investigated antibody response to ECoV in horses inoculated with BCoV vaccine. Virus neutralization tests showed that antibody titers against ECoV increased in all six horses tested at 14 days post inoculation, although the antibody titers were lower against ECoV than against BCoV. This study showed that BCoV vaccine provides horses with antibodies against ECoV to some extent. It is unclear whether antibodies provided by BCoV vaccine are effective against ECoV, and therefore ECoV challenge studies are needed to evaluate efficacy of the vaccine in the future.


title: European Human Rights Dimension of the Online Access to Cultural Heritage in Times of the COVID-19 Outbreak

text: The 1948 Universal Declaration of Human Rights recognized that “everyone has the right freely to participate in the cultural life of the community, to enjoy the arts and to share in scientific advancement and its benefits”. As a result, cultural rights have been understood as inseparable from human rights and require protection mechanisms within particular international (including regional) legal systems. The European continent is proud to have developed one of the most effective mechanisms of the human rights protection by establishing the Council of Europe and adopting the European Court of Human Rights. The recent outbreak of the COVID-19 reformulated many concepts of access to human rights and possibilities to enjoy freedoms. Even if access to culture (access to cultural heritage) has been available online for many years, it is the time of globally occurring lockdowns that forced people to stay home and found themselves in a situation when all of a sudden online access to culture became the only way of access to culture. The article aims to analyze the current situation in Europe by asking questions if and how online access to culture is recognized and protected under the Council of Europe’s mechanisms with special emphasis on the case-law of the European Court of Human Rights in this field.


title: Worldwide Reduction in MERS Cases and Deaths since 2016

text: Since 2012, Middle East respiratory syndrome (MERS) coronavirus has infected 2,442 persons worldwide. Case-based data analysis suggests that since 2016, as many as 1,465 cases and 293–520 deaths might have been averted. Efforts to reduce the global MERS threat are working, but countries must maintain vigilance to prevent further infections.


title: Time for T? Immunoinformatics addresses vaccine design for neglected tropical and emerging infectious diseases

text: Vaccines have been invaluable for global health, saving lives and reducing healthcare costs, while also raising the quality of human life. However, newly emerging infectious diseases (EID) and more well-established tropical disease pathogens present complex challenges to vaccine developers; in particular, neglected tropical diseases, which are most prevalent among the world’s poorest, include many pathogens with large sizes, multistage life cycles and a variety of nonhuman vectors. EID such as MERS-CoV and H7N9 are highly pathogenic for humans. For many of these pathogens, while their genomes are available, immune correlates of protection are currently unknown. These complexities make developing vaccines for EID and neglected tropical diseases all the more difficult. In this review, we describe the implementation of an immunoinformatics-driven approach to systematically search for key determinants of immunity in newly available genome sequence data and design vaccines. This approach holds promise for the development of 21st century vaccines, improving human health everywhere.


title: Import seltener, aber lebensbedrohlicher und hochansteckender Erreger: Heutige Situation und Ausblick

text: Internists should expect to be the first contact for patients with rare, but highly contagious, life-threatening illnesses. Although certainly not encountered often, it is associated with significant consequences. Thus, physicians should be familiar with viral hemorrhagic fevers: filoviruses cause Ebola and Marburg fever, arenaviruses cause Lassa fever and South American hemorrhagic fevers, and the bunyaviruses cause among others Crimean–Congo hemorrhagic fever. Furthermore, physicians should be familiar with highly contagious respiratory infections, such as hantavirus pulmonary syndrome, pneumonic plague, and Middle East respiratory syndrome (MERS).


Mild infection of a novel H7N9 avian influenza virus in children in Shanghai


title: SARS‐CoV‐2 Seroconversion in Humans: A Detailed Protocol for a Serological Assay, Antigen Production, and Test Setup

text: In late 2019, cases of atypical pneumonia were detected in China. The etiological agent was quickly identified as a betacoronavirus (named SARS‐CoV‐2), which has since caused a pandemic. Several methods allowing for the specific detection of viral nucleic acids have been established, but these only allow detection of the virus during a short period of time, generally during acute infection. Serological assays are urgently needed to conduct serosurveys, to understand the antibody responses mounted in response to the virus, and to identify individuals who are potentially immune to re‐infection. Here we describe a detailed protocol for expression of antigens derived from the spike protein of SARS‐CoV‐2 that can serve as a substrate for immunological assays, as well as a two‐stage serological enzyme‐linked immunosorbent assay (ELISA). These assays can be used for research studies and for testing in clinical laboratories. © 2020 The Authors. Current Protocols in Microbiology published by Wiley Periodicals LLC. Basic Protocol 1: Mammalian cell transfection and protein purification Basic Protocol 2: A two‐stage ELISA for high‐throughput screening of human serum samples for antibodies binding to the spike protein of SARS‐CoV‐2


title: Building a Multi-Institutional and Interdisciplinary Team to Develop a Zoonotic Tuberculosis Roadmap

text: Tuberculosis (TB), as the major infectious disease in the world, has devastating consequences for not only humans, but also cattle and several wildlife species. This disease presents additional challenges to human and veterinary health authorities given the zoonotic nature of the pathogens responsible for the disease across species. One of the main public health challenges regarding zoonotic TB (ZTB) caused by Mycobacterium bovis is that the true incidence of this type of TB in humans is not known and is likely to be underestimated. To effectively address challenges posed by ZTB, an integrated One Health approach is needed. In this manuscript, we describe the rationale, major steps, timeline, stakeholders, and important events that led to the assembling of a true integrated multi-institutional and interdisciplinary team that accomplished the ambitious goal of developing a ZTB roadmap, published in October, 2017. It outlines key activities to address the global challenges regarding the prevention, surveillance, diagnosis, and treatment of ZTB. We discuss and emphasize the importance of integrated approaches to be able to accomplish the short (year 2020) and medium term (year 2025) goals outlined in the ZTB roadmap.


title: The Porcine MicroRNA Transcriptome Response to Transmissible Gastroenteritis Virus Infection

text: Transmissible gastroenteritis virus (TGEV; Coronaviridae family) causes huge economic losses to the swine industry. MicroRNAs (miRNAs) play a regulatory role in viral infection and may be involved in the mammalian immune response. Here, we report a comprehensive analysis of host miRNA expression in TGEV-infected swine testis (ST) cells. Deep sequencing generated 3,704,353 and 2,763,665 reads from uninfected ST cells and infected ST cells, respectively. The reads were aligned to known Sus scrofa pre-miRNAs in miRBase 19, identifying 284 annotated miRNAs. Certain miRNAs were differentially regulated during TGEV infection. 59 unique miRNAs displayed significant differentially expression between the normal and TGEV-infected ST cell samples: 15 miRNAs were significantly up-regulated and 44 were significantly down-regulated. Stem-loop RT-PCR was carried out to determine the expression levels of specific miRNAs in the two samples, and the results were consistent with those of sequencing. Gene ontology enrichment analysis of host target genes demonstrated that the differentially expressed miRNAs are involved in regulatory networks, including cellular process, metabolic process, immune system process. This is the first report of the identification of ST cell miRNAs and the comprehensive analysis of the miRNA regulatory mechanism during TGEV infection, which revealed the miRNA molecular regulatory mechanisms for the viral infection, expression of viral genes and the expression of immune-related genes. The results presented here will aid research on the prevention and treatment of viral diseases.


title: FDA approved drugs as potential Ebola treatments

text: In the search for treatments for the Ebola Virus, multiple screens of FDA drugs have led to the identification of several with promising in vitro activity. These compounds were not originally developed as antivirals and some have been further tested in mouse in vivo models. We put forward the opinion that some of these drugs could be evaluated further and move into the clinic as they are already FDA approved and in many cases readily available. This may be important if there is a further outbreak in future and no other therapeutic is available.


title: Continuous physiological monitoring using wearable technology to inform individual management of infectious diseases, public health and outbreak responses

text: Abstract Optimal management of infectious diseases is guided by up-to-date information at the individual and public health level. For infections of global importance including emerging pandemics such as COVID-19 or prevalent endemic diseases such like dengue, identifying patients at risk of severe disease and clinical deterioration can be challenging given the majority present with a mild illness. In our article, we describe the use of wearable technology for continuous physiological monitoring in healthcare. Deployment of wearables in hospital settings for the management of infectious diseases, or in the community to support syndromic surveillance during outbreaks could provide significant, cost effective advantages and improve healthcare delivery. We highlight a range of promising technologies employed by wearable devices and discuss the technical and ethical issues relating to implementation in the clinic, with specific focus on low- and middle- income countries. Finally, we propose a set of essential criteria for the roll-out of wearable technology for clinical use.


title: Modelling the evolution trajectory of COVID-19 in Wuhan, China: Experience and suggestions

text: Abstract Objectives In December 2019, a novel coronavirus disease (COVID-19) emerged in Wuhan city, China, which has subsequently led to a global pandemic. At the time of writing, COVID-19 in Wuhan appears to be in the final phase and under control. However, many other countries, especially the US, Italy and Spain, are still in the early phases and dealing with increasing cases every day. Therefore, this article aims to summarise and share the experience of controlling the spread of COVID-19 in Wuhan and provide effective suggestions to enable other countries to save lives. Study Design Data from the National Health Commission of China is used to investigate the evolution trajectory of COVID-19 in Wuhan and discuss the impacts of the intervention strategies. Methods A four-stage modified Susceptible-Exposed-Infectious-Removed (SEIR) model is presented. This model considers many influencing factors, including chunyun (the Spring festival), sealing off the city and constructing the Fang Cang shelter hospitals. In addition, a novel method is proposed to address the abnormal data on 12-13 February as a result of changing diagnostic criteria. Four different scenarios are considered to capture different intervention measures in practice. The exposed population in Wuhan who moved out prior to sealing off the city have also been identified and an analysis on where they had gone was performed using the Baidu migration index. Results The results demonstrate that the four-stage model was effective in forecasting the peak, size and duration of COVID-19. We found that the combined intervention measures are the only effective way to control the spread and not a single one of them can be omitted. We estimate that England will be another epicentre due to its incorrect response at the initial stages of COVID-19. Fortunately, big data technology can help provide early warnings to new areas of the pandemic. Conclusions The four-stage SEIR model was effective in capturing the evolution trajectory of COVID-19. Based on the model analysis, several effective suggestions are proposed to prevent and control the pandemic for countries that are still in the initial phases.


title: From spectators to implementers: civil society organizations involved in AIDS programmes in China

text: Background Over the past 20 years, civil society organizations (CSOs) in China have significantly increased their involvement in the AIDS response. This article aims to review the extent of civil society participation in China AIDS programmes over the past two decades. Methods A desk review was conducted to collect Chinese government policies, project documents and published articles on civil society participation of HIV/AIDS programmes in China over the past two decades. Assessment focused on five aspects: (i) the political environment; (ii) access to financial resources; (iii) the number of CSOs working on HIV/AIDS; (iv) the scope of work; and (v) the impact of CSO involvement on programmes. Results The number of CSOs specificly working on HIV/AIDS increased from 0 before 1988 to over 400 in 2009. Among a sample of 368 CSOs, 135 (36.7%) were registered. CSOs were primarily supported by international programmes. Government financial support to CSOs has increased from USD248 000 in 2002 to USD1.46 million in 2008. Initially, civil society played a minimal role. It is now widely involved in nearly all aspects of HIV/AIDS-related prevention, treatment and care efforts, and has had a positive impact; for example, increased adherence of anti-retroviral treatment and HIV testing among hard-to-reach groups. The main challenges faced by CSOs include registration, capacity and long-term financial support. Conclusion CSOs have significantly increased their participation and contribution to HIV/AIDS programmes in China. Policies for registration and financial support to CSOs need to be developed to enable them to play an even greater role in AIDS programmes.


title: Comprehensive Detection and Identification of Seven Animal Coronaviruses and Human Respiratory Coronavirus 229E with a Microarray Hybridization Assay

text: Based on microarray hybridization, a diagnostic test for coronavirus infection was developed using eight coronavirus strains: canine coronavirus (CCoV), feline infectious peritonitis virus (FIPV), feline coronavirus (FCoV), bovine coronavirus (BCoV), porcine respiratory coronavirus (PRCoV), turkey enteritis coronavirus (TCoV), transmissible gastroenteritis virus (TGEV), and human respiratory coronavirus (HRCoV). Up to 104 cDNA clones of eight viruses were obtained by reverse transcription PCR with different pairs of primers designed for each virus and a pair of universal primers designed for the RNA polymerase gene of coronavirus. Total RNAs extracted from virus were reverse transcribed, followed by multi-PCR amplification and labeled with Cy3-dCTP. All labeled cDNAs and prepared gene chips were subjected to specific hybridization. The results showed that extensive cross-reaction existed between CCoV, FCoV, FIPV, TGEV and PRCoV, while there was no cross-reaction between BCoV, TCoV and HRCoV. The ultimate specific gene chip was developed with DNA fragments reamplified from the chosen recombinant plasmids without cross-reaction between different coronaviruses. The hybridization results showed that this gene chip could specifically identify and distinguish the eight coronaviruses and the sensitivity of the chip may be 1,000× more sensitive than PCR, indicating that it can be used for the diagnosis of eight coronavirus infections at the same time.


title: Collateral Benefits on Other Respiratory Infections during Fighting COVID-19

text: Abstract Purpose: Influenza virus infection is associated with a high disease burden. COVID-19 caused by SARS-CoV-2 has become a pandemic outbreak since January 2020. Taiwan has effectively contained COVID-19 community transmission. We aimed to validate whether fighting COVID-19 could help to control other respiratory infections in Taiwan. Method: We collected week-case data of severe influenza, invasive Streptococcus pneumoniae disease and death toll from pneumonia among 25 calendar weeks of the influenza season for four years (2016-2020), which were reported to Taiwan CDC. Trend and slope differences between years were compared. Result: A downturn trend of severe influenza, invasive Streptococcus pneumoniae disease and the death toll from pneumonia per week in 2019/2020 season and significant trend difference in comparison to previous seasons were noted, especially after initiation of several disease prevention measures to fight potential COVID-19 outbreak in Taiwan. Conclusions: Fighting COVID-19 achieved collateral benefits on significant reductions of severe influenza burden, invasive Streptococcus pneumoniae disease activity, and the death toll from pneumonia reported to CDC in Taiwan.


title: Capture ELISA systems for the detection of bovine coronavirus-specific IgA and IgM antibodies in milk and serum

text: Abstract Isotype-capture ELISAs for BCV-specific IgA and IgM were developed and tested on milk and serum samples from Swedish cattle. The capture ELISAs showed higher sensitivity than indirect ELISAs for detection of BCV-specific IgA and IgM. In the capture ELISAs the agreement between detection in milk and serum samples was 94% for IgA and 86% for IgM. The correlation between log10 titres in milk and serum was r=0.82 (P<0.001) for IgA and 0.84 (P<0.001) for IgM. Milk seemed a better target than serum for diagnosing specific IgA at low levels. There was no variation in the isotype-specific BCV antibody titres between healthy quarters of the same udder, but subclinical mastitis was associated with higher levels of IgA antibodies and weak false IgM positive reactions in undiluted milk. Bovine IgA and IgM antibodies in milk and serum showed high stability towards freezing and thawing and storage at room temperature. The antibody responses to BCV were followed in milk and serum from six dairy cows and in serum from four calves for a period of 1 year after an outbreak of winter dysentery (WD). In this outbreak some animals became reinfected with BCV. The IgA and IgM capture ELISAs differentiated between primarily BCV infected and reinfected animals. In the primarily infected cattle, IgM antibodies were first detected in milk and serum four to nine days after the first WD symptoms observed, and were subsequently detected for at least 2–3 weeks. IgM was also detected in the reinfected cows, but mostly at lower levels and for a shorter period of time than in the primarily infected animals. In milk, however, the IgM response of the reinfected cows was detected for a longer period of time than in serum. Six months after the outbreak, IgA was still detected in both serum and milk of all six cows and also in serum of one calf. The reinfected cows showed higher and more long-lasting peak levels of IgA in milk and serum than the primarily infected cows, indicating boosting of the IgA response.


title: Hemagglutinin from the H5N1 Virus Activates Janus Kinase 3 to Dysregulate Innate Immunity

text: Highly pathogenic avian influenza viruses (HPAIVs) cause severe disease in humans. There are no effective vaccines or antiviral therapies currently available to control fatal outbreaks due in part to the lack of understanding of virus-mediated immunopathology. In our study, we used hemagglutinin (HA) of H5N1 virus to investigate the related signaling pathways and their relationship to dysregulated innate immune reaction. We found the HA of H5N1 avian influenza triggered an abnormal innate immune signalling in the pulmonary epithelial cells, through an unusual process involving activation of Janus kinase 3 (JAK3) that is exclusively associated with γc chain and is essential for signaling via all γc cytokine receptors. By using a selective JAK3 inhibitor and JAK3 knockout mice, we have, for the first time, demonstrated the ability to target active JAK3 to counteract injury to the lungs and protect immunocytes from acute hypercytokinemia -induced destruction following the challenge of H5N1 HA in vitro and in vivo. On the basis of the present data, it appears that the efficacy of selective JAK3 inhibition is likely based on its ability to block multiple cytokines and protect against a superinflammatory response to pathogen-associated molecular patterns (PAMPs) attack. Our findings highlight the potential value of selective JAK3 inhibitor in treating the fatal immunopathology caused by H5N1 challenge.


title: Associations between bovine coronavirus and bovine respiratory syncytial virus infections and animal performance in Swedish dairy herds

text: Abstract To assess the economic impact of bovine coronavirus (BCV) and bovine respiratory syncytial virus (BRSV) infections, accurate estimates of their associated effects on animal performance are needed. This study aimed to quantify the variation in individual test-day milk yield and somatic cell count, risk of reproductive failure after first service of dairy cows, and risk of death of calves and heifers according to the BCV and BRSV status of the herd. Three types of status were defined for BCV and BRSV infections, based on 1) the dynamics over a 7-mo period of BCV- and BRSV-specific antibody levels in pooled milk of primiparous cows; 2) the possible occurrence of presumably BCV- and BRSV-related clinical outbreaks; and 3) the combination of both pieces of information. A total of 36,184 test days, 2,716 cows with a first service, and 4,104 calves and heifers in 65 Swedish herds were included in the analyses. Animal performance associated with BCV and BRSV infections was quantified using hierarchical mixed generalized and survival models, after adjustment for covariates known to influence the performance under study. A significant reduction in milk yield was observed for cows in presumably BRSV recently infected herds, as well as in herds having a presumably BRSV-related clinical outbreak (of 0.57 and 0.91kg/d, respectively), compared with cows in presumably infection-free herds. There was also a significant increase in somatic cell count (of 12,000 cells/mL) for cows located in herds with a BRSV outbreak. The risk of failure after first service, as well as the risk of death in calf and heifer, was numerically higher in BRSV-infected herds, although this was not statistically significant. In contrast, BCV infection herd status, as defined in the present study, was not significantly associated with any production losses in animals from infected herds compared with those in infection-free herds.


title: Narcissus tazetta lectin shows strong inhibitory effects against respiratory syncytial virus, influenza A (H1N1, H3N2, H5N1) and B viruses

text: A mannose-binding lectin (Narcissus tazetta lectin [NTL]) with potent antiviral activity was isolated and purified from the bulbs of the Chinese daffodil Narcissus tazetta var. chinensis, using ion exchange chromatography on diethylaminoethyl (DEAE)-cellulose, affinity chromatography on mannose-agarose and fast protein liquid chromatography (FPLC)-gel filtration on Superose 12. The purified lectin was shown to have an apparent molecular mass of 26 kDa by gel filtration and 13 kDa by SDS-PAGE, indicating that it is probably a dimer with two identical subunits. The cDNA-derived amino acid sequence of NTL as determined by molecular cloning also reveals that NTL protein contains a mature polypeptide consisting of 105 amino acids and a C-terminal peptide extension. Three-dimensional modelling study demonstrated that the NTL primary polypeptide contains three subdomains, each with a conserved mannose-binding site. It shows a high homology of about 60%–80% similarity with the existing monocot mannose-binding lectins. NTL could significantly inhibit plaque formation by the human respiratory syncytial virus (RSV) with an IC(50) of 2.30 µg/ml and exhibit strong antiviral properties against influenza A (H1N1, H3N2, H5N1) and influenza B viruses with IC(50) values ranging from 0.20 µg/ml to 1.33 µg/ml in a dose-dependent manner. It is worth noting that the modes of antiviral action of NTL against RSV and influenza A virus are significantly different. NTL is effective in the inhibition of RSV during the whole viral infection cycle, but the antiviral activity of NTL is mainly expressed at the early stage of the viral cycle of influenza A (H1N1) virus. NTL with a high selective index (SI=CC(50)/IC(50)≥141) resulting from its potent antiviral activity and low cytotoxicity demonstrates a potential for biotechnological development as an antiviral agent.


title: WHO's budgetary allocations and burden of disease: a comparative analysis

text: BACKGROUND: Ministers of health, donor agencies, philanthropists, and international agencies will meet at Bamako, Mali, in November, 2008, to review global priorities for health research. These individuals and organisations previously set health priorities for WHO, either through its regular budget or extra-budgetary funds. We asked what insights can be gained as to their priorities from previous decisions within the context of WHO. METHODS: We compared the WHO biennial budgetary allocations with the burden of disease from 1994–95 to 2008–09. We obtained data from publicly available WHO sources and examined whether WHO allocations varied with the burden of disease (defined by death and disability-adjusted life years) by comparing two WHO regions—Western Pacific and Africa—that are at differing stages of epidemiological transition. We further assessed whether the allocations differed on the basis of the source of funds (assessed and voluntary contributions) and the mechanism for deciding how funds were spent. FINDINGS: We noted that WHO budget allocations were heavily skewed toward infectious diseases. In 2006–07, WHO allocated 87% of its total budget to infectious diseases, 12% to non-communicable diseases, and less than 1% to injuries and violence. We recorded a similar distribution of funding in Africa, where nearly three-quarters of mortality is from infectious disease, and in Western Pacific, where three-quarters of mortality is from non-communicable disease. In both regions, injuries received only 1% of total resources. The skew towards infectious diseases was substantially greater for the WHO extra-budget, which is allocated by donors and has risen greatly in recent years, than for the WHO regular budget, which is decided on by member states through democratic mechanisms and has been held at zero nominal growth. INTERPRETATION: Decision makers at Bamako should consider the implications of the present misalignment of global health priorities and disease burden for health research worldwide. Funds allocated by external donors substantially differ from those allocated by WHO member states. The meeting at Bamako provides an opportunity to consider how this disparity might be addressed. FUNDING: None.


Cutaneous lupus erythematosus patients in a high‐epidemic COVID‐19 area, Bergamo, Italy


title: Transmission or Within-Host Dynamics Driving Pulses of Zoonotic Viruses in Reservoir–Host Populations

text: Progress in combatting zoonoses that emerge from wildlife is often constrained by limited knowledge of the biology of pathogens within reservoir hosts. We focus on the host–pathogen dynamics of four emerging viruses associated with bats: Hendra, Nipah, Ebola, and Marburg viruses. Spillover of bat infections to humans and domestic animals often coincides with pulses of viral excretion within bat populations, but the mechanisms driving such pulses are unclear. Three hypotheses dominate current research on these emerging bat infections. First, pulses of viral excretion could reflect seasonal epidemic cycles driven by natural variations in population densities and contact rates among hosts. If lifelong immunity follows recovery, viruses may disappear locally but persist globally through migration; in either case, new outbreaks occur once births replenish the susceptible pool. Second, epidemic cycles could be the result of waning immunity within bats, allowing local circulation of viruses through oscillating herd immunity. Third, pulses could be generated by episodic shedding from persistently infected bats through a combination of physiological and ecological factors. The three scenarios can yield similar patterns in epidemiological surveys, but strategies to predict or manage spillover risk resulting from each scenario will be different. We outline an agenda for research on viruses emerging from bats that would allow for differentiation among the scenarios and inform development of evidence-based interventions to limit threats to human and animal health. These concepts and methods are applicable to a wide range of pathogens that affect humans, domestic animals, and wildlife.


title: Characterization and analysis of an infectious bronchitis virus strain isolated from southern China in 2013

text: BACKGROUND: Infectious bronchitis is a severe disease caused by infectious bronchitis virus (IBV) that affects fowl flocks worldwide. The understanding of the mechanisms involved in IBV evolution and variation would provide important theoretical basis for prevention and control of the disease in the future. METHODS: IBV strain GD was isolated from southern China in 2013 and the complete genome sequencing and phylogenetic analysis were performed. RESULTS: The genome of approximately 27,680 nt comprised six genes, with insertions and mutations in most of the structural genes. The S1 gene showed the highest identity to strain TW2575/98 isolated in Taiwan, and was distantly related to the H120 vaccine strain. Phylogenetic analysis showed that the S1 gene of strain GD was also related to that of TW-type strains. Recombination analysis indicated that strain GD was a chimera whose putative parental strains belonged to the QX- and TW-type subgroups. CONCLUSIONS: An increasing number of TW-type strains have been isolated from China in recent years, which is in agreement with our findings, suggesting the emergence and increased prevalence of new TW-type strains in southern China.


title: The Acute Respiratory Infection Consortium: A Multi-Site, Multi-Disciplinary Clinical Research Network in the Department of Defense

text: INTRODUCTION: Acute respiratory infections (ARI) result in substantial annual morbidity among military personnel and decrease operational readiness. Herein, we summarize the research efforts of the Infectious Disease Clinical Research Program (IDCRP) related to ARIs. METHODS: The ARI Research Area of the IDCRP was established in response to the 2009 emergence of pandemic influenza A/H1N1. That year, IDCRP investigators deployed the ARI Consortium Natural History Study (ARIC NHS), a multi-centered, longitudinal observational study to assess etiology, epidemiology, and clinical characteristics of influenza-like illness (ILI) and severe acute respiratory infections (SARI) in the U.S. military. The success of this initial effort spurred implementation of several new initiatives. These include the FluPlasma trial, designed to evaluate the efficacy of hyperimmune anti-influenza plasma for the treatment of severe influenza; the self-administered live-attenuated influenza vaccine (SNIF) trial, which assessed the immunogenicity and acceptance of a self-administered live-attenuated influenza vaccine in military personnel; the Study to Address Threats of ARI in Congregate Military Populations (ATARI), a prospective study of ILI transmission, etiology and epidemiology in recruits; and the Flu Breath Test (FBT) study, a preliminary study of exhaled volatile organic compounds (VOC) in influenza patients. In addition, the InFLUenza Patient-Reported Outcome (FLU-PRO) survey, a daily diary to measure influenza symptoms during clinical trials, was developed. Lastly, the Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED) study, a two-year randomized trial designed to compare the effectiveness of the three types of licensed vaccines, launched in Fall 2018. RESULTS: The on-going ARIC NHS has enrolled over 2000 ILI and SARI cases since its inception, providing data on burden and clinical manifestations of ARI in military personnel and their families. The FluPlasma 2 trial concluded subject enrollment in 2018. Preliminary results from ATARI study show a high frequency of respiratory viruses circulating during the first two weeks of recruit training. Based on assessment of FLU-PRO responses, which were found to be reliable and reproducible, the survey may be a useful tool in clinical trials and epidemiological studies. The Flu Breath Study will complete enrollment in 2019. Findings from PAIVED are intended to provide evidence needed for assessing influenza vaccination policy in the military. CONCLUSIONS: The ARI burden in the armed services remains significant every year and the threat is dynamic given emergent and evolving threats, such as influenzas. With strong successes to date, future initiatives of the ARI Research Area will focus on interventional studies, ARI transmission dynamics in congregate military settings, and determinants of risk of pandemic influenza and other emergent respiratory viruses.


title: Phylogenomics and bioinformatics of SARS-CoV

text: Tracing the history of molecular changes in coronaviruses using phylogenetic methods can provide powerful insights into the patterns of modification to sequences that underlie alteration to selective pressure and molecular function in the SARS-CoV (severe acute respiratory syndrome coronavirus) genome. The topology and branch lengths of the phylogenetic relationships among the family Coronaviridae, including SARS-CoV, have been estimated using the replicase polyprotein. The spike protein fragments S1 (involved in receptor-binding) and S2 (involved in membrane fusion) have been found to have different mutation rates. Fragment S1 can be further divided into two regions (S1A, which comprises approximately the first 400 nucleotides, and S1B, comprising the next 280) that also show different rates of mutation. The phylogeny presented on the basis of S1B shows that SARS-CoV is closely related to MHV (murine hepatitis virus), which is known to bind the murine receptor CEACAM1. The predicted structure, accessibility and mutation rate of the S1B region is also presented. Because anti-SARS drugs based on S2 heptads have short half-lives and are difficult to manufacture, our findings suggest that the S1B region might be of interest for anti-SARS drug discovery.


title: Coronavirus Disease 2019 in a Hemodialysis Patient

text: There has been a global outbreak of the coronavirus disease 2019 (COVID-19) since December 2019. Here, we describe the case of a 49-year-old male undergoing maintenance hemodialysis (HD) who got infected with COVID-19 and our experience in performing HD for him. The patientâ€™s symptoms and lung imaging changes were atypical. However, his lymphocyte range decreased upon admission and the polymerase chain reaction of the pharyngeal swab for the ÂCOVID-19 nucleic acid was positive. The patient developed respiratory failure and required mechanical ventilation 8Â days after admission. In the end, he died from multiple organ dysfunction syndrome. The difficulties in diagnosis, infection control, and treatment of COVID-19 in maintenance HD patients are discussed in this report.


title: The molecular biology of nairoviruses, an emerging group of tick-borne arboviruses

text: The nairoviruses are a rapidly emerging group of tick-borne bunyaviruses that includes pathogens of humans (Crimean-Congo hemorrhagic fever virus [CCHFV]) and livestock (Nairobi sheep disease virus [NSDV], also known as Ganjam virus), as well as a large number of viruses for which the normal vertebrate host has not been established. Studies on this group of viruses have been fairly limited, not least because CCHFV is a BSL4 human pathogen, restricting the number of labs able to study the live virus, while NSDV, although highly pathogenic in naive animals, is not seen as a threat in developed countries, making it a low priority. Nevertheless, recent years have seen significant progress in our understanding of the biology of these viruses, particularly that of CCHFV, and this article seeks to draw together our existing knowledge to generate an overall picture of their molecular biology, underlining areas of particular ignorance for future studies.


title: Management of COVID-19 Pandemic in Spanish Inflammatory Bowel Disease Units: Results From a National Survey

text: BACKGROUND: The outbreak of COVID-19 has rapidly evolved into a pandemic that has represented a challenge to health systems worldwide. Inflammatory bowel disease (IBD) units have been forced to change their practices to address the disease and to ensure the quality of care. METHODS: We conducted a national survey among IBD gastroenterologist members of the Spanish Working Group on Crohn’s Disease and Colitis regarding changes of practice, IBD treatments, and diagnosis and treatment of COVID-19. RESULTS: We received 54 answers from Spanish hospitals. One hundred percent of the IBD units rescheduled onsite visits to telematic consultation, and elective endoscopic and surgical procedures were delayed. Protective measures were also taken in the infusion units (100% of health centers) and hospital pharmacies, with 40.7% sending subcutaneous medications to patients. No switching between intravenous and subcutaneous anti-tumor necrosis factor drugs were made. We also found that 96.1% of IBD units advised their patients to maintain treatment if they were asymptomatic for COVID-19. For patients with COVID-19 symptoms, 92.6% of IBD units referred them to primary care or the emergency department. In addition, 7.5% of IBD units made a COVID-19 diagnosis through polymerase chain reaction and/or chest x-ray. Modifications in IBD treatment and treatment recommended for COVID-19 are also discussed. CONCLUSIONS: We report a representative national survey of changes made in the structure, diagnosis of COVID-19, and modifications in IBD treatments within IBD units.


title: Pathogenicity of porcine G9P[23] and G9P[7] rotaviruses in piglets

text: Abstract G9 group A rotaviruses (RVAs) are considered important pathogens in pigs and humans, and pigs are hypothesized to be a potential host reservoir for human. However, intestinal and extra-intestinal pathogenicity and viremia of porcine G9 RVAs has remained largely unreported. In this study, colostrum-deprived piglets were orally infected with a porcine G9P[23] or G9P[7] strain. Histopathologically, both strains induced characteristic small intestinal lesions. Degeneration and necrosis of parenchymal cells were observed in the extra-intestinal tissues, but most predominantly in the mesenteric lymph nodes (MLNs). RVA antigen was continuously detected in the small intestinal mucosa and MLNs, but only transiently in cells of the liver, lung, and choroid plexus. Viral RNA levels were much higher in the feces and the MLNs compared to other tissues. The onset of viremia occurred at day post infection (DPI) 1 with the amount of viral RNA reaching its peak at DPI 3 or 5, before decreasing significantly at DPI 7 and remaining detectable until DPI 14. Our data suggest that porcine G9 RVAs have a strong small intestinal tropism, are highly virulent for piglets, have the ability to escape the small intestine, spread systemically via viremia, and replicate in extra-intestinal tissues. In addition, MLNs might act as a secondary site for viral amplification and the portal of systemic entry. These results add to our understanding of the pathogenesis of human G9 RVAs, and the validity of the pig model for use with both human and pig G9 RVAs in further studies.


title: Comparison of electronic microarray to enzyme hybridization assay for multiplex reverse-transcriptase PCR detection of common respiratory viruses in children

text: A new assay, composed of the NGEN RVA (Nanogen, Inc., San Diego, CA; Prodesse, Inc., Waukesha, WI), which is a pair of analyte-specific reagents that allow the multiplex reverse transcriptase polymerase chain reaction (RT-PCR) and electronic microarray detection of influenza virus A and B, respiratory syncytial virus A and B, and human parainfluenza virus types 1, 2, and 3, was evaluated in comparison with the Hexaplex (Prodesse), a multiplex RT-PCR–enzyme hybridization assay. Comparisons included the detection of respiratory viruses from whole-virus stocks (ATCC) and from frozen pediatric respiratory specimens collected at Children's Hospital of Wisconsin between 1991 and October 1998. After the retesting of six indeterminants and 20 discrepants, overall agreement improved to 96% on the positives and 100% on negatives, with only eight specimens still discrepant. The RVA reagents allow a rapid, sensitive, and specific assay for detecting seven of the most common respiratory viruses in children.


La radiología en el diagnóstico de la neumonía por SARS-CoV-2 (COVID-19)


title: Supporting people with diabetes during a pandemic

text: In this issue, Joensen and colleagues present the first data we have seen on the impact and experience of diabetes through the lens of the COVID-19 pandemic. The research was completed in Denmark in March 2020, in the context of a marked shutdown of economic and social activities across the country, but without the devastating death tolls experienced by other Organisation for Economic Co-operation and Development (OECD) countries. There are several notable findings, which have global relevance, and we should take the time to reflect on these for our own localized contexts.


title: When Blackness Does Not Fade After a Pandemic: An Appeal to Acknowledge the Unequal Burden of Social Isolation

text: Social distancing is one of the few tools that the everyman has to combat the Coronavirus disease. However, for those who are subject to racialized stereotypes about work productivity, educational ability, and other assumptions, the choice to socially distance can have many unintended consequences. This article is an appeal to our posterity, inviting a conversation about how we will remember the Coronavirus’ impact on our lives. Will we selectively provide compassion for the racial groups we perceive more favorable when this is over? Or will we play favorites when it is time to pick up the pieces? This article provides scenarios and commentary on how social distancing could affect Black American populations – regardless of income or socioeconomic status. It argues that history has not been kind to Black Americans who have bought into mass national causes, and that there is an opportunity here to act differently.


title: Comparative efficacy of a recombinant feline interferon omega in refractory cases of calicivirus-positive cats with caudal stomatitis: a randomised, multi-centre, controlled, double-blind study in 39 cats

text: Chronic caudal stomatitis with alveolar/buccal mucositis in calicivirus-positive cats is the most severe presentation of feline chronic gingivostomatitis. Refractory cases are helped by antibiotic and anti-inflammatory treatments often including glucocorticoids. In order to evaluate the comparative efficacy of oromucosal administration of recombinant feline interferon omega (rFeIFN-ω) versus oral administration of glucocorticoids, a randomised, multi-centre, controlled, double-blind study was performed in 39 cats. The progression of behavioural, clinical and lesional scores was assessed over 90 days. Daily oromucosal treatment with 0.1 MU of rFeIFN-ω was associated with a significant improvement of clinical lesions (caudal stomatitis and alveolar/buccal mucositis) and a decrease of pain scores from D0 to D90. Although no such statistical improvement was noticed in the prednisolone group, there was, however, no significant difference between the two groups for most of the parameters, except pain at D60 and D90.


title: Transmissible gastroenteritis virus (TGEV)-based vectors with engineered murine tropism express the rotavirus VP7 protein and immunize mice against rotavirus

text: Abstract A coronavirus vector based on the genome of the porcine transmissible gastroenteritis virus (TGEV) expressing the rotavirus VP7 protein was constructed to immunize and protect against rotavirus infections in a murine model. The tropism of this TGEV-derived vector was modified by replacing the spike S protein with the homologous protein from mouse hepatitis virus (MHV). The rotavirus gene encoding the VP7 protein was cloned into the coronavirus cDNA. BALB/c and STAT1-deficient mice were inoculated with the recombinant viral vector rTGEVS-MHV–VP7, which replicates in the intestine and spreads to other organs such as liver, spleen and lungs. TGEV-specific antibodies were detected in all the inoculated BALB/c mice, while rotavirus-specific antibodies were found only after immunization by the intraperitoneal route. Partial protection against rotavirus-induced diarrhea was achieved in suckling BALB/c mice born to dams immunized with the recombinant virus expressing VP7 when they were orally challenged with the homotypic rotavirus strain.


title: Activation of the Unfolded Protein Response and Inhibition of Translation Initiation during Coronavirus Infection

text: Coronaviruses (CoV), such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), are of medical importance with high mortality rates and significant zoonotic and pandemic potential. Here, we apply ribosome profiling and parallel RNASeq to globally analyse changes in the host cell translatome and transcriptome upon infection with mouse hepatitis virus, strain A59 (MHV-A59), a model murine coronavirus in the same genus as SARS-CoV and MERS-CoV. We observed translational upregulation of ATF4, ATF5 and Ddit3 and activation of the unfolded protein response (UPR). Phosphorylation of eIF2α led to the global inhibition of translation and a substantial increase in empty 80S ribosomes. A drug that inhibits the UPR attenuates virus growth suggesting that MHV may have evolved to subvert the UPR to its own advantage. We also investigated an artefact of cycloheximide pretreatment in ribosome profiling whereby ribosomes accumulate at the 5’ end of coding sequences in stressed cells but not in unstressed or untreated cells, thus extending earlier studies in yeast to mammalian cells. The study sheds light on the mechanisms of CoV translational shutoff and reveals a potential new therapeutic strategy.


title: Antimicrobial activity of Eucalyptus camaldulensis Dehn. plant extracts and essential oils: A review

text: Abstract Eucalyptus has become one of the world’s most widely planted genera and E. camaldulensis (The River Red Gum) is a plantation species in many parts of the world. The plant traditional medical application indicates great antimicrobial properties, so E. camaldulensis essential oils and plant extracts have been widely examined. Essential oil of E. camaldulensis is active against many Gram positive (0.07–1.1%) and Gram negative bacteria (0.01–3.2%). The antibacterial effect is confirmed for bark and leaf extracts (conc. from 0.08 μg/mL to 200 mg/mL), with significant variations depending on extraction procedure. Eucalyptus camaldulensis essential oil and extracts are among the most active against bacteria when compared with those from other species of genus Eucalyptus. The most fungal model organisms are sensitive to 0.125–1.0% of E. camaldulensis essential oil. The extracts are active against C. albicans (0.2–200 mg/mL leaf extracts and 0.5 mg/mL bark extracts), and against various dermatophytes. Of particular importance is considerable the extracts’ antiviral activity against animal and human viruses (0.1–50 μg/mL). Although the antiprotozoal activity of E. camaldulensis essential oil and extracts is in the order of magnitude of concentration several hundred mg/mL, it is considerable when taking into account current therapy cost, toxicity, and protozoal growing resistance. Some studies show that essential oils’ and extracts’ antimicrobial activity can be further potentiated in combinations with antibiotics (beta-lactams, fluorochinolones, aminoglycosides, polymyxins), antivirals (acyclovir), and extracts of other plants (e.g. Annona senegalensis; Psidium guajava). The present data confirm the river red gum considerable antimicrobial properties, which should be further examined with particular attention to the mechanisms of antimicrobial activity.


title: Testing the Efficacy of Homemade Masks: Would They Protect in an Influenza Pandemic?

text: OBJECTIVE: This study examined homemade masks as an alternative to commercial face masks. METHODS: Several household materials were evaluated for the capacity to block bacterial and viral aerosols. Twenty-one healthy volunteers made their own face masks from cotton t-shirts; the masks were then tested for fit. The number of microorganisms isolated from coughs of healthy volunteers wearing their homemade mask, a surgical mask, or no mask was compared using several air-sampling techniques. RESULTS: The median-fit factor of the homemade masks was one-half that of the surgical masks. Both masks significantly reduced the number of microorganisms expelled by volunteers, although the surgical mask was 3 times more effective in blocking transmission than the homemade mask. CONCLUSION: Our findings suggest that a homemade mask should only be considered as a last resort to prevent droplet transmission from infected individuals, but it would be better than no protection. (Disaster Med Public Health Preparedness. 2013;0:1–6)


title: Isatin derivatives in reactions with phosphorus(III–V) compounds

text: [Image: see text] In this review we generalize and analyze information about reactions between isatin and three-, four-, and five-coordinate phosphorus compounds, published between 1966 and 2014.


COVID-19: Advice from the Canadian Association of Gastroenterology for Endoscopy Facilities, as of March 16, 2020


title: Mannose-Binding Lectin and Susceptibility to Schistosomiasis

text: Background. Human ficolin 2 (encoded by FCN2) and mannose-binding lectin (encoded by MBL2) bind to specific pathogen-associated molecular patterns, activate the complement lectin cascade in a similar manner, and are associated with several infectious diseases. Our recently published study established certain FCN2 promoter variants and ficolin-2 serum levels as protective factors against schistosomiasis. Methods. We used the Nigerian cohort from our recently published study, which included 163 Schistosoma haematobium–infected individuals and 183 matched healthy subjects, and investigated whether MBL deficiency and MBL2 polymorphisms are associated with schistosomiasis. Results. MBL serum levels were significantly higher in controls and were associated with protection (P < .0001). The −550H minor allele was significantly associated with protection (P = .03), and the heterozygous genotypes −550HL were observed to confer protection (P = .03). The MBL2*HYPA haplotype was significantly associated with protection (P = .03), with significantly higher serum MBL levels in controls (P = .00073). The heterozygous 6-bp deletion in the promoter was observed to be a susceptibility factor in schistosomiasis (P = .03). Conclusions. In agreement with findings from our recently published study, the findings reported here support the observation that MBL is also associated with protection in schistosomiasis.


title: Increased susceptibility of SARS-CoV2 infection on Oral Cancer patients; Cause and effects: An Hypothesis

text: In 2019, a new coronavirus (SARS CoV2) infecting Humans has emerged in Wuhan, China which caused an unprecedented pandemic involving at least 185 countries infecting 2.5 million people till date. This virus is transmitted directly or indirectly through the upper aerodigestive tract. As it is evident from the recent studies that SARS-CoV-2 requires host enzyme Furin to activate receptor binding domain of its S protein and host Angiotensin Convertase Enzyme 2 (ACE2) is required as binding receptor, facilitating the entry of virus into the host cell. Evidence from literature shows that oral cancer tissues as well as paracarcinoma tissue exhibit higher expression of both Furin and ACE2, giving rise to the hypothesis that patients with oral cancer have higher chances of SARS CoV2 infection. It is also hypothesised that there will be increased severity of disease due to facilitated entry of the virus into the cells. Therefore, we suggest oral cancer patients require extra attention during COVID-19 pandemic and re-evaluation of current treatment paradigms in oral oncology is also needed.


Virus and eukaryote fusogen superfamilies


title: The possible impairment of respiratory‐related neural loops may be associated with the silent pneumonia induced by SARS‐CoV‐2

text: As compared to many other viral pulmonary infections, there existed several peculiar manifestations in the COVID‐19 patients, including the “silence” of pneumonia in both mild and severe cases and a long intensive care unit stay for those requiring invasive mechanical ventilation. Similar silent pneumonia has been documented in the infection induced by H5N1 influenza virus HK483, and was found to result from the direct attack of the virus on the bronchopulmonary C‐fibers at the early stage and the final infection in the brainstem at the late stage. The long stay of critical patients in the intensive care unit is possibly due to the depression of central respiratory drive, which resulted in the failure to wean from the mechanic ventilation. Carotid and aortic bodies and bronchopulmonary C‐fibers are two key peripheral components responsible for the chemosensitive responses in the respiratory system, while triggering respiratory reflexes depends predominantly on the putative chemosensitive neurons located in the pontomedullary nuclei. In view of the findings for H5N1 influenza virus, the silence of pneumonia induced by SARS‐CoV‐2 may be due to the possible impairment of peripheral chemosensitive reflexes as well as the damage to the respiratory‐related central neurons. (195 words) This article is protected by copyright. All rights reserved.


title: Antibacterial properties of Ag/TiO(2)/PDA nanofilm on anodized 316L stainless steel substrate under illumination by a normal flashlight

text: The demand of medical materials for rapid and efficient elimination of bacteria has seen a dramatic surge over the past few years. In this study, antibacterial nanofilms with reactive oxygen species were generated by photocatalysis. To prepare these nanofilms, Ag and amorphous TiO(2) nanoparticles decorated on polydopamine (PDA) were coated on three-dimensional (3D) nanopore arrays, which was fabricated on a substrate of anodized stainless steel. All the antibacterial tests were conducted with a household flashlight, which may be considered as a practical approach for antibacterial materials. The photoelectrochemical property of the 3D Ag/TiO(2)/PDA nanofilm on 316L stainless steel (Ag/TiO(2)/PDA SS) was about 15 times higher than that of the annealed Ag/TiO(2)/PDA SS, and consequently, it exhibited higher antibacterial activity. The enhanced photoelectrochemical property is attributed to the successful separation of electrons (amorphous TiO(2)) and holes (Ag nanoparticles). Further, when a plate containing 3D Ag/TiO(2)/PDA SS was irradiated with visible light just for 10 min, it immediately destroyed the bacteria in 10(6) CFU/mL without any bacterial colony. After five weeks, there were still no bacterial colonies in the plate corresponding to Ag/TiO(2)/PDA SS under visible light, while Ag/TiO(2)/PDA SS in dark had a negligible effect on the bacteria, i.e., the antibacterial mechanism through direct contact and ion dissolution was not efficient. The excellent antibacterial properties of 3D Ag/TiO(2)/PDA SS illuminated by flashlight provides an efficient, facile, and cost-effective technique for the development of antibacterial medical materials to meet the increasing demand of eliminating bacterial infections. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10853-020-04610-w) contains supplementary material, which is available to authorized users.


title: SARS Transmission among Hospital Workers in Hong Kong

text: Despite infection control measures, breakthrough transmission of severe acute respiratory syndrome (SARS) occurred for many hospital workers in Hong Kong. We conducted a case-control study of 72 hospital workers with SARS and 144 matched controls. Inconsistent use of goggles, gowns, gloves, and caps was associated with a higher risk for SARS infection (unadjusted odds ratio 2.42 to 20.54, p < 0.05). The likelihood of SARS infection was strongly associated with the amount of personal protection equipment perceived to be inadequate, having <2 hours of infection control training, and not understanding infection control procedures. No significant differences existed between the case and control groups in the proportion of workers who performed high-risk procedures, reported minor protection equipment problems, or had social contact with SARS-infected persons. Perceived inadequacy of personal protection equipment supply, infection control training <2 hours, and inconsistent use of personal protection equipment when in contact with SARS patients were significant independent risk factors for SARS infection.


title: Filovirus proteins for antiviral drug discovery: A structure/function analysis of surface glycoproteins and virus entry

text: Abstract This review focuses on the recent progress in our understanding of filovirus protein structure/function and its impact on antiviral research. Here we focus on the surface glycoprotein GP1,2 and its different roles in filovirus entry. We first describe the latest advances on the characterization of GP gene-overlapping proteins sGP, ssGP and Δ-peptide. Then, we compare filovirus surface GP1,2 proteins in terms of structure, synthesis and function. As they bear potential in drug-design, the discovery of small organic compounds inhibiting filovirus entry is a currently very active field. Although it is at an early stage, the development of antiviral drugs against Ebola and Marburg virus entry might prove essential to reduce outbreak-associated fatality rates through post-exposure treatment of both suspected and confirmed cases.


title: Chapter 5 Aeromicrobiology

text: Biological material including microorganisms and toxins can be found in air or the atmosphere, and the study of this area is termed “aeromicrobiology.” Airborne biological materials are known as bioaerosols. This chapter introduces the basics of aeromicrobiology including the nature of bioaerosols and fundamentals of the aeromicrobiological (AMB) pathway. The nature of the atmosphere as a microbial habitat, and the factors that influence microbial survival in the air are described. This is followed by a discussion of extramural aeromicrobiology related to aerosolization of indigenous soil pathogens; influenza pandemics; microbiology in the clouds; agriculture; waste disposal; and airborne toxins. Intramural microbiology within buildings is discussed with respect to public health within buildings, hospitals and laboratories. Finally, measures to control bioaerosols including biosafety in the laboratory are documented.


title: Infection and vasculitis

text: Vasculitis may be associated with infection, immunization or anti-microbial drugs. Infections are responsible for a number of different types of vasculitis. Conversely, patients with vasculitis may develop infections, which sometimes mimic relapse. The aim of this review is to summarize the various aspects of the inter-relationship between vasculitis and infection, and the physiopathological mechanisms involved, in light of our current knowledge from animal models. Currently, a causal relationship between infection and vasculitis has only been established in a few instances and many mechanisms remain hypothetical. This inter-relationship is further assessed from the point of view of clinical presentation and therapeutic options, based on case reports and prospective observational data.


title: The Surgeon’s Role During the Coronavirus Pandemic

text: The coronavirus pandemic has disrupted delivery of healthcare globally, forcing healthcare providers at all levels to adjust their methods of care. Surgeons in the community must respond accordingly and not only take necessary precautions during patient management, but also find opportunities to better educate patients moving forward. Additionally, to best preserve personal protective equipment and staffing resources, surgeons should thoroughly assess their patient load and determine which planned surgeries can be safely delayed to a later date. While not necessarily on the front lines of the pandemic response, surgeons have a vital role in maintaining the public health in the time of crisis.


title: Crystallization and preliminary X-ray crystallographic analysis of a nonstructural protein 15 mutant from Human coronavirus 229E

text: Nonstructural protein 15 (nsp15), also called endoribonuclease, is a gene product of open reading frame 1b (ORF 1b) in coronaviruses. It is an important enzyme in the transcription/replication process involved in discontinuous negative-strand RNA synthesis. In this work, mutants of nsp15 from Human coronavirus 229E (HCoV-229E) were made based on structural analysis of the homologous nsp15s in Severe acute respiratory syndrome coronavirus (SARS-CoV) and Mouse hepatitis virus (MHV). The I26A/N52A mutant of nsp15 was overexpressed, purified and crystallized, and this mutant led to a trimeric form rather than hexamers or monomers. Crystals of trimeric nsp15 were obtained by the hanging-drop vapour-diffusion method using polyethylene glycol as a precipitant and diffracted to 2.5 Å resolution. The crystals belonged to space group C222(1), with unit-cell parameters a = 85.9, b = 137.5, c = 423.1 Å, α = β = γ = 90°.


title: Effect of the Ebola-virus-disease epidemic on malaria case management in Guinea, 2014: a cross-sectional survey of health facilities

text: BACKGROUND: The ongoing west Africa Ebola-virus-disease epidemic has disrupted the entire health-care system in affected countries. Because of the overlap of symptoms of Ebola virus disease and malaria, the care delivery of malaria is particularly sensitive to the indirect effects of the current Ebola-virus-disease epidemic. We therefore characterise malaria case management in the context of the Ebola-virus-disease epidemic and document the effect of the Ebola-virus-disease epidemic on malaria case management. METHODS: We did a cross-sectional survey of public health facilities in Guinea in December, 2014. We selected the four prefectures most affected by Ebola virus disease and selected four randomly from prefectures without any reported cases of the disease. 60 health facilities were sampled in Ebola-affected and 60 in Ebola-unaffected prefectures. Study teams abstracted malaria case management indicators from registers for January to November for 2013 and 2014 and interviewed health-care workers. Nationwide weekly surveillance data for suspect malaria cases reported between 2011 and 2014 were analysed independently. Data for malaria indicators in 2014 were compared with previous years. FINDINGS: We noted substantial reductions in all-cause outpatient visits (by 23 103 [11%] of 214 899), cases of fever (by 20249 [15%] of 131 330), and patients treated with oral (by 22 655 [24%] of 94 785) and injectable (by 5219 [30%] of 17 684) antimalarial drugs in surveyed health facilities. In Ebola-affected prefectures, 73 of 98 interviewed community health workers were operational (74%, 95% CI 65–83) and 35 of 73 were actively treating malaria cases (48%, 36–60) compared with 106 of 112 (95%, 89–98) and 102 of 106 (96%, 91–99), respectively, in Ebola-unaffected prefectures. Nationwide, the Ebola-virus-disease epidemic was estimated to have resulted in 74 000 (71 000–77 000) fewer malaria cases seen at health facilities in 2014. INTERPRETATION: The reduction in the delivery of malaria care because of the Ebola-virus-disease epidemic threatens malaria control in Guinea. Untreated and inappropriately treated malaria cases lead to excess malaria mortality and more fever cases in the community, impeding the Ebola-virus-disease response. FUNDING: Global Fund to Fight AIDS, Tuberculosis and Malaria, and President’s Malaria Initiative.


title: Human Enterovirus C105, China, 2017

text: We report a case of enterovirus C105 infection in an 11-year-old girl with lower respiratory tract symptoms that was identified through the Respiratory Virus Surveillance System, which covers 30 sentinel hospitals in all 16 districts of Beijing, China. The presence of this virus strain in China confirmed its geographically wide distribution.


title: Impact of media reports on the early spread of COVID-19 epidemic

text: Media reports can modify people’s knowledge of emerging infectious diseases, and thus changing the public attitudes and behaviors. However, how the media reports affect the development of COVID-19 epidemic is a key public health issue. Here the Pearson correlation and cross-correlation analyses are conducted to find the statistically significant correlations between the number of new hospital notifications for COVID-19 and the number of daily news items for twelve major websites in China from January 11th to February 6th 2020. To examine the implication for transmission dynamics of these correlations, we proposed a novel model, which embeds the function of individual behaviour change (media impact) into the intensity of infection. The nonlinear least squares estimation is used to identify the best-fit parameter values in the model from the observed data. To determine impact of key parameters with media impact and control measures for the later outcome of the outbreak, we also carried out the uncertainty and sensitivity analyses. These findings confirm the importance of the responses of individuals to the media reports, and the crucial role of experts and governments in promoting the public under self-quarantine. Therefore, for mitigating epidemic COVID-19, the media publicity should be focused on how to guide people’s behavioral changes by experts, and the management departments and designated hospitals of the COVID-19 should take effective quarantined measures, which are critical for the control of the disease.


title: Multiple sites of recombination within the RNA genome of foot-and-mouth disease virus

text: Abstract Recombinant foot-and-mouth disease viruses were isolated from cells infected with a mixture of temperature-sensitive (ts) mutants belonging to different subtype strains. In order to select for recombination events in many different regions of the genome, crosses were performed between various pairs of mutants, with ts mutations in different regions of the genome. ts + progeny were analysed by electrofocusing virus-induced proteins and RNase T1 fingerprinting of their RNA. All but 5 out of 43 independent isolates, from nine crosses, proved to have recombinant RNA genomes. Maps of these genomes, based on a knowledge of the locations of the unique oligonucleotides, were constructed. Most could be interpreted as being the products of single genetic cross-overs, although three recombinants were formed by two cross-overs each. Cross-overs in at least twelve distinct regions of the genome were identified. This evidence of a large number of recombination sites suggests that RNA recombination in picornaviruses is a general, as opposed to a site-specific, phenomenon.


title: Anthelmintic PF1022A: stepwise solid-phase synthesis of a cyclodepsipeptide containing N-methyl amino acids

text: Abstract Cyclodepsipeptides of the enniation-, PF1022-, and verticilide-family represent a diverse class of highly interesting natural products with respect to their manifold biological activities. However, until now no stepwise solid-phase synthesis has been accomplished due to the difficult combination of N-methyl amino acids and hydroxycarboxylic acids. We report here the first stepwise solid-phase synthesis of the anthelmintic cyclooctadepsipeptide PF1022A based on an Fmoc/THP-ether protecting group strategy on Wang-resin. The standard conditions of our synthesis allow an unproblematic adaption to an automated peptide synthesizer.


title: Growing pains

text: Protein microarrays are coming of age, and the development of specialized technologies is extending their high-throughput capabilities. Michael Eisenstein reports.


title: Establishment of cell line from embryonic tissue of Pipistrellus ceylonicus bat species from India & its susceptibility to different viruses

text: BACKGROUND & OBJECTIVES: Pipistrellus ceylonicus bat species is widely distributed in South Asia, with additional populations recorded in China and Southeast Asia. Bats are the natural reservoir hosts for a number of emerging zoonotic diseases. Attempts to isolate bat-borne viruses in various terrestrial mammalian cell lines have sometimes been unsuccessful. The bat cell lines are useful in isolation and propagation of many of the viruses harboured by bats. New stable bat cell lines are needed to help such investigations and to assist in the study of bat immunology and virus-host interactions. In this study we made an attempt to develop a cell line from P. ceylonicus bats. METHODS: An effort was made to establish cell line from embryo of P. ceylonicus species of bat after seeding to Dulbecco's modified eagle medium (DMEM) supplemented with 10 per cent foetal bovine serum; a primary cell line was established and designated as NIV-BtEPC. Mitochondrial DNA profile analysis was done using cyt-b and ND-1 gene sequences from the cell line. Phylogenetic tree was constructed using neighbour-joining algorithm for cyt-b and ND-1 genes with 1000-bootstrap replicates. RESULTS: NIV-BtEPC cell line was susceptible to Chandipura (CHPV) and novel adenovirus (BtAdv-RLM) isolated from Rousettus leschenaulti from India but did not support multiplication of a number of Bunyaviruses, Alphaviruses and Flavivirus. This might be useful for isolation of a range of viruses and investigation of unknown aetiological agents. INTERPRETATION & CONCLUSIONS: In this study, a new bat cell line was developed from P. ceylonicus. This cell line was successfully tested for the susceptibility to Chandipura and BtAdv-RLM virus isolated from bats. The approach developed and optimised in this study may be applicable to the other species of bats and this established cell line can be used to facilitate virus isolation and basic research into virus-host interaction.


title: Combating COVID-19 with integrated traditional Chinese and Western medicine in China

text: COVID-19, an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout the world. China has achieved initial success in containing this highly infectious disease with integrated traditional Chinese and Western medicine. Current findings have shown that the Chinese protocol can reduce the incidence of severe or critical events, improve clinical recovery and help alleviate symptoms such as cough or fever. The inclusion of traditional Chinese medicine (TCM) in this protocol is based on its successful experience in fighting against pestilence. To date there are 133 ongoing registered clinical studies on TCM/integrated traditional Chinese and Western medicine. Although there are no high-quality clinical evidences, pharmacological studies have suggested that Chinese medicine is effective for COVID-19 probably through its host-directed regulation and certain antiviral effects.


title: p38 MAPK inhibition: A promising therapeutic approach for COVID-19

text: COVID-19, caused by the SARS-CoV-2 virus, is a major source of morbidity and mortality due to its inflammatory effects in the lungs and heart. The p38 MAPK pathway plays a crucial role in the release of pro-inflammatory cytokines such as IL-6 and has been implicated in acute lung injury and myocardial dysfunction. The overwhelming inflammatory response in COVID-19 infection may be caused by disproportionately upregulated p38 activity, explained by two mechanisms. First, angiotensin-converting enzyme 2 (ACE2) activity is lost during SARS-CoV-2 viral entry. ACE2 is highly expressed in the lungs and heart and converts Angiotensin II into Angiotensin 1–7. Angiotensin II signals proinflammatory, pro-vasoconstrictive, pro-thrombotic activity through p38 MAPK activation, which is countered by Angiotensin 1–7 downregulation of p38 activity. Loss of ACE2 upon viral entry may tip the balance towards destructive p38 signaling through Angiotensin II. Second, SARS-CoV was previously shown to directly upregulate p38 activity via a viral protein, similar to other RNA respiratory viruses that may hijack p38 activity to promote replication. Given the homology between SARS-CoV and SARS-CoV-2, the latter may employ a similar mechanism. Thus, SARS-CoV-2 may induce overwhelming inflammation by directly activating p38 and downregulating a key inhibitory pathway, while simultaneously taking advantage of p38 activity to replicate. Therapeutic inhibition of p38 could therefore attenuate COVID-19 infection. Interestingly, a prior preclinical study showed protective effects of p38 inhibition in a SARS-CoV mouse model. A number of p38 inhibitors are in the clinical stage and should be considered for clinical trials in serious COVID-19 infection.


title: Automatic online news monitoring and classification for syndromic surveillance

text: Abstract Syndromic surveillance can play an important role in protecting the public's health against infectious diseases. Infectious disease outbreaks can have a devastating effect on society as well as the economy, and global awareness is therefore critical to protecting against major outbreaks. By monitoring online news sources and developing an accurate news classification system for syndromic surveillance, public health personnel can be apprised of outbreaks and potential outbreak situations. In this study, we have developed a framework for automatic online news monitoring and classification for syndromic surveillance. The framework is unique and none of the techniques adopted in this study have been previously used in the context of syndromic surveillance on infectious diseases. In recent classification experiments, we compared the performance of different feature subsets on different machine learning algorithms. The results showed that the combined feature subsets including Bag of Words, Noun Phrases, and Named Entities features outperformed the Bag of Words feature subsets. Furthermore, feature selection improved the performance of feature subsets in online news classification. The highest classification performance was achieved when using SVM upon the selected combination feature subset.


title: COVID‐19 treatment by repurposing drugs until the vaccine is in sight

text: Corona virus disease (COVID‐19) has created pandemic in the world as declared by WHO on March 12, 2020. It is a viral disease caused by SARS‐CoV 2 virus and has affected large populations in over 120 countries. There is no specific treatment available and management is empirical. Until such time that an effective vaccine is available for COVID‐19 viral infection, one can repurpose known therapeutic drug molecules such as angiotensin receptor 2 blocker, a commonly used antihypertensive drug, to control COVID‐19 virus from gaining entry into the host cell by blocking the angiotensin receptor. Clinical trials should also be undertaken to use statins, which are lipid‐lowering drugs but have anti‐inflammatory and immunomodulatory properties to prevent acute lung injury in COVID‐19 infection.


title: Nidovirus Infections: Experimental Model Systems of Human Neurologic Diseases

text: The presence of terminally differentiated slow- and non-dividing cells in the central nervous system (CNS) provides a safe harbor for viral persistence and latency and constitutes a unique immunologic environment for viral infections. Studies of experimental model systems of viral infections of the CNS provide insight into mechanisms of viral persistence and immune-mediated pathology. Nidoviruses are comprised of 2 families of viruses, coronaviruses and arteriviruses, and are common pathogens of humans and a variety of animal species. Both families of viruses contain neurotropic strains that produce experimental neurologic diseases in rodents. These include acute meningitis and encephalitis; acute poliomyelitis; and chronic inflammatory, immune-mediated, demyelination. Coronavirus-induced demyelinating disease mimics many of the pathologic features of Multiple Sclerosis (MS).