title: Broadly Reactive Polymerase Chain Reaction for Pathogen Detection in Canine Granulomatous Meningoencephalomyelitis and Necrotizing Meningoencephalitis

text: BACKGROUND: Granulomatous meningoencephalomyelitis (GME) and necrotizing meningoencephalitis (NME) are common inflammatory conditions of the central nervous system of dogs. Infectious pathogens, particularly viruses, are suspected to contribute to the etiopathogenesis of GME and NME. HYPOTHESIS: Broadly reactive PCR might aid in the identification of infectious agents in GME and NME. ANIMALS: Sixty‐eight client‐owned dogs evaluated by necropsy at 1 university referral hospital. METHODS: A mixed prospective/retrospective case‐control study was performed. Brain tissue prospectively collected at necropsy from GME, NME, and control cases was evaluated by broadly reactive polymerase chain reaction (PCR) for adenoviruses, bunyaviruses, coronaviruses, enteroviruses, flaviviruses, herpesviruses, paramyxoviruses, and parechoviruses. In addition, these tissues were retrospectively evaluated for the presence of mycoplasmas by PCR, culture, and immunohistochemistry (IHC). RESULTS: Brain tissue was collected from 11 GME and 27 NME cases and 30 controls. Viral nucleic acids were not identified in the 6 GME cases, 25 NME cases, and 2 controls evaluated by viral PCR. Mycoplasma canis was identified by Mycoplasma genus PCR in 1/5 GME and 4/25 NME cases and subsequently was cultured from 4/5 GME and 4/8 NME cases as well as 2/9 controls. The IHC did not detect M. canis in any of the 11 GME and 27 NME cases or 14 controls evaluated with strain PG14 polyclonal antiserum. CONCLUSIONS AND CLINICAL IMPORTANCE: The negative results suggest that viral pathogens are not common in the brain tissue of dogs with GME and NME. Further investigation is warranted to determine the importance of M. canis in cases of GME and NME.


title: Rhinitis in children less than 6 years of age: current knowledge and challenges

text: Rhinitis is a disease of the upper airway characterized by runny and/or blocked nose and/or sneezing. Though not viewed as a life threatening condition, it is also recognized to impose significant burden to the quality of life of sufferers and their caretakers and imposes an economic cost to society. Through a PubMed online search of the literature from 2006 to September 2011, this paper aims to review the published literature on rhinitis in young children below the age of 6 years. It is apparent from epidemiology studies that rhinitis in this age group is a relatively common problem. The condition has a heterogenous etiology with classification into allergic and non-allergic rhinitis. Respiratory viral infections may play a role in the pathogenesis of long standing rhinitis, but definitive studies are still lacking. Treatment guidelines for management are lacking for this age group, and is a significant unmet need. Although the consensus is that co-morbidities including otitis media with effusion, adenoidal hypertrophy and asthma, are important considerations of management of these children. Pharmacotherapy is limited for young children especially for those below the age of 2 years. This review underscores the lack of understanding of rhinitis in early childhood and therefore the need for further research in this area.


title: BAL fluid analysis in the identification of infectious agents in patients with hematological malignancies and pulmonary infiltrates

text: The present study aims to evaluate the diagnostic yield of bronchoalveolar lavage (BAL) fluid in patients with hematological malignancies and describe the most common pathogens detected in BAL fluid (BALF.) An analysis of 480 BALF samples was performed in patients with hematological malignancies over a period of 7 years. The results of culture methods, PCR, and immunoenzymatic sandwich microplate assays for Aspergillus galactomannan (GM) in BALF were analyzed. Further, the diagnostic thresholds for Aspergillus GM and Pneumocystis jiroveci were also calculated. Microbiological findings were present in 87% of BALF samples. Possible infectious pathogens were detected in 55% of cases; 32% were classified as colonizing. No significant difference in diagnostic yield or pathogen spectrum was found between non-neutropenic and neutropenic patients. There was one significant difference in BALF findings among intensive care units (ICU) versus non-ICU patients for Aspergillus spp. (22% versus 9%, p = 0.03). The most common pathogens were Aspergillus spp. (n = 86, 33% of BAL with causative pathogens) and Streptococcus pneumoniae (n = 46, 18%); polymicrobial etiology was documented in 20% of cases. A quantitative PCR value of > 1860 cp/mL for Pneumocystis jirovecii was set as a diagnostic threshold for pneumocystis pneumonia. The absorbance index of GM in BALF of 0.5 was set as a diagnostic threshold for aspergillosis. The examination of BAL fluid revealed the presence of pathogen in more than 50% of cases and is, therefore, highly useful in this regard when concerning pulmonary infiltrates. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12223-019-00712-4) contains supplementary material, which is available to authorized users.


title: Pure Viral Sepsis Secondary to Community-Acquired Pneumonia in Adults: Risk and Prognostic Factors

text: We investigated the risk and prognostic factors of pure viral sepsis in adult patients with community-acquired pneumonia (CAP), using the Sepsis-3 definition. Pure viral sepsis was found in 3% of all patients (138 of 4028) admitted to the emergency department with a diagnosis of CAP, 19% of those with CAP (138 of 722) admitted to the intensive care unit, and 61% of those (138 of 225) with a diagnosis of viral CAP. Our data indicate that males and patients aged ≥65 years are at increased risk of viral sepsis.


title: The limits and boundaries of digital disconnection

text: This editorial introduces a themed section aimed to spark further reflections on the limits and boundaries of disconnection as a form of critique, activism and response to the pervasiveness of digital devices, platforms, and infrastructures. We outline two key limits in current thinking about disconnection: first, the universalist discourse of disconnection, which contrasts with the reality of a profound inequality of access to both connection and disconnection across the globe, and second, the fact that connectivity not only involves digital media users but also those who are materially not connected to the network. This introduction also reflects on the changing meanings of being connected and disconnected to digital networks and platforms at a time when the Covid-19 pandemic forces many people around the world to remain physically separated from others due to lockdown and quarantine measures.


title: Quantifying the impact of community quarantine on SARS transmission in Ontario: estimation of secondary case count difference and number needed to quarantine

text: BACKGROUND: Community quarantine is controversial, and the decision to use and prepare for it should be informed by specific quantitative evidence of benefit. Case-study reports on 2002-2004 SARS outbreaks have discussed the role of quarantine in the community in transmission. However, this literature has not yielded quantitative estimates of the reduction in secondary cases attributable to quarantine as would be seen in other areas of health policy and cost-effectiveness analysis. METHODS: Using data from the 2003 Ontario, Canada, SARS outbreak, two novel expressions for the impact of quarantine are presented. Secondary Case Count Difference (SCCD) reflects reduction in the average number of transmissions arising from a SARS case in quarantine, relative to not in quarantine, at onset of symptoms. SCCD was estimated using Poisson and negative binomial regression models (with identity link function) comparing the number of secondary cases to each index case for quarantine relative to non-quarantined index cases. The inverse of this statistic is proposed as the number needed to quarantine (NNQ) to prevent one additional secondary transmission. RESULTS: Our estimated SCCD was 0.133 fewer secondary cases per quarantined versus non-quarantined index case; and a NNQ of 7.5 exposed individuals to be placed in community quarantine to prevent one additional case of transmission in the community. This analysis suggests quarantine can be an effective preventive measure, although these estimates lack statistical precision. CONCLUSIONS: Relative to other health policy areas, literature on quarantine tends to lack in quantitative expressions of effectiveness, or agreement on how best to report differences in outcomes attributable to control measure. We hope to further this discussion through presentation of means to calculate and express the impact of population control measures. The study of quarantine effectiveness presents several methodological and statistical challenges. Further research and discussion are needed to understand the costs and benefits of enacting quarantine, and this includes a discussion of how quantitative benefit should be communicated to decision-makers and the public, and evaluated.


title: The effect of smoking on influenza, influenza vaccination efficacy and on the antibody response to influenza vaccination

text: Abstract We examined the relation between cigarette smoking and (1) the occurrence of influenza, (2) the efficacy of influenza vaccination and (3) the antibody response to influenza vaccination in fifteen family practices in South-Limburg, the Netherlands, during the influenza season 1991–1992. Data were used from a randomized double-blind placebo-controlled trial into the efficacy of influenza vaccination in which smoking status was measured 10 weeks after the start of the trial. A total of 1838 subjects aged 60 years or older, of whom 1531 subjects (321 smokers, 1152 non-smokers and 58 cigar/pipe smokers) who returned the smoking questionnaire and were not previously vaccinated, were used in the analyses. The main outcome measures were serological influenza (fourfold increase of antibody titre between 3 weeks and 5 months after vaccination); clinical influenza as determined by criteria of the Dutch Sentinel Stations from self reported symptoms in postal questionnaires 10 weeks and 5 months after vaccination; increases after vaccination and decreases after 5 months in logarithmic titres of antibody against the vaccine strains. No relation between smoking and either serological or clinical influenza was found, although the risk for serological influenza was slightly (not significantly) elevated in smokers compared to non-smokers. A statistical interaction was found between smoking and vaccination when serological influenza was the outcome measure indicating that the efficacy of vaccination was greater in smokers than in non-smokers (comparison of model with and without interaction; likelihood ratio test, p<0.0001). This finding is supported by a greater titre rise 3 weeks after vaccination for two out of four strains, but not by the antibody response after vaccination in previous studies on influenza and other infectious diseases. Also, this possible difference of immunogenicity is not reflected in a better protection for clinical influenza. The rise in antibody titre 3 weeks after vaccination was higher in smokers for A/Singapore/6/86 and B/Beijing/11/87, but not for the other two strains. Decline in titres after 5 months was similar for smokers and non-smokers. We conclude that smoking has no clinical or preventive significance for risk of influenza in the elderly.


title: VSITA, an Improved Approach of Target Amplification in the Identification of Viral Pathogens

text: Abstract Objective Unbiased next generation sequencing (NGS) is susceptible to interference from host or environmental sequences. Consequently, background depletion and virome enrichment techniques are usually needed for clinical samples where viral load is much lower than background sequences. Methods A viral Sequence Independent Targeted Amplification (VSITA) approach using a set of non-ribosomal and virus-enriched octamers (V8) was developed and compared with traditionally used random hexamers (N6). Forty-five archived clinical samples of different types were used in parallel to compare the V8 and N6 enrichment performance of viral sequences and removal performance of ribosomal sequences in the step of reverse transcription followed by quantitative PCR (qPCR). Ten sera samples from patients with fever of unknown origin and 10 feces samples from patients with diarrhea of unknown origin were used in comparison of V8 and N6 enrichment performance following NGS analysis. Results A minimum 30 hexamers matching to viral reference sequences (sense and antisense) were selected from a dataset of random 4,096 (46) hexamers (N6). Two random nucleotides were added to the 5' end of the selected hexamers, and 480 (30 × 42) octamers (V8) were obtained. In general, VSITA approach showed higher enrichment of virus-targeted cDNA and enhanced ability to remove unwanted ribosomal sequences in the majorities of 45 predefined clinical samples. Moreover, VSITA combined with NGS enabled to detect not only more viruses but also achieve more viral reads hit and higher viral genome coverage in 20 clinical samples with diarrhea or fever of unknown origin. Conclusion The VSITA approach designed in this study is demonstrated to possess higher sensitivity and broader genome coverage than traditionally used random hexamers in the NGS-based identification of viral pathogens directly from clinical samples.


title: Assessment of in vitro prophylactic and therapeutic efficacy of chloroquine against chikungunya virus in vero cells

text: The resurgence of Chikungunya virus (CHIKV) in the form of unprecedented and explosive epidemics in India and the Indian Ocean islands after a gap of 32 years is a major public health concern. Currently, there is no specific therapy available to treat CHIKV infection. In the present study, the in vitro prophylactic and therapeutic effects of chloroquine on CHIKV replication in Vero cells were investigated. Inhibitory effects were observed when chloroquine was administered pre‐infection, post‐infection, and concurrent with infection, suggesting that chloroquine has prophylactic and therapeutic potential. The inhibitory effects were confirmed by performing a plaque reduction neutralization test (PRNT), real‐time reverse transcriptase (RT)‐PCR analysis of viral RNA levels, and cell viability assays. Chloroquine diminished CHIKV infection in a dose‐dependent manner, with an effective concentration range of 5–20 µM. Concurrent addition of drug with virus, or treatment of cells prior to infection drastically reduced virus infectivity and viral genome copy number by ≥99.99%. The maximum inhibitory effect of chloroquine was observed within 1–3 hr post‐infection (hpi), and treatment was ineffective once the virus successfully passed through the early stages of infection. The mechanism of inhibition of virus activity by chloroquine involved impaired endosomal‐mediated virus entry during early stages of virus replication, most likely through the prevention of endocytosis and/or endosomal acidification, based on a comparative evaluation using ammonium chloride, a known lysosomotropic agent. J. Med. Virol. 82: 817–824, 2010. © 2010 Wiley‐Liss, Inc.


title: IoT PCR for pandemic disease detection and its spread monitoring

text: Abstract During infectious disease outbreaks, the centers for disease control need to monitor particular areas. Considerable effort has been invested in the development of portable, user-friendly, and cost-effective systems for point-of-care (POC) diagnostics, which could also create an Internet of Things (IoT) for healthcare via a global network. However, at present IoT based on a functional POC instrument is not available. Here we show a fast, user-friendly, and affordable IoT system based on a miniaturized polymerase chain reaction device. We demonstrated the system’s capability by amplification of complementary deoxyribonucleic acid (cDNA) of the dengue fever virus. The resulting data were then automatically uploaded via a Bluetooth interface to an Android-based smartphone and then wirelessly sent to a global network, instantly making the test results available anywhere in the world. The IoT system presented here could become an essential tool for healthcare centers to tackle infectious disease outbreaks identified either by DNA or ribonucleic acid.


title: Pharmacokinetics of Anti-HBV Polyoxometalate in Rats

text: Polyoxometalates are non-nucleoside analogs that have been proven to exhibit broad-spectrum antiviral activity. In particular, Cs(2)K(4)Na[SiW(9)Nb(3)O(40)].H(2)O 1 shows low toxicity and high activity against HBV. The preclinical pharmacokinetics of Compound 1 in rats were characterized by establishing and applying inductively coupled plasma-mass spectrometry method to determine the concentration of W in plasma, urine, feces, bile and organ samples. The quantitative ICP-MS method demonstrated good sensitivity and application in the pharmacokinetics study of polyoxometalates. The pharmacokinetic behavior of Compound 1 after intravenous or oral administration fit a two-compartment model. T(max) ranges from 0.1 h to 3 h and the T(1/2) of Compound 1 is between 20 h and 30 h. The absolute bioavailability of Compound 1 at 45, 180 and 720 mg/kg groups were 23.68%, 14.67% and 11.93%, respectively. The rates of plasma protein binding of Compound 1 at 9, 18 and 36 mg/ml of Compound 1 are 62.13±9.41%, 71.20±24.98% and 49.00±25.59%, respectively. Compound 1 was widely distributed throughout the body, and high levels of compound 1 were found in the kidney and liver. The level of Compound 1 in excretion was lower: 30% for urine, 0.28% for feces and 0.42% for bile, respectively. For elaborate pharmacokinetic characteristics to be fully understood, the metabolism of Compound 1 needs to be studied further.


title: Impact of the COVID-19 pandemic on cancer treatment: the patients’ perspective

text: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has inevitable consequences for medical care of non-COVID-19 patients. To assess the impact of this pandemic on oncological care, a nationwide survey was conducted among cancer patients in the Netherlands. METHODS: The patients’ perspective on oncological care was investigated using an online survey between March 29(th) 2020 and April 18(th) 2020. The survey consisted of 20 questions on four topics: patients’ characteristics, contact with the hospital, consequences of the COVID-19 pandemic, and concerns about COVID-19. RESULTS: 5302 cancer patients completed this nationwide survey. Overall, 30% of patients reported consequences for their oncological treatment or follow-up. In the majority of cases this resulted in conversion from hospital visit to consultation by phone or video. The most frequently adjusted treatments were chemotherapy (30%) and immunotherapy (32%). Among patients with delay and discontinuation of treatment, respectively 55% and 63% of patients were (very) concerned about these consequences of the COVID-19 pandemic. Consequences were independent of regional differences in COVID-19 incidence. However, patients in regions with high COVID-19 incidence were significantly more concerned. CONCLUSION: This is the first study investigating perspectives of cancer patients during the COVID-19 pandemic. The study demonstrates the significant impact of the COVID-19 crisis on oncological care, indicating the need for psycho-oncological support during this pandemic.


title: Crise du COVID-19: impacts dans notre Service de Santé au travail

text: Résumé La crise sanitaire internationale du COVID-19 nous a tous bouleversés. En temps de catastrophe, tous nos fonctionnements sont affectés, y compris dans notre service de santé au travail, depuis deux mois. Ce témoignage vient éclairer notre réflexion, au moment du déconfinement en France, pour ouvrir de nouveaux horizons. Abstract The international COVID-19 outbreak has upset us all. In times of disaster, all of our collectives processes are affected, including our occupational health department, for the past two months. This testimony comes to enlighten our reflection, at a time of lock down in France, to open new horizons.


title: M1 aminopeptidases as drug targets: broad applications or therapeutic niche?

text: M1 aminopeptidase enzymes are a diverse family of metalloenzymes characterized by conserved structure and reaction specificity. Excluding viruses, M1 aminopeptidases are distributed throughout all phyla, and have been implicated in a wide range of functions including cell maintenance, growth and development, and defense. The structure and catalytic mechanism of M1 aminopeptidases are well understood, and make them ideal candidates for the design of small‐molecule inhibitors. As a result, many research groups have assessed their utility as therapeutic targets for both infectious and chronic diseases of humans, and many inhibitors with a range of target specificities and potential therapeutic applications have been developed. Herein, we have aimed to address these studies, to determine whether the family of M1 aminopeptidases does in fact present a universal target for the treatment of a diverse range of human diseases. Our analysis indicates that early validation of M1 aminopeptidases as therapeutic targets is often overlooked, which prevents the enzymes from being confirmed as drug targets. This validation cannot be neglected, and needs to include a thorough characterization of enzymes’ specific roles within complex physiological pathways. Furthermore, any chemical probes used in target validation must be carefully designed to ensure that specificity over the closely related enzymes has been achieved. While many drug discovery programs that target M1 aminopeptidases remain in their infancy, certain inhibitors have shown promise for the treatment of a range of conditions including malaria, hypertension, and cancer.


title: Population density and basic reproductive number of COVID-19 across United States counties

text: The basic reproductive number (R0) is a function of contact rates among individuals, transmission probability, and duration of infectiousness. We sought to determine the association between population density and R0 of SARS-CoV-2 across U.S. counties, and whether population density could be used as a proxy for contact rates. We conducted a cross-sectional analysis using linear mixed models with random intercept and fixed slopes to assess the association of population density and R0. We also assessed whether this association was differential across county-level main mode of transportation-to-work percentage. Counties with greater population density have greater rates of transmission of SARS-CoV-2, likely due to increased contact rates in areas with greater density. The effect of population density and R0 was not modified by private transportation use. Differential R0 by population density can assist in more accurate predictions of the rate of spread of SARS-CoV-2 in areas that do not yet have active cases.


title: Synergistic China–US Ecological Research is Essential for Global Emerging Infectious Disease Preparedness

text: The risk of a zoonotic pandemic disease threatens hundreds of millions of people. Emerging infectious diseases also threaten livestock and wildlife populations around the world and can lead to devastating economic damages. China and the USA—due to their unparalleled resources, widespread engagement in activities driving emerging infectious diseases and national as well as geopolitical imperatives to contribute to global health security—play an essential role in our understanding of pandemic threats. Critical to efforts to mitigate risk is building upon existing investments in global capacity to develop training and research focused on the ecological factors driving infectious disease spillover from animals to humans. International cooperation, particularly between China and the USA, is essential to fully engage the resources and scientific strengths necessary to add this ecological emphasis to the pandemic preparedness strategy. Here, we review the world’s current state of emerging infectious disease preparedness, the ecological and evolutionary knowledge needed to anticipate disease emergence, the roles that China and the USA currently play as sources and solutions to mitigating risk, and the next steps needed to better protect the global community from zoonotic disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10393-020-01471-2) contains supplementary material, which is available to authorized users.


title: Complete Genomic and Ultrastructural Analysis of a Nam Dinh Virus Isolated from Culex pipiens quinquefasciatus in China*

text: The Nam Dinh virus (NDiV) was isolated from Culex quinquefasciatus in Shenzhen, China, for the first time, in 2011. In this study, we characterized the ultrastructure of NDiV, determined its complete genome sequence and made comparisons with other known nidoviruses. Electron microscopic observation revealed that the NDiV strain isolated in China produced viral nucleocapsid-like particles and vesicles in host cells. The extracellular virions were enveloped and were spherical with short spikes. The complete genome sequence of the newly isolated NDiV was submitted to the GenBank database (GenBank accession number KF522691). Sequencing of the viral genome showed that the homologies of NDiV isolated in China and Vietnam were greater than 94.0% and 89.0% at the nucleotide and amino acid sequence levels, respectively. Moreover, gene substitution was detected, whereas insertions and deletions were not. A phylogenetic tree analysis showed that these viruses belong to the genus Alphamesonivirus1 of the family Mesoniviridae. The similarity between the two viruses regarding morphological and molecular biological characteristics indicates that the molecular genetics of NDiV are conservative and that the regional differences are unlikely to have a significant effect. This is the first report of the isolation and complete sequencing of a mesonivirus in mainland China.


title: Mepolizumab Therapy for Recalcitrant Eosinophilic Annular Erythema in an Adult: A Case Report and Review of Treatment Options

text: Eosinophilic annular erythema (EAE) is a rare condition with a chronic relapsing and remitting course, characterized by the presence of annular or polycyclic erythematous and plaque lesions and prominent tissue eosinophilia on histopathology. There is an ongoing discussion on whether EAE is a subset of Wells syndrome (eosinophilic cellulitis) or a separate entity. To date, few cases of EAE have been reported in the literature; of these, about 40 cases were in adults and fewer than ten cases were in children. Given the rarity of this condition, there are no clear recommendations for its management. Systemic corticosteroids and antimalarials are the most commonly used medications used to treat EAE, but many cases have been reported in the literature that are resistant to treatment with these medications. Here, we present a 65-year-old female with EAE refractory to numerous systemic therapies (corticosteroids, hydroxychloroquine, dapsone, doxycycline, methotrexate) who showed a good response to mepolizumab, a humanized monoclonal antibody that blocks interleukin-5. To the best of our knowledge, this is the first reported case of mepolizumab therapy in a patient with EAE. We also review other treatment strategies that have been used to manage this condition to date. Targeting cytokines crucial for the functioning of eosinophils may be a novel direction in the management of EAE, but prospective, double-blinded and placebo-controlled studies are needed to provide further evidence.


title: Chapter 12 Noncoding RNAs in Retrovirus Replication

text: Abstract Although a limited percentage of the genome produces proteins, approximately 90% is transcribed, indicating important roles for noncoding RNA (ncRNA). It is now known that these ncRNAs have a multitude of cellular functions ranging from the regulation of gene expression to roles as structural elements in ribonucleoprotein complexes. ncRNA is also represented at nearly every step of viral life cycles. This chapter will focus on ncRNAs of both host and viral origin and their roles in retroviral life cycles. Cellular ncRNA represents a significant portion of material packaged into retroviral virions and includes transfer RNAs, 7SL RNA, U RNA, and vault RNA. Initially thought to be random packaging events, these host RNAs are now proposed to contribute to viral assembly and infectivity. Within the cell, long ncRNA and endogenous retroviruses have been found to regulate aspects of the retroviral life cycle in diverse ways. Additionally, the HIV-1 transactivating response element RNA is thought to impact viral infection beyond the well-characterized role as a transcription activator. RNA interference, thought to be an early version of the innate immune response to viral infection, can still be observed in plants and invertebrates today. The ability of retroviral infection to manipulate the host RNAi pathway is described here. Finally, RNA-based therapies, including gene editing approaches, are being explored as antiretroviral treatments and are discussed.


title: Early Short Course Corticosteroids in Hospitalized Patients with COVID-19

text: BACKGROUND: There is no proven antiviral or immunomodulatory therapy for COVID-19. The disease progression associated with the pro-inflammatory host response prompted us to examine the role of early corticosteroid therapy in patients with moderate to severe COVID-19. METHODS: We conducted a single pre-test, single post-test quasi-experiment in a multi-center health system in Michigan from March 12 to March 27, 2020. Adult patients with confirmed moderate to severe COVID were included. A protocol was implemented on March 20, 2020 using early, short-course, methylprednisolone 0.5 to 1 mg/kg/day divided in 2 intravenous doses for 3 days. Outcomes of standard of care (SOC) and early corticosteroid groups were evaluated, with a primary composite endpoint of escalation of care from ward to ICU, new requirement for mechanical ventilation, and mortality. All patients had at least 14 days of follow-up. RESULTS: We analyzed 213 eligible subjects, 81 (38%) and 132 (62%) in SOC and early corticosteroid groups, respectively.The composite endpoint occurred at a significantly lower rate in the early corticosteroid group (34.9% vs. 54.3%, p=0.005). This treatment effect was observed within each individual component of the composite endpoint. Significant reduction in median hospital length of stay was also observed in the early corticosteroid group (8 vs. 5 days, p < 0.001). Multivariate regression analysis demonstrated an independent reduction in the composite endpoint at 14-days controlling for other factors (aOR: 0.41; 95% CI [0.22 – 0.77]). CONCLUSION: An early short course of methylprednisolone in patients with moderate to severe COVID-19 reduced escalation of care and improved clinical outcomes.


title: Chapter 8.1 Immunoassay Applications in Veterinary Diagnostics

text: This chapter explains the technology and chemistry behind veterinary immunoassays. There is extensive coverage of infectious disease diagnosis and assessment of immune status using immunoassays for feline, canine, porcine, equine, bovine and avian applications, including the assay technology commonly used. There is also a section on the assessment of the reproductive or metabolic status of cats and dogs.


Summarizing societal guidelines regarding bronchoscopy during the COVID‐19 pandemic


Serum Amyloid A Is Not Useful in the Diagnosis of Severe Acute Respiratory Syndrome


title: Antiviral activity of carbohydrate-binding agents against Nidovirales in cell culture

text: Abstract Coronaviruses are important human and animal pathogens, the relevance of which increased due to the emergence of new human coronaviruses like SARS-CoV, HKU1 and NL63. Together with toroviruses, arteriviruses, and roniviruses the coronaviruses belong to the order Nidovirales. So far antivirals are hardly available to combat infections with viruses of this order. Therefore, various antiviral strategies to counter nidoviral infections are under evaluation. Lectins, which bind to N-linked oligosaccharide elements of enveloped viruses, can be considered as a conceptionally new class of virus inhibitors. These agents were recently evaluated for their antiviral activity towards a variety of enveloped viruses and were shown in most cases to inhibit virus infection at low concentrations. However, limited knowledge is available for their efficacy towards nidoviruses. In this article the application of the plant lectins Hippeastrum hybrid agglutinin (HHA), Galanthus nivalis agglutinin (GNA), Cymbidium sp. agglutinin (CA) and Urtica dioica agglutinin (UDA) as well as non-plant derived pradimicin-A (PRM-A) and cyanovirin-N (CV-N) as potential antiviral agents was evaluated. Three antiviral tests were compared based on different evaluation principles: cell viability (MTT-based colorimetric assay), number of infected cells (immunoperoxidase assay) and amount of viral protein expression (luciferase-based assay). The presence of carbohydrate-binding agents strongly inhibited coronaviruses (transmissible gastroenteritis virus, infectious bronchitis virus, feline coronaviruses serotypes I and II, mouse hepatitis virus), arteriviruses (equine arteritis virus and porcine respiratory and reproductive syndrome virus) and torovirus (equine Berne virus). Remarkably, serotype II feline coronaviruses and arteriviruses were not inhibited by PRM-A, in contrast to the other viruses tested.


title: A phased approach to unlocking during the COVID‐19 pandemic—Lessons from trend analysis

text: BACKGROUND: The COVID‐19 pandemic has led to radical political control of social behaviour. The purpose of this paper is to explore data trends from the pandemic regarding infection rates/policy impact and draw learning points for informing the unlocking process. METHODS: The daily published cases in England in each of 149 Upper Tier Local Authority (UTLA) areas were converted to Average Daily Infection Rate (ADIR), an R value—the number of further people infected by one infected person during their infectious phase with Rate of Change of Infection Rate (RCIR) also calculated. Stepwise regression was carried out to see what local factors could be linked to differences in local infection rates. FINDINGS: By the 19th April 2020 the infection R has fallen from 2.8 on 23rd March before the lockdown and has stabilised at about 0.8 sufficient for suppression. However, there remain significant variations between England regions. Regression analysis across UTLAs found that the only factor relating to reduction in ADIR was the historic number of confirmed number infection/000 population, There is, however, wide variation between Upper Tier Local Authorities (UTLA) areas. Extrapolation of these results showed that unreported community infection may be 150 times higher than reported cases, providing evidence that by the end of the 2nd week in April, 26.8% of the population may already have had the disease and so have increased immunity. INTERPRETATION: Analysis of current case data using infectious ratio has provided novel insight into the current national state and can be used to make better‐informed decisions about future management of restricted social behaviour and movement.


title: The building of social resilience in Sichuan after the Wenchuan earthquake: A perspective of the socio-government interactions

text: Abstract In November 2007, China implemented its Emergency Response Law to ensure national unified leadership and collaboration when responding to emergencies. In recent years, China’s main focuses for enhancing disaster management have included emergency preparation, emergency management, and legal system mechanisms. However, its well-designed management system faced a great challenge during the Wenchuan earthquake in 2008. By examining the literature on the development of disaster management, we realized that enhancing self-organization in communities can effectively resolve problems caused by collective actions and strengthen resilience to disasters. In the decade since the Wenchuan earthquake, the literature has focused more on empowering communities during disaster management in China. However, literature on the compatibility of social resilience and the government-dominant model in China is still scant. This study investigates China’s current disaster management system design; specifically, it identifies ways and methods for counteracting any conflicts between disaster management under social synergies and China’s emergency management system. It further explores what factors facilitate the balance between social synergies and the emergency management system if the two concepts were fused together. Using case studies, in-depth interviews, and a focus group in the field of public administration, this study collected qualitative data to understand the changes in China’s disaster management system since the Wenchuan earthquake as well as provide recommendations for future reform.


title: Molecular epidemiology and phylogenetic analysis of porcine epidemic diarrhea virus (PEDV) field isolates in Korea

text: Porcine epidemic diarrhea virus (PEDV) has caused devastating enteric disease in Korean pig farms since its first identification in 1992 in Korea. In the present study, the molecular epidemiology, genetic diversity, and phylogenetic relationship of Korean PEDV field isolates to other reference strains were analyzed using the complete E gene. Genetic analysis showed that each PEDV group had several unique characteristics, which indicated that a specific group PEDVs may be differentiated from another group PEDVs. Phylogenetic analysis showed that recent prevalent Korean PEDV field isolates are closely related to the Chinese field strains and differ genetically from the European strains and the vaccine strains used in Korea, which raises questions of whether a new-type PEDV vaccine may be necessary for preventing PEDV infection more effectively in Korea. Notably, a large deletion identified only in the attenuated DR13 can be utilized as a genetic marker, and the methods developed in this study will help to rapidly detect and differentiate PEDVs.


title: Application of montmorillonite in bentonite as a pharmaceutical excipient in drug delivery systems

text: Montmorillonite is a multifunctional clay mineral and a major component of bentonite. Montmorillonite has been used in various industrial and pharmaceutical fields due to its unique characteristics, which include swelling and adsorption. The high adsorption capacity of montmorillonite contributes to increase drug entrapment and sustained-release of drugs. Montmorillonite generally sustains drug release in many formulations by strongly adsorbing to the drug. In addition, montmorillonite enhances the dissolution rate and bioavailability of hydrophobic drugs. Moreover, montmorillonite was applied to form composites with other polymer-based delivery systems. Thus, montmorillonite could be applied to formulate diverse drug delivery systems to control and/or improve the pharmaceutical properties of drugs, including solubility, dissolution rate, and absorption. In this review, perspectives of applying montmorillonite as a pharmaceutical excipient in drug delivery systems are discussed.


title: A Library of Nucleotide Analogues Terminate RNA Synthesis Catalyzed by Polymerases of Coronaviruses that Cause SARS and COVID-19

text: SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 worldwide pandemic. We previously demonstrated that five nucleotide analogues inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), including the active triphosphate forms of Sofosbuvir, Alovudine, Zidovudine, Tenofovir alafenamide and Emtricitabine. We report here the evaluation of a library of nucleoside triphosphate analogues with a variety of structural and chemical features as inhibitors of the RdRps of SARS-CoV and SARS-CoV-2. These features include modifications on the sugar (2’ or 3’ modifications, carbocyclic, acyclic, or dideoxynucleotides) or on the base. The goal is to identify nucleotide analogues that not only terminate RNA synthesis catalyzed by these coronavirus RdRps, but also have the potential to resist the viruses’ exonuclease activity. We examined these nucleotide analogues for their ability to be incorporated by the RdRps in the polymerase reaction and to prevent further incorporation. While all 11 molecules tested displayed incorporation, 6 exhibited immediate termination of the polymerase reaction (triphosphates of Carbovir, Ganciclovir, Stavudine and Entecavir; 3’-OMe-UTP and Biotin-16-dUTP), 2 showed delayed termination (Cidofovir diphosphate and 2’-OMe-UTP), and 3 did not terminate the polymerase reaction (2’-F-dUTP, 2’-NH(2)-dUTP and Desthiobiotin-16-UTP). The coronaviruses possess an exonuclease that apparently requires a 2’-OH at the 3’-terminus of the growing RNA strand for proofreading. In this study, all nucleoside triphosphate analogues evaluated form Watson-Crick-like base pairs. The nucleotide analogues demonstrating termination either lack a 2’-OH, have a blocked 2’-OH, or show delayed termination. Thus, these nucleotide analogues are of interest for further investigation to evaluate whether they can evade the viral exonuclease activity. Prodrugs of five of these nucleotide analogues (Cidofovir, Abacavir, Valganciclovir/Ganciclovir, Stavudine and Entecavir) are FDA-approved medications for treatment of other viral infections, and their safety profiles are well established. After demonstrating potency in inhibiting viral replication in cell culture, candidate molecules can be rapidly evaluated as potential therapies for COVID-19.


title: The Efficacy and Safety of Triazavirin for COVID-19: A Trial Protocol

text: The coronavirus disease 2019 (COVID-19), a pneumonia caused by a novel coronavirus, was reported in December 2019. COVID-19 is highly contagious and has rapidly developed from a regional epidemic into a global pandemic. As yet, no effective drugs have been found to treat this virus. This study, an ongoing multicenter and blind randomized controlled trial (RCT), is being conducted at ten study sites in Heilongjiang Province, China, to investigate the efficacy and safety of Triazavirin (TZV) versus its placebo in COVID-19 patients. A total of 240 participants with COVID-19 are scheduled to be enrolled in this trial. Participants with positive tests of throat swab virus nucleic acid are randomized (1:1) into two groups: standard therapy plus TZV or standard therapy plus placebo for a 7-day treatment with a 21-day follow-up. The primary outcome is the time to clinical improvement of the subjects. Secondary outcomes include clinical improvement rate, time to alleviation of fever, mean time and proportion of obvious inflammatory absorption in the lung, conversion rate of repeated negative virus nucleic acid tests, mortality rate, and conversion rate to severe and critically severe patients. Adverse events, serious adverse events, liver function, kidney function and concurrent treatments will be monitored and recorded throughout the trial. The results of this trial should provide evidence-based recommendations to clinicians for the treatment of COVID-19.


title: Posterior reversible encephalopathy syndrome in patients with COVID-19

text: OBJECTIVE: To report four patients with coronavirus disease 2019 (COVID-19) who developed posterior reversible encephalopathy syndrome (PRES). METHODS: Patient data was abstracted from medical records at Weill Cornell Medical Center. RESULTS: Four patients with SARS-CoV-2 infection and PRES were identified. The patients' ages ranged from 64 to 74 years, and two were women. All four patients were admitted to the hospital with acute respiratory distress syndrome requiring intensive care unit admission and mechanical ventilation. PRES was diagnosed after persistent confusion, lethargy, new focal neurological deficits, or seizures were noted, with evidence of seizures on electroencephalogram for two of the patients. Imaging confirmed the presence of cerebral vasogenic edema. All four patients had elevated blood pressure and renal injury in the days preceding PRES diagnosis, as well as evidence of systemic inflammation and systemic hypercoagulability. Symptoms of PRES improved with blood pressure control. CONCLUSIONS: Our four cases demonstrate the occurrence of PRES in critically-ill patients with COVID-19. PRES should be considered in the differential for acute neurological deficits and seizures in this setting.


title: Inhibitory effects of bee venom and its components against viruses in vitro and in vivo

text: Bee venom (BV) from honey bee (Apis Melifera L.) contains at least 18 pharmacologically active components including melittin (MLT), phospholipase A(2) (PLA(2)), and apamin etc. BV is safe for human treatments dose dependently and proven to possess different healing properties including antibacterial and antiparasitidal properties. Nevertheless, antiviral properties of BV have not well investigated. Hence, we identified the potential antiviral properties of BV and its component against a broad panel of viruses. Co-incubation of non-cytotoxic amounts of BV and MLT, the main component of BV, significantly inhibited the replication of enveloped viruses such as Influenza A virus (PR8), Vesicular Stomatitis Virus (VSV), Respiratory Syncytial Virus (RSV), and Herpes Simplex Virus (HSV). Additionally, BV and MLT also inhibited the replication of non-enveloped viruses such as Enterovirus-71 (EV-71) and Coxsackie Virus (H3). Such antiviral properties were mainly explained by virucidal mechanism. Moreover, MLT protected mice which were challenged with lethal doses of pathogenic influenza A H1N1 viruses. Therefore, these results provides the evidence that BV and MLT could be a potential source as a promising antiviral agent, especially to develop as a broad spectrum antiviral agent.


The impact of the Coronavirus (COVID-19) pandemic on maternity care in Europe


Asthma and COVID: What are the Important Questions?


Sintomatología digestiva y COVID-19: importancia de descartar patología quirúrgica asociada


title: COVID-19–related Genes in Sputum Cells in Asthma. Relationship to Demographic Features and Corticosteroids

text: Rationale: Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 (angiotensin-converting enzyme 2), and TMPRSS2 (transmembrane protease serine 2) mediate viral infection of host cells. We reasoned that differences in ACE2 or TMPRSS2 gene expression in sputum cells among patients with asthma may identify subgroups at risk for COVID-19 morbidity. Objectives: To determine the relationship between demographic features and sputum ACE2 and TMPRSS2 gene expression in asthma. Methods: We analyzed gene expression for ACE2 and TMPRSS2, and for ICAM-1 (intercellular adhesion molecule 1) (rhinovirus receptor as a comparator) in sputum cells from 330 participants in SARP-3 (Severe Asthma Research Program-3) and 79 healthy control subjects. Measurements and Main Results: Gene expression of ACE2 was lower than TMPRSS2, and expression levels of both genes were similar in asthma and health. Among patients with asthma, male sex, African American race, and history of diabetes mellitus were associated with higher expression of ACE2 and TMPRSS2. Use of inhaled corticosteroids (ICS) was associated with lower expression of ACE2 and TMPRSS2, but treatment with triamcinolone acetonide did not decrease expression of either gene. These findings differed from those for ICAM-1, where gene expression was increased in asthma and less consistent differences were observed related to sex, race, and use of ICS. Conclusions: Higher expression of ACE2 and TMPRSS2 in males, African Americans, and patients with diabetes mellitus provides rationale for monitoring these asthma subgroups for poor COVID-19 outcomes. The lower expression of ACE2 and TMPRSS2 with ICS use warrants prospective study of ICS use as a predictor of decreased susceptibility to SARS-CoV-2 infection and decreased COVID-19 morbidity.


title: A Melting Curve-Based Multiplex RT-qPCR Assay for Simultaneous Detection of Four Human Coronaviruses

text: Human coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1 are common respiratory viruses associated with acute respiratory infection. They have a global distribution. Rapid and accurate diagnosis of HCoV infection is important for the management and treatment of hospitalized patients with HCoV infection. Here, we developed a melting curve-based multiplex RT-qPCR assay for simultaneous detection of the four HCoVs. In the assay, SYTO 9 was used to replace SYBR Green I as the fluorescent dye, and GC-modified primers were designed to improve the melting temperature (Tm) of the specific amplicon. The four HCoVs were clearly distinguished by characteristic melting peaks in melting curve analysis. The detection sensitivity of the assay was 3 × 10(2) copies for HCoV-OC43, and 3 × 10(1) copies for HCoV-NL63, HCoV-229E and HCoV-HKU1 per 30 μL reaction. Clinical evaluation and sequencing confirmation demonstrated that the assay was specific and reliable. The assay represents a sensitive and reliable method for diagnosis of HCoV infection in clinical samples.


title: Alarm bells over MERS coronavirus

text: Middle East coronavirus is causing alarm among researchers and international health officials. Neil Bennet looks at the unfolding situation.


title: Onset Patterns and Course of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

text: Background: Epidemiologic studies of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) have examined different aspects of this disease separately but few have explored them together. Objective: Describe ME/CFS onset and course in one United States-based cohort. Methods: One hundred and fifty subjects fitting Fukuda 1994 CFS criteria completed a detailed survey concerning the initial and subsequent stages of their illness. Descriptive statistics, graphs, and tables were used to illustrate prevalence and patterns of characteristics. Results: The most common peri-onset events reported by subjects were infection-related episodes (64%), stressful incidents (39%), and exposure to environmental toxins (20%). For 38% of subjects, more than 6 months elapsed from experiencing any initial symptom to developing the set of symptoms comprising their ME/CFS. Over time, the 12 most common symptoms persisted but declined in prevalence, with fatigue, unrefreshing sleep, exertion-related sickness, and flu-like symptoms declining the most (by 20–25%). Conversely, cognitive symptoms changed the least in prevalence, rising in symptom ranking. Pregnancy, menopause, and menstrual cycles exacerbated many women's symptoms. Fatigue-related function was not associated with duration of illness or age; during the worst periods of their illness, 48% of subjects could not engage in any productive activity. At the time of survey, 47% were unable to work and only 4% felt their condition was improving steadily with the majority (59%) describing a fluctuating course. Ninety-seven percent suffered from at least one other illness: anxiety (48%), depression (43%), fibromyalgia (39%), irritable bowel syndrome (38%), and migraine headaches (37%) were the most diagnosed conditions. Thirteen percent came from families where at least one other first-degree relative was also afflicted, rising to 27% when chronic fatigue of unclear etiology was included. Conclusions: This paper offers a broad epidemiologic overview of one ME/CFS cohort in the United States. While most of our findings are consistent with prior studies, we highlight underexamined aspects of this condition (e.g., the evolution of symptoms) and propose new interpretations of findings. Studying these aspects can offer insight and solutions to the diagnosis, etiology, pathophysiology, and treatment of this condition.


title: Preparation of virus-like particle mimetic nanovesicles displaying the S protein of Middle East respiratory syndrome coronavirus using insect cells

text: Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in 2012, and over 2000 infections and 800 deaths have been confirmed in 27 countries. However, to date, no commercial vaccine is available. In this study, structural proteins of MERS-CoV were expressed in silkworm larvae and Bm5 cells for the development of vaccine candidates against MERS-CoV and diagnostic methods. The spike (S) protein of MERS-CoV lacking its transmembrane and cytoplasmic domains (SΔTM) was secreted into the hemolymph of silkworm larvae using a bombyxin signal peptide and purified using affinity chromatography. The purified SΔTM forms small nanoparticles as well as the full-length S protein and has the ability to bind human dipeptidyl peptidase 4 (DPP4), which is a receptor of MERS-CoV. These results indicate that bioactive SΔTM was expressed in silkworm larvae. To produce MERS-CoV-like particles (MERS-CoV-LPs), the coexpression of spike proteins was performed in Bm5 cells and envelope (E) and membrane (M) proteins secreted E and M proteins extracellularly, suggesting that MERS-CoV-LPs may be formed. However, this S protein was not displayed on virus-like particles (VLPs) even though E and M proteins were secreted into the culture supernatant. By surfactant treatment and mechanical extrusion using S protein- or three structural protein-expressing Bm5 cells, S protein-displaying nanovesicles with diameters of approximately 100-200 nm were prepared and confirmed by immuno-TEM. The mechanical extrusion method is favorable for obtaining uniform recombinant protein-displaying nanovesicles from cultured cells. The purified SΔTM from silkworm larvae and S protein-displaying nanovesicles from Bm5 cells may lead to the development of nanoparticle-based vaccines against MERS-CoV and the diagnostic detection of MERS-CoV.


title: The ADRP domain from a virulent strain of infectious bronchitis virus is not sufficient to confer a pathogenic phenotype to the attenuated Beaudette strain

text: The replicase gene of the coronavirus infectious bronchitis virus (IBV) encodes 15 non-structural proteins (nsps). Nsp 3 is a multi-functional protein containing a conserved ADP-ribose-1″-phosphatase (ADRP) domain. The crystal structures of the domain from two strains of IBV, M41 (virulent) and Beaudette (avirulent), identified a key difference; M41 contains a conserved triple-glycine motif, whilst Beaudette contains a glycine-to-serine mutation that is predicted to abolish ADRP activity. Although ADRP activity has not been formally demonstrated for IBV nsp 3, Beaudette fails to bind ADP-ribose. The role of ADRP in virulence was investigated by generating rIBVs, based on Beaudette, containing either a restored triple-glycine motif or the complete M41 ADRP domain. Replication in vitro was unaffected by the ADRP modifications and the in vivo phenotype of the rIBVs was found to be apathogenic, indicating that restoration of the triple-glycine motif is not sufficient to restore virulence to the apathogenic Beaudette strain.


ROTURA TRAQUEAL YATROGÉNICA EN EL CONTEXTO DE LA ACTUAL INFECCIÓN POR COVID-19. A PROPÓSITO DE DOS CASOS


title: Differences of SARS-CoV-2 Shedding Duration in Sputum and Nasopharyngeal Swab Specimens among Adult Inpatients with COVID-19

text: Abstract Background The viral shedding duration of SARS-CoV-2 has not been fully defined. Consecutive detection of SARS-CoV-2 RNA from respiratory tract specimens is essential for determining duration of virus shedding and providing evidence to optimize the clinical management of COVID-19. Research Question What are the shedding durations of SARS-CoV-2 RNA in upper and lower respiratory tract specimens respectively? What are their associated risk factors? Study Design and Methods: A total of 68 patients with COVID-19 admitted to Wuhan Taikang Tongji Hospital and Huoshenshan Hospital from February 10, 2020 to March 20, 2020 were recruited. Consecutive SARS-CoV-2 RNA detection from paired specimens of nasopharyngeal swab (NPS) and sputum were carried out. The clinical characteristics of patients were recorded for further analysis. Results SARS-CoV-2 RNA was detected from NPS in 48 (70.6%) patients, and from sputum specimens in 30 (44.1%) patients. The median duration of viral shedding from sputum specimens (34 days, IQR 24-40 days) was significantly longer than from NPS (19 days, IQR 14-25 days; P<0.001). Elderly age was an independent factor associated with prolonged virus shedding time of SARS-CoV-2 (HR 1.71, 1.01-2.93). It was noteworthy that in 9 patients the viral RNA was detected in sputum after NPS turned negative. Chronic lung disease and steroids were associated with virus detection in sputum, and diabetes mellitus was associated with virus detection in both NPS and sputum. Interpretation These findings may impact a test based clearance discharge criteria given patients with COVID-19 may shed virus longer in their lower respiratory tracts, with potential implication for prolonged transmission risk. In addition, more attention should be given to elderly patients who might have prolonged viral shedding duration.


title: Inhibitors of bovine parvovirus, coronavirus and rotavirus in precolostral and fetal bovine sera

text: Abstract Eleven, 11 and 2 of 11 precolostral sera from normal calves and 13, 14 and 9 of 14 sera from normal fetuses, 7 to 10 months of gestation, neutralized bovine parvovirus, coronavirus and rotavirus, respectively. When assayed by single radial immunodiffusion, all the sera contained IgG at 360 to 1400 mg/dl, and some of them had much smaller amounts of IgM or IgA. Most of the neutralizing activities against bovine coronavirus and rotavirus were readily inactivated by treatment with acetone or 2-mercaptoethanol. Some sera fractionated by Sephadex G-200 gel filtration or starch block electrophoresis had neutralizing activities against bovine parvovirus or coronavirus in fractions containing no detectable amounts of immunoglobulins. These observations seem to indicate the presence of substance(s), other than immunoglobulins, capable of inhibiting replication of bovine parvovirus, coronavirus or rotavirus. The chemical nature and the mode of action of the inhibitors await elucidation.


title: Healthcare Ethics During a Pandemic

text: As clinicians and support personnel struggle with their responsibilities to treat during the current COVID-19 pandemic, several ethical issues have emerged. Will healthcare workers and support staff fulfill their duty to treat in the face of high risks? Will institutional and government leaders at all levels do the right things to help alleviate healthcare workers risks and fears? Will physicians be willing to make hard, resource-allocation decisions if they cannot first husband or improvise alternatives? With our healthcare facilities and governments unprepared for this inevitable disaster, front-line doctors, advanced providers, nurses, EMS, and support personnel struggle with acute shortages of equipment—both to treat patients and protect themselves. With their personal and possibly their family’s lives and health at risk, they must weigh the option of continuing to work or retreat to safety. This decision, made daily, is based on professional and personal values, how they perceive existing risks—including available protective measures, and their perception of the level and transparency of information they receive. Often, while clinicians get this information, support personnel do not, leading to absenteeism and deteriorating healthcare services. Leadership can use good risk communication (complete, widely transmitted, and transparent) to align healthcare workers’ risk perceptions with reality. They also can address the common problems healthcare workers must overcome to continue working (ie, risk mitigation techniques). Physicians, if they cannot sufficiently husband or improvise lifesaving resources, will have to face difficult triage decisions. Ideally, they will use a predetermined plan, probably based on the principles of Utilitarianism (maximizing the greatest good) and derived from professional and community input. Unfortunately, none of these plans is optimal.


title: Patientenzahlen im Rahmen der COVID-19-Pandemie in einer zentralen Notaufnahme

text: BACKGROUND: Since end of March, the health care system in Germany has been placed into a state of emergency in order to gain resources for the spreading coronavirus disease 2019 (COVID-19) pandemic. The overall goal of this study is to evaluate the number of emergency room patients at the time of the pandemic in order to draw conclusions about the influence of the COVID 19 pandemic on the number of patients in an emergency department. MATERIALS AND METHODS: With this descriptive epidemiologic study we collected and analyzed anonymized patient-related data of 19,357 cases presenting to the emergency department of the Klinikum rechts der Isar (Munich) from 01 February 2019 to 30 April 2019 and from 01 February 2020 to 30 April 2020. RESULTS: Despite an increase in the number of patients from 2019 to 2020, there was a significant drop in the number of emergencies from February to March 2020 and proceeding in April to a level below that of 2019. This was particularly observed in the field of trauma surgery, with a 40% decrease in the number of patients. With regard to the individual complaint patterns in March 2020, it was found that an increased incidence of malaise (+47%) and breathing problems (+36%) was recorded, whereas back pain (−41%), wounds (−29%), thoracic (−24%) and abdominal pain (−23%) were significantly less common than in the previous year. In terms of the severity of the complaints, the decline was mainly due to complaints with a low degree of urgency. CONCLUSION: In the course of the COVID-19 pandemic we observed a significant decline in the number of patients in one of the largest emergency rooms in Munich. This has to be avoided with existing hospital capacities, in order to prevent potential damage to health caused by postponed or missing emergency presentations.


title: Chapter 2 Viral Channel-Forming Proteins

text: Abstract Channel-forming proteins are found in a number of viral genomes. In some cases, their role in the viral life cycle is well understood, in some cases it needs still to be elucidated. A common theme is that their mode of action involves a change of electrochemical or proton gradient across the lipid membrane which modulates the viral or cellular activity. Blocking these proteins can be a suitable therapeutic strategy as for some viruses this may be “lethal.” Besides the many biological relevant questions still to be answered, there are also many open questions concerning the biophysical side as well as structural information and the mechanism of function on a molecular level. The immanent biophysical issues are addressed and the work in the field is summarized.


title: The HLA Region and Autoimmune Disease: Associations and Mechanisms of Action

text: The HLA region encodes several molecules that play key roles in the immune system. Strong association between the HLA region and autoimmune disease (AID) has been established for over fifty years. Association of components of the HLA class II encoded HLA-DRB1-DQA1-DQB1 haplotype has been detected with several AIDs, including rheumatoid arthritis, type 1 diabetes and Graves’ disease. Molecules encoded by this region play a key role in exogenous antigen presentation to CD4+ Th cells, indicating the importance of this pathway in AID initiation and progression. Although other components of the HLA class I and III regions have also been investigated for association with AID, apart from the association of HLA-B*27 with ankylosing spondylitis, it has been difficult to determine additional susceptibility loci independent of the strong linkage disequilibrium (LD) with the HLA class II genes. Recent advances in the statistical analysis of LD and the recruitment of large AID datasets have allowed investigation of the HLA class I and III regions to be re-visited. Association of the HLA class I region, independent of known HLA class II effects, has now been detected for several AIDs, including strong association of HLA-B with type 1 diabetes and HLA-C with multiple sclerosis and Graves’ disease. These results provide further evidence of a possible role for bacterial or viral infection and CD8+ T cells in AID onset. The advances being made in determining the primary associations within the HLA region and AIDs will not only increase our understanding of the mechanisms behind disease pathogenesis but may also aid in the development of novel therapeutic targets in the future.


ASE Statement on Protection of Patients and Echocardiography Service Providers During the 2019 Novel Coronavirus Outbreak


title: Covid-19 et remaniement des défenses contre la dépression chez les soignants en Ehpad

text: Résumé Les réponses des Ehpad à la pandémie et au confinement actuel révèlent et amplifient les défenses habituelles des soignants contre la dépression. Le fait que le danger de mort et l’obligation d’enfermer les résidents viennent de l’extérieur, et le maniement permanent des mesures de protection physique ne suppriment pas le sentiment d’inutilité et l’angoisse de mort qu’ils tolèrent ou évitent d’ordinaire. L’auteur montre qu’ils ajoutent au contraire à leur inquiétude et par conséquent à leur besoin de parole et d’écoute. Summary The responses of nursing homes to the present pandemic and lock-down reveal and amplify the usual defensive mechanisms deployed by professional caregivers against depression. The danger of death and the need to confine the residents, both coming from the outside world, and the permanent management of physical protective measures do not remove the feeling of uselessness and the anxiety of death that the nursing staff habitually tolerates or avoids. On the contrary, these aspects add to caregivers’ need to talk and be listened to.


title: Infectious without symptoms

text: It is easy to spread the virus without realising you are ill, reports Graham Lawton


WHO lowers figures on SARS infections


Chapter 4 The natural history of multiple sclerosis


title: Definitive Care for the Critically Ill During a Disaster: Current Capabilities and Limitations From a Task Force for Mass Critical Care Summit Meeting, January 26–27, 2007, Chicago, IL

text: In the twentieth century, rarely have mass casualty events yielded hundreds or thousands of critically ill patients requiring definitive critical care. However, future catastrophic natural disasters, epidemics or pandemics, nuclear device detonations, or large chemical exposures may change usual disaster epidemiology and require a large critical care response. This article reviews the existing state of emergency preparedness for mass critical illness and presents an analysis of limitations to support the suggestions of the Task Force on Mass Casualty Critical Care, which are presented in subsequent articles. Baseline shortages of specialized resources such as critical care staff, medical supplies, and treatment spaces are likely to limit the number of critically ill victims who can receive life-sustaining interventions. The deficiency in critical care surge capacity is exacerbated by lack of a sufficient framework to integrate critical care within the overall institutional response and coordination of critical care across local institutions and broader geographic areas.


title: Evolutionary Dynamics of MERS-CoV: Potential Recombination, Positive Selection and Transmission

text: Middle East respiratory syndrome coronavirus (MERS-CoV) belongs to beta group of coronavirus and was first discovered in 2012. MERS-CoV can infect multiple host species and cause severe diseases in human. We conducted a series of phylogenetic and bioinformatic analyses to study the evolution dynamics of MERS-CoV among different host species with genomic data. Our analyses show: 1) 28 potential recombinant sequences were detected and they can be classified into seven potential recombinant types; 2) The spike (S) protein of MERS-CoV was under strong positive selection when MERS-CoV transmitted from their natural host to human; 3) Six out of nine positive selection sites detected in spike (S) protein are located in its receptor-binding domain which is in direct contact with host cells; 4) MERS-CoV frequently transmitted back and forth between human and camel after it had acquired the human-camel infection capability. Together, these results suggest that potential recombination events might have happened frequently during MERS-CoV’s evolutionary history and the positive selection sites in MERS-CoV’s S protein might enable it to infect human.


title: Biosynthesis of the active compounds of Isatis indigotica based on transcriptome sequencing and metabolites profiling

text: BACKGROUD: Isatis indigotica is a widely used herb for the clinical treatment of colds, fever, and influenza in Traditional Chinese Medicine (TCM). Various structural classes of compounds have been identified as effective ingredients. However, little is known at genetics level about these active metabolites. In the present study, we performed de novo transcriptome sequencing for the first time to produce a comprehensive dataset of I. indigotica. RESULTS: A database of 36,367 unigenes (average length = 1,115.67 bases) was generated by performing transcriptome sequencing. Based on the gene annotation of the transcriptome, 104 unigenes were identified covering most of the catalytic steps in the general biosynthetic pathways of indole, terpenoid, and phenylpropanoid. Subsequently, the organ-specific expression patterns of the genes involved in these pathways, and their responses to methyl jasmonate (MeJA) induction, were investigated. Metabolites profile of effective phenylpropanoid showed accumulation pattern of secondary metabolites were mostly correlated with the transcription of their biosynthetic genes. According to the analysis of UDP-dependent glycosyltransferases (UGT) family, several flavonoids were indicated to exist in I. indigotica and further identified by metabolic profile using UPLC/Q-TOF. Moreover, applying transcriptome co-expression analysis, nine new, putative UGTs were suggested as flavonol glycosyltransferases and lignan glycosyltransferases. CONCLUSIONS: This database provides a pool of candidate genes involved in biosynthesis of effective metabolites in I. indigotica. Furthermore, the comprehensive analysis and characterization of the significant pathways are expected to give a better insight regarding the diversity of chemical composition, synthetic characteristics, and the regulatory mechanism which operate in this medical herb.


title: Rapid Detection of Mycobacterium tuberculosis by Recombinase Polymerase Amplification

text: Improved access to effective tests for diagnosing tuberculosis (TB) has been designated a public health priority by the World Health Organisation. In high burden TB countries nucleic acid based TB tests have been restricted to centralised laboratories and specialised research settings. Requirements such as a constant electrical supply, air conditioning and skilled, computer literate operators prevent implementation of such tests in many settings. Isothermal DNA amplification technologies permit the use of simpler, less energy intensive detection platforms more suited to low resource settings that allow the accurate diagnosis of a disease within a short timeframe. Recombinase Polymerase Amplification (RPA) is a rapid, low temperature isothermal DNA amplification reaction. We report here RPA-based detection of Mycobacterium tuberculosis complex (MTC) DNA in <20 minutes at 39°C. Assays for two MTC specific targets were investigated, IS6110 and IS1081. When testing purified MTC genomic DNA, limits of detection of 6.25 fg (IS6110) and 20 fg (IS1081)were consistently achieved. When testing a convenience sample of pulmonary specimens from suspected TB patients, RPA demonstrated superior accuracy to indirect fluorescence microscopy. Compared to culture, sensitivities for the IS1081 RPA and microscopy were 91.4% (95%CI: 85, 97.9) and 86.1% (95%CI: 78.1, 94.1) respectively (n = 71). Specificities were 100% and 88.6% (95% CI: 80.8, 96.1) respectively. For the IS6110 RPA and microscopy sensitivities of 87.5% (95%CI: 81.7, 93.2) and 70.8% (95%CI: 62.9, 78.7) were obtained (n = 90). Specificities were 95.4 (95% CI: 92.3,98.1) and 88% (95% CI: 83.6, 92.4) respectively. The superior specificity of RPA for detecting tuberculosis was due to the reduced ability of fluorescence microscopy to distinguish Mtb complex from other acid fast bacteria. The rapid nature of the RPA assay and its low energy requirement compared to other amplification technologies suggest RPA-based TB assays could be of use for integration into a point-of-care test for use in resource constrained settings.


title: Human coronaviruses: Clinical features and phylogenetic analysis

text: Abstract Strains of human coronavirus (HCoV), namely HCoV-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1, primarily infect the upper respiratory and gastrointestinal tracts and are the most common cause of non-rhinovirus-induced common cold in humans. Although the manifestations of coronavirus infection (i.e., rhinorrhea, sneezing, cough, nasal obstruction, and bronchitis) are generally self-limiting in healthy adults, certain strains such as HCoV-NL63 and HCoV-HKU1 can cause severe lower respiratory tract infection and febrile seizure, especially in infants, people of advanced age, and immunocompromised hosts. In 2003, a novel HCoV strain was identified as the causative agent of the severe acute respiratory syndrome (SARS) epidemic that began in Asia in 2002. The strain has hence been referred to as SARS-CoV. In addition, as recently as September 2012, another novel HCoV, human betacoronavirus 2c EMC2012, was identified as being the cause of fever, renal failure, pneumonia, and severe respiratory distress in two patients in the Middle East. Phylogenetic analysis has revealed highly conserved sequences of ORF1ab, spike, nucleocapsid, and envelope protein genes, but not membrane protein genes, between human betacoronavirus 2c EMC2012 and SARS-CoV. This review focuses on the differences in the genomes of certain HCoV strains, the pathogenesis of said strains, and recent developments in the establishment of therapeutic agents that might aid in the treatment of patients with such infections.


title: MERS-CoV recombination: implications about the reservoir and potential for adaptation

text: Recombination is a process that unlinks neighboring loci allowing for independent evolutionary trajectories within genomes of many organisms. If not properly accounted for, recombination can compromise many evolutionary analyses. In addition, when dealing with organisms that are not obligately sexually reproducing, recombination gives insight into the rate at which distinct genetic lineages come into contact. Since June 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 1,106 laboratory-confirmed infections, with 421 MERS-CoV-associated deaths as of 16 April 2015. Although bats are considered as the likely ultimate source of zoonotic betacoronaviruses, dromedary camels have been consistently implicated as the source of current human infections in the Middle East. In this article, we use phylogenetic methods and simulations to show that MERS-CoV genome has likely undergone numerous recombinations recently. Recombination in MERS-CoV implies frequent co-infection with distinct lineages of MERS-CoV, probably in camels given the current understanding of MERS-CoV epidemiology.


title: Mutations, Recombination and Insertion in the Evolution of 2019-nCoV

text: The 2019 novel coronavirus (2019-nCoV or SARS-CoV-2) has spread more rapidly than any other betacoronavirus including SARS-CoV and MERS-CoV. However, the mechanisms responsible for infection and molecular evolution of this virus remained unclear. We collected and analyzed 120 genomic sequences of 2019-nCoV including 11 novel genomes from patients in China. Through comprehensive analysis of the available genome sequences of 2019-nCoV strains, we have tracked multiple inheritable SNPs and determined the evolution of 2019-nCoV relative to other coronaviruses. Systematic analysis of 120 genomic sequences of 2019-nCoV revealed co-circulation of two genetic subgroups with distinct SNPs markers, which can be used to trace the 2019-nCoV spreading pathways to different regions and countries. Although 2019-nCoV, human and bat SARS-CoV share high homologous in overall genome structures, they evolved into two distinct groups with different receptor entry specificities through potential recombination in the receptor binding regions. In addition, 2019-nCoV has a unique four amino acid insertion between S1 and S2 domains of the spike protein, which created a potential furin or TMPRSS2 cleavage site. Our studies provided comprehensive insights into the evolution and spread of the 2019-nCoV. Our results provided evidence suggesting that 2019-nCoV may increase its infectivity through the receptor binding domain recombination and a cleavage site insertion. Novel 2019-nCoV sequences revealed the evolution and specificity of betacoronavirus with possible mechanisms of enhanced infectivity.


title: Coronavirus disease 2019: What we know?

text: In late December 2019, a cluster of unexplained pneumonia cases has been reported in Wuhan, China. A few days later, the causative agent of this mysterious pneumonia was identified as a novel coronavirus. This causative virus has been temporarily named as severe acute respiratory syndrome coronavirus 2 and the relevant infected disease has been named as coronavirus disease 2019 (COVID‐19) by the World Health Organization, respectively. The COVID‐19 epidemic is spreading in China and all over the world now. The purpose of this review is primarily to review the pathogen, clinical features, diagnosis, and treatment of COVID‐19, but also to comment briefly on the epidemiology and pathology based on the current evidence.


title: Research on infectious diseases requires better coordination

text: This special supplement of Nature Medicine, directed at the topic of emerging infectious diseases, is very timely. Recent high-profile outbreaks have highlighted the global risk that infectious agents, both new and old, represent for society. The experience of severe acute respiratory syndrome (SARS) shows the risk posed by emerging infectious diseases, but also the power of strongly coordinated global surveillance and public health measures, coupled with scientific research, to keep infection under control(1,2). Diseases such as drug-resistant malaria continue to be threats. There is a need to enhance global resources to investigate, detect and respond to emerging infections, and to appropriately coordinate and direct research efforts to meet the challenges presented by these diseases.


SARS‐CoV‐2 and Streptococcus pneumoniae coinfection as a cause of severe pneumonia in an infant


title: Structural plasticity of SARS-CoV-2 3CL M(pro) active site cavity revealed by room temperature X-ray crystallography

text: The COVID-19 disease caused by the SARS-CoV-2 coronavirus has become a pandemic health crisis. An attractive target for antiviral inhibitors is the main protease 3CL M(pro) due to its essential role in processing the polyproteins translated from viral RNA. Here we report the room temperature X-ray structure of unliganded SARS-CoV-2 3CL M(pro), revealing the ligand-free structure of the active site and the conformation of the catalytic site cavity at near-physiological temperature. Comparison with previously reported low-temperature ligand-free and inhibitor-bound structures suggest that the room temperature structure may provide more relevant information at physiological temperatures for aiding in molecular docking studies.


title: A phylogenomic data-driven exploration of viral origins and evolution

text: The origin of viruses remains mysterious because of their diverse and patchy molecular and functional makeup. Although numerous hypotheses have attempted to explain viral origins, none is backed by substantive data. We take full advantage of the wealth of available protein structural and functional data to explore the evolution of the proteomic makeup of thousands of cells and viruses. Despite the extremely reduced nature of viral proteomes, we established an ancient origin of the “viral supergroup” and the existence of widespread episodes of horizontal transfer of genetic information. Viruses harboring different replicon types and infecting distantly related hosts shared many metabolic and informational protein structural domains of ancient origin that were also widespread in cellular proteomes. Phylogenomic analysis uncovered a universal tree of life and revealed that modern viruses reduced from multiple ancient cells that harbored segmented RNA genomes and coexisted with the ancestors of modern cells. The model for the origin and evolution of viruses and cells is backed by strong genomic and structural evidence and can be reconciled with existing models of viral evolution if one considers viruses to have originated from ancient cells and not from modern counterparts.


Bioinformatics in China: A Personal Perspective


title: Escherichia coli YmdB regulates biofilm formation independently of its role as an RNase III modulator

text: BACKGROUND: Ribonuclease III (RNase III) activity modulates hundreds of genes in Escherichia coli (E. coli). YmdB, a member of the macrodomain protein family, is one of known trans-acting regulators of RNase III activity; however, the significance of its regulatory role in specific bacterial cellular processes and related genes has not been determined. YmdB overexpression was used to model YmdB-induced RNase III inhibition in vivo, and microarray analysis identified gene targets and cellular processes related to RNase III inhibition. RESULTS: The expression of >2,000 E. coli genes was modulated by YmdB induction; 129 genes were strongly regulated, of which 80 have not been reported as RNase III targets. Of these, ten are involved in biofilm formation. Significantly, YmdB overexpression also inhibited biofilm formation via a process that is not uniquely dependent upon RNase III inhibition. Moreover, biofilm formation is interdependently regulated by RpoS, a known stress response regulator and biofilm inhibitor, and by YmdB. CONCLUSIONS: This is the first global profile of target genes modulated by YmdB-induced RNase III inhibition in E. coli, and the data reveal a novel, hitherto unrecognized regulatory role for YmdB in biofilm modulation.


title: Vaccination against Viruses

text: Abstract Most vaccines in use today are the result of empirical development. The mechanism of action of many vaccines in common use remains incompletely understood. Understanding how such vaccines protect is an ongoing subject of study using increasingly sophisticated immunological tools, such as B cell and T cell repertoire and transcriptome analysis. Such tools are also being applied to the design of vaccines against those viral targets that have evaded vaccine-mediated protection thus far. As basic immunological science intersects with the practicalities of assuring vaccine safety, tolerability, efficacy, and consistency in the clinic, the practical utility of more sophisticated immunological measures for vaccine development may be determined by whether they can be reduced to simply executed, highly standardized, reproducible assays with outcomes that have clear interpretations for vaccine development and use. Basic immunology, empirical vaccine testing, and regulatory science are all necessary contributors to developing the next generation of vaccines, including vaccines effective against the pathogens for which vaccines are not currently available.


title: Global responses of health science librarians to the COVID‐19 (Corona virus) pandemic: a desktop analysis

text: The COVID‐19 pandemic has posed significant challenges for health science librarians. During this pandemic, librarians are playing an active role by increasing the public’s awareness of the virus, maintaining document delivery services and providing research support. This paper uses the method of desktop analysis of the websites of selected library associations to identify the responses of health science librarians to the COVID‐19 pandemic. The study highlights significant initiatives taken by some health science librarians which can be replicated by others to meet the needs of library users in the COVID‐19 health crisis. JM


title: Investigation of the Quantity of Exhaled Aerosols Released into the Environment during Nebulisation

text: Background: Secondary inhalation of medical aerosols is a significant occupational hazard in both clinical and homecare settings. Exposure to fugitive emissions generated during aerosol therapy increases the risk of the unnecessary inhalation of medication, as well as toxic side effects. Methods: This study examines fugitively-emitted aerosol emissions when nebulising albuterol sulphate, as a tracer aerosol, using two commercially available nebulisers in combination with an open or valved facemask or using a mouthpiece with and without a filter on the exhalation port. Each combination was connected to a breathing simulator during simulated adult breathing. The inhaled dose and residual mass were quantified using UV spectrophotometry. Time-varying fugitively-emitted aerosol concentrations and size distributions during nebulisation were recorded using aerodynamic particle sizers at two distances relative to the simulated patient. Different aerosol concentrations and size distributions were observed depending on the interface. Results: Within each nebuliser, the facemask combination had the highest time-averaged fugitively-emitted aerosol concentration, and values up to 0.072 ± 0.001 mg m(−3) were recorded. The placement of a filter on the exhalation port of the mouthpiece yielded the lowest recorded concentrations. The mass median aerodynamic diameter of the fugitively-emitted aerosol was recorded as 0.890 ± 0.044 µm, lower the initially generated medical aerosol in the range of 2–5 µm. Conclusions: The results highlight the potential secondary inhalation of exhaled aerosols from commercially available nebuliser facemask/mouthpiece combinations. The results will aid in developing approaches to inform policy and best practices for risk mitigation from fugitive emissions.


title: NRAV, a Long Noncoding RNA, Modulates Antiviral Responses through Suppression of Interferon-Stimulated Gene Transcription

text: Long noncoding RNAs (lncRNAs) modulate various biological processes, but their role in host antiviral responses is largely unknown. Here we identify a lncRNA as a key regulator of antiviral innate immunity. Following from the observation that a lncRNA that we call negative regulator of antiviral response (NRAV) was dramatically downregulated during infection with several viruses, we ectopically expressed NRAV in human cells or transgenic mice and found that it significantly promotes influenza A virus (IAV) replication and virulence. Conversely, silencing NRAV suppressed IAV replication and virus production, suggesting that reduction of NRAV is part of the host antiviral innate immune response to virus infection. NRAV negatively regulates the initial transcription of multiple critical interferon-stimulated genes (ISGs), including IFITM3 and MxA, by affecting histone modification of these genes. Our results provide evidence for a lncRNA in modulating the antiviral interferon response.


title: Middle East respiratory syndrome coronavirus: epidemiology and disease control measures

text: The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in 2012 resulted in an increased concern of the spread of the infection globally. MERS-CoV infection had previously caused multiple health-care-associated outbreaks and resulted in transmission of the virus within families. Community onset MERS-CoV cases continue to occur. Dromedary camels are currently the most likely animal to be linked to human MERS-CoV cases. Serologic tests showed significant infection in adult camels compared to juvenile camels. The control of MERS-CoV infection relies on prompt identification of cases within health care facilities, with institutions applying appropriate infection control measures. In addition, determining the exact route of transmission from camels to humans would further add to the control measures of MERS-CoV infection.


title: Development of immunoglobulin G enzyme-linked immunosorbent assay for the serodiagnosis of severe acute respiratory syndrome

text: Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel SARS-associated coronavirus (SARS-CoV). The clinical characteristics are high fever, rapidly progressive diffuse pneumonitis and respiratory distress. It is highly infectious through intimate contact or direct contact with infectious body fluids. Outbreaks within communities and hospitals have been reported. Development of rapid and reliable diagnostic tools is urgently needed. We developed an immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA), using whole virus antigen of SARS-CoV. Eighty-six serum samples collected from patients who were hospitalized for other causes were examined to determine the cut-off O.D. value. The cut-off O.D. value was defined as 0.175 by calculating the mean O.D. value of the 86 sera plus 3 standard deviations. To determine the sensitivity and specificity of the ELISA, 56 positive sera and 204 negative sera were tested. The sensitivity was 96.4% and the specificity was 100%. The results suggest that the IgG ELISA using whole virus antigen of SARS-CoV has a high sensitivity and specificity in detecting SARS IgG antibodies. This IgG ELISA is a powerful tool for serodiagnosis of SARS.


title: Factors in association with acceptability of A/H1N1 vaccination during the influenza A/H1N1 pandemic phase in the Hong Kong general population

text: A random population-based telephone survey (n = 301) was conducted among the Hong Kong general population in July 2009. Past history of seasonal influenza vaccination (OR = 2.59–3.13) was associated with intention to take up A/H1N1 vaccination under three hypothetical scenarios (provided at <HK$100, HK$100–200 and >HK$200). Adjusting background variables, other significant factors were identified by stepwise models: perceived side effects (OR = 0.33), family members’ recommendations and friends’ acceptability toward the vaccine (OR = 2.80–4.74). In contrast to other studies on seasonal influenza and A/H1N1 vaccination, perceived susceptibility and perceived severity related to influenza A/H1N1 were non-significant. Cultural differences may therefore exist.


title: A viral infection explanation for Kawasaki disease in general and for COVID-19 virus-related Kawasaki disease symptoms

text: SARS-CoV-2, a new virus that appeared in Wuhan, China, in 2019 has approximately an 80% genomic match to the Severe Acute Respiratory Symptom (SARS) virus, which is known to come from a bat virus. Symptoms of Kawasaki disease in general and incomplete Kawasaki disease have been seen in a subset of pediatric patients having a current or previous infection of SARS-CoV-2. A viral infection, such as a SARS-CoV-2 virus infection, could result in extensive antigen–antibody immune complexes that cannot be quickly cleared in a subset of patients and thus create a type III hypersensitivity immune reaction and cause Kawasaki disease or Kawasaki disease symptoms (also known as multisystem inflammatory syndrome) in a subset of patients. Extensive binding of antibodies to viral antigens can create antigen–antibody immune complexes, which, if not eliminated in certain individuals having dysfunctional complement systems, can start inflammatory type III hypersensitivity symptoms, including protease releases that can disrupt epithelium, mesothelium, and endothelium basement membranes, and induce pervasive inflammation throughout the body. This could continue after SARS-CoV-2 infections end if the first wave of protease attacks on basement membranes created new secondary autoantibodies and new uncleared antigen–antibody immune complexes.


title: Correlates of protective immunity for Ebola vaccines: implications for regulatory approval by the animal rule

text: Ebola virus infection is a highly lethal disease for which there are no effective therapeutic or preventive treatments. Several vaccines have provided immune protection in laboratory animals, but because outbreaks occur unpredictably and sporadically, vaccine efficacy cannot be proven in human trials, which is required for traditional regulatory approval. The Food and Drug Administration has introduced the 'animal rule', to allow laboratory animal data to be used to show efficacy when human trials are not logistically feasible. In this Review, we describe immune correlates of vaccine protection against Ebola virus in animals. This research provides a basis for bridging the gap from basic research to human vaccine responses in support of the licensing of vaccines through the animal rule.


title: Perturbations in neuroinflammatory pathways are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors

text: Abstract Paclitaxel is a common chemotherapy drug associated with the development of chronic paclitaxel-induced peripheral neuropathy (PIPN). PIPN is associated with neuroinflammatory mechanisms in pre-clinical studies. Here, we evaluated for differential gene expression (DGE) in peripheral blood between breast cancer survivors with and without PIPN and for neuroinflammatory (NI) related signaling pathways and whole-transcriptome profiles from other experiments. Pathway impact analysis identified 8 perturbed NI related pathways. Expression profile analysis found 15 experiments having similar whole-transcriptome profiles of DGE related to neuroinflammation and PIPN. These findings suggest that perturbations in pathways associated with neuroinflammation are found in cancer survivors with PIPN.


title: Zinc Chelation Specifically Inhibits Early Stages of Dengue Virus Replication by Activation of NF-κB and Induction of Antiviral Response in Epithelial Cells

text: Zinc is an essential micronutrient which regulates diverse physiological functions and has been shown to play a crucial role in viral infections. Zinc has a necessary role in the replication of many viruses, however, antiviral action of zinc has also been demonstrated in in vitro infection models most likely through induction of host antiviral responses. Therefore, depending on the host machinery that the virus employs at different stages of infection, zinc may either facilitate, or inhibit virus infection. In this study, we show that zinc plays divergent roles in rotavirus and dengue virus infections in epithelial cells. Dengue virus infection did not perturb the epithelial barrier functions despite the release of virus from the basolateral surface whereas rotavirus infection led to disruption of epithelial junctions. In rotavirus infection, zinc supplementation post-infection did not block barrier disruption suggesting that zinc does not affect rotavirus life-cycle or protects epithelial barriers post-infection suggesting the involvement of cellular pathways in the beneficial effect of zinc supplementation in enteric infections. Zinc depletion by N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN) inhibited dengue virus and Japanese encephalitis virus (JEV) infection but had no effect on rotavirus. Time-of-addition experiments suggested that zinc chelation affected both early and late stages of dengue virus infectious cycle and zinc chelation abrogated dengue virus RNA replication. We show that transient zinc chelation induces ER stress and antiviral response by activating NF-kappaB leading to induction of interferon signaling. These results suggest that modulation of zinc homeostasis during virus infection could be a component of host antiviral response and altering zinc homeostasis may act as a potent antiviral strategy against flaviviruses.


title: Coronavirus Disease and New-Onset Atrial Fibrillation: Two Cases

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in a considerable amount of morbidity and mortality worldwide since December 2019. Patients with coronavirus disease (COVID-19) most commonly present with respiratory manifestations, while cardiac manifestations were reported as a complication and seldom as a presenting feature. We report two cases of new-onset atrial fibrillation occurring in middle-aged men with no significant past medical history. The first patient presented with symptomatic atrial fibrillation; however, during his hospitalization course, he developed a fever, which led to the diagnosis of infection with SARS-CoV-2. The second patient presented from urgent care after being diagnosed with COVID-19 associated with newly diagnosed atrial fibrillation. Both patients were treated symptomatically for COVID-19 and discharged home after reverting to sinus rhythm. Physicians should be aware of the variable clinical presentations of COVID-19, especially in new or worsening cardiac illnesses, in order to practice the appropriate personal protection practices. More studies are needed to identify the viral mechanisms leading to the dysregulation of cardiac rhythm.