title: The alcohol industry lobby and Hong Kong’s zero wine and beer tax policy

text: BACKGROUND: Whereas taxation on alcohol is becoming an increasingly common practice in many countries as part of overall public health measures, the Hong Kong Special Administrative Region Government is bucking the trend and lowered its duties on wine and beer by 50 percent in 2007. In 2008, Hong Kong removed all duties on alcohol except for spirits. The aim of this paper is to examine the case of Hong Kong with its history of changes in alcohol taxation to explore the factors that have driven such an unprecedented policy evolution. METHODS: The research is based on an analysis of primary documents. Searches of official government documents, alcohol-related industry materials and other media reports on alcohol taxation for the period from 2000 to 2008 were systematically carried out using key terms such as “alcohol tax” and “alcohol industry”. Relevant documents (97) were indexed by date and topic to undertake a chronological and thematic analysis using Nvivo8 software. RESULTS: Our analysis demonstrates that whereas the city’s changing financial circumstances and the Hong Kong Special Administrative Region Government’s strong propensity towards economic liberalism had, in part, contributed to such dramatic transformation, the alcohol industry’s lobbying tactics and influence were clearly the main drivers of the policy decision. The alcohol industry’s lobbying tactics were two-fold. The first was to forge a coalition encompassing a range of catering and trade industries related to alcohol as well as industry-friendly lawmakers so that these like-minded actors could find common ground in pursuing changes to the taxation policy. The second was to deliberately promote a blend of ideas to garner support from the general public and to influence the perception of key policy makers. CONCLUSIONS: Our findings suggest that the success of aggressive industry lobbying coupled with the absence of robust public health advocacy was the main driving force behind the unparalleled abolition of wine and beer duties in Hong Kong. Strong public health alliance and advocacy movement are needed to counteract the industry’s continuing aggressive lobby and promotion of alcoholic beverages.


title: Serum IFN-γ–induced protein 10 (IP-10) as a biomarker for severity of acute respiratory infection in healthy adults

text: BACKGROUND: The inflammatory chemokine, interferon-gamma inducible protein of 10 kDa (IP-10), is a biomarker associated with several conditions. OBJECTIVES: This study investigated serum concentrations of IP-10 in healthy individuals who developed acute respiratory infection (ARI). The hypothesis is that serum IP-10 concentrations correlate with ARI severity and detection of viral pathogens. STUDY DESIGN: Data come from a randomized controlled trial measuring the effects of mindfulness meditation or exercise on ARI (Clinical Trials ID: NCT01654289). Healthy adults ages 30–69 were followed for a single season for ARI incidence and severity. This trial is ongoing, and the investigators are still blinded. When a participant reported ARI symptoms, nasal swab and lavage for PCR-based viral identification and blood samples were collected within the first 72 hours of ARI symptoms. Serum IP-10 concentrations were measured by ELISA (R&D Systems, Inc. Quantikine ELISA, Minneapolis, MN). ARI severity was measured using the validated Wisconsin Upper Respiratory Symptom Survey (WURSS-24) until the ARI episode resolved. RESULTS: Serum IP-10 concentrations from 225 ARI episodes correlated with ARI global severity (rho 0.28 [95% CI: 0.15–0.39]; p<0.001). IP-10 concentrations were higher with an ARI in which a viral pathogen was detected compared to no viral pathogen detected (median 366 pg/ml [IQR: 227–486] vs 163 pg/ml [IQR: 127–295], p<0.0001). Influenza infections had higher IP-10 concentrations than coronavirus, enterovirus or rhinovirus, and paramyxovirus. CONCLUSION: Serum IP-10 concentration correlates with ARI global severity. Also, IP-10 concentration measured early in the course of the ARI correlates with the daily severity, duration, and illness symptoms.


title: Pituitary tumor resection in a patient with SARS-CoV-2 (COVID-19) infection. A case report and suggested airway management guidelines

text: Abstract The 2020 pandemic caused by the novel coronavirus, COVID-19, had its headquarters in China. It causes Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and presents a broad spectrum of clinical manifestations, ranging from entirely asymptomatic through severe acute respiratory failure and death. Presuming a significant quantity of ventilator-dependent patients, several institutions strategically delayed elective surgeries. Particularly procedures performed involving the nasal mucosa, such as a transsphenoidal approach of the pituitary gland, considering the tremendous level of viral shedding. Nevertheless, critical cases demand expeditious resolution. Those situations are severe pituitary apoplexy, declining consciousness level, or risk of acute visual loss. This case presents a successful urgent perioperative management of a 47 year-old male COVID-19 positive patient who presented to the Emergency Department with a left frontal headache that culminated with diplopia, left eye ptosis, and left visual acuity loss after 5 days. Transsphenoidal hypophysectomy was uneventfully performed, and the patient was discharged from the hospital on postoperative day four. It additionally describes in detail the University of Mississippi Medical Center airway management algorithm for patients infected with the novel coronavirus who need emergent surgical attention.


title: Safety and Pharmacokinetics of Intravenous Zanamivir Treatment in Hospitalized Adults With Influenza: An Open-label, Multicenter, Single-Arm, Phase II Study

text: Background. Intravenous zanamivir is a neuraminidase inhibitor suitable for treatment of hospitalized patients with severe influenza. Methods. Patients were treated with intravenous zanamivir 600 mg twice daily, adjusted for renal impairment, for up to 10 days. Primary outcomes included adverse events (AEs), and clinical/laboratory parameters. Pharmacokinetics, viral load, and disease course were also assessed. Results. One hundred thirty patients received intravenous zanamivir (median, 5 days; range, 1–11) a median of 4.5 days (range, 1–7) after onset of influenza; 83% required intensive care. The most common influenza type/subtype was A/H1N1pdm09 (71%). AEs and serious AEs were reported in 85% and 34% of patients, respectively; serious AEs included bacterial pulmonary infections (8%), respiratory failure (7%), sepsis or septic shock (5%), and cardiogenic shock (5%). No drug-related trends in safety parameters were identified. Protocol-defined liver events were observed in 13% of patients. The 14- and 28-day all-cause mortality rates were 13% and 17%. No fatalities were considered zanamivir related. Pharmacokinetic data showed dose adjustments for renal impairment yielded similar zanamivir exposures. Ninety-three patients, positive at baseline for influenza by quantitative polymerase chain reaction, showed a median decrease in viral load of 1.42 log(10) copies/mL after 2 days of treatment. Conclusions. Safety, pharmacokinetic and clinical outcome data support further investigation of intravenous zanamivir. Clinical Trials Registration NCT01014988.


title: Relative Immunogenicity and Protection Potential of Candidate Yersinia Pestis Antigens against Lethal Mucosal Plague Challenge in Balb/C Mice

text: Yersinia Pestis Outer proteins, plasminogen activator protease and Yop secretion protein F are necessary for the full virulence of Yesinia pestis and have been proposed as potential protective antigens for vaccines against plague. In the current study, we used DNA immunization as a tool to study the relative protective immunity of these proteins with a standardized intranasal challenge system in mice. While the natural full length gene sequences for most of these Y. pestis proteins did not display a good level of protein expression in vitro when delivered by a DNA vaccine vector, the overall immunogenicity of these wild type gene DNA vaccines was low in eliciting antigen-specific antibody responses and gene sequence modifications improved both of these parameters. However, even modified YopD, YopO and YscF antigens were only able to partially protect immunized mice at various levels against lethal challenge with Y. pestis KIM 1001 strain while no protection was observed with either the YopB or Pla antigens. These results demonstrate that DNA immunization is effective in screening, optimizing and comparing optimal antigen designs and immunogenicity of candidate antigens for the development of a subunit-based plague vaccine.


title: Genetic variability human respiratory syncytial virus subgroups A and B in Turkey during six successive epidemic seasons, 2009‐2015

text: Human respiratory syncytial virus (HRSV) is most important viral respiratory pathogen of acute lower respiratory tract infections in infants and young children worldwide. The circulating pattern and genetic characteristics in the HRSV attachment glycoprotein gene were investigated in Turkey during six consecutive seasons from 2009 to 2015. HRSVA was dominant in the all epidemic seasons except 2011‐2012 season. Partial sequences of the HVR2 region of the G gene of 479 HRSVA and 135 HRSVB were obtained. Most Turkish strains belonged to NA1, ON1, and BA9, which were the predominant genotypes circulating worldwide. Although three novel genotypes, TR‐A, TR‐BA1, and TR‐BA2, were identified, they were not predominant. Clinical data were available for 69 HRSV‐positive patients who were monitored due to acute lower respiratory tract illness. There were no significant differences in the clinical diagnosis, hospitalization rates, laboratory findings and treatment observed between the HRSVA and HRSVB groups, and co‐infections in this study. The major population afflicted by HRSV infections included infants and children between 13 and 24 months of age. We detected that the CB1, GB5, and THB strains clustered in the same branch with a bootstrap value of 100%. CB‐B and BA12 strains clustered in the same branch with a bootstrap value of 65%. The BA11 genotype was clustered in the BA9 genotype in our study. The present study may contribute on the molecular epidemiology of HRSV in Turkey and provide data for HRSV strains circulating in local communities and other regions worldwide.


title: Oral Vaccination with the Porcine Rotavirus VP4 Outer Capsid Protein Expressed by Lactococcus lactis Induces Specific Antibody Production

text: The objective of this study to design a delivery system resistant to the gastrointestinal environment for oral vaccine against porcine rotavirus. Lactococcus lactis NZ9000 was transformed with segments of vP4 of the porcine rotavirus inserted into the pNZ8112 surface-expression vector, and a recombinant L. lactis expressing VP4 protein was constructed. An approximately 27 kDa VP4 protein was confirmed by SDS-PAGE , Western blot and immunostaining analysis. BALB/c mice were immunized orally with VP4-expression recombinant L. lactis and cellular, mucosal and systemic humoral immune responses were examined. Specific anti-VP4 secretory IgA and IgG were found in feces, ophthalmic and vaginal washes and in serum. The induced antibodies demonstrated neutralizing effects on porcine rotavirus infection on MA104 cells. Our findings suggest that oral immunization with VP4-expressing L. lactis induced both specific local and systemic humoral and cellular immune responses in mice.


title: Low dose radiation as a treatment for COVID‐19 pneumonia: a threat or real opportunity?

text: Low‐dose radiation is known to induce anti‐inflammatory responses and has been historically used for treating infectious diseases such as pneumonia. As the outbreak of COVID‐19 continues globally and effective treatment methods are lacking, low‐dose radiation has drawn increasing attention recently. While some are optimistic about the clinical adoption of low‐dose radiation for the treatment of COVID‐19, others have significant concerns about its effectiveness and safety. This is the premise debated in this month's Point/Counterpoint.


title: Geographic Access to High Capability Severe Acute Respiratory Failure Centers in the United States

text: OBJECTIVE: Optimal care of adults with severe acute respiratory failure requires specific resources and expertise. We sought to measure geographic access to these centers in the United States. DESIGN: Cross-sectional analysis of geographic access to high capability severe acute respiratory failure centers in the United States. We defined high capability centers using two criteria: (1) provision of adult extracorporeal membrane oxygenation (ECMO), based on either 2008–2013 Extracorporeal Life Support Organization reporting or provision of ECMO to 2010 Medicare beneficiaries; or (2) high annual hospital mechanical ventilation volume, based 2010 Medicare claims. SETTING: Nonfederal acute care hospitals in the United States. MEASUREMENTS AND MAIN RESULTS: We defined geographic access as the percentage of the state, region and national population with either direct or hospital-transferred access within one or two hours by air or ground transport. Of 4,822 acute care hospitals, 148 hospitals met our ECMO criteria and 447 hospitals met our mechanical ventilation criteria. Geographic access varied substantially across states and regions in the United States, depending on center criteria. Without interhospital transfer, an estimated 58.5% of the national adult population had geographic access to hospitals performing ECMO and 79.0% had geographic access to hospitals performing a high annual volume of mechanical ventilation. With interhospital transfer and under ideal circumstances, an estimated 96.4% of the national adult population had geographic access to hospitals performing ECMO and 98.6% had geographic access to hospitals performing a high annual volume of mechanical ventilation. However, this degree of geographic access required substantial interhospital transfer of patients, including up to two hours by air. CONCLUSIONS: Geographic access to high capability severe acute respiratory failure centers varies widely across states and regions in the United States. Adequate referral center access in the case of disasters and pandemics will depend highly on local and regional care coordination across political boundaries.


title: A virus-like particle vaccine platform elicits heightened and hastened local lung mucosal antibody production after a single dose

text: We show that a model antigen, ovalbumin (OVA), can be chemically conjugated to the exterior of a small heat shock protein (sHsp) cage that has structural similarities to virus-like particles (VLPs). OVA-sHsp conjugation efficiency was dependent upon the stoichiometry and the length of the small molecule linker utilized, and the attachment position on the sHsp cage. When conjugated OVA-sHsp was delivered intranasally to naïve mice, the resulting immune response to OVA was accelerated and intensified, and OVA-specific IgG1 responses were apparent within 5 days after a single immunizing dose, illustrating its utility for vaccine development. If animals were pretreated with a disparate VLP, P22 (a non-replicative bacteriophage capsid), before OVA-sHsp conjugate immunization, OVA-specific IgG1 responses were apparent already by 4 days after a single immunizing dose of conjugate in OVA-naïve mice. Additionally, the mice pretreated with P22 produced high titer mucosal IgA, and isotype-switched OVA-specific serum IgG. Similarly, sHsp pretreatment enhanced the accumulation of lung germinal center B cells, T follicular helper cells, and increased polymeric Ig receptor expression, priming the lungs for subsequent IgG and IgA responses to influenza virus challenge. Thus, sHsp nanoparticles elicited quick and intense antibody responses and these accelerated responses could similarly be induced to antigen chemically conjugated to the sHsp. Pretreatment of mice with P22 further accelerated the onset of the antibody response to OVA-sHsp, demonstrating the utility of conjugating antigens to VLPs for pre-, or possibly post-exposure prophylaxis of lung, all without the need for adjuvant.


title: Lung infection caused by Pseudomonas aeruginosa in a CD26/DPP4 deficient F344 rat model

text: BACKGROUND: Pseudomonas aeruginosa (PA) is the most important opportunistic pathogen in causing nosocomial infections and, furthermore, poses a permanent threat for severe chronic infections in patients with cystic fibrosis or COPD. The transmembrane protein CD26 with dipeptidyl peptidase-4 (DPP4) activity shows an increased expression in inflamed tissue. We tested whether CD26/DPP4 deficiency leads to reduced inflammation and decreased structural damage when infected with PA. METHODS: CD26/DPP4(+) and CD26/DPP4(−) rats were instilled intratracheally with NaCl (controls) or with PA. Six hours later, bacterial distribution was detected with the in vivo imaging system 200 (IVIS). Lungs were then processed for molecular biology, light and electron microscopy and analyzed qualitatively, quantitatively and stereologically. Bacterial numbers were determined in homogenized lungs. RESULTS: Compared to saline treated controls, in both infected groups (1) the acinar airspace was significantly increased, (2) the volume density of the alveolar epithelium was significantly decreased, (3) the septal thickness was significantly reduced, (4) more than 40% of the alveolar epithelial surface was damaged, and up to 36% of the epithelial surface was covered with edema. In infected CD26(−) rats, the increase in lung weight was significantly less pronounced, the portion of edematous alveolar airspace was significantly lower and the part of edema interspersed with PA was decreased significantly. CONCLUSIONS: CD26/DPP4 deficiency resulted in reduced pulmonary edema under sublethal PA infection, implicating a role for CD26 in infection progression. The partly pronounced structural damage may mask further possible influences of CD26 on the inflammatory response.


title: Derivation of a novel SARS–coronavirus replicon cell line and its application for anti-SARS drug screening

text: Abstract The severe acute respiratory syndrome (SARS) outbreak in 2002, which had a high morbidity rate and caused worldwide alarm, remains untreated today even though SARS was eventually isolated and controlled. Development and high-throughput screening of efficacious drugs is therefore critical. However, currently there remains a lack of such a safe system. Here, the generation and characterization of the first selectable, SARS–coronavirus (SARS–CoV)-based replicon cell line which can be used for screening is described. Partial SARS–CoV cDNAs and antibiotic resistance/reporter gene DNA were generated and assembled in vitro to produce the replicon transcription template, which was then transcribed in vitro to generate the replicon RNA. The latter was introduced into a mammalian cell line and the transfected cells were selected for by antibiotic application. For the antibiotic-resistant cell lines thus generated, the expression of reporter gene was ensured by continued monitoring using fluorescent microscopy and flow cytometry. The suitability of this replicon cell line in drug screening was demonstrated by testing the inhibitory effect of several existing drugs and the results demonstrate that the SARS–CoV replicon cell lines provide a safe tool for the identification of SARS–CoV replicase inhibitors. The replicon cell lines thus developed can be applied to high-throughput screening for anti-SARS drugs without the need to grow infectious SARS–CoV.


title: Prevalence of Diabetes in the 2009 Influenza A (H1N1) and the Middle East Respiratory Syndrome Coronavirus: A Systematic Review and Meta-Analysis

text: Over the past two decades a number of severe acute respiratory infection outbreaks such as the 2009 influenza A (H1N1) and the Middle East respiratory syndrome coronavirus (MERS-CoV) have emerged and presented a considerable global public health threat. Epidemiologic evidence suggests that diabetic subjects are more susceptible to these conditions. However, the prevalence of diabetes in H1N1 and MERS-CoV has not been systematically described. The aim of this study is to conduct a systematic review and meta-analysis of published reports documenting the prevalence of diabetes in H1N1 and MERS-CoV and compare its frequency in the two viral conditions. Meta-analysis for the proportions of subjects with diabetes was carried out in 29 studies for H1N1 (n=92,948) and 9 for MERS-CoV (n=308). Average age of H1N1 patients (36.2±6.0 years) was significantly younger than that of subjects with MERS-CoV (54.3±7.4 years, P<0.05). Compared to MERS-CoV patients, subjects with H1N1 exhibited 3-fold lower frequency of cardiovascular diseases and 2- and 4-fold higher prevalence of obesity and immunosuppression, respectively. The overall prevalence of diabetes in H1N1 was 14.6% (95% CI: 12.3-17.0%; P<0.001), a 3.6-fold lower than in MERS-CoV (54.4%; 95% CI: 29.4-79.5; P<0.001). The prevalence of diabetes among H1N1 cases from Asia and North America was ~two-fold higher than those from South America and Europe. The prevalence of diabetes in MERS-CoV cases is higher than in H1N1. Regional comparisons suggest that an etiologic role of diabetes in MERS-CoV may exist distinctive from that in H1N1.


title: Featuring COVID-19 cases via screening symptomatic patients with epidemiologic link during flu season in a medical center of central Taiwan

text: Abstract Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CO-V-2), was first reported in Wuhan, Hubei province, China has now rapidly spread over 50 countries. For the prevention and control of infection, Taiwan Centers for Disease Control initiated testing of SARS-CoV-2 on January 24th 2020 for persons suspected with this disease. Until February 28th, 43 flu-like symptomatic patients were screened in China Medical University Hospital. Methods Two patients were confirmed positive for SARS-CoV-2 infection by rRT-PCR as COVID-19 patients A and B. Causative pathogens for included patients were detected using FilmArray™ Respiratory Panel. We retrospectively analyzed the clinical presentations, laboratory data, radiologic findings, and travel and exposure contact histories, of the COVID-19 patients in comparison to those with other respiratory infections. Results Through contact with Taiwan No. 19 case patient on 27th January, COVID-19 patients A and B were infected. Both patients had no identified comorbidities and developed mild illness with temporal fever, persistent cough, and lung interstitial infiltrates. Owing to the persistence of positive SARS-CoV-2 in respiratory specimen, the two COVID-19 patients are still in the isolation rooms despite recovery until 10th of March. The results of FilmArrayTM Respiratory Panel revealed 22 of the 41 non-COVID-19 patients were infected by particular pathogens. In general, seasonal respiratory pathogens are more prevalent than SARS-CoV-2 in symptomatic patients in non- COVID-19 endemic area during the flu season. Since all patients shared similar clinical and laboratory findings, expanded surveillance of detailed exposure history for suspected patients and application of rapid detection tools are highly recommended.


title: COVID-19 in India: Are Biological and Environmental Factors Helping to Stem the Incidence and Severity?

text: The ongoing Corona virus (COVID-19) pandemic has witnessed global political responses of unimaginable proportions. Many nations have implemented lockdowns that involve mandating citizens not to leave their residences for non-essential work. The Indian government has taken appropriate and commendable steps to curtail the community spread of COVID-19. While this may be extremely beneficial, this perspective discusses the other reasons why COVID-19 may have a lesser impact on India. We analyze the current pattern of SARS-CoV-2 transmission, testing, and mortality in India with an emphasis on the importance of mortality as a marker of the clinical relevance of COVID-19 disease. We also analyze the environmental and biological factors which may lessen the impact of COVID-19 in India. The importance of cross-immunity, innate immune responses, ACE polymorphism, and viral genetic mutations are discussed.


Commentary: Rethinking Surgical Protocols in the Covid-19 Era


title: Identification of secreted and membrane-bound bat immunoglobulin using a Microchiropteran-specific mouse monoclonal antibody

text: Abstract Bat immunity has received increasing attention because some bat species are being decimated by the fungal disease, White Nose Syndrome, while other species are potential reservoirs of zoonotic viruses. Identifying specific immune processes requires new specific tools and reagents. In this study, we describe a new mouse monoclonal antibody (mAb) reactive with Eptesicus fuscus immunoglobulins. The epitope recognized by mAb BT1-4F10 was localized to immunoglobulin light (lambda) chains; hence, the mAb recognized serum immunoglobulins and B lymphocytes. The BT1-4F10 epitope appeared to be restricted to Microchiropteran immunoglobulins and absent from Megachiropteran immunoglobulins. Analyses of sera and other E. fuscus fluids showed that most, if not all, secreted immunoglobulins utilized lambda light chains. Finally, mAb BT1-4F10 permitted the identification of B cell follicles in splenic white pulp. This Microchiropteran-specific mAb has potential utility in seroassays; hence, this reagent may have both basic and practical applications for studying immune process.


COVID-19: a novel zoonotic disease caused by a coronavirus from China: what we know and what we don’t


title: Validation of predictors of disease severity and outcomes in COVID-19 patients: a descriptive and retrospective study

text: Abstract Background The severity and outcome of COVID-19 cases has been associated with percentage of circulating lymphocytes (LYM%), levels of C-reactive protein (CRP), interleukin 6 (IL-6), procalcitonin (PCT), lactic acid (LA) and viral load (ORF1ab Ct). However, the predictive power of each of these indicators in disease classification and prognosis remains largely unclear. Methods we retrospectively collected information on the above parameters in 142 patients with COVID-19, stratifying them by survival or disease severity. Findings CRP, PCT, IL-6, LYM% and ORF1ab Ct were significantly altered between survivors and non-survivors. LYM%, CRP and IL-6 were the most sensitive and reliable factors in distinguishing between survivors and non-survivors. These indicators were significantly different between critically ill and severe/moderate patients. Only LYM% levels were significantly different between severe and moderate types. Among all the investigated indicators, LYM% was the most sensitive and reliable in discriminating between critically ill, severe and moderate types, and between survivors and non-survivors. Conclusions CRP, PCT, IL-6, LYM% and ORF1ab Ct, but not LA, could predict prognosis and guide classification of COVID-19 patients. LYM% was the most sensitive and reliable predictor for disease typing and prognosis. We recommend that LYM% be further investigated in the management of COVID-19.


title: Direct Observation of Membrane Insertion by Enveloped Virus Matrix Proteins by Phosphate Displacement

text: Enveloped virus release is driven by poorly understood proteins that are functional analogs of the coat protein assemblies that mediate intracellular vesicle trafficking. We used differential electron density mapping to detect membrane integration by membrane-bending proteins from five virus families. This demonstrates that virus matrix proteins replace an unexpectedly large portion of the lipid content of the inner membrane face, a generalized feature likely to play a role in reshaping cellular membranes.


COVID-19 and Health Disparities: the Reality of “the Great Equalizer”


title: Evidence-based support for the all-hazards approach to emergency preparedness

text: BACKGROUND: During the last decade there has been a need to respond and recover from various types of emergencies including mass casualty events (MCEs), mass toxicological/chemical events (MTEs), and biological events (pandemics and bio-terror agents). Effective emergency preparedness is more likely to be achieved if an all-hazards response plan is adopted. OBJECTIVES: To investigate if there is a relationship among hospitals' preparedness for various emergency scenarios, and whether components of one emergency scenario correlate with preparedness for other emergency scenarios. METHODS: Emergency preparedness levels of all acute-care hospitals for MCEs, MTEs, and biological events were evaluated, utilizing a structured evaluation tool based on measurable parameters. Evaluations were made by professional experts in two phases: evaluation of standard operating procedures (SOPs) followed by a site visit. Relationships among total preparedness and different components' scores for various types of emergencies were analyzed. RESULTS: Significant relationships were found among preparedness for different emergencies. Standard Operating Procedures (SOPs) for biological events correlated with preparedness for all investigated emergency scenarios. Strong correlations were found between training and drills with preparedness for all investigated emergency scenarios. CONCLUSIONS: Fundamental critical building blocks such as SOPs, training, and drill programs improve preparedness for different emergencies including MCEs, MTEs, and biological events, more than other building blocks, such as equipment or knowledge of personnel. SOPs are especially important in unfamiliar emergency scenarios. The findings support the adoption of an all-hazards approach to emergency preparedness.


title: Structural bioinformatics analysis of free cysteines in protein environments

text: Abstract Cysteine has been considered as a “hydrophilic” amino acid because of its pK a and its ability to form (weak) hydrogen bonds. However, cysteines are found mostly in hydrophobic environments, either in S–S (disulphide) form or in free cysteine form. When free cysteines are found on the surface of proteins, they are often involved in catalytic residues, as in cysteine proteases, P-loop phosphatases, etc. Additionally, a unique property of cysteines is that their side-chain volume is different from all other amino acids. This study is focused on the discrimination between structural versus active free cysteines based on a local environment analysis which does not appear to have been attempted previously. We have demonstrated the corresponding structural positions associated with free cysteines in their three-dimensional localization environment. We examined protein samples including nine, sequenced, coronavirus proteases and cysteine-rich non-membrane proteins. Our present study shows that the sequential environments of free cysteines of coronavirus proteases are rather hydrophobic and that the free cysteines of non-membrane proteases have a higher amount of contacts to hydrophobic residues and lower amount of contacts to polar or charged residues.


COVID-19 et Masso-Kinésithérapie


title: Nucleocapsid Phosphorylation and RNA Helicase DDX1 Recruitment Enables Coronavirus Transition from Discontinuous to Continuous Transcription

text: Coronaviruses contain a positive-sense single-stranded genomic (g) RNA, which encodes nonstructural proteins. Several subgenomic mRNAs (sgmRNAs) encoding structural proteins are generated by template switching from the body transcription regulatory sequence (TRS) to the leader TRS. The process preferentially generates shorter sgmRNA. Appropriate readthrough of body TRSs is required to produce longer sgmRNAs and full-length gRNA. We find that phosphorylation of the viral nucleocapsid (N) by host glycogen synthase kinase-3 (GSK-3) is required for template switching. GSK-3 inhibition selectively reduces the generation of gRNA and longer sgmRNAs, but not shorter sgmRNAs. N phosphorylation allows recruitment of the RNA helicase DDX1 to the phosphorylated-N-containing complex, which facilitates template readthrough and enables longer sgmRNA synthesis. DDX1 knockdown or loss of helicase activity markedly reduces the levels of longer sgmRNAs. Thus, coronaviruses employ a unique strategy for the transition from discontinuous to continuous transcription to ensure balanced sgmRNAs and full-length gRNA synthesis.


title: Emerging study on the transmission of the Novel Coronavirus (COVID-19) from urban perspective: Evidence from China

text: This study presents an in-depth investigation on the transmission of the novel coronavirus (COVID-19) from the urban perspective. It focuses on the “aftermath” of the outbreak and the spread of the infection among cities. Especially, this study provides insights of the fundamentals of the factors that may affect the spread of the infection in cities, where the marginal effects of some most influential factors to the virus transmission are estimated. It reveals that the distance to epicenter is a very strong influential factor, and is negatively linked with the spread of COVID-19. In addition, subway, wastewater and residential garbage are positively connected with the virus transmission. Moreover, both urban area and population density are negatively associated with the spread of COVID-19 at the early stage of the epidemic. Furthermore, this study also provides high precision estimation of the number of COVID-19 infection in Wuhan city, which is the epicenter of the outbreak in China. Based on the real-world data of cities outside Wuhan on March 2, 2020, the estimated number is 56,944.866 (mean value), which is very close to the officially reported number. The methodology and main conclusions shown in this paper are of general interest, and they can be applied to other countries to help understand the local transmission of COVID-19 as well.


title: A Scoping Review of Registered Clinical Trials of Cellular Therapy for COVID-19 and a Framework for Accelerated Synthesis of Trial Evidence – FAST Evidence

text: Abstract The urgent need for safe and effective treatments for COVID-19 has fueled the launch of many parallel complex studies of cellular therapies with small to modest enrolment projections. By pooling data from multiple studies that are similar, we can increase the ability to achieve sufficient power to determine effectiveness more quickly through metanalysis. A scoping review of registered clinical trials using cell-based interventions for COVID-19 was conducted to identify candidate studies for metanalysis that could support an accelerated regulatory review. ClinicalTrials.gov and WHO International Clinical Trials Registry Platform were searched April 23, 2020. Trials were included if they utilized cell or cell-derived products to treat or prevent COVID-19. Fifty-four registered cellular therapy trials were identified and included for analysis. Studies of mesenchymal stromal cells (MSCs; 41 studies; 1129 subjects projected to receive cells) and natural killer (NK) cells (5 studies; 135 projected to received cells) were observed most commonly. A subset of studies are controlled (34 studies, or 63%), including 27 studies of MSCs and 3 of NK cells. While heterogeneity in study design exists, the cumulative projected enrolment of patients from similar studies appears sufficient to allow the detection of meaningful differences in clinically important outcomes such as mortality, admission to intensive care and need for mechanical ventilation by September 2020 – sooner than any individual study could determine effectiveness. MSCs are the predominant cell type in registered trials for severe or critical COVID-19 and represent the most promising candidates for future metanalysis. Sufficient pooled sample size to detect clinically important reductions in multiple outcomes, including mortality, is anticipated by September 2020, but may require accessing supplementary data to align outcome reporting. Regulatory approval, funding and implementation by cell manufacturing partners will be accelerated by our framework for rapid metanalysis.


title: Determination of 5′-leader sequences from radically disparate strains of porcine reproductive and respiratory syndrome virus reveals the presence of highly conserved sequence motifs

text: We determined the untranslated 5′-leader sequence for three different isolates of porcine reproductive and respiratory syndrome virus (PRRSV): pathogenic European- and American-types, as well as an American-type vaccine strain. 5′-leader from European- and American-type PRRSV differed in length (220 and 190 nt, respectively), and exhibited only approximately 50% nucleotide homology. Nevertheless, highly conserved areas were identified in the leader of all 3 PRRSV isolates, which constitute candidate motifs for binding of protein(s) involved in viral replication. These comparative data provide a priori knowledge for mutational identification of virulence determinants in the 5′ nontranslated part of the PRRSV genome.


title: Myristoylation of the small envelope protein of porcine reproductive and respiratory syndrome virus is non-essential for virus infectivity but promotes its growth

text: Abstract The small envelope (E) protein of porcine reproductive and respiratory syndrome virus (PRRSV) is known to possess the properties of an ion-channel protein, and in the present study we show that the PRRSV E protein is N-terminal myristoylated. The PRRSV E protein contains the consensus motif of 1MGxxxS6 for myristoylation, and in the presence of 2-hydroxymyristic acid, the virus titer decreased by 2.5logTCID50 and the level of viral RNA was reduced significantly. When the glycine at position 2 was mutated to alanine (G2A) using an infectious cDNA clone, a viable virus was recoverable and a mutant PRRSV was obtained. The titers of G2A mutant virus were 2.0×104 and 1.0×106 TCID50/ml for ‘passage-2’ and ‘passage-3’ viruses, respectively, in PAM cells, and these titers were significantly lower than those of wild-type PRRSV. When treated with the myristoylation inhibitor, the G2A mutant virus was resistant to the drug. The data show that the PRRSV E protein myristoylation is non-essential for PRRSV infectivity but promotes the growth of the virus.


title: COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms

text: Researchers around the world join forces to reconstruct the molecular processes of the virus-host interactions aiming to combat the cause of the ongoing pandemic.


Reply to “Could a mannequin simplify rhinopharyngeal swab collection in COVID 19 patients?”


title: Experience and suggestion of medical practices for burns during the outbreak of COVID-19

text: COVID-19 is spreading almost all over the world at present, which is infected by 2019 novel coronavirus (2019-nCoV). It was epidemic firstly in Hubei province of China. The Chinese government has formally set COVID-19 in the statutory notification and control system for infectious diseases according to the Law of the People’s Republic of China on the Prevention and Treatment of Infectious Diseases. China currently is still struggling to defend COVID-19 though great achievements and progresses are being got. Burn Department is one of sections in clinics with the highest infectious risk of COVID-19. Based on our own experiences and the guidelines on the diagnosis and treatment of COVID-19 (7th Version) with other regulations and literatures, we put forward this experience and suggestion of medical practices for burns during the outbreak of COVID-19. We hope these experiences and suggestions could benefit for our international colleagues during the pandemic of the COVID-19.


Silver Linings Pandemic


title: Detection of SARS Coronavirus

text: The emergence of severe acute respiratory syndrome (SARS) and its subsequent worldwide spread challenged the global public health community to confront a novel infectious disease. The infection is caused by a coronavirus of animal origin. In this epidemic, molecular detections of SARS coronavirus RNA were shown to be useful for the early diagnosis of SARS. Although this pathogen was eradicated in humans, SARS or SARS-like viruses might reemerge from animals or from laboratory incidents. In this chapter, we describe several polymerase chain reaction (PCR) protocols for detecting SARS coronaviruses. These assays were routinely used for clinical diagnosis during the SARS outbreak.


title: N-acetylpenicillamine inhibits the replication of porcine reproductive and respiratory syndrome virus in vitro

text: Nitric oxide (NO) was proposed to be an important molecule against some microorganisms. In this study, we investigated the inhibitory effect of NO on the infection by porcine reproductive and respiratory syndrome virus (PRRSV) in vitro and the role of NO in the defense against PRRSV. Our results indicated that exogenous NO did not inhibit PRRSV infection. Unexpectedly, N-acetylpenicillamine (NAP), a commonly used compound as negative control for NO-producing reagents, inhibited PRRSV replication. Thus, the inhibition effect of NAP on PRRSV replication was further explored. We found that the maximal inhibition effect of NAP on PRRSV replication was achieved upon treatment 1 h after virus infection and the virus yield was reduced by approximately 50 fold in the presence of 400 μM NAP. An obvious inhibitory effect on viral RNA and protein synthesis was also observed. However, the inhibitory effect was only achieved at early phase of virus infection. The normal virus yield could be restored upon the removal of NAP treatment. The inhibitory effect might be caused by sulfhydryl-reducing capacity and metal chelating properties of NAP. These studies suggested that (i) NO production or NO synthase (NOS) expression profiling may not be a reliable index for the immune response to PRRSV; (ii) NAP could inhibit the replication of PRRSV.


title: Novel Coronavirus Infection (COVID‐19) in Children Younger Than One Year: A Systematic Review of Symptoms, Management and Outcomes

text: AIM: This aim of this systematic review and meta‐analysis was to evaluate the clinical characteristics of COVID‐19 in neonates and children under one year of age. METHODS: A systematic literature review of the MEDLINE, PubMed, CINAHL, Embase and EBSCO databases was carried out for studies from 1 January to 7 April 2020. We included all papers that addressed clinical manifestations, laboratory results, imaging findings and outcomes in infants and neonates. RESULTS: Our search identified 77 peer‐reviewed papers and 18 papers covering 160 infants were reviewed. One paper was from Vietnam and the other 17 were from China: eight were cross‐sectional studies, eight were case reports, one was a case series and one was a prospective cohort study. The most common clinical symptoms were fever (54%) and cough (33%). Most infants were treated symptomatically, with frequent use of various empirical medications. Infants and neonates tended to have more severe COVID‐19 disease than older children: 11 (7%) were admitted to intensive care and one infant died. The mortality rate was 0.006%, with favourable outcomes in most cases. CONCLUSION: Infants and neonates were more vulnerable to more severe COVID‐19 disease than older children, but morbidity and mortality were low.


45th ESCP-NSF international symposium on clinical pharmacy: clinical pharmacy tackling inequalities and access to health care. Oslo, Norway, 5–7 October 2016


title: Anti‐Dengue‐Virus Activity and Structure–Activity Relationship Studies of Lycorine Derivatives

text: Dengue is a systemic viral infection that is transmitted to humans by Aedes mosquitoes. No vaccines or specific therapeutics are currently available for dengue. Lycorine, which is a natural plant alkaloid, has been shown to possess antiviral activities against flaviviruses. In this study, a series of novel lycorine derivatives were synthesized and assayed for their inhibition of dengue virus (DENV) in cell cultures. Among the lycorine analogues, 1‐acetyllycorine exhibited the most potent anti‐DENV activity (EC(50)=0.4 μm) with a reduced cytotoxicity (CC(50)>300 μm), which resulted in a selectivity index (CC(50)/EC(50)) of more than 750. The ketones 1‐acetyl‐2‐oxolycorine (EC(50)=1.8 μm) and 2‐oxolycorine (EC(50)=0.5 μm) also exhibited excellent antiviral activities with low cytotoxicity. Structure–activity relationships for the lycorine derivatives against DENV are discussed. A three‐dimensional quantitative structure–activity relationship model was established by using a comparative molecular‐field analysis protocol in order to rationalize the experimental results. Further modifications of the hydroxy group at the C1 position with retention of a ketone at the C2 position could potentially lead to inhibitors with improved overall properties.


title: Chapter 13 Epidemiology of Viral Infections

text: Abstract Epidemiology is the study of the distribution, the dynamics, and the determinants of diseases in populations. The risk of virus infection and/or clinical disease is determined by characteristics both of the virus, and the levels of innate and acquired resistance in the community. Virus transmission is affected by behavioral, environmental, and ecological factors. Knowledge of these factors contributes to evidence-based policy decisions as to how best to control and prevent virus diseases. Considerable use of genome sequencing of isolates now provides useful information as to the identification of outbreak sources as well as informing the design and testing of candidate vaccines.


title: Comparing Luminex NxTAG‐Respiratory Pathogen Panel and RespiFinder‐22 for multiplex detection of respiratory pathogens

text: Respiratory tract infection (RTI) involves a variety of viruses and bacteria, which can be conveniently detected by multiplex nucleic acid amplification testing (NAT). To compare the novel Luminex‐based NxTAG‐Respiratory Pathogen Panel (NxTAG‐RPP) with the routine multiplex‐ligation‐NAT based RespiFinder‐22® (RF‐22), 282 respiratory specimens including nasopharyngeal swabs (71%), broncho‐alveolar lavage (27%), throat swabs, tracheal secretions, and sputum (2%) from 116 children and 155 adults were extracted using a Corbett CAS1200 (Qiagen), and analyzed in parallel by the routine RF‐22 and NxTAG‐RPP. Concordant results were obtained in 263 (93.3%) cases consisting of concordant positives in 167 (59.2%) and concordant negatives in 96 (34%). Results were discordant in 19 (6.7%) consisting of 15 positive:negative, and 4 negative:positive results by NxTAG‐RPP versus RF‐22, respectively. Co‐infections were observed in 10.3% with NxTAG‐RPP and in 5.9% with RF‐22. Most additional viral pathogens identified by the NxTAG‐RPP involved dual infections with rhinovirus and RSV. Discordant samples were mainly due to low genome signals of C(t) less than 36, when retested by QNAT suggesting a higher sensitivity of the NxTAG‐RPP, also when detecting multiple infections. Hands‐on time after extraction for 24 and 96 samples was 0.25 and <0.5 hr for the NxTAG‐RPP, and 2 and 4 hr for the RF‐22, respectively. The median turn‐around time was 6 hr (range 5–7 hr) for NxTAG‐RPP and 12 hr (range 8–16 hr) for RF‐22. The NxTAG‐RPP showed comparable detection rates for most respiratory pathogens, while hands‐on and turn‐around time were considerably shorter. The clinical significance of detecting multiple viruses needs further clinical evaluation. J. Med. Virol. 88:1319–1324, 2016. © 2016 Wiley Periodicals, Inc.


title: Detection and characterization of respiratory viruses causing acute respiratory illness and asthma exacerbation in children during three different seasons (2011–2014) in Mexico City

text: BACKGROUND: Viral infections play a significant role in causing acute respiratory infections (ARIs) and exacerbations of chronic diseases. Acute respiratory infections are now the leading cause of mortality in children worldwide, especially in developing countries. Recently, human rhinovirus (HRV) infection has been emerged as an important cause of pneumonia and asthma exacerbation. OBJECTIVES: To determine the role of several viral agents principally, respiratory syncytial virus, and HRV in children with ARIs and their relationship with asthma exacerbation and pneumonia. METHODS: Between October 2011 and March 2014, 432 nasopharyngeal samples of children <15 years of age with ARI hospitalized at a referral hospital for respiratory diseases were tested for the presence of respiratory viruses using a multiplex RT-qPCR. Clinical, epidemiological, and demographic data were collected and associated with symptomatology and viral infections. RESULTS: Viral infections were detected in at least 59·7% of the enrolled patients, with HRV (26·6%) being the most frequently detected. HRV infections were associated with clinical features of asthma and difficulty in breathing such as wheezing (P = 0·0003), supraesternal (P = 0·046), and xiphoid retraction (P = 0·030). HRV subtype C (HRV-C) infections were associated with asthma (P = 0·02). CONCLUSIONS: Human rhinovirus was the virus most commonly detected in pediatric patients with ARI. There is also an association of HRV-C infection with asthma exacerbation, emphasizing the relevance of this virus in severe pediatric respiratory disease.


title: Homodimerisation-independent cleavage of dsRNA by a pestiviral nicking endoribonuclease

text: The glycoprotein E(rns) plays a central role in the biology of the pestivirus bovine viral diarrhea virus (BVDV). This soluble endonuclease mediates the escape from an interferon (IFN) response in the infected fetus, thereby permitting the establishment of persistent infection. Viral single-stranded (ss) and double-stranded (ds) RNA act as potent IFN inducing signals and we previously showed that E(rns) efficiently cleaves these substrates, thereby inhibiting an IFN response that is crucial for successful fetal infection. Considering that a large variety of RNases and DNases require dimerisation to cleave double-stranded substrates, the activity of E(rns) against dsRNA was postulated to depend on homodimer formation mediated by disulfide bonds involving residue Cys171. Here, we show that monomeric E(rns) is equally able to cleave dsRNA and to inhibit dsRNA-induced IFN synthesis as the wild-type form. Furthermore, both forms were able to degrade RNA within a DNA/RNA- as well as within a methylated RNA/RNA-hybrid, with the DNA and the methylated RNA strand being resistant to degradation. These results support our model that E(rns) acts as ‘nicking endoribonuclease’ degrading ssRNA within double-stranded substrates. This efficiently prevents the activation of IFN and helps to maintain a state of innate immunotolerance in persistently infected animals.


title: Gateway cloning is compatible with protein secretion from Pichia pastoris

text: Abstract Secretion of a recombinant protein from the yeast Pichia pastoris requires the presence of a signal peptide at the amino terminus. Maintaining the full amino acid sequence of the signal peptide is thought to be important for proper signal processing and protein secretion. We show that at least for one protein, a synthetic human interferon, the presence of a Gateway recombination site within the signal peptide is fully compatible with high levels of protein secretion. The amino termini of the secreted interferon proteins cloned with Gateway and cloned with restriction enzymes and ligase are identical, and the proteins were highly active in biological assays. Compatibility with Gateway cloning simplifies construction of plasmids directing secretion of recombinant proteins from P. pastoris.


No Association of COVID-19 transmission with temperature or UV radiation in Chinese cities


title: Emergency Medicine of the Ferret

text: Common emergency conditions seen in the ferret include insulinoma, cardiomyopathy, and urethral obstruction. When developing a diagnostic and therapeutic plan, the ferret veterinarian must seek a balance between species-specific information and information extrapolated from cat and dog medicine. The therapeutic plan must always include close and careful monitoring. Significant changes in the status of these small patients can occur extremely quickly in the course of providing basic supportive care, such as intravenous fluids or supplemental heat.


title: Environmental sampling for respiratory pathogens in Jeddah airport during the 2013 Hajj season

text: BACKGROUND: Respiratory tract infections (RTIs) are common during the Hajj season and are caused by a variety of organisms, which can be transmitted via the air or contaminated surfaces. We conducted a study aimed at sampling the environment in the King Abdul Aziz International (KAAI) Airport, Pilgrims City, Jeddah, during Hajj season to detect respiratory pathogens. METHODS: Active air sampling was conducted using air biosamplers, and swabs were used to sample frequently touched surfaces. A respiratory multiplex array was used to detect bacterial and viral respiratory pathogens. RESULTS: Of the 58 environmental samples, 8 were positive for at least 1 pathogen. One air sample (1 of 18 samples, 5.5%) tested positive for influenza B virus. Of the 40 surface samples, 7 (17.5%) were positive for pathogens. These were human adenovirus (3 out of 7, 42.8%), human coronavirus OC43/HKU1 (3 out of 7, 42.8%), Haemophilus influenzae (1 out of 7, 14.2%), and Moraxella catarrhalis (1 out of 7, 14.2%). Chair handles were the most commonly contaminated surfaces. The handles of 1 chair were cocontaminated with coronavirus OC43/HKU1 and H influenzae. CONCLUSION: Respiratory pathogens were detected in the air and on surfaces in the KAAI Airport in Pilgrims City. Larger-scale studies based on our study are warranted to determine the role of the environment in transmission of respiratory pathogens during mass gathering events (eg, Hajj) such that public health preventative measures might be better targeted.


title: Chapter 24 Coronaviridae

text: Publisher Summary Coronavirus and coronavirus-like infections are described in swine, cattle, horses, cats, dogs, rats, birds, bats, rabbits, ferrets, mink, and various wildlife species, although many coronavirus infections are subclinical or asymptomatic. In humans, coronaviruses are included in the spectrum of viruses that cause the common cold and, recently, severe acute respiratory syndrome (SARS), which is a zoonosis. This chapter explains that the family Coronaviridae is included with the families Arteriviridae and Roniviridae in the order nidovirales; viruses in these three families share a distinctive replication strategy. The genus Coronavirus contains a substantial number of pathogens of mammals and birds that individually cause a remarkable variety of diseases, including pneumonia, reproductive disease, enteritis, polyserositis, sialodacryoadenitis, hepatitis, encephalomyelitis, nephritis, and various other disorders. The genus Coronavirus can be subdivided into at least three cluster groups on the basis of genetic and serologic properties, with subgroups in two of these. Group 1a includes transmissible gastroenteritis virus of swine, porcine respiratory coronavirus, canine coronavirus, feline enteric coronavirus, ferret and mink coronaviruses, and spotted hyena coronavirus. Group 1b includes certain human coronaviruses, porcine epidemic diarrhea virus, and bat coronavirus. Group 2a includes mouse hepatitis virus, bovine coronavirus, sialodacryoadenitis virus of rats, porcine hemagglutinating encephalomyelitis virus, canine respiratory coronavirus, and other human coronaviruses. Group 2b includes human SARS coronavirus and civet cat, raccoon dog, and horseshoe bat coronaviruses. Group 3 includes avian infectious bronchitis virus, turkey coronavirus, and several potential but still largely uncharacterized new species from ducks, geese, and pigeons.


title: Identification of a Severe Acute Respiratory Syndrome Coronavirus-Like Virus in a Leaf-Nosed Bat in Nigeria

text: Bats are reservoirs for emerging zoonotic viruses that can have a profound impact on human and animal health, including lyssaviruses, filoviruses, paramyxoviruses, and severe acute respiratory syndrome coronaviruses (SARS-CoVs). In the course of a project focused on pathogen discovery in contexts where human-bat contact might facilitate more efficient interspecies transmission of viruses, we surveyed gastrointestinal tissue obtained from bats collected in caves in Nigeria that are frequented by humans. Coronavirus consensus PCR and unbiased high-throughput pyrosequencing revealed the presence of coronavirus sequences related to those of SARS-CoV in a Commerson’s leaf-nosed bat (Hipposideros commersoni). Additional genomic sequencing indicated that this virus, unlike subgroup 2b CoVs, which includes SARS-CoV, is unique, comprising three overlapping open reading frames between the M and N genes and two conserved stem-loop II motifs. Phylogenetic analyses in conjunction with these features suggest that this virus represents a new subgroup within group 2 CoVs.


Equine coronavirus, a possible cause for adult horse enteric disease outbreaks


title: Economic Consequences of the COVID-19 Outbreak: the Need for Epidemic Preparedness

text: COVID-19 is not only a global pandemic and public health crisis; it has also severely affected the global economy and financial markets. Significant reductions in income, a rise in unemployment, and disruptions in the transportation, service, and manufacturing industries are among the consequences of the disease mitigation measures that have been implemented in many countries. It has become clear that most governments in the world underestimated the risks of rapid COVID-19 spread and were mostly reactive in their crisis response. As disease outbreaks are not likely to disappear in the near future, proactive international actions are required to not only save lives but also protect economic prosperity.


title: Specific elevation of DcR3 in sera of sepsis patients and its potential role as a clinically important biomarker of sepsis

text: Because of its potentially important role in the pathogenesis of sepsis, the expression of soluble decoy receptor 3 (DcR3) was investigated in sera of sepsis patients. The serum levels of DcR3 and its TNF-like ligand TL1A and homologous decoy receptor OPG were quantified by ELISA. The values of DcR3 to diagnose sepsis were analyzed by receiver-operating characteristic (ROC) curves. The results showed that DcR3 was significantly elevated in sepsis compared to SIRS (systemic inflammatory response syndrome), a condition similar to sepsis but resulting from noninfectious insults. DcR3 showed superior area under the ROC curve (AUC, 0.958) compared to poor AUCs of TL1A and OPG. At a cut-off of 3.24 ng/ml, DcR3 predicted sepsis from SIRS with 96% sensitivity and 82.6% specificity. DcR3 also predicted sepsis from cancer and inflammatory bowel disease with equally excellent values. Therefore, DcR3 serum level has the potential to serve as a reliable biomarker of sepsis.


title: Vitamin D concentrations and COVID-19 infection in UK Biobank

text: Abstract Background and aims COVID-19 and low levels of vitamin D appear to disproportionately affect black and minority ethnic individuals. We aimed to establish whether blood 25-hydroxyvitamin D (25(OH)D) concentration was associated with COVID-19 risk, and whether it explained the higher incidence of COVID-19 in black and South Asian people. Methods UK Biobank recruited 502,624 participants aged 37–73 years between 2006 and 2010. Baseline exposure data, including 25(OH)D concentration and ethnicity, were linked to COVID-19 test results. Univariable and multivariable logistic regression analyses were performed for the association between 25(OH)D and confirmed COVID-19, and the association between ethnicity and both 25(OH)D and COVID-19. Results Complete data were available for 348,598 UK Biobank participants. Of these, 449 had confirmed COVID-19 infection. Vitamin D was associated with COVID-19 infection univariably (OR = 0.99; 95% CI 0.99–0.999; p = 0.013), but not after adjustment for confounders (OR = 1.00; 95% CI = 0.998–1.01; p = 0.208). Ethnicity was associated with COVID-19 infection univariably (blacks versus whites OR = 5.32, 95% CI = 3.68–7.70, p-value<0.001; South Asians versus whites OR = 2.65, 95% CI = 1.65–4.25, p-value<0.001). Adjustment for 25(OH)D concentration made little difference to the magnitude of the association. Conclusions Our findings do not support a potential link between vitamin D concentrations and risk of COVID-19 infection, nor that vitamin D concentration may explain ethnic differences in COVID-19 infection.


title: The Detection of an Unidentified Type of Adenovirus in the Stools of Calves with Weak Calf Syndrome by Use of a Commercial Kit Designed for the Detection of Human Adenoviruses

text: An outbreak of polyarthritis in newborn calves in a large collective dairy herd was characterized by intra‐articular blood‐tinged synoviae, blood tainted faeces and massive subcorneal haemorrhages. Faecal samples from eight clinical newborn cases, 10 from unrelated dairy farms and 10 faecal samples from healthy calves were examined by the Rida(®) Quick rotavirus/adenovirus‐combi test . A specific adenovirus antigen precipitin‐line was seen in the reaction in all the faecal samples from the diseased calves (n = 8), while all the others (n = 20) were negative. In addition, the same positive reaction was noted when one aqueous humor and two synovial samples were tested with this kit. Several other enteropathogens were found sporadically, but no conclusive significance could be attributed to their presence. Bovine viral diarrhoea and infectious bovine rhinothracheitis viruses as well as Chlamydia spp. and Mycoplasma spp. were not involved in this episode.


title: Toward a quantification of risks at the nexus of conservation and health: The case of bushmeat markets in Lao PDR

text: Abstract Trade of bushmeat and other wildlife for human consumption presents a unique set of challenges to policy-makers who are confronted with multiple trade-offs between conservation, food security, food safety, culture and tradition. In the face of these complex issues, risk assessments supported by quantitative information would facilitate evidence-based decision making. We propose a conceptual model for disease transmission risk analysis, inclusive of these multiple other facets. To quantify several processes included in this conceptual model we conducted questionnaire surveys with wildlife consumers and vendors in semi-urban centers in Lao People's Democratic Republic (Lao PDR, Laos) and direct observations of consumer behaviors. Direct observation of market stalls indicated an estimated average of 10 kg bushmeat biomass per stall per hour. The socio-demographic data suggested that consumption of bushmeat in urban areas was not for subsistence but rather driven by dietary preference and tradition. Consumer behavioral observations indicated that each animal receives an average of 7 contacts per hour. We provide other key parameters to estimate the risk of disease transmission from bushmeat consumption and illustrate their use in assessing the total public health and socio-economic impact of bushmeat consumption. Pursuing integrative approaches to the study of bushmeat consumption is essential to develop effective and balanced policies that support conservation, public health, and rural development goals.


title: The clinical impact of PCR‐based point‐of‐care diagnostic in respiratory tract infections in children

text: BACKGROUND: Children are commonly affected by respiratory tract infections. Based on clinical symptoms, laboratory evaluation, and imaging, the causative pathogen often cannot be delineated. Point‐of‐care‐testing systems that provide an opportunity for fast detection of common viruses and some bacteria can therefore influence treatment's options. We aimed to examine whether the Biofire® FilmArray® has an effect on antibiotic treatment, duration of antibiotic therapy, and length of hospital stay within a pediatric cohort. METHODS: We included children who were admitted to inpatient treatment with an acute respiratory tract infection from 02/2017 to 04/2018 using the FA respiratory panel for pathogen detection. The study group data were compared to the retrospective data of children admitted from 02/2016 to 02/2017, using a proprietary multiplex RT‐PCR. RESULTS: A total of 322 children of the study group and 464 children of the control group were analyzed for clinical symptoms, laboratory findings, antibiotic treatment, and length of hospital stay. There was no significant reduction (P < .05) of antibiotic treatment and length of hospital stay. CRP, prehospital antibiotic treatment, antibiotic treatment, past medical history, age, and further pathogen detection showed a significant impact on antibiotic therapy, duration of antibiotic treatment, and length of hospital stay. CONCLUSION: The use of the FA did not result in a significant reduction of antibiotic treatment or in length of hospital stay. Other parameters had a more significant impact. Therefore, we suggest that standard operation procedures with therapy guidelines are necessary to provide an effective application of POCT systems.


title: Should patients with obesity be more afraid of COVID‐19?

text: COVID‐19 crisis has lasted since the late 2019 to the present day. The severity of the disease is positively correlated with several factors, such as age and coexisting diseases. Furthermore, obesity is increasingly considered as a yet another risk factor, particularly, because it has been observed that people suffering from excessive body weight may experience a more severe course of COVID‐19 infection. On the basis of current research, in our nonsystematic review, we have investigated the extent to which obesity can affect the SARS‐CoV‐2 course and identify the potential mechanisms of the disease. We have also described the role of proper nutrition, physical activity and other aspects relevant to the management of obesity.


title: Baseline pulmonary levels of CD8+ T cells and NK cells inversely correlate with expression of the SARS-CoV-2 entry receptor ACE2

text: Coronavirus disease 19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and currently has detrimental human health, community and economic impacts around the world. In SARS-CoV-2-infected lung, induction of immune cell-recruiting cytokines is initially poor. When induction does occur, this may in fact exacerbate infection. These observations suggest that baseline levels of leukocytes, already residing in the lung prior to infection, may be important for orchestrating an effective early immune response. Hence, we performed “in silico flow cytometry” on 1,927 human lung tissues to deconvolute the levels of seven leukocyte types involved in triggering an acute anti-viral cellular immune response. Baseline levels of CD8+ T cells, resting natural killer (NK) cells and activated NK cells are significantly lower in lung tissues with high expression of the SARS-CoV-2 host cell entry receptor ACE2. We observe this in univariate analyses, in multivariate analyses that include sex, age, race, body mass index and smoking history, and in two independent datasets. Elevated ACE2 expression increases sensitivity to coronavirus infection. Thus, our results suggest that a subgroup of individuals may be exceedingly susceptible to COVID-19 due to concomitant high preexisting ACE2 expression and low baseline cytotoxic lymphocyte levels in the lung.


title: Viral respiratory infections in elderly patients and patients with chronic obstructive pulmonary disease

text: Abstract Patients with chronic obstructive pulmonary disease (COPD) and elderly individuals are prone to the development of significant lower respiratory tract symptoms from colds caused by viral respiratory pathogens. Longitudinal surveillance studies conducted to assess the impact of viral respiratory tract pathogens on morbidity and mortality in each of these at-risk populations demonstrate that there is a substantial burden of disease from viral respiratory infection (VRI), including rhinovirus infections, with respect to utilization of health-care resources. Despite a similar rate of occurrence of VRI among subjects with COPD and the control group, a cohort with moderate to severe COPD had a 2-fold increase in medical resource utilization, including clinician visits, emergency center visits, and hospitalizations. In surveillance studies of respiratory viruses in the elderly, regular seasonal infections with rhinoviruses cause substantial morbidity, which has been largely underappreciated and underreported.


title: Assessment of first-year post-graduate residents: Usefulness of multiple tools

text: Abstract Background Objective Structural Clinical Examination (OSCE) usually needs a large number of stations with long test time, which usually exceeds the resources available in a medical center. We aimed to determine the reliability of a combination of Direct Observation of Procedural Skills (DOPS), Internal Medicine in-Training Examination (IM-ITE®) and OSCE, and to verify the correlation between the small-scale OSCE+DOPS+IM-ITE®-composited scores and 360-degree evaluation scores of first year post-graduate (PGY1) residents. Methods Between 2007 January to 2010 January, two hundred and nine internal medicine PGY1 residents completed DOPS, IM-ITE® and small-scale OSCE at our hospital. Faculty members completed 12-item 360-degree evaluation for each of the PGY1 residents regularly. Results The small-scale OSCE scores correlated well with the 360-degree evaluation scores (r = 0.37, p < 0.021). Interestingly, the addition of DOPS scores to small-scale OSCE scores [small-scale OSCE+DOPS-composited scores] increased it's correlation with 360-degree evaluation scores of PGY1 residents (r = 0.72, p < 0.036). Further, combination of IM-ITE® score with small-scale OSCE+DOPS scores [small-scale OSCE+DOPS+IM-ITE®-composited scores] markedly enhanced their correlation with 360-degree evaluation scores (r = 0.85, p < 0.016). Conclusion The strong correlations between 360-degree evaluation and small-scale OSCE+DOPS+IM-ITE®-composited scores suggested that both methods were measuring the same quality. Our results showed that the small-scale OSCE, when associated with both the DOPS and IM-ITE®, could be an important assessment method for PGY1 residents.


Going global – Travel and the 2019 novel coronavirus


Obesity as a risk factor for greater severity of COVID-19 in patients with metabolic associated fatty liver disease


title: A study on the psychological needs of nurses caring for patients with coronavirus disease 2019 from the perspective of the existence, relatedness, and growth theory

text: Abstract Objective This study aimed to explore the psychological needs of nurses caring for patients with coronavirus disease 2019(COVID-19) and to propose corresponding interventions. Methods In-depth interviews were conducted with 10 nurses who cared for patients with COVID-19. Interview data were analyzed by category analysis from the perspective of the existence, relatedness, and growth theory (ERG). Results The existence needs were mainly reflected in health and security needs, whereas the relatedness needs consisting mainly of interpersonal needs, humanistic concern needs, and family needs; further, the growth needs were mainly reflected as a strong need for knowledge. Existence needs were the main needs during the epidemic, with health and security needs influencing each other. Humanistic concern needs were the most important of the relatedness needs; interpersonal and family needs were also growing. Conclusion It is found that the existence, relatedness, and growth needs coexist in clinical nurses. It is helpful to take effective interventions to meet their needs if the needs of nurses caring for COVID-19 patients could be perceived well.


title: Publication of the Korea-WHO Cooperation History — 70 Years of Working Together for Heath: World Health Organization and the Republic of Korea

text: The World Health Organization (WHO) have been in collaborative efforts with the Republic of Korea in keeping of and for better health for all for the past decades. From the control of parasites to building of community health system in rural places, the works has now resulted in healthier Korea than ever, and has transformed the role of engaging as the world leader in contribution of health and development. Seventy years of independence, war, and poverty, transforming from a recipient country of official development assistance to a significant donor to the global society, we have emphasized the importance of international cooperation and the role of WHO in the past years in Korea and neighboring countries. Looking back of the past is meaningful to diagnose the present problems, and to foresee the future of our world.


title: Comparative molecular epidemiology of two closely related coronaviruses, bovine coronavirus (BCoV) and human coronavirus OC43 (HCoV-OC43), reveals a different evolutionary pattern

text: Abstract Bovine coronaviruses (BCoVs) are widespread around the world and cause enteric or respiratory infections among cattle. The current study includes 13 samples from BCoVs collected in Normandy during an 11-year period (from 2003 to 2014), 16 French HCoV-OC43s, and 113 BCoVs or BCoVs-like sequence data derived from partial or complete genome sequences available on GenBank. According to a genotyping method developed previously for HCoV-OC43, BCoVs and BCoVs-like are distributed on three main sub-clusters named C1, C2, and C3. Sub-cluster C1 includes BCoVs and BCoVs-like from America and Asia. Sub-cluster C2 includes BCoVs from Europe. Sub-cluster C3 includes prototype, vaccine, or attenuated BCoV strains. The phylogenetic analyses revealed the monophyletic status of the BCoVs from France reported here for the first time. Moreover, BCoV exhibits a relative genetic stability when compared to HCoV-OC43 we previously described from the same region. The numerous recombination detected between HCoV-OC43 were much less frequent for BCoV. The analysis points thus to the influence of different evolutive constraints in these two close groups.


title: Topology of evolving, mutagenized viral populations: quasispecies expansion, compression, and operation of negative selection

text: BACKGROUND: The molecular events and evolutionary forces underlying lethal mutagenesis of virus (or virus extinction through an excess of mutations) are not well understood. Here we apply for the first time phylogenetic methods and Partition Analysis of Quasispecies (PAQ) to monitor genetic distances and intra-population structures of mutant spectra of foot-and-mouth disease virus (FMDV) quasispecies subjected to mutagenesis by base and nucleoside analogues. RESULTS: Phylogenetic and PAQ analyses have revealed a highly dynamic variation of intrapopulation diversity of FMDV quasispecies. The population diversity first suffers striking expansions in the presence of mutagens and then compressions either when the presence of the mutagenic analogue was discontinued or when a mutation that decreased sensitivity to a mutagen was selected. The pattern of mutations found in the populations was in agreement with the behavior of the corresponding nucleotide analogues with FMDV in vitro. Mutations accumulated at preferred genomic sites, and dn/ds ratios indicate the operation of negative (or purifying) selection in populations subjected to mutagenesis. No evidence of unusually elevated genetic distances has been obtained for FMDV populations approaching extinction. CONCLUSION: Phylogenetic and PAQ analysis provide adequate procedures to describe the evolution of viral sequences subjected to lethal mutagenesis. These methods define the changes of intra-population structure more precisely than mutation frequencies and Shannon entropies. PAQ is very sensitive to variations of intrapopulation genetic distances. Strong negative (or purifying) selection operates in FMDV populations subjected to enhanced mutagenesis. The quantifications provide evidence that extinction does not imply unusual increases of intrapopulation complexity, in support of the lethal defection model of virus extinction.


title: Impact of Potential COVID‐19 Treatment on South African Water Sources Already Threatened by Pharmaceutical Pollution

text: After a cluster of human pneumonia cases in Wuhan City (China) on 7 January 2020 a novel coronavirus, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) was identified as the causative agent of the disease COVID‐19 (World Health Organization (WHO). 2020). This article is protected by copyright. All rights reserved.


title: The Pivotal Role of Pharmacists During the 2019 Coronavirus Pandemic

text: Summary The Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected over three million patients worldwide with an estimated mortality rate of 5%. Owing to the diversity of training and variety of positions within the pharmacy department, pharmacists are uniquely positioned in the hospital setting to play a pivotal role during the pandemic. The purpose of this article is to highlight the experiences and impactful interventions made by pharmacists practicing in a community teaching hospital at the center of the COVID-19 surge in New York City. Although often underrecognized, pharmacists are well-equipped to develop treatment plans based on the evolving literature, positively impact patient outcomes by responding to inpatient emergencies, and optimize medication orders to conserve and maintain a healthy supply of medications for the hospital.


title: Pulmonary vascular dysfunction in ARDS

text: Acute respiratory distress syndrome (ARDS) is characterised by diffuse alveolar damage and is frequently complicated by pulmonary hypertension (PH). Multiple factors may contribute to the development of PH in this setting. In this review, we report the results of a systematic search of the available peer-reviewed literature for papers that measured indices of pulmonary haemodynamics in patients with ARDS and reported on mortality in the period 1977 to 2010. There were marked differences between studies, with some reporting strong associations between elevated pulmonary arterial pressure or elevated pulmonary vascular resistance and mortality, whereas others found no such association. In order to discuss the potential reasons for these discrepancies, we review the physiological concepts underlying the measurement of pulmonary haemodynamics and highlight key differences between the concepts of resistance in the pulmonary and systemic circulations. We consider the factors that influence pulmonary arterial pressure, both in normal lungs and in the presence of ARDS, including the important effects of mechanical ventilation. Pulmonary arterial pressure, pulmonary vascular resistance and transpulmonary gradient (TPG) depend not alone on the intrinsic properties of the pulmonary vascular bed but are also strongly influenced by cardiac output, airway pressures and lung volumes. The great variability in management strategies within and between studies means that no unified analysis of these papers was possible. Uniquely, Bull et al. (Am J Respir Crit Care Med 182:1123–1128, 2010) have recently reported that elevated pulmonary vascular resistance (PVR) and TPG were independently associated with increased mortality in ARDS, in a large trial with protocol-defined management strategies and using lung-protective ventilation. We then considered the existing literature to determine whether the relationship between PVR/TPG and outcome might be causal. Although we could identify potential mechanisms for such a link, the existing evidence does not allow firm conclusions to be drawn. Nonetheless, abnormally elevated PVR/TPG may provide a useful index of disease severity and progression. Further studies are required to understand the role and importance of pulmonary vascular dysfunction in ARDS in the era of lung-protective ventilation.


title: Development of reverse-transcription loop-mediated isothermal amplification assay for rapid detection and differentiation of dengue virus serotypes 1–4

text: BACKGROUND: Dengue virus (DENV), the most widely prevalent arbovirus, continues to be a threat to human health in the tropics and subtropics. Early and rapid detection of DENV infection during the acute phase of illness is crucial for proper clinical patient management and preventing the spread of infection. The aim of the current study was to develop a specific, sensitive, and robust reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) assay for detection and differentiation of DENV1-4 serotypes. RESULTS: The method detection primers, which were designed to target the different DENV serotypes, were identified by inspection of multiple sequence alignments of the non-structural protein (NS) 2A of DENV1, NS4B of DENV2, NS4A of DENV3 and the 3′ untranslated region of the NS protein of DENV4. No cross-reactions of the four serotypes were observed during the tests. The detection limits of the DENV1-4-specific RT-LAMP assays were approximately 10-copy templates per reaction. The RT-LAMP assays were ten-fold more sensitive than RT-PCR or real-time PCR. The diagnostic rate was 100 % for clinical strains of DENV, and 98.9 % of the DENV-infected patients whose samples were tested were detected by RT-LAMP. Importantly, no false-positives were detected with the new equipment and methodology that was used to avoid aerosol contamination of the samples. CONCLUSION: The RT-LAMP method used in our study is specific, sensitive, and suitable for further investigation as a useful alternative to the current methods used for clinical diagnosis of DENV1-4, especially in hospitals and laboratories that lack sophisticated diagnostic systems.


title: Dietary Intake of Vitamin D from Dairy Products Reduces the Risk of Osteoporosis

text: Background: Vitamin D and calcium are important dietary compounds that affect bone mass, even if other minerals (potassium, zinc, etc.) and vitamins (A, C and K) are also involved. Vitamin D and certain minerals, in fact, play an important role in calcium homeostasis and calcium absorption. Hip fracture incidence is higher in Europe and the United States, where calcium is frequently included in the human diet; while the occurrence of these fractures is lower in developing countries, where diets are often poor in calcium. This condition is named the “calcium paradox”, and may be partially explained by phosphate toxicity, which can negatively affect mineral metabolism. It is important to maintain correct dietary calcium-phosphate balance in order to have a healthy life, reducing the risk of osteoporotic fractures in older people. Vitamin D can also act as a hormone; vitamin D2 (ergocalciferol) is derived from the UV-B radiation of ergosterol, the natural vitamin D precursor detected in plants, fungi, and invertebrates. Vitamin D3 (cholecalciferol) is synthesized by sunlight exposure from 7-dehydrocholesterol, a precursor of cholesterol that can also act as provitamin D3. Dietary intake of vitamin D3 is essential when the skin is exposed for short periods to ultraviolet B light (UV-B), a category of invisible light rays such as UV-A and UV-C. This can be considered the usual situation in northern latitudes during the winter season, or the typical lifestyle for older people and/or for people with very white delicate skin. The actual recommended daily intake of dietary vitamin D is strictly correlated with age, ranging from 5 μg for infants, children, teenagers, and adults—including pregnant and lactating women—to 15 μg for people over 65 years.


title: Prevention, diagnosis and treatment of venous thromboembolism in patients with COVID-19: CHEST Guideline and Expert Panel Report

text: Abstract: Background Emerging evidence shows that severe COVID-19 can be complicated by a significant coagulopathy, that likely manifests in the form of both microthrombosis and venous thromboembolism (VTE). This recognition has led to the urgent need for practical guidance regarding prevention, diagnosis, and treatment of VTE. Methods A group of approved panelists developed key clinical questions by using the PICO (population, intervention, comparator, and outcome) format that addressed urgent clinical questions regarding the prevention, diagnosis and treatment of venous thromboembolism in patients with COVID-19. MEDLINE (via PubMed or Ovid), Embase and Cochrane Controlled Register of Trials were systematically searched for relevant literature and references were screened for inclusion. Validated evaluation tools were used to grade the level of evidence to support each recommendation. When evidence did not exist, guidance was developed based on consensus using the modified Delphi process. Results The systematic review and critical analysis of the literature based on13 PICO questions resulted in 22 statements. Very little evidence exists in the COVID-19 population. The panel thus used expert consensus and existing evidence-based guidelines to craft the guidance statements. Conclusions The evidence on the optimal strategies to prevent, diagnose, and treat venous thromboembolism in patients with COVID-19 is sparse, but rapidly evolving.


title: How Polyomaviruses Exploit the ERAD Machinery to Cause Infection

text: To infect cells, polyomavirus (PyV) traffics from the cell surface to the endoplasmic reticulum (ER) where it hijacks elements of the ER-associated degradation (ERAD) machinery to penetrate the ER membrane and reach the cytosol. From the cytosol, the virus transports to the nucleus, enabling transcription and replication of the viral genome that leads to lytic infection or cellular transformation. How PyV exploits the ERAD machinery to cross the ER membrane and access the cytosol, a decisive infection step, remains enigmatic. However, recent studies have slowly unraveled many aspects of this process. These emerging insights should advance our efforts to develop more effective therapies against PyV-induced human diseases.


title: Passive antibody therapy in COVID-19

text: For over a century, transfusion of convalescent plasma from recovered individuals has been tried as a therapeutic approach when a novel pathogen emerges. As the world awaits SARS-CoV-2 vaccines to be tested and safely deployed, the rapidity with which antiviral monoclonal antibodies can be isolated and engineered offers an attractive alternative option for passive immunization.


title: Towards effective COVID-19 vaccines: Updates, perspectives and challenges (Review)

text: In the current context of the pandemic triggered by SARS-COV-2, the immunization of the population through vaccination is recognized as a public health priority. In the case of SARS-COV-2, the genetic sequencing was done quickly, in one month. Since then, worldwide research has focused on obtaining a vaccine. This has a major economic impact because new technological platforms and advanced genetic engineering procedures are required to obtain a COVID-19 vaccine. The most difficult scientific challenge for this future vaccine obtained in the laboratory is the proof of clinical safety and efficacy. The biggest challenge of manufacturing is the construction and validation of production platforms capable of making the vaccine on a large scale.


title: Age-related factors in cyclosporine-induced syngeneic graft-versus-host disease: regulatory role of marrow-derived T lymphocytes

text: The present studies have evaluated the effect of age on the induction of syngeneic graft-versus-host disease (SGVHD) after syngeneic bone marrow transplantation (BMT) and cyclosporine (CsA) therapy. The results clearly document an inverse correlation of age with the incidence of SGVHD. Virtually a 100% incidence of SGVHD occurs in Lewis rats when syngeneic BMT and CsA therapy are started when the animals are 4 wk of age. Thereafter, there is a dramatic decline in the incidence of SGVHD with the increasing age of the animals. Although the age of the recipient was important, the most significant effect was the age of the marrow donor. Marrow from animals 6 mo of age was virtually incapable of eliciting SGVHD after BMT and CsA therapy. Furthermore, mixing the marrow from mature and immature animals resulted in a decreased incidence of SGVHD, implicating a regulatory effect present in the marrow from older rats. This regulatory effect was due to the presence of mature T cells in the marrow from animals 6 mo of age. Despite the fact that marrow from young animals possesses mature T lymphocytes, this regulatory activity was absent, suggesting that the host resistance mediated by T lymphocytes develops as the animal ages. These data further implicate the importance of a host resistance mechanism in preventing the induction of SGVHD with CsA, which appears to be mediated by the clonal inactivation of autoreactive cells.


title: Price wars and price collusion in China's airline markets

text: Abstract In the absence of an effective antitrust law, both fare wars and price collusion have been pervasive in China's airline markets, causing concern for both airlines and consumers. A study of monthly airfare data from 2002 to 2004 confirms that fare wars occur periodically, as well as price collusion. Both tend to be short-lived. The fact that collusion is more likely to occur in January and April when demand is high, as revealed by China Eastern's and China Southern's price-war and collusion models, has been confirmed by interview information obtained from the airlines' sales managers. However, there is also evidence in these models suggesting that collusion can be more easily formed when demand is low. High airport concentration measured by the HHI may facilitate collusion in certain circumstances, but it may also lead to more price wars under other conditions. Concentration in both airports and routes does not appear to systematically affect the occurrence of fare wars and collusion in all the models estimated. We also reject the possibility that mutual forbearance due to multimarket contact plays any important anti-competitive role in China's airline markets.


title: Contribution of IDO to human respiratory syncytial virus infection

text: IDO is an enzyme that participates in the degradation of tryptophan (Trp), which is an essential amino acid necessary for vital cellular processes. The degradation of Trp and the metabolites generated by the enzymatic activity of IDO can have immunomodulating effects, notably over T cells, which are particularly sensitive to the absence of Trp and leads to the inhibition of T cell activation, cell death, and the suppression of T cell effector functions. Noteworthy, T cells participate in the cellular immune response against the human respiratory syncytial virus (hRSV) and are essential for viral clearance, as well as the total recovery of the host. Furthermore, inadequate or non‐optimal polarization of T cells is often seen during the acute phase of the disease caused by this pathogen. Here, we discuss the capacity of hRSV to exploit the immunosuppressive features of IDO to reduce T cell function, thus acquiring relevant aspects during the biology of the virus. Additionally, we review studies on the influence of IDO over T cell activation and its relationship with hRSV infection.


title: Pleural effusion disease in rabbits. Properties of the aetiological agent

text: The size and heat sensitivity of Pleural effusion disease (PED) agent or virus (PEDV) propagated in rabbits were examined. The infectious particles were estimated to be between 25 and 50 nm by filtration. Residual infectivity of infectious serum was 0.1 per cent after heating at 56° C for 4 hours. PEDV and the Stockholm agent appeared identical concerning pathogenic and immunogenic properties by infection experiments and protection tests in rabbits. Two of the three PEDV isolates were less pathogenic but appeared immunogenically identical to PEDV. The third isolate, obtained from the laboratory, which several years previously had supplied material for demonstration of the Stockholm agent, differed from PEDV in pathogenic and immunogenic properties. Serological examinations of paired rabbit sera did not indicate any antigenic relationship between PEDV and representative members of the two mammalian coronavirus antigenic groups. It is concluded that the aetiological agent of PED is a virus not belonging to the coronaviridae.


title: Epidemiology and clinical presentation of the four human parainfluenza virus types

text: BACKGROUND: Human parainfluenza viruses (HPIVs) are important causes of upper respiratory tract illness (URTI) and lower respiratory tract illness (LRTI). To analyse epidemiologic and clinical characteristics of the four types of human parainfluenza viruses (HPIVs), patients with acute respiratory tract illness (ARTI) were studied in Guangzhou, southern China. METHODS: Throat swabs (n=4755) were collected and tested from children and adults with ARTI over a 26-month period, and 4447 of 4755 (93.5%) patients’ clinical presentations were recorded for further analysis. RESULTS: Of 4755 patients tested, 178 (3.7%) were positive for HPIV. Ninety-nine (2.1%) samples were positive for HPIV-3, 58 (1.2%) for HPIV-1, 19 (0.4%) for HPIV-2 and 8 (0.2%) for HPIV-4. 160/178 (88.9%) HPIV-positive samples were from paediatric patients younger than 5 years old, but no infant under one month of age was HPIV positive. Seasonal peaks of HPIV-3 and HPIV-1 occurred as autumn turned to winter and summer turned to autumn. HPIV-2 and HPIV-4 were detected less frequently, and their frequency of isolation increased when the frequency of HPIV-3 and HPIV-1 declined. HPIV infection led to a wide spectrum of symptoms, and more “hoarseness” (p=0.015), “abnormal pulmonary breathing sound” (p<0.001), “dyspnoea” (p<0.001), “pneumonia” (p=0.01), and “diarrhoea” (p<0.001) presented in HPIV-positive patients than HPIV-negative patients. 10/10 (100%) HPIV-positive adult patients (≥14 years old) presented with systemic influenza-like symptoms, while 90/164 (54.9%) HPIV-positive paediatric patients (<14 years old) presented with these symptoms (p=0.005). The only significant difference in clinical presentation between HPIV types was “Expectoration” (p<0.001). Co-infections were common, with 33.3%–63.2% of samples positive for the four HPIV types also testing positive for other respiratory pathogens. However, no significant differences were seen in clinical presentation between patients solely infected with HPIV and patients co-infected with HPIV and other respiratory pathogens. CONCLUSIONS: HPIV infection led to a wide spectrum of symptoms, and similar clinical manifestations were found in the patients with four different types of HPIVs. The study suggested pathogenic activity of HPIV in gastrointestinal illness. The clinical presentation of HPIV infection may differ by patient age.


title: Fatal parvovirus B19 infections: a report of two autopsy cases

text: Parvovirus B19 (PVB19) commonly infects children and is usually asymptomatic. Lethal outcomes of PVB19 infection are unusual; nevertheless, the two cases reported here are rare examples of PVB19-induced hemophagocytic syndrome and myocarditis in infants and children. The two cases show the indisputable usefulness of immunohistochemistry and in situ hybridization in the detection of PVB19. In the death investigations, histopathological examinations provided stronger evidence than did serology or molecular biology. The cases also highlight the importance of forensic autopsy in vaccine-related death. As vaccine-related deaths are what people fear and may cause declines in vaccination rates, it is important to clarify deaths temporally or causally associated with vaccine administration.


Pandemic cities: Between mimicry and trickery


title: Conquest of COVID‐19. Publish it to Death?

text: Some diseases can be cured by medical interventions, others not. When not, are there other approaches to control or cure? One possibility is to try to publish a disease to death, a therapy strategy first proposed by my late colleague Prof. David Golde from UCLA (see below). Here I consider whether this strategy is working in the fight against severe acute respiratory syndrome‐cornavirsu‐2 (SARS‐CoV‐2) pandemic and the associated coronavirus infectious disease‐2019 (COVID‐19).


title: Global dynamics for a Filippov epidemic system with imperfect vaccination

text: Abstract Given imperfect vaccination we extend the existing non-smooth models by considering susceptible and vaccinated individuals enhance the protection and control strategies once the number of infected individuals exceeds a certain level. On the basis of global dynamics of two subsystems, for the formulated Filippov system, we examine the sliding mode dynamics, the boundary equilibrium bifurcations, and the global dynamics. Our main results show that it is possible that the pseudo-equilibrium exists and is globally stable, or the pseudo-equilibrium, the disease-free equilibrium and the real equilibrium are tri-stable, or the pseudo-equilibrium and the real equilibrium are bi-stable, or the pseudo-equilibrium and disease-free equilibrium are bi-stable, which depend on the threshold value and other parameter values. The global stability of the disease-free equilibrium or pseudo-equilibrium reveals that we may eradicate the disease or maintain the number of infected individuals at a previously given value. Further, the bi-stability and tri-stability imply that whether the number of infected individuals tends to zero or a previously given value or other positive values depends on the parameter values and the initial states of the system. This emphasizes the importance of threshold policy and challenges in the control of infectious diseases if without perfect vaccines.


An invisible hand has guided clinical endocrinology toward an unexpected future