title: Design and performance testing of quantitative real time PCR assays for influenza A and B viral load measurement

text: Abstract Background: The antiviral effect of anti-influenza drugs such as zanamivir may be demonstrated in patients as an increased rate of decline in viral load over a time course of treatment as compared with placebo. Historically this was measured using plaque assays, or Culture Enhanced Enzyme Linked Immunosorbent Assay (CE-ELISA). Objectives: to develop and characterise real time quantitative PCR (qPCR) assays to measure influenza A and B viral load in clinical samples, that offer improvements over existing methods, in particular virus infectivity assays. Study design: The dynamic range and robustness were established for the real time qPCR assays along with stability of the assay components. Cross validation of the real time PCR assays with CE-ELISA was performed by parallel testing of both serial dilutions of three different subtypes of cultured virus and a panel of influenza positive throat swab specimens. Results: the assays were specific for influenza A and B and the dynamic ranges were at least seven logs. The assay variability was within acceptable limits but increased towards the lower limit of quantification, which was 3.33 log10 viral cDNA copies/ml of virus transport medium (ten viral RNA copies/PCR). The components of the assay were robust enough to withstand extended storage and several freeze–thaw cycles. For the real time PCR assays the limit of quantification was equivalent to the virus infectivity cut off, which equates to a 93-fold increase in sensitivity. Conclusion: Well characterised real time PCR assays offer significant improvements over the existing methods for measuring the viral load of strains of influenza A and B in clinical specimens.


title: Ginseng, the natural effectual antiviral: Protective effects of Korean Red Ginseng against viral infection

text: Korean Red Ginseng (KRG) is a heat-processed ginseng developed by the repeated steaming and air-drying of fresh ginseng. Compared with fresh ginseng, KRG has been shown to possess greater pharmacological activities and stability because of changes that occur in its chemical constituents during the steaming process. In addition to anticancer, anti-inflammatory, and immune-modulatory activities, KRG and its purified components have also been shown to possess protective effects against microbial infections. Here, we summarize the current knowledge on the properties of KRG and its components on infections with human pathogenic viruses such as respiratory syncytial virus, rhinovirus, influenza virus, human immunodeficiency virus, human herpes virus, hepatitis virus, norovirus, rotavirus, enterovirus, and coxsackievirus. Additionally, the therapeutic potential of KRG as an antiviral and vaccine adjuvant is discussed.


title: Triage

text: This review provides an overview of triaging critically ill or injured patients during mass casualty incidents due to events such as disasters, pandemics, or terrorist incidents. Questions clinicians commonly have, including “what is triage?,” “when to triage?,” “what are the types of disaster triage?,” “how to triage?,” “what are the ethics of triage?,” “how to govern triage?,” and “what research is required on triage?,” are addressed.


title: Comparison of the Etiology of Viral Respiratory Illnesses in Inner-City and Suburban Infants

text: Background. The risk of developing childhood asthma has been linked to the severity and etiology of viral respiratory illnesses in early childhood. Since inner-city infants have unique environmental exposures, we hypothesized that patterns of respiratory viral infections would also be distinct. Methods. We compared the viral etiology of respiratory illnesses in 2 groups: a cohort of 515 infants from 4 inner-city areas and a cohort of 285 infants from mainly suburban Madison, Wisconsin. Nasal secretions were sampled during periods of respiratory illness and at 1 year of age and were analyzed for viral pathogens by multiplex polymerase chain reaction. Results. Overall, inner-city infants had lower rates of viral detection. Considering specific viruses, sick urban infants had lower rates of detectable rhinovirus or respiratory syncytial virus infection and higher rates of adenovirus infection. Every urban site had a higher proportion of adenovirus-positive samples associated with illnesses (10%–21%), compared with Madison (6%). Conclusions. These findings provide evidence that inner-city babies have different patterns of viral respiratory illnesses than babies who grow up in a more suburban location. These findings raise important questions about the etiology of virus-negative illnesses in urban infants and the possibility of long-term consequences of early life infections with adenovirus in this population.


Chapter 58 Transgenic Plants for Mucosal Vaccines


title: Innate defences against viraemia

text: Human blood plasma has been reported to possess nonspecific antiviral activity. This activity is due to several preexisting naturally occurring molecules that are either active against individual members or a family of viruses. These molecules, however, have not been adequately studied to reveal their molecular structures and mechanisms of action presumably because of their low and nonspecific antiviral action. Therefore, their possible role against viraemia remains unknown. Recently, two naturally occurring nonspecific broad‐spectrum antiviral agents, University of Texas Inhibitor β (UTIβ) glycoprotein and high density lipoprotein, have been described in human serum. They are active against DNA and RNA viruses and one of them, UTIβ, possesses significant antiviral activity of 40 units/mL. Since preexisting antiviral molecules in serum appear to be the only defence mechanisms available at the onset of viral infection they may have protective significance against viraemia. In view of this potential, we have undertaken to review the properties of these innate viral inhibitory molecules. Copyright © 2000 John Wiley & Sons, Ltd.


title: Global Transport Networks and Infectious Disease Spread

text: Air, sea and land transport networks continue to expand in reach, speed of travel and volume of passengers and goods carried. Pathogens and their vectors can now move further, faster and in greater numbers than ever before. Three important consequences of global transport network expansion are infectious disease pandemics, vector invasion events and vector-borne pathogen importation. This review briefly examines some of the important historical examples of these disease and vector movements, such as the global influenza pandemics, the devastating Anopheles gambiae invasion of Brazil and the recent increases in imported Plasmodium falciparum malaria cases. We then outline potential approaches for future studies of disease movement, focussing on vector invasion and vector-borne disease importation. Such approaches allow us to explore the potential implications of international air travel, shipping routes and other methods of transport on global pathogen and vector traffic.


title: Migrating a lab-developed MERS-CoV real-time PCR to 3 “Sample to Result” systems: experiences on optimization and validation

text: Abstract The goal of the study was to adapt our Middle East respiratory syndrome coronavirus (MERS-CoV) lab-developed test (LDT) to 3 “Sample to Result” (S2R) systems: BD MAX (BD), ELITe InGenius (ELITechGroup), and ARIES (Luminex). The BD MAX and InGenius system allowed use of lab-developed primers and TaqMan probes, while ARIES required conversion to MultiCode primers for melting curve analysis. Each device required ≤1 day of training and assay optimization. No discordant results were noted after analysis of 32 External Quality Control (EQC) samples. On a 10-fold dilution series of a MERS-CoV–positive EQC sample, InGenius obtained the highest detection rate. Laboratory technicians rated the ARIES as the user-friendliest. It also required the least hands-on time. BD MAX had the lowest turnaround time and highest throughput. While each device had distinguishing system properties with associated (dis)advantages, the 3 S2R systems were comparable in terms of assay development and validation.


title: Transcriptional profiling of Vero E6 cells over-expressing SARS-CoV S2 subunit: Insights on viral regulation of apoptosis and proliferation

text: Abstract We have previously demonstrated that over-expression of spike protein (S) of severe acute respiratory syndrome coronavirus (SARS-CoV) or its C-terminal subunit (S2) is sufficient to induce apoptosis in vitro. To further investigate the possible roles of S2 in SARS-CoV-induced apoptosis and pathogenesis of SARS, we characterized the host expression profiles induced upon S2 over-expression in Vero E6 cells by oligonucleotide microarray analysis. Possible activation of mitochondrial apoptotic pathway in S2 expressing cells was suggested, as evidenced by the up-regulation of cytochrome c and down-regulation of the Bcl-2 family anti-apoptotic members. Inhibition of Bcl-2-related anti-apoptotic pathway was further supported by the diminution of S2-induced apoptosis in Vero E6 cells over-expressing Bcl-xL. In addition, modulation of CCN E2 and CDKN 1A implied the possible control of cell cycle arrest at G1/S phase. This study is expected to extend our understanding on the pathogenesis of SARS at a molecular level.


title: Clinical characteristics of a case series of children with coronavirus disease 2019

text: We reported the clinical characteristics of a case series of 10 patients with coronavirus disease 2019 (COVID‐19) aged from 1 year to 18 years. Seven patients had contact with confirmed COVID‐19 family members before onset. Fever (4 [40.0%]) and cough (3 [30.0%]) were the most common symptoms. No patient showed leucopenia and lymphopenia on admission. Pneumonia was observed in chest CT images in 5 (50.0%) patients. Five (50.0%) patients received antiviral treatment. No patient had severe complications or developed a severe illness in our study. Our study indicated that COVID‐19 children present less severe symptoms and have better outcomes.


title: Lung Ultrasound for Cardiologists in the Time of COVID-19

text: Lung ultrasound (LUS) is a point-of-care ultrasound (POCUS) technique used for its portability, widespread availability, and ability to provide real-time diagnostic information procedural guidance. LUS outperforms lung auscultation and chest X-ray, and is an alternative to chest computed tomography in select cases. Cardiologists may enhance their physical and echocardiographic examination with the addition of LUS. We present a practical guide to LUS, including device selection, scanning, findings, and interpretation. We outline a 3-point scanning protocol using 2D and M-mode imaging to evaluate the pleural line, pleural space, and parenchyma. We describe LUS findings and interpretation for common causes of respiratory failure. We provide guidance specific of COVID-19, which at the time of writing is responsible for a global pandemic. In this context, LUS emerges as a particularly useful tool for the diagnosis and management of patients with cardiopulmonary disease.


title: A manual acupuncture treatment attenuates common cold and its symptoms: a case series report from South Korea

text: Abstract OBJECTIVE To investigate beneficial effects of manual acupuncture on common cold periods and its symptoms depended on the difference onset time of common cold, within 36 h or over than that. To prove effects of manual acupuncture on common cold, a retrospective chart review was conducted. METHODS Chart data for patients with common cold who were treated with only manual acupuncture with fulfilling Jackson scales and satisfaction at the end of each treatment were collected via multi-centers of Oriental hospitals, Oriental medicine clinics and covalent hospital in South Korea. Totally 187 patients were divided into two groups, Group I (115 patients, within 36 h) and Group II (72 patients, onset time of cold over than 36 h). Finally 120 patients were observed until entire resolution of cold symptoms. RESULTS Group I showed significant decreases the median durations of completely recovery (3 days; 95% CI 3.0-4.0) as compared with Group II (6 days; 95% CI 4.0-7.0, P < 0.001). The manual acupuncture beneficially worked for reduction rate of common cold symptoms by 50% after initial treatment, decreased cold symptoms, and reduced cold duration. CONCLUSION Manual acupuncture beneficially affected common cold and its symptoms. Moreover it is more susceptibility on the early time of onset cold.


Value of RVP in clinical settings: older adults


title: H1N1 influenza is here

text: Summary On 11 June WHO announced that the spread of H1N1 had reached pandemic phase 6. Since then countries around the world have increased their planning and preparedness for the continuing pandemic. Guidelines have been issued and circulated but confusion continues over their interpretation. We need to remind ourselves of the principles behind control measures and educate and reinforce standard infection control procedures in the acute hospital setting.


title: Incidence, risk factors and clinical outcomes of acute kidney injury associated with scrub typhus: a retrospective study of 510 consecutive patients in South Korea (2001–2013)

text: OBJECTIVES: Renal involvement in scrub typhus ranges from simple urinary abnormalities to acute kidney injury (AKI) leading to death. This study evaluated the incidence, predictors and prognosis of AKI associated with scrub typhus according to the RIFLE (risk, injury, failure, loss, end-stage kidney disease) criteria. METHODS: We retrospectively evaluated the medical records of patients diagnosed with scrub typhus from January 2001 to November 2013 in Gyeongsang National University Hospital. RESULTS: During the study period, 510 patients were diagnosed with scrub typhus and the incidence of AKI was 35.9%. There were 132 (25.9%) patients at risk, 37 (7.3%) with injury and 14 (2.7%) with failure. In comparison with the non-AKI group, the AKI group was older (73.9 vs 63.4 years, p<0.001) and had more comorbidities such as hypertension, diabetes mellitus and chronic kidney disease (CKD). AKI frequently occurs in hypertensive patients taking angiotensin receptor blockers or ACE inhibitors (p=0.002), and in patients with diabetes with higher glycated haemoglobin levels (p=0.033). Haematuria and proteinuria were more frequent in the AKI group. There was no relationship between the severity of proteinuria and occurrence of AKI. Intensive care unit admission and death were more frequent in the AKI group. The renal function of most patients with AKI recovered without sequelae, except for 1 patient who had underlying CKD. Multivariate analysis showed that age, presence of CKD, serum albumin level and time to hospital presentation after symptom onset were independent predictors of AKI in patients with scrub typhus. CONCLUSIONS: Our current results suggest that the presence of underlying CKD, older age, lower serum albumin level and time to hospital presentation after symptom onset were important risk factors to determine occurrence of AKI. Whether earlier diagnosis and treatment in patients with the above risk factors reduce the incidence and severity of AKI deserves to be investigated.


title: Phylogenetic analysis of the first four SARS‐CoV‐2 cases in Chile

text: The current pandemic caused by the new coronavirus is a worldwide public health concern. To aboard this emergency, and like never before, scientific groups around the world have been working in a fast and coordinated way to get the maximum of information about this virus when it has been almost 3 months since the first cases were detected in Wuhan province in China. The complete genome sequences of around 450 isolates are available, and studies about similarities and differences among them and with the close related viruses that caused similar epidemics in this century. In this work, we studied the complete genome of the first four cases of the new coronavirus disease in Chile, from patients who traveled to Europe and Southeast Asia. Our findings reveal at least two different viral variants entries to Chilean territory, coming from Europe and Asia. We also sub‐classified the isolates into variants according to punctual mutations in the genome. Our work contributes to global information about transmission dynamics and the importance to take control measures to stop the spread of the infection.


title: T-cell apoptosis in autoimmune diseases: termination of inflammation in the nervous system and other sites with specialized immune-defense mechanisms

text: Abstract We have studied T-cell apoptosis in animal models of human autoimmune disorders of the nervous system and in other tissues devoid of specialized immune-defense mechanisms. Our data suggest that the CNS has high potential for elimination of T-cell-dependent inflammation, whereas this mechanism is less effective in the PNS, and is almost absent in other tissues such as muscle and skin. Interestingly, several conventional and novel immunotherapeutic approaches, such as glucocorticosteroid and high-dose antigen therapy, induce T-cell apoptosis in situ. In vitro experiments suggest different scenarios for the mechanisms by which specific cellular and humoral elements in the nervous system synergize and sensitize T cells for apoptosis in vivo. We also discuss regulatory, proapoptotic mechanisms, such as the Fas–FasL system and galectin-1, that have been utilized in other tissues to mediate immune protection.


title: Perceptions on the risk communication strategy during the 2013 avian influenza A/H7N9 outbreak in humans in China: a focus group study

text: OBJECTIVE: To identify the general public’s perceptions of the overall risk communication strategy carried out by Chinese public health agencies during the first wave of avian influenza A(H7N9) outbreak in humans in 2013. METHODS: Participants were recruited from communities in Beijing, Lanzhou and Hangzhou, China in May and June 2013 by convenience sampling. Demographics and other relevant information were collected using a self-administered questionnaire. Focus group interviews were conducted using a set of nine pre-developed questions and a tested moderator guide. The interviews were audio recorded and were transcribed verbatim. The constant comparative method was used to identify trends and themes. RESULTS: A total of nine focus group interviews, with 94 participants recruited from nine communities, were conducted. Most participants received H7N9 information via television and the Internet. Most the participants appreciated the transparency and timeliness of the information released by the government. They expressed a sense of trust in the recommended public health advice and followed most of them. The participants suggested that the government release more information about clinical treatment outcomes, have more specific health recommendations that are practical to their settings and expand the use of new media channels for risk communication. CONCLUSION: The public perceived the overall risk communication strategy by the Chinese public health agencies as effective, though the moderator had a governmental agency title that might have biased the results. There is a need to expand the use of social media for risk communication in the future.


title: Determination of parvovirus antibodies in canine serum using magnetic bead‐based chemiluminescence immunoassay

text: Canine parvovirus type 2 (CPV‐2), as a highly contagious and potentially fatal disease of dogs and many other carnivores, usually causes severe gastroenteritis and myocarditis. Therefore, it is very necessary and urgent to have an accurate method to determine the CPV‐2 antibodies (CPV‐2‐Ab) in canine samples. Here, a magnetic bead–based chemiluminescence immunoassay was established and optimized to detect the concentration of CPV‐2‐Ab in serum. And a commercial assay was also used to evaluate the consistency with our method. After optimization of the detective system, the CPV‐2‐Ab was captured by CPV‐antigen‐magnetic bead (8.3 µg/mL); then combined with the conjugation of anti‐canine IgG antibody‐acridinium ester (0.36 µg/mL). Finally, collected the signal (read the luminosity) after 1 H reaction time. The linear correlation coefficient (R(2)) is 0.9924. The limit of detection (sensitivity) is 0.36 ng/mL (the linear dynamic range: 1.32–93.75 ng/mL), and the average recovery is 100.89% without cross‐reactions with other canine viral antibodies. The results’ correlation between commercial assays and this method is 0.9888. This immunoassay establishes that it has high sensitivity, accuracy, and specificity in clinical analysis, indicating that this method could be suitable for quantitative detection of CPV‐2‐Ab and evaluation of vaccination effect.


title: Adenovirus Species C Is Associated With Chronic Suppurative Lung Diseases in Children

text: Background. The role of human adenoviruses (HAdVs) in chronic respiratory disease pathogenesis is recognized. However, no studies have performed molecular sequencing of HAdVs from the lower airways of children with chronic endobronchial suppuration. We thus examined the major HAdV genotypes/species, and relationships to bacterial coinfection, in children with protracted bacterial bronchitis (PBB) and mild bronchiectasis (BE). Methods. Bronchoalveolar lavage (BAL) samples of 245 children with PBB or mild (cylindrical) BE were included in this prospective cohort study. HAdVs were genotyped (when possible) in those whose BAL had HAdV detected (HAdV(+)). Presence of bacterial infection (defined as ≥10(4) colony-forming units/mL) was compared between BAL HAdV(+) and HAdV negative (HAdV(−)) groups. Immune function tests were performed including blood lymphocyte subsets in a random subgroup. Results. Species C HAdVs were identified in 23 of 24 (96%) HAdV(+) children; 13 (57%) were HAdV-1 and 10 (43%) were HAdV-2. An HAdV(+) BAL was significantly associated with bacterial coinfection with Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae (odds ratio [OR], 3.27; 95% confidence interval, 1.38–7.75; P = .007) and negatively associated with Staphylococcus aureus infection (P = .03). Young age was related to increased rates of HAdV(+). Blood CD16 and CD56 natural killer cells were significantly more likely to be elevated in those with HAdV (80%) compared with those without (56.1%) (P = .027). Conclusions. HAdV-C is the major HAdV species detected in the lower airways of children with PBB and BE. Younger age appears to be an important risk factor for HAdV(+) of the lower airways and influences the likelihood of bacterial coinfection.


title: A human behavior integrated hierarchical model of airborne disease transmission in a large city

text: Abstract Epidemics of infectious diseases such as SARS, H1N1, and MERS threaten public health, particularly in large cities such as Hong Kong. We constructed a human behavior integrated hierarchical (HiHi) model based on the SIR (Susceptible, Infectious, and Recovered) model, the Wells-Riley equation, and population movement considering both spatial and temporal dimensions. The model considers more than 7 million people, 3 million indoor environments, and 2566 public transport routes in Hong Kong. Smallpox, which could be spread through airborne routes, is studied as an example. The simulation is based on people's daily commutes and indoor human behaviors, which were summarized by mathematical patterns. We found that 59.6%, 18.1%, and 13.4% of patients become infected in their homes, offices, and schools, respectively. If both work stoppage and school closure measures are taken when the number of infected people is greater than 1000, an infectious disease will be effectively controlled after 2 months. The peak number of infected people will be reduced by 25% compared to taking no action, and the time of peak infections will be delayed by about 40 days if 90% of the infected people go to hospital during the infectious period. When ventilation rates in indoor environments increase to five times their default settings, smallpox will be naturally controlled. Residents of Kowloon and the north part of Hong Kong Island have a high risk of infection from airborne infectious diseases. Our HiHi model reduces the calculation time for infection rates to an acceptable level while preserving accuracy.


Mutational Analysis of MHV-A59 Replicase Protein-NSP10


title: Building a PubMed knowledge graph

text: PubMed(®) is an essential resource for the medical domain, but useful concepts are either difficult to extract or are ambiguous, which has significantly hindered knowledge discovery. To address this issue, we constructed a PubMed knowledge graph (PKG) by extracting bio-entities from 29 million PubMed abstracts, disambiguating author names, integrating funding data through the National Institutes of Health (NIH) ExPORTER, collecting affiliation history and educational background of authors from ORCID(®), and identifying fine-grained affiliation data from MapAffil. Through the integration of these credible multi-source data, we could create connections among the bio-entities, authors, articles, affiliations, and funding. Data validation revealed that the BioBERT deep learning method of bio-entity extraction significantly outperformed the state-of-the-art models based on the F1 score (by 0.51%), with the author name disambiguation (AND) achieving an F1 score of 98.09%. PKG can trigger broader innovations, not only enabling us to measure scholarly impact, knowledge usage, and knowledge transfer, but also assisting us in profiling authors and organizations based on their connections with bio-entities.


title: Clinical Course of Avian Influenza A(H5N1) in Patients at the Persahabatan Hospital, Jakarta, Indonesia, 2005–2008

text: Background Limited understanding of the presentation and course of influenza A(H5N1) infection in humans hinders evidence-based management. Methods We reviewed the case records of patients admitted to the Persahabatan Hospital (RSP), Jakarta, Indonesia, with influenza A(H5N1) confirmed by real-time polymerase chain reaction. Results Twenty-two previously well patients, aged 3 to 47 years (median 24.5 years), were identified. All attended a clinic or hospital after a median of 2 days of illness (range 0–7). Times to first dose of oseltamivir (three died before receiving oseltamivir) were 2 to 12 days (median 7 days), administered mostly (n = 15) at RSP. Nineteen patients required mechanical ventilation. Deaths numbered 18 (case fatality = 82%) occurring within hours to 6 days of RSP admission, corresponding to 6 to 16 days of illness. Admission hyperglycemia (≥ 140 mg/dL), unrelated to steroids or known underlying diabetes mellitus, and elevated D-dimer levels (0.81–5.2 mg/L, upper limit of normal < 0.5 mg/L) were present in 14/21 (67%) and 20/21 (95%) patients, respectively. Fibrinogen concentrations were mostly low/normal at 129.9 to 517.9 mg/dL (median 241.1, normal 200–400 mg/dL), whereas C-reactive protein (9/11) and ferritin (6/8) levels were increased. Risk factors for death (univariate analysis) included: (1) increased D-dimers, (2) hyperglycema, (3) increased urea, (4) more extensive chest radiograph shadowing, and (5) lower admission oxygen saturation. Conclusions Early diagnosis and effective treatment of human influenza A(H5N1) infection remains challenging. Most patients were referred late with advanced disease. Oseltamivir had limited clinical impact. Elevated D-dimer levels, consistent with fibrinolysis, and hyperglycemia warrant more research to determine their underlying mechanisms and optimal treatment.


title: Prognostic Usefulness of Blood Leukocyte Changes in Canine Parvoviral Enteritis

text: Background: Despite treatment, many dogs still die of complications related to canine parvoviral (CPV) enteritis. Effective prognostication would be beneficial in managing this disease. Hypothesis: We hypothesize that the occurrence of leukocytopenias at admission and at 24 and 48 hours after admission, and changes in absolute leukocyte counts over time, could be used to predict outcome. Animals: Sixty‐two puppies with confirmed CPV. Methods: A prospective study was performed. CBC was performed daily until discharge or death (in which case a postmortem examination was performed). Results: Of the nonsurvivors (10/62; 16%), 9 died because of complications of the disease and 1 was euthanized because of a poor prognosis. There was a statistical significant difference in the occurrence of leukocytopenias between groups at 24 and 48 hours postadmission. The survivors showed a significant increase over time in certain leukocyte types (specifically lymphocytes) compared with values at admission. The positive predictive value for survivors was high. Nonsurvivors had marked thymic and lymphoid atrophy and marked bone marrow hypocellularity. Conclusion: An accurate prognosis could be obtained at 24 hours after admission by evaluating the change in total leukocyte, band neutrophil, lymphocyte, monocyte, and eosinophil counts.


title: Correction to: Dying with SARS-CoV-2 infection—an autopsy study of the first consecutive 80 cases in Hamburg, Germany

text: The affiliation of the author Martin Aepfelbacher was incorrectly assigned in the manuscript. Martin Aepfelbacher is affiliated to the Institute of Microbiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, instead.


title: Characterization of blood mononuclear cells producing IFNα following induction by coronavirus-infected cells (porcine transmissible gastroenteritis virus)

text: Abstract Porcine blood mononuclear cells (PBMC) were shown to produce interferon-α (IFNα) following incubation with cells infected by a coronavirus, transmissible gastroenteritis virus. Monoclonal antibodies (mAb) with specificities for leukocyte subsets and major histocompatibility complex (MHC) antigens were used to characterize IFNα producer cells. The production of IFNα was found to be a function of non-phagocytic, non-adherent, non-T, non-B, CD4+ (and to a lesser extent CD8+) MHC-class-II-positive cells. Furthermore, addition of anti-MHC (class II) mAb during PBMC incubation with virus-infected cells reduced IFN yields, suggesting that masking of these surface antigens alters PBMC responsiveness to IFN induction.


title: Association of Diabetes Mellitus with Disease Severity and Prognosis in COVID-19: A Retrospective Cohort Study

text: Abstract The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, China, and was characterized as a pandemic by the World Health Organization. Diabetes is an established risk associated with poor clinical outcomes, but the association of diabetes with COVID-19 has not been reported yet. Methods In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital in Wuhan, China, recruited from January 29 to February 12, 2020. The clinical features, treatment strategies and prognosis data were collected and analyzed. Prognosis was followed up until March 12, 2020. Results Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease conditions with more complications, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR]=3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR=1.19; 95% CI: 1.08, 1.31) were associated with the fatality due to COVID-19, adjusting for potential confounders. Conclusions Diabetes mellitus is associated with increased disease severity and a higher risk of mortality in patients with COVID-19.


title: SARS-CoV-2: diagnostic and design conundrums, and the male factor infertility

text: The question on whether SARS-CoV-2 (Severe acute respiratory syndrome-related coronavirus (SARS-CoV or SARS-CoV-2, Covid-19) can be harboured in testes and/or the semen is currently unanswered. It is essential to understand the limitations of both antibody and real time polymerase chain reaction (RT-PCR) tests in interpreting SARS-CoV-2 data in relation to semen and testicular tissues analyses without appropriate controls. Here we critically analyse the evidence so far and the possible implications. The diagnostic test limitations posed in both sampling and testing methodologies, their validation, and relevancy in interpreting data are also highlighted.


title: Modelling of evaporation of cough droplets in inhomogeneous humidity fields using the multi-component Eulerian-Lagrangian approach

text: Abstract This study employed a multi-component Eulerian-Lagrangian approach to model the evaporation and dispersion of cough droplets in quiescent air. The approach is featured with a continuity equation being explicitly solved for water vapor, which allows comprehensively considering the effects of inhomogeneous humidity field on droplets evaporation and movement. The computational fluid dynamics (CFD) computations based on the approach achieved a satisfactory agreement with the theoretical models reported in the literature. The results demonstrated that the evaporation-generated vapor and super-saturated wet air exhaled from the respiratory tracks forms a “vapor plume” in front of the respiratory track opening, which, despite the short life time, significantly impedes the evaporation of the droplets captured in it. The study also revealed that due to the droplet size reduction induced by evaporation, both the number density of airborne droplets and mass concentration of inhalable pathogens remarkably increased, which can result in a higher risk of infection. Parametric studies were finally conducted to evaluate the factors affecting droplet evaporation. Summary The study demonstrated the importance of considering inhomogeneous humidity field when modelling the evaporation and dispersion of cough droplets. The multi-component Eulerian-Lagrangian model presented in this study provides a comprehensive approach to address different influential factors in a wide parametric range, which will enhance the assessment of the health risks associated with droplet exposure.


title: Small Indian mongooses and masked palm civets serve as new reservoirs of Bartonella henselae and potential sources of infection for humans

text: Abstract The prevalence and genetic properties of Bartonella species were investigated in small Indian mongooses and masked palm civets in Japan. Bartonella henselae, the causative agent of cat-scratch disease (CSD) was isolated from 15.9% (10/63) of the mongooses and 2.0% (1/50) of the masked palm civets, respectively. The bacteraemic level ranged from 3.0 × 101 to 8.9 × 103 CFU/mL in mongooses and was 7.0 × 103 CFU/mL in the masked palm civet. Multispacer typing (MST) analysis based on nine intergenic spacers resulted in the detection of five MST genotypes (MSTs 8, 14, 37, 58 and 59) for the isolates, which grouped in lineage 1 with MST genotypes of isolates from all CSD patients and most of the cats in Japan. It was also found that MST14 from the mongoose strains was the predominant genotype of cat and human strains. This is the first report on the isolation of B. henselae from small Indian mongooses and masked palm civets. The data obtained in the present study suggest that these animals serve as new reservoirs for B. henselae, and may play a role as potential sources of human infection.


title: Key References in Infectious Diseases Pharmacotherapy

text: Most health care practitioners are challenged to maintain knowledge of contemporary practice issues in many therapeutic disciplines. Like many other areas, infectious diseases pharmacotherapy continues to evolve because of new information regarding disease epidemiology and new treatment options. Emerging infections and resistance further compound the need for information. To assist clinicians in identifying such important new information, we compiled a list of key references on infectious diseases pharmacotherapy published over the last 2 years.


title: Genetic diversity of avian infectious bronchitis virus in China in recent years

text: Abstract In this study, 213 infectious bronchitis viruses (IBVs) were isolated from samples collected from 801 flocks suspected to be infected with IBV from January 2016 to December 2017 in China. By using complete nucleotide sequences of S1 gene we determined the phylogeny of these IBV isolates, which in turn allowed us to define six lineages/genotypes, a number of recombinants and a novel variant. The GI-19 lineage was the most frequently isolated type in China in recent years. Although scattered mutations in the S1 gene among the GI-19 lineage viruses were observed, we also noted different sublineages in the GI-19 lineage with unique mutations, suggesting a high degree of S1 gene variation since they were first isolated in the mid-1990s. We also isolated a number of vaccine-like viruses from vaccinated diseased chickens, although more work is needed to differentiate the reisolation of vaccine strains from field strains of the same serotype. One of the important findings in this study is that the prevalence of the TW I type viruses in GI-7 lineage has been increasing in recent years in China. Another important finding is that recombination events occurred between the predominant GI-19 lineage and the commonly used 4/91 vaccine, which gave rise to distinct IBV isolates. In addition, a novel IBV isolate, together with a reference strain in GenBank database, were found to form a novel lineage/genotype that was remarkably distinct from established lineages. The characteristics of the antigenicity, tissue tropism, pathogenicity and complete genome were required for further investigation for the recombinants and the viruses in different sublineages and novel lineages. Meanwhile, permanent monitoring of circulating strains was needed to monitor the emerging viruses and rationally modify vaccination strategies in the field situation.


title: The Adjuvanticity of an O. volvulus-Derived rOv-ASP-1 Protein in Mice Using Sequential Vaccinations and in Non-Human Primates

text: Adjuvants potentiate antigen-specific protective immune responses and can be key elements promoting vaccine effectiveness. We previously reported that the Onchocerca volvulus recombinant protein rOv-ASP-1 can induce activation and maturation of naïve human DCs and therefore could be used as an innate adjuvant to promote balanced Th1 and Th2 responses to bystander vaccine antigens in mice. With a few vaccine antigens, it also promoted a Th1-biased response based on pronounced induction of Th1-associated IgG2a and IgG2b antibody responses and the upregulated production of Th1 cytokines, including IL-2, IFN-γ, TNF-α and IL-6. However, because it is a protein, the rOv-ASP-1 adjuvant may also induce anti-self-antibodies. Therefore, it was important to verify that the host responses to self will not affect the adjuvanticity of rOv-ASP-1 when it is used in subsequent vaccinations with the same or different vaccine antigens. In this study, we have established rOv-ASP-1's adjuvanticity in mice during the course of two sequential vaccinations using two vaccine model systems: the receptor-binding domain (RBD) of SARS-CoV spike protein and a commercial influenza virus hemagglutinin (HA) vaccine comprised of three virus strains. Moreover, the adjuvanticity of rOv-ASP-1 was retained with an efficacy similar to that obtained when it was used for a first vaccination, even though a high level of anti-rOv-ASP-1 antibodies was present in the sera of mice before the administration of the second vaccine. To further demonstrate its utility as an adjuvant for human use, we also immunized non-human primates (NHPs) with RBD plus rOv-ASP-1 and showed that rOv-ASP-1 could induce high titres of functional and protective anti-RBD antibody responses in NHPs. Notably, the rOv-ASP-1 adjuvant did not induce high titer antibodies against self in NHPs. Thus, the present study provided a sound scientific foundation for future strategies in the development of this novel protein adjuvant.


Avoiding Disinformation Traps in COVID-19


title: Chapter 10 Nanoparticles and the control of oral biofilms

text: Abstract Nanoparticles, novel in size, shape, and surface chemistry when compared to more conventional materials, offer additional functional properties to a range of possible oral applications, from drug-delivery systems to dental implant coatings. Exploitation of the toxic properties of nanoparticles to bacteria, viruses, and fungi has increased markedly over recent years. Metal and metal oxide nanoparticles and their incorporation into other materials have been of particular interest. The potential of nanoparticles to control the formation of biofilms within the oral cavity, as a function of their antimicrobial, anti-adhesive, and delivery capabilities, is coming under close scrutiny. However, optimum formulation of materials at the nanoscale does require innovative physical and chemical approaches.


The Nation‐State after the Virus


title: Potential Pathogenicity of Inqulinus limosus in a Pediatric Patient with Cystic Fibrosis

text: PRESENTATION: Patient is a 6-year-old male with CF, MRSA colonization, and pancreatic insufficiency that presented with worsening ppFEV1 and systemic symptoms despite multiple interventions. BAL grew NTM, Stenotrophomonas maltophilia, and Inquilinus limosus, a rare organism found in patients with CF. COURSE: I. limosus treatment was deferred. Despite treatment of other pathogens, symptoms worsened. I. limosus was targeted with meropenem, amikacin, and ciprofloxacin along with clindamycin for MRSA colonization. Within weeks, symptoms had resolved with ppFEV1 improvement. DISCUSSION: This case discusses the importance of a rare organism in the CF population. Targeting I.limosus was key to recovery, revealing its potential pathogenicity.


title: Todesfälle in neun Regionen Italiens im Februar/März 2020: „Mortalitäts-Exzess-Lupe“ für SARS-CoV-2/COVID-19-Epidemiologie in Deutschland

text: Italy is particularly affected by SARS-CoV-2/COVID-19. Recently, Colombo and Impicciatore compared the deaths in 1084 selected municipalities between 21 February 2020 and 21 March 2020 with deaths in the same time period in 2015 to 2019. We extend analyses of data from the Italian National Institute of Statistics (ISTAT) and calculate SMRs for all causes of death in the nine selected regions of Italy, separately for men and women and summarized. We analyze the effect of covariables by Poisson modelling and discuss the limitations of the current elaborations. We conclude: In agreement with Colombo and Impicciatore, in the particular corona situation, this “mortality excess loupe” – assuming otherwise constant determinants of death – can be a virus-test-independent tool to determine mortality effects of SARS-CoV-2. The current “loupe” is focused on municipalities with increases of more than 20% deaths in March 2020 compared to the average deaths on the same days in 2015–2019. The time window of investigation could be opened before 21 February 2020 to detect masked increases in mortality before the first “COVID-19 death” was ascertained. The current “loupe” conveys pronounced mortality increases also in regions that were not considered to be corona hotspots. In this respect, even in the absence of representative virus test results, mortality data can be important indicators of the distribution or spread of a newly acting factor. Overall, it is advisable to carry out SMR analyses for Germany on a regular basis, differentiated by region, gender, age group and cause of death. Such analyses can contribute to the early detection and evaluation of the severity of a deadly pandemic (“burden of disease”) as well as to monitoring the dynamic spread of a factor such as SARS-CoV-2. SMR analyses can also be used to assess and evaluate both desired and undesired effects of measures taken against SARS-CoV-2/COVID-19 – and possibly other epidemics or pandemics.


title: Chapter 1 Graphical representation and mathematical characterization of protein sequences and applications to viral proteins

text: Abstract Graphical representation and numerical characterization (GRANCH) of nucleotide and protein sequences is a new field that is showing a lot of promise in analysis of such sequences. While formulation and applications of GRANCH techniques for DNA/RNA sequences started just over a decade ago, analyses of protein sequences by these techniques are of more recent origin. The emphasis is still on developing the underlying technique, but significant results have been achieved in using these methods for protein phylogeny, mass spectral data of proteins and protein serum profiles in parasites, toxicoproteomics, determination of different indices for use in QSAR studies, among others. We briefly mention these in this chapter, with some details on protein phylogeny and viral diseases. In particular, we cover a systematic method developed in GRANCH to determine conserved surface exposed peptide segments in selected viral proteins that can be used for drug and vaccine targeting. The new GRANCH techniques and applications for DNAs and proteins are covered briefly to provide an overview to this nascent field.


title: Diauxic shift-dependent relocalization of decapping activators Dhh1 and Pat1 to polysomal complexes

text: Dhh1 and Pat1 in yeast are mRNA decapping activators/translational repressors thought to play key roles in the transition of mRNAs from translation to degradation. However, little is known about the physical and functional relationships between these proteins and the translation machinery. We describe a previously unknown type of diauxic shift-dependent modulation of the intracellular locations of Dhh1 and Pat1. Like the formation of P bodies, this phenomenon changes the spatial relationship between components involved in translation and mRNA degradation. We report significant spatial separation of Dhh1 and Pat1 from ribosomes in exponentially growing cells. Moreover, biochemical analyses reveal that these proteins are excluded from polysomal complexes in exponentially growing cells, indicating that they may not be associated with active states of the translation machinery. In contrast, under diauxic growth shift conditions, Dhh1 and Pat1 are found to co-localize with polysomal complexes. This work suggests that Dhh1 and Pat1 functions are modulated by a re-localization mechanism that involves eIF4A. Pull-down experiments reveal that the intracellular binding partners of Dhh1 and Pat1 change as cells undergo the diauxic growth shift. This reveals a new dimension to the relationship between translation activity and interactions between mRNA, the translation machinery and decapping activator proteins.


title: Modeling site-specific amino-acid preferences deepens phylogenetic estimates of viral sequence divergence

text: Molecular phylogenetics is often used to estimate the time since the divergence of modern gene sequences. For highly diverged sequences, such phylogenetic techniques sometimes estimate surprisingly recent divergence times. In the case of viruses, independent evidence indicates that the estimates of deep divergence times from molecular phylogenetics are sometimes too recent. This discrepancy is caused in part by inadequate models of purifying selection leading to branch-length underestimation. Here we examine the effect on branch-length estimation of using models that incorporate experimental measurements of purifying selection. We find that models informed by experimentally measured site-specific amino-acid preferences estimate longer deep branches on phylogenies of influenza virus hemagglutinin. This lengthening of branches is due to more realistic stationary states of the models, and is mostly independent of the branch-length extension from modeling site-to-site variation in amino-acid substitution rate. The branch-length extension from experimentally informed site-specific models is similar to that achieved by other approaches that allow the stationary state to vary across sites. However, the improvements from all of these site-specific but time homogeneous and site independent models are limited by the fact that a protein’s amino-acid preferences gradually shift as it evolves. Overall, our work underscores the importance of modeling site-specific amino-acid preferences when estimating deep divergence times—but also shows the inherent limitations of approaches that fail to account for how these preferences shift over time.


title: Initial human transmission dynamics of the pandemic (H1N1) 2009 virus in North America

text: Background Between 5 and 25 April 2009, pandemic (H1N1) 2009 caused a substantial, severe outbreak in Mexico, and subsequently developed into the first global pandemic in 41 years. We determined the reproduction number of pandemic (H1N1) 2009 by analyzing the dynamics of the complete case series in Mexico City during this early period. Methods We analyzed three mutually exclusive datasets from Mexico City Distrito Federal which constituted all suspect cases from 15 March to 25 April: confirmed pandemic (H1N1) 2009 infections, non‐pandemic influenza A infections and patients who tested negative for influenza. We estimated the initial reproduction number from 497 suspect cases identified prior to 20 April, using a novel contact network methodology incorporating dates of symptom onset and hospitalization, variation in contact rates, extrinsic sociological factors, and uncertainties in underreporting and disease progression. We tested the robustness of this estimate using both the subset of laboratory‐confirmed pandemic (H1N1) 2009 infections and an extended case series through 25 April, adjusted for suspected ascertainment bias. Results The initial reproduction number (95% confidence interval range) for this novel virus is 1·51 (1·32–1·71) based on suspected cases and 1·43 (1·29–1·57) based on confirmed cases before 20 April. The longer time series (through 25 April) yielded a higher estimate of 2·04 (1·84–2·25), which reduced to 1·44 (1·38–1·51) after correction for ascertainment bias. Conclusions The estimated transmission characteristics of pandemic (H1N1) 2009 suggest that pharmaceutical and non‐pharmaceutical mitigation measures may appreciably limit its spread prior the development of an effective vaccine.


title: Infection Risk Assessment of COVID-19 through Aerosol Transmission: a Case Study of South China Seafood Market

text: [Image: see text] The Corona Virus Disease 2019 (COVID-19) is rapidly spreading throughout the world. Aerosol is a potential transmission route. We conducted the quantitative microbial risk assessment (QMRA) to evaluate the aerosol transmission risk by using the South China Seafood Market as an example. The key processes were integrated, including viral shedding, dispersion, deposition in air, biologic decay, lung deposition, and the infection risk based on the dose–response model. The available hospital bed for COVID-19 treatment per capita (1.17 × 10(–3)) in Wuhan was adopted as a reference for manageable risk. The median risk of a customer to acquire SARS-CoV-2 infection via the aerosol route after 1 h of exposure in the market with one infected shopkeeper was about 2.23 × 10(–5) (95% confidence interval: 1.90 × 10(–6) to 2.34 × 10(–4)). The upper bound could increase and become close to the manageable risk with multiple infected shopkeepers. More detailed risk assessment should be conducted in poorly ventilated markets with multiple infected cases. The uncertainties were mainly due to the limited information on the dose–response relation and the viral shedding which need further studies. The risk rapidly decreased outside the market due to the dilution by ambient air and became below 10(–6) at 5 m away from the exit.


title: Roles for endocytosis in lentiviral replication

text: Endocytosis is essential for the entry of many viruses into cells. The primate lentiviruses [human immunodeficiency virus (HIV) 1 and 2, and the simian immunodeficiency viruses (SIVs)], however, use endocytosis in other aspects of their life cycles. Here, the authors describe the ways in which the endocytic pathway is used by HIV and SIV and discuss the mechanisms through which endocytosis may contribute to the pathogenic properties of these viruses.


title: Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft

text: Since the 2002–2003 severe acute respiratory syndrome (SARS) outbreak prompted a search for the natural reservoir of the SARS coronavirus, numerous alpha- and betacoronaviruses have been discovered in bats around the world. Bats are likely the natural reservoir of alpha- and betacoronaviruses, and due to the rich diversity and global distribution of bats, the number of bat coronaviruses will likely increase. We conducted a surveillance of coronaviruses in bats in an abandoned mineshaft in Mojiang County, Yunnan Province, China, from 2012–2013. Six bat species were frequently detected in the cave: Rhinolophus sinicus, Rhinolophus affinis, Hipposideros pomona, Miniopterus schreibersii, Miniopterus fuliginosus, and Miniopterus fuscus. By sequencing PCR products of the coronavirus RNA-dependent RNA polymerase gene (RdRp), we found a high frequency of infection by a diverse group of coronaviruses in different bat species in the mineshaft. Sequenced partial RdRp fragments had 80%–99% nucleic acid sequence identity with well-characterized Alphacoronavirus species, including BtCoV HKU2, BtCoV HKU8, and BtCoV1, and unassigned species BtCoV HKU7 and BtCoV HKU10. Additionally, the surveillance identified two unclassified betacoronaviruses, one new strain of SARS-like coronavirus, and one potentially new betacoronavirus species. Furthermore, coronavirus co-infection was detected in all six bat species, a phenomenon that fosters recombination and promotes the emergence of novel virus strains. Our findings highlight the importance of bats as natural reservoirs of coronaviruses and the potentially zoonotic source of viral pathogens. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s12250-016-3713-9 and is accessible for authorized users.


title: Long non-coding RNA expression profiles in different severity EV71-infected hand foot and mouth disease patients

text: Abstract Enterovirus 71 (EV71) is associated with the severe hand foot and mouth disease (HFMD) outcomes, however the host-virus interaction mechanism and the pathogenesis remain poorly understood. Long non-coding RNAs (lncRNAs) are involved in variety physiological and pathological processes, but the functions of lncRNAs in EV71 infection remain elusive. Here we profiled the expression of lncRNAs in peripheral blood mononuclear cells (PBMCs) from EV71-infected mild patients, severe patients as well as the healthy controls, and identified 8541 lncRNAs were differentially expressed. Focused on the dynamic changed lncRNAs, we performed systematic bioinformatics analysis with Series Test of Cluster (STC) algorithm, Gene Ontology (GO) analysis, pathway analysis and lncRNA-mRNA co-expression network analysis, and revealed the potential functions and related pathways of these lncRNAs were associated with immunity and inflammation during the clinical process of EV71-infected HFMD. Among the significant dynamic changed lncRNAs, ten lncRNAs were screened whose expression were further validated in EV71-infected mild patients, severe patients and healthy control. These results shed light on the potential roles of lncRNAs in EV71-infected HFMD, especially in distinguishing the mild and severe cases for early diagnose and treatment, moreover, provide deeper insight into the mechanism of EV71-induced immune and inflammatory responses, as well as the pathogenesis of the imbalanced inflammation in severe EV71 infection.


Catching a glimpse: Corona‐life and its micro‐politics in academia


title: Integrating pharmaceutical systems strengthening in the current global health scenario: three ‘uncomfortable truths’

text: The response to emergency public health challenges such as HIV, TB, and malaria has been successful in mobilising resources and scaling up treatment for communicable diseases. However, many of the remaining challenges in improving access to and appropriate use of medicines and services require pharmaceutical systems strengthening. Incorporating pharmaceutical systems strengthening into global health programmes requires recognition of a few ‘truths’. Systems strengthening is a lengthy and resource-intensive process that requires sustained engagement, which may not align with the short time frame for achieving targets in vertical-oriented programmes. Further, there is a lack of clarity on what key metrics associated with population and patient level outcomes should be tracked for systems strengthening interventions. This can hinder advocacy and communication with decision makers regarding health systems investments. Moving forward, it is important to find ways to balance the inherent tensions between the short-term focus on the efficiency of vertical programmes and broader, longer-term health and development objectives. Global health programme design should also shift away from a narrow view of medicines primarily as an input commodity to a more comprehensive view that recognizes the various structures and processes and their interactions within the broader health system that help ensure access to and appropriate use of medicines and related services.


title: Prolonged respiratory viral shedding in transplant patients

text: Respiratory viral infections are frequent causes of morbidity in transplant patients. We screened symptomatic adult transplant recipients for respiratory viruses in a cohort of patients attending a referral medical center in Brazil. The duration of viral shedding and the prevalence of viral codetections were also determined. During a 1‐year period (2011–2012), swabs were obtained from 50 patients. An in‐house polymerase chain reaction panel designed to detect 10 viruses was used. Viruses were identified in 19 (38%) patients, particularly parainfluenza III (32%) and the respiratory syncytial virus (20%); multiple viruses were identified in 26% of patients. Prolonged viral shedding was observed with 60% of individuals excreting viruses for >10 days. The clinical and epidemiologic relevance of prolonged viral shedding remains to be determined.


title: Emerging trends in inhaled drug delivery

text: Ideally, inhaled therapy is driven by the needs of specific disease management. Lung biology interfaces with inhaler performance to allow optimal delivery of therapeutic agent for disease treatment. Inhalation aerosol products consist of the therapeutic agent, formulation, and device. The manufacturing specifications on each of the components, and their combination, allow accurate and reproducible control of measures of quality and in-vitro performance. These product variables in combination with patient variables, including co-ordination skill during inhaler use, intrinsic lung biology, disease and consequent pulmonary function, contribute to drug safety and efficacy outcomes. Due to the complexity of pulmonary drug delivery, predicting biological outcomes from first principles has been challenging. Ongoing research appears to offer new insights that may allow accurate prediction of drug behavior in the lungs. Disruptive innovations were characteristic of research and development in inhaled drug delivery at the end of the last century. Although there were relatively few new inhaled products launched in the first decade of the new millennium it was evident that the earlier years of exploration resulted in maturation of commercially successful technologies. A significant increase in new and generic products has occurred in the last decade and technical, regulatory and disease management trends are emerging. Some of these developments can trace their origins to earlier periods of creativity in the field while others are a reflection of advances in other areas of basic and computer sciences and engineering. Select biological and technical advances are highlighted with reflections on the potential to impact future clinical and regulatory considerations.


title: Dynamics of Population Immunity Due to the Herd Effect in the COVID-19 Pandemic.

text: The novel Coronavirus 2 Severe Acute Respiratory Syndrome (SARS-Cov-2) has led to the Coronavirus Disease 2019 (COVID-19) pandemic, which has surprised health authorities around the world, quickly producing a global health crisis. Different actions to cope with this situation are being developed, including confinement, different treatments to improve symptoms, and the creation of the first vaccines. In epidemiology, herd immunity is presented as an area that could also solve this new global threat. In this review, we present the basis of herd immunology, the dynamics of infection transmission that induces specific immunity, and how the application of immunoepidemiology and herd immunology could be used to control the actual COVID-19 pandemic, along with a discussion of its effectiveness, limitations, and applications.


title: Collaborated effort against SARS‐CoV‐2 outbreak in China

text: A previously unknown beta coronavirus, SARS‐CoV‐2, was discovered from a cluster of patients with pneumonia of unknown cause in Wuhan since the end of 2019. Ever since the start of COVID‐19, government administrations, academic institutions, and technology enterprises are under unprecedented cooperation in controlling this outbreak from pathogen identification, epidemic situation assessment, to outbreak containment. Timely identification, isolation, and whole‐genome sequencing of SARS‐CoV‐2 have laid the foundation for effective control of this novel infection. With the increasing case numbers worldwide, more real‐time information is emerging, changing our understandings to SARS‐CoV‐2 outbreak, and nonetheless refining the outbreak control responses. The efficient management of COVID‐19 requires global collaboration and an efficient share of information.


title: Ginseng integrative supplementation for seasonal acute upper respiratory infections: a systematic review and meta-analysis

text: BACKGROUND: The aim of the review was to assess whether ginseng can be a useful supplementation for seasonal acute upper respiratory infections (SAURIs). METHODS: All clinical studies investigating ginseng efficacy for the treatment or prevention of SAURIs were included in the review. Medline, EMBASE, Web of Science, Scopus, Cochrane Library, Google Scholar were systematically screened for relevant articles up to May 26th, 2020. The risk of bias was assessed with the Cochrane tool (RoB 2). RESULTS: Nine articles (describing ten trials about P. ginseng or P. quinquefolius) were included in the review. Evidence globally indicated some useful activity of intervention when administered in adjunct to influenza vaccination. The results of our quantitative synthesis suggested a significant effect on SAURIs incidence (RR = 0.69 [95% C.I. 0.52 to 0.90], p < 0.05), as well as a significant reduction of their duration if only studies with healthy individuals were included in the analysis (MD=-3.11 [95% C.I. -5.81 to -0.40], p < 0.05). However, the risk of bias was high-to-unclear for most included trials, and publication bias couldn't be excluded. DISCUSSION: Limitations of existing evidence don’t allow to draw conclusions on the topic. Nevertheless, it is not excluded that ginseng supplementation in adjunct to influenza vaccination and standard care might be useful for SAURIs prevention and management in healthy adult subjects, but further high-quality trials are needed to support this hypothesis. OTHER: This research was not funded. The protocol was registered in PROSPERO under the following code: CRD42020156235.


title: Pooled nasopharyngeal and oropharyngeal samples for the identification of respiratory viruses in adults

text: A pooled sample of oropharyngeal swabs, nasopharyngeal swabs and nasopharyngeal washings, taken from each of 1,000 subjects, was compared to separate specimens from the same sampling. Multiplex real-time polymerase chain reaction (mqRT-PCR) was used to identify 12 respiratory viruses. Two hundred and forty-three (97%) of the 251 viruses identified in the separate samples were also identified in the mixed samples. The sensitivity rate was identical at 100% for all virus groups except coronaviruses. This sensitivity rate clearly justifies the use of pooled samples instead of separate samples for clinical and epidemiological purposes. The reduction in costs attained from the use of pooled samples may represent a critical advantage when considering its use in extensive clinical and epidemiological studies.


title: Prevalence of antibodies against feline coronavirus and Chlamydophila felis in Swedish cats

text: Serum samples from 214 Swedish cats with no signs of infectious disease were analysed for the presence of antibodies against Chlamydophila felis (Cp felis), while 209 of these were also analysed for feline coronavirus (FCoV) antibodies. The prevalence of antibodies against Cp felis was 11%, with no significant difference between purebred and mixed breed cats. The overall prevalence of antibodies against FCoV was 31%, significantly higher among pure breed cats (65%) than among mixed breed cats (17%). A high proportion of cats with antibodies against FCoV had relatively high antibody titres, and was therefore likely to be shedding FCoV in faeces. For Cp felis, the majority of seropositive animals had relatively low antibody titres, and the risk of these animals infecting others is not known.


title: Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations

text: Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms. Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections. Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations. Exogenous interferon-β reverses these effects. FP suppression of interferon may occur through inhibition of TLR3- and RIG-I virus-sensing pathways. Mice deficient in the type I interferon-α/β receptor (IFNAR1(−/−)) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection. This study identifies type I interferon as a central regulator of antibacterial immunity and mucus production. Suppression of interferon by ICS during virus-induced COPD exacerbations likely mediates pneumonia risk and raises suggestion that inhaled interferon-β therapy may protect.


title: A novel intracellularly expressed NS5B-specific nanobody suppresses bovine viral diarrhea virus replication

text: Abstract Bovine viral diarrhea virus (BVDV) infection causes significant economic losses to the cattle industry worldwide and still represents a huge pressure on agricultural production. Thus, the development of novel anti-BVDV strategies are urgently needed. The nonstructural protein 5 (NS5B) of BVDV is essential for viral replication. Further, the camel single-domain antibody (nanobody) represents a promising antiviral approach with the advantages of small size, stable structure, high specificity and solubility, and the recognition of specific epitopes. However, no NS5B-specific nanobodies against BVDV have been reported. In this study, NS5B-specific nanobodies were isolated from a phage display library of variable domains of Camellidae heavy chain-only antibodies (VHHs). Further, an MDBK cell line stably expressing Nb1 was established to explore antiviral activity. Results showed that Nb1 could markedly suppress BVDV replication and interact with the BVDV NS5B protein. This suggests that nanobodies have potential for the development of novel antiviral drugs against BVDV infection.


title: Poor positive predictive value of influenza‐like illness criteria in adult transplant patients: a case for multiplex respiratory virus PCR testing

text: BACKGROUND: Respiratory viral infections (RVIs) are a significant cause of morbidity and mortality among transplant patients. The CDC's influenza‐like illness (ILI) criteria (fever ≥100°F with cough and/or sore throat) are a screening tool for influenza with unknown applicability to the transplant population. METHODS: We reviewed all respiratory virus PCR tests performed on adult patients with a history of solid organ (SOT) or stem cell transplantation (HSCT) during the 2012–2013 influenza season. The positive (PPV) and negative predictive values (NPV) of ILI criteria were calculated. RESULTS: Of 126 transplant patients (66 HSCT, 60 SOT), 54 (42.8%) tested positive for an RVI by PCR: 24 influenza and 30 non‐influenza. Of 30 patients who met ILI criteria, 12 (40%) were positive for influenza. The PPV and NPV of ILI for influenza were 50% and 82.4%, respectively. Mortality was low (3.7%), but morbidity was high (14.8% required ICU stay) among transplant patients diagnosed with RVI. CONCLUSIONS: Influenza and non‐influenza RVIs are associated with significant morbidity among transplant patients. CDC ILI criteria correlate poorly with PCR‐positive cases of influenza in transplant patients, but may be useful in excluding the diagnosis. Routine RVI PCR testing is recommended for better diagnosis and improved antiviral use in transplant patients with suspected RVI.


Wheezing in children: Approaches to diagnosis and management


title: First Case of Systemic Coronavirus Infection in a Domestic Ferret (Mustela putorius furo) in Peru

text: A domestic ferret from Lima, Peru, died after ten days of non‐specific clinical signs. Based on pathology, immunohistochemistry and molecular analysis, ferret systemic coronavirus (FRSCV)‐associated disease was diagnosed for the first time in South America. This report highlights the potential spread of pathogens by the international pet trade.


title: Coronaviruses and arteriviruses display striking differences in their cyclophilin A-dependence during replication in cell culture

text: Abstract Cyclophilin A (CypA) is an important host factor in the replication of a variety of RNA viruses. Also the replication of several nidoviruses was reported to depend on CypA, although possibly not to the same extent. These prior studies are difficult to compare, since different nidoviruses, cell lines and experimental set-ups were used. Here, we investigated the CypA dependence of three distantly related nidoviruses that can all replicate in Huh7 cells: the arterivirus equine arteritis virus (EAV), the alphacoronavirus human coronavirus 229E (HCoV-229E), and the betacoronavirus Middle East respiratory syndrome coronavirus (MERS-CoV). The replication of these viruses was compared in the same parental Huh7 cells and in CypA-knockout Huh7 cells generated using CRISPR/Cas9-technology. CypA depletion reduced EAV yields by ~ 3-log, whereas MERS-CoV progeny titers were modestly reduced (3-fold) and HCoV-229E replication was unchanged. This study reveals that the replication of nidoviruses can differ strikingly in its dependence on cellular CypA.


title: Chapter 654 DESC1 and HAT Peptidases

text: The third edition of the Handbook of Proteolytic Enzymes aims to be a comprehensive reference work for the enzymes that cleave proteins and peptides, and contains over 800 chapters. Each chapter is organized into sections describing the name and history, activity and specificity, structural chemistry, preparation, biological aspects, and distinguishing features for a specific peptidase. The subject of Chapter 654 is DESC1 and HAT Peptidases. Keywords Serine protease, transmembrane, SEA, HAT, DESC.


title: Evaluation and comparison of statistical methods for early temporal detection of outbreaks: A simulation-based study

text: The objective of this paper is to evaluate a panel of statistical algorithms for temporal outbreak detection. Based on a large dataset of simulated weekly surveillance time series, we performed a systematic assessment of 21 statistical algorithms, 19 implemented in the R package surveillance and two other methods. We estimated false positive rate (FPR), probability of detection (POD), probability of detection during the first week, sensitivity, specificity, negative and positive predictive values and F(1)-measure for each detection method. Then, to identify the factors associated with these performance measures, we ran multivariate Poisson regression models adjusted for the characteristics of the simulated time series (trend, seasonality, dispersion, outbreak sizes, etc.). The FPR ranged from 0.7% to 59.9% and the POD from 43.3% to 88.7%. Some methods had a very high specificity, up to 99.4%, but a low sensitivity. Methods with a high sensitivity (up to 79.5%) had a low specificity. All methods had a high negative predictive value, over 94%, while positive predictive values ranged from 6.5% to 68.4%. Multivariate Poisson regression models showed that performance measures were strongly influenced by the characteristics of time series. Past or current outbreak size and duration strongly influenced detection performances.


title: Translating Big Data into Smart Data for Veterinary Epidemiology

text: The increasing availability and complexity of data has led to new opportunities and challenges in veterinary epidemiology around how to translate abundant, diverse, and rapidly growing “big” data into meaningful insights for animal health. Big data analytics are used to understand health risks and minimize the impact of adverse animal health issues through identifying high-risk populations, combining data or processes acting at multiple scales through epidemiological modeling approaches, and harnessing high velocity data to monitor animal health trends and detect emerging health threats. The advent of big data requires the incorporation of new skills into veterinary epidemiology training, including, for example, machine learning and coding, to prepare a new generation of scientists and practitioners to engage with big data. Establishing pipelines to analyze big data in near real-time is the next step for progressing from simply having “big data” to create “smart data,” with the objective of improving understanding of health risks, effectiveness of management and policy decisions, and ultimately preventing or at least minimizing the impact of adverse animal health issues.


title: CRISPR-Cas9 Mediated RNase L Knockout Regulates Cellular Function of PK-15 Cells and Increases PRV Replication

text: Ribonuclease L (RNase L) is an important antiviral endoribonuclease regulated by type I IFN. RNase L is activated by viral infection and dsRNA. Because the role of swine RNase L (sRNase L) is not fully understood, in this study, we generated a sRNase L knockout PK-15 (KO-PK) cell line through the CRISPR/Cas9 gene editing system to evaluate the function of sRNase L. After transfection with CRISPR-Cas9 followed by selection using puromycin, sRNase L knockout in PK-15 cells was further validated by agarose gel electrophoresis, DNA sequencing, and Western blotting. The sRNase L KO-PK cells failed to trigger RNA degradation and induced less apoptosis than the parental PK-15 cells after transfected with poly (I: C). Furthermore, the levels of ISGs mRNA in sRNase L KO-PK cells were higher than those in the parental PK-15 cells after treated with poly (I: C). Finally, both wild type and attenuated pseudorabies viruses (PRV) replicated more efficiently in sRNase L KO-PK cells than the parental PK-15 cells. Taken together, these findings suggest that sRNase L has multiple biological functions including cellular single-stranded RNA degradation, induction of apoptosis, downregulation of transcript levels of ISGs, and antiviral activity against PRV. The sRNase L KO-PK cell line will be a valuable tool for studying functions of sRNase L as well as for producing PRV attenuated vaccine.


title: 4-Hydroxy-2-quinolones 139. Synthesis, structure, and antiviral activity of N-R-amides of 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acids

text: Dialkylaminoalkylamides of 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acids have been obtained as potential antiviral agents. The special features of the spatial structure of one example of the synthesized compounds have been studied. Results are given of the investigation of cytotoxicity and antiviral activity in relation to type 1 herpes virus and coronavirus.


title: Live poultry market closure and avian influenza A (H7N9) infection in cities of China, 2013–2017: an ecological study

text: BACKGROUND: Previous studies have proven that the closure of live poultry markets (LPMs) was an effective intervention to reduce human risk of avian influenza A (H7N9) infection, but evidence is limited on the impact of scale and duration of LPMs closure on the transmission of H7N9. METHOD: Five cities (i.e., Shanghai, Suzhou, Shenzhen, Guangzhou and Hangzhou) with the largest number of H7N9 cases in mainland China from 2013 to 2017 were selected in this study. Data on laboratory-confirmed H7N9 human cases in those five cities were obtained from the Chinese National Influenza Centre. The detailed information of LPMs closure (i.e., area and duration) was obtained from the Ministry of Agriculture. We used a generalized linear model with a Poisson link to estimate the effect of LPMs closure, reported as relative risk reduction (RRR). We used classification and regression trees (CARTs) model to select and quantify the dominant factor of H7N9 infection. RESULTS: All five cities implemented the LPMs closure, and the risk of H7N9 infection decreased significantly after LPMs closure with RRR ranging from 0.80 to 0.93. Respectively, a long-term LPMs closure for 10–13 weeks elicited a sustained and highly significant risk reduction of H7N9 infection (RRR = 0.98). Short-time LPMs closure with 2 weeks in every epidemic did not reduce the risk of H7N9 infection (p > 0.05). Partially closed LPMs in some suburbs contributed only 35% for reduction rate (RRR = 0.35). Shenzhen implemented partial closure for first 3 epidemics (p > 0.05) and all closure in the latest 2 epidemic waves (RRR = 0.64). CONCLUSION: Our findings suggest that LPMs all closure in whole city can be a highly effective measure comparing with partial closure (i.e. only urban closure, suburb and rural remain open). Extend the duration of closure and consider permanently closing the LPMs will help improve the control effect. The effect of LPMs closure seems greater than that of meteorology on H7N9 transmission.


title: The 2019-new coronavirus epidemic: evidence for virus evolution

text: There is concern about a new coronavirus, the 2019-nCoV, as a global public health threat. In this article, we provide a preliminary evolutionary and molecular epidemiological analysis of this new virus. A phylogenetic tree has been built using the 15 available whole genome sequence of 2019-nCoV and 12 whole genome sequences highly similar sequences available in gene bank (5 from SARS, 2 from MERS and 5 from Bat SARS-like Coronavirus). FUBAR analysis shows that the Nucleocapsid and the Spike Glycoprotein has some sites under positive pressure while homology modelling helped to explain some molecular and structural differences between the viruses. The phylogenetic tree showed that 2019.nCoV significantly clustered with Bat SARS-like Coronavirus sequence isolated in 2015, whereas structural analysis revealed mutation in S and nucleocapsid proteins. From these results, 2019nCoV could be considered a coronavirus distinct from SARS virus, probably transmitted from bats or another host where mutations conferred upon it the ability to infect humans.


title: Cross-species transmission and emergence of novel viruses from birds

text: Birds, the only living member of the Dinosauria clade, are flying warm-blooded vertebrates displaying high species biodiversity, roosting and migratory behavior, and a unique adaptive immune system. Birds provide the natural reservoir for numerous viral species and therefore gene source for evolution, emergence and dissemination of novel viruses. The intrusions of human into natural habitats of wild birds, the domestication of wild birds as pets or racing birds, and the increasing poultry consumption by human have facilitated avian viruses to cross species barriers to cause zoonosis. Recently, a novel adenovirus was exclusively found in birds causing an outbreak of Chlamydophila psittaci infection among birds and humans. Instead of being the primary cause of an outbreak by jumping directly from bird to human, a novel avian virus can be an augmenter of another zoonotic agent causing the outbreak. A comprehensive avian virome will improve our understanding of birds’ evolutionary dynamics.


title: From street canyon microclimate to indoor environmental quality in naturally ventilated urban buildings: Issues and possibilities for improvement

text: Abstract Many buildings in urban areas are more or less naturally ventilated. A good understanding of the current status and issues of indoor environmental quality (IEQ) in naturally ventilated urban buildings and the association with urban microclimate is fundamental for improving their IEQ. This paper reviews past studies on (a) the microclimate in urban street canyons, (b) the potential influence of such microclimate on IEQ of nearby naturally ventilated buildings, and (c) the real-life IEQ status in these buildings. The review focuses mainly on studies conducted by on-site measurements. The microclimate in urban street canyons is characterized by low wind speed, high surface temperature difference, high pollutant concentration, and high noise level. Insufficient ventilation rates and excessive penetration of outdoor pollutants are two key risks involved in naturally ventilated urban buildings. Existing knowledge suggests that reasonable urban planning and careful building envelope design are the primary methods to ensure acceptable IEQ and maximize the utilization of natural ventilation. However, quantitative studies of both microclimate in street canyons and IEQ in buildings are still highly insufficient in many aspects, which make cross comparison and influencing factors analysis currently impossible. Based on the limitations of previous studies and the current issues of naturally ventilated urban buildings, suggestions are made for future studies to better understand and improve IEQ in naturally ventilated urban buildings.


title: Interleukin‐6 Receptor Antagonist Therapy to Treat SARS‐CoV‐2 Driven Inflammatory Syndrome in a Renal Transplant Recipient

text: Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a pandemic that is evolving rapidly at present with unprecedented global health and societal implications. Herein, we report a case of successful treatment of SARS‐CoV‐2 induced inflammatory syndrome by utilization of the interleukin‐6 receptor antagonist (IL‐6Ra) tocilizumab.


Use of masks by health care workers


title: Development of hepatic lesions in male Fischer-344 rats fed AIN-76A purified diet

text: Abstract The suitability of the AIN-76A diet for Fischer-344 rats was investigated. This diet, proposed by the American Institute of Nutrition for use when a purified diet composed of refined ingredients and added vitamins and minerals is required, was tested in Sprague-Dawley rats. Male weanling Fischer-344 rats were fed three different lots of the AIN-76A diet from two suppliers. Increase in body weights and food consumption were compared to animals fed a cereal-based control diet. Animals were sacrificed at various intervals and tissues were taken for histopathological observation. By 8 weeks moderate to marked periportal lipidosis developed in livers of all rats fed the AIN-76A diet. Liver-body weight ratios over the 8-week period were significantly higher in rats fed AIN-76A diets compared to rats fed the control diet. However, growth rates of rats fed the AIN-76A diet were similar to growth rates of controls. Some rats fed the AIN-76A diet developed severe hemorrhagic lesions. The AIN-76A diet in its present form is not suitable for use with male Fischer-344 rats.


title: Digital Dashboard Design Using Multiple Data Streams for Disease Surveillance With Influenza Surveillance as an Example

text: BACKGROUND: Great strides have been made exploring and exploiting new and different sources of disease surveillance data and developing robust statistical methods for analyzing the collected data. However, there has been less research in the area of dissemination. Proper dissemination of surveillance data can facilitate the end user's taking of appropriate actions, thus maximizing the utility of effort taken from upstream of the surveillance-to-action loop. OBJECTIVE: The aims of the study were to develop a generic framework for a digital dashboard incorporating features of efficient dashboard design and to demonstrate this framework by specific application to influenza surveillance in Hong Kong. METHODS: Based on the merits of the national websites and principles of efficient dashboard design, we designed an automated influenza surveillance digital dashboard as a demonstration of efficient dissemination of surveillance data. We developed the system to synthesize and display multiple sources of influenza surveillance data streams in the dashboard. Different algorithms can be implemented in the dashboard for incorporating all surveillance data streams to describe the overall influenza activity. RESULTS: We designed and implemented an influenza surveillance dashboard that utilized self-explanatory figures to display multiple surveillance data streams in panels. Indicators for individual data streams as well as for overall influenza activity were summarized in the main page, which can be read at a glance. Data retrieval function was also incorporated to allow data sharing in standard format. CONCLUSIONS: The influenza surveillance dashboard serves as a template to illustrate the efficient synthesization and dissemination of multiple-source surveillance data, which may also be applied to other diseases. Surveillance data from multiple sources can be disseminated efficiently using a dashboard design that facilitates the translation of surveillance information to public health actions.


title: Global research trends of Middle East respiratory syndrome coronavirus: a bibliometric analysis

text: BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is a virus that causes severe viral pneumonia in humans, known to have a high mortality rate and a similarity in clinical symptoms with severe acute respiratory syndrome coronavirus. It was first isolated in Kingdom of Saudi Arabia (KSA) in 2012 and after that, MERS-CoV exhibited outbreaks in several regions of the world. This study aimed to assess the characteristics of publications involving MERS-CoV at global level by using a bibliometric analysis. METHODS: Scopus database was searched on March 4, 2016 for MERS-CoV publications published between 2012 and 2015. It was performed on the same day in order to avoid the possible bias came from update on the database because the metrics are changing over time. All publication types were considered; however publications as errata were excluded. Analysis parameters include year of publication, publication type, patterns of international collaboration, research institutions, journals, impact factor, h-index, language, and times cited. RESULTS: A total of 883 MERS-CoV research publications were published across the world. The MERS-CoV-associated publications were originated from 92 countries/territories, indicating the international spread of MERS-CoV research. The USA was the largest contributor, with 319 articles published over 4 years, followed by KSA (113 articles). The total number of citations for these publications has already achieved 8,015, with an average of 9.01 citations per each publication. The h-index for MERS-CoV-associated publications was 48. The USA also have the highest h-index (32), followed by KSA (26) and UK (22). Netherland produced the greatest proportion of publications with international research collaboration (72.7 %) followed by the UK (71 %) and Germany (69.1 %) out of the total number of publications for each country. CONCLUSIONS: There is a rapid increase in research activities related to MERS-CoV from 2012 to 2015. This study demonstrates that the MERS-CoV related literature has grown to be more extensive and global over the past 4 years. The bulk of publications in the field of MERS-CoV research are published by high-income countries such as the USA. Furthermore, the USA, the UK and KSA may have higher quality of articles according to the value of h-index.


title: Association of inflammatory markers with the severity of COVID-19: a meta-analysis

text: Abstract Objectives Studies reported associations of inflammatory markers with the severity of COVID-19, but conclusions were inconsistent. We aimed to provide an overview of the association of inflammatory markers with severity of COVID-19. Methods We searched PubMed, Embase, Cochrane Library, Wanfang and China National Knowledge Infrastructure (CNKI) database until March 20, 2020. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were pooled using random or fixed-effects models. Results A total of 16 studies comprising of 3962 patients with COVID-19 were included in our analysis. Random-effect results demonstrated that patients with COVID-19 in nonsevere group had lower levels for CRP (WMD = -41.78 mg/l, 95% CI = [-52.43, -31.13], P < 0.001), PCT (WMD = -0.13 ng/ml, 95% CI = [-0.20, -0.05], P < 0.001), IL-6 (WMD = -21.32 ng/l, 95% CI = [-28.34, -14.31], P < 0.001), ESR (WMD = −8 mm/h, 95% CI = [-14, -2], P = 0.005), SAA (WMD = -43.35 μg/ml, 95% CI = [-80.85, -5.85], P = 0.020) and serum ferritin (WMD = -398.80 mg/l, 95% CI = [-625.89, -171.71], P < 0.001), compared with those in severe group. Moreover, survivors had a lower level for IL-6 than non-survivors (WMD = -4.80 ng/ml, 95% CI = [-5.87, -3.73], P < 0.001). These results were consistent through sensitivity analysis and publication bias assessment. Conclusions The meta-analysis highlights the association of inflammatory markers with the severity of COVID-19. Measurement of inflammatory markers might assist clinicians to monitor and evaluate the severity and prognosis of COVID-19.


title: Viral Agents Causing Acute Respiratory Infections in Children under Five: A Study from Eastern India

text: Background. Acute respiratory infections (ARIs) are important cause of mortality and morbidity in children under five in developing country. Methods. This observational study was conducted over two-year period in a tertiary care teaching hospital of Eastern India. Nasal and throat swabs were collected, transported to the laboratory at 2–8°C in viral transport media, and then processed for detection of viruses using mono/multiplex real-time polymerase chain reaction. Results. A total of 300 children aged 2–60 months with ARIs were included. The most common age group affected with LRI was 2–12 mo and with URI was >12–60 mo. Viruses were detected in 248 cases. In URI, 77 were positive for single virus and 19 were positive for more than one virus; in LRI, 113 were positive for single virus and 12 were positive for more than one virus. The most common viruses isolated from URI cases were rhinovirus and adenovirus. The most common viruses isolated from LRI cases were respiratory syncytial virus and influenza virus. Most cases occurred in the months of January, December, and August. Conclusion. Viruses constitute a significant cause of ARI in children under five. RSV, ADV, RV, and IFV were the most prevalent viruses isolated.


title: Nursery pig growth performance and tissue accretion modulation due to porcine epidemic diarrhea virus or porcine deltacoronavirus challenge

text: Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) are both members of the family Coronaviridae which induce clinical signs of diarrhea, dehydration, and in some circumstances, mortality. Most research has been focused on isolation, genome sequencing, pathogenicity, and virulence of these viruses, but there is little information on long-term growth performance and tissue accretion of pigs inoculated with PEDV or PDCoV. Therefore, our objective was to determine the effect of PEDV or PDCoV infection on growth performance and tissue accretion over 42 d following inoculation. A total of 75 Choice Genetics Large White Pureline barrows and gilts (BW = 10.81 ± 0.81 kg) at approximately 2 wk post-wean and naïve for PEDV and PDCoV were selected. Pigs were allotted based on BW and sex, stratified across 3 treatments with 8 pens per treatment. Treatments were: 1) Control (n = 8); 2) PEDV inoculated (n = 8); and 3) PDCoV inoculated (n = 8). On day post inoculation (dpi) 2, 5, 7, and 14 pigs were euthanized for tissue collection and analyses from these tissues are discussed elsewhere. Pen feed intake and BW were recorded on dpi 2, 5, 7, and weekly thereafter until dpi 42. On 1 designated pig per pen, initial and final body composition was determined using dual-energy X-ray absorptiometry (DXA) and tissue accretion rates were calculated over 6 wk test period. Peak PEDV infection was noted at 3 dpi compared with 4 dpi for PDCoV pigs as determined by fecal swab quantitative real-time PCR (RT-PCR). Control pigs remained negative for PEDV and PDCoV throughout the experiment. Overall, Control and PDCoV pigs did not differ in ADG, ADFI or G:F (P > 0.05). Compared to Control and PDCoV pigs, the overall 42 d ADFI was reduced in the challenged PEDV pigs (P < 0.05) by 19 and 27%, respectively. PEDV did not significantly reduce the overall ADG or G:F compared with Control and PDCoV pigs; however, the biggest reduction in ADG and ADFI for PEDV pigs was within 14 dpi compared to the Control pigs (P < 0.05). Whole body tissue accretion was altered due to PED, with fat, lean, protein, and bone mineral accretion reductions by 24, 20, 21, and 42%, respectively (P < 0.05) compared with Control pigs. Overall, nursery pig performance was greatly impacted by PEDV challenge. Surprisingly, the PDCoV challenge did not negatively influence nursery pig performance. This study provides further insight into the longitudinal impact swine enteric coronaviruses have on growing pigs.


title: Toward a Durable Anti‐HIV Gene Therapy Based on RNA Interference

text: Basic research in the field of molecular biology led to the discovery of the mechanism of RNA interference (RNAi) in Caenorhabditis elegans in 1998. RNAi is now widely appreciated as an important gene control mechanism in mammals, and several RNAi‐based gene‐silencing applications have already been used in clinical trials. In this review I will discuss RNAi approaches to inhibit the pathogenic human immunodeficiency virus type 1 (HIV‐1), which establishes a chronic infection that would most likely require a durable gene therapy approach. Viruses, such as HIV‐1, are particularly difficult targets for RNAi attack because they mutate frequently, which allows viral escape by mutation of the RNAi target sequence. Combinatorial RNAi strategies are required to prevent viral escape.


title: Geo-temporal distribution of 1,688 Chinese healthcare workers infected with COVID-19 in severe conditions—A secondary data analysis

text: INTRODUCTION: The COVID-19 outbreak is posing an unprecedented challenge to healthcare workers. This study analyzes the geo-temporal effects on disease severity for the 1,688 Chinese healthcare workers infected with COVID-19. METHODS: Using the descriptive results recently reported by the Chinese CDC, we compare the percentage of infected healthcare workers in severe conditions over time and across three areas in China, and the fatality rate of infected healthcare workers with all the infected individuals in China aged 22–59 years. RESULTS: Among the infected Chinese healthcare workers whose symptoms onset appeared during the same ten-day period, the percentage of those in severe conditions decreased significantly from 19.7% (Jan 11–20) to 14.4% (Jan 21–31) to 8.7% (Feb 1–11). Across the country, there was also a significant difference in the disease severity, with Wuhan being the most severe (17.3%), followed by Hubei Province (10.2%), and the rest of China (6.6%). The case fatality rate for the 1,688 infected Chinese healthcare workers was significantly lower than that for the 29,798 infected patients aged 20–59 years—0.3% (5/1,688) vs. 0.65% (193/29,798), respectively. CONCLUSION: The disease severity among infected healthcare workers improved considerably over a short period of time in China. The more severe conditions in Wuhan compared to the rest of the country may be attributable to the draconian lockdown. The clinical outcomes of infected Chinese healthcare workers may represent a more accurate estimation of the severity of COVID-19 for those who have access to quality healthcare.