title: Archetype analysis of older adult immunization decision-making and implementation in 34 countries

text: The global population of adults over 65 years of age is growing rapidly and is expected to double by 2050. Countries will face substantial health, economic and social burden deriving from vaccine-preventable diseases (VPDs) such as influenza, pneumonia and herpes zoster in older adults. It will be essential that countries utilize several public health strategies, including immunization. Understanding the different approaches countries have taken on adult immunization could help provide future learnings and technical support for adult vaccines within life-course immunization strategies. In this study, we describe the priorities and approaches that underlie adult immunization decision-making and implementation processes in 32 high-and-middle-income countries and two territories (“34 countries”) who recommend adult vaccines in their national schedule. We conducted an archetype analysis based on a subset of two dozen indicators abstracted from a larger database. The analysis was based on a mixed-methods study, including results from 120 key informant interviews in six countries and a landscape review of secondary data from 34 countries. We found four distinct archetypes: disease prevention-focused; health security-focused; evolving adult focus; and, child-focused and cost-sensitive. The highest performing countries belonged to the disease prevention-focused and health security archetypes, although there was a range of performance within each archetype. Considering common barriers and facilitators of decision-making and implementation of adult vaccines within a primary archetype could help provide a framework for strategies to support countries with similar needs and approaches. It can also help in developing context-specific policies and guidance, including for countries prioritizing adult immunization programs in light of COVID-19. Further research may be beneficial to further refine archetypes and expand the understanding of what influences success within them. This can help advance policies and action that will improve vaccine access for older adults and build a stronger appreciation of the value of immunization amongst a variety of stakeholders.


title: The impact of persistent bacterial bronchitis on the pulmonary microbiome of children

text: Persistent bacterial bronchitis is a leading cause of chronic wet cough in young children. This study aimed to characterise the respiratory bacterial microbiota of healthy children and to assess the impact of the changes associated with the development of persistent bacterial bronchitis. Blind, protected brushings were obtained from 20 healthy controls and 24 children with persistent bacterial bronchitis, with an additional directed sample obtained from persistent bacterial bronchitis patients. DNA was extracted, quantified using a 16S rRNA gene quantitative PCR assay prior to microbial community analysis by 16S rRNA gene sequencing. No significant difference in bacterial diversity or community composition (R2 = 0.01, P = 0.36) was observed between paired blind and non-blind brushes, showing that blind brushings are a valid means of accessing the airway microbiota. This has important implications for collecting lower respiratory samples from healthy children. A significant decrease in bacterial diversity (P < 0.001) and change in community composition (R2 = 0.08, P = 0.004) was observed between controls and patients. Bacterial communities within patients with PBB were dominated by Proteobacteria, and indicator species analysis showed that Haemophilus and Neisseria were significantly associated with the patient group. In 15 (52.9%) cases the dominant organism by sequencing was not identified by standard routine clinical culture. The bacteria present in the lungs of patients with persistent bacterial bronchitis were less diverse in terms of richness and evenness. The results validate the clinical diagnosis, and suggest that more attention to bacterial communities in children with chronic cough may lead to more rapid recognition of this condition with earlier treatment and reduction in disease burden.


Lesiones Cutáneas Tipo Perniosis Durante La Epidemia Covid-19


title: 4 Urbanization and the social ecology of emerging infectious diseases

text: Publisher Summary The advent and effective use of new drugs, vaccines, insecticides, treatment, and prevention strategies during and following World War II reinforced public health programs already in place, and provided the tools needed to bring many of the worst diseases under control. Smallpox was eradicated using a mass vaccination strategy. The major successes in controlling infectious diseases in the 1950s and 1960s was followed by two coincident global trends that would have an impact on the dramatic reemergence of infectious diseases in the waning years of the twentieth century. The first was the redirection of the resources that were once used to control infectious diseases to other public health priorities, such as the “War on Cancer” in the early 1970s. The perception that infectious diseases were no longer a problem led to decreased resources, widespread deterioration of public health infrastructure to deal with infectious diseases, and complacency among government and public health officials as well as the public. This trend included medical education with a deemphasis on preventive medicine and a strong focus on curative medicine in medical schools. The second trend was the sharply increasing and unprecedented rate of human population growth following World War II that has continued for 60 years. Increasing human numbers have been a principal factor leading to uncontrolled urbanization, changes in agriculture, land use and animal husbandry practices, and accelerated globalization, all of which have been major and interrelated drivers of the reemergence of epidemic infectious diseases.


title: Impact of Influenza on Pneumococcal Vaccine Effectiveness during Streptococcus pneumoniae Infection in Aged Murine Lung

text: Changes in innate and adaptive immune responses caused by viral imprinting can have a significant direct or indirect influence on secondary infections and vaccine responses. The purpose of our current study was to investigate the role of immune imprinting by influenza on pneumococcal vaccine effectiveness during Streptococcus pneumoniae infection in the aged murine lung. Aged adult (18 months) mice were vaccinated with the pneumococcal polyvalent vaccine Pneumovax (5 mg/mouse). Fourteen days post vaccination, mice were instilled with PBS or influenza A/PR8/34 virus (3.5 × 10(2) PFU). Control and influenza-infected mice were instilled with PBS or S. pneumoniae (1 × 10(3) CFU, ATCC 6303) on day 7 of infection and antibacterial immune responses were assessed in the lung. Our results illustrate that, in response to a primary influenza infection, there was diminished bacterial clearance and heightened production of pro-inflammatory cytokines, such as IL6 and IL1β. Vaccination with Pneumovax decreased pro-inflammatory cytokine production by modulating NFҡB expression; however, these responses were significantly diminished after influenza infection. Taken together, the data in our current study illustrate that immune imprinting by influenza diminishes pneumococcal vaccine efficacy and, thereby, may contribute to increased susceptibility of older persons to a secondary infection with S. pneumoniae.


Psychotropics drugs with cationic amphiphilic properties may afford some protection against SARS-CoV-2: a mechanistic hypothesis


title: Chapter 12 Coronaviridae

text: Publisher Summary Coronaviruses are spherical, lipid-containing, enveloped particles with tear-dropshaped surface projections or peplomers. The genome is one molecule of ssRNA and the virions characteristically contain three major structural protein classes. The antigenic relationships of coronaviruses present a complex pattern. The geographic distribution of many coronaviruses is worldwide. Biological vectors of coronaviruses have not been reported, and the natural hosts form the major reservoirs for further infection. Coronavirus particles contain three major protein classes, within which the polypeptides vary in number and molecular weight between species. The apparent size and shapes of coronaviruses can vary considerably. Coronavirus particles are spherical, although negatively stained air-dried particles are often pleomorphic. The morphology of coronavirus surface projections can vary considerably between different strains. The conventional structure on negative staining consists of tear-drop-shaped projections, although cone-shaped projections are also observed. In all these cases, the projections have the same length of about 20 nm. Other coronaviruses have short as well as 20-nm projections. Projections with blebs on thin stalks have been reported for other coronaviruses.


title: COVID-19 and MS disease-modifying therapies

text: OBJECTIVE: To address concerns regarding the effect of MS disease-modifying therapies (DMTs) on the expression of coronavirus 2019 (COVID-19). METHODS: Review of the current state of knowledge regarding the viral etiology of COVID-19, mechanisms of injury by SARS-CoV-2 infection, and the effect of individual DMTs on the risk of infection and COVID-19 disease expression. RESULTS: Although data are limited, MS DMTs do not obviously increase the risk of acquiring symptomatic SARS-CoV-2 infection. The severe morbidity and mortality of SARS-CoV-2 appear to be largely the consequence of an overly robust immune response rather than the consequence of unchecked viral replication. The effects of specific MS DMTs on the immune response that may increase the risk of impaired viral clearance and their potential counterbalancing beneficial effects on the development of COVID-19–associated acute respiratory distress syndrome are reviewed. CONCLUSION: Although there is currently insufficient real-world experience to definitively answer the question of the effect of a specific MS DMT on COVID-19, registries presently in nascent form should provide these answers. This review provides an approach to addressing these concerns while the data are being accumulated. Early insights suggest that the risk of infection and associated morbidity of COVID-19 in this population is little different than that of the population at large.


title: Hydropathic characteristics of adenovirus hexons

text: The complete nucleotide sequence and the predicted amino acid sequence of the adenovirus type 7 hexon gene were determined. The hydro-pathy of the hexon proteins from human adenovirus types 2, 3, 4, 5, 7, 12, 16, 40, 41, and 48, bovine adenovirus type 3, murine adenovirus type 1, and avian adenovirus types 1 and 10 was analysed. The presence of purines and pyrimid-ines in the second position of the codons was correlated to hydrophilicity and hydrophobicity, respectively. Comparison of the hydrophilicity plots of eight hexons showed seven hypervariable regions to be distributed on the surface. A large portion of the hypervariable regions manifests hydrophilicity. The strength of the surface charge accumulated on the hydrophilic and hydrophobic regions correlated to the tissue tropism of the different adenovirus types. Analysis of codon usage for adenovirus hexons showed that among synony-mous codons those with cytidine in the third position were preferably used to a great extent. Analysis of the nucleotide and amino acid sequence pair distances and the phylogenetic tree of 14 hexon proteins showed members of subgenera B, D and E to be closely related, especially Ad4 and Ad16, and subgenus A to be closely related to subgenus F.


title: Could HIV infection alter the clinical course of SARS‐CoV‐2 infection? When less is better

text: Recently, the first case of HIV and SARS‐CoV‐2 infection was reported in the literature. With this letter, we proposed a hypothesis that could explain the interaction between HIV infection and the clinical course of SARS‐CoV‐2 infection. This article is protected by copyright. All rights reserved.


title: Synthetic peptides derived from SARS coronavirus S protein with diagnostic and therapeutic potential

text: Abstract The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is an important viral structural protein. Based on bioinformatics analysis, 10 antigenic peptides derived from the S protein sequence were selected and synthesized. The antigenicity and immunoreactivity of all the peptides were tested in vivo and in vitro. Four peptides (P6, P8, P9 and P10) which contain B cell epitopes of the S protein were identified, and P8 peptide was confirmed in vivo to have a potential in serological diagnosis. By using a syncytia formation model, we tested the neutralization ability of all 10 peptides and their corresponding antibodies. It is interesting to find that P8 and P9 peptides inhibited syncytia formation, suggesting that the P8 and P9 spanning regions may provide a good target for anti-SARS-CoV drug design. Our data suggest that we have identified peptides derived from the S protein of SARS-CoV, which are useful for SARS treatment and diagnosis.


title: Rationale for the clinical use of adipose-derived mesenchymal stem cells for COVID-19 patients

text: In late 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan, capital city of Hubei province in China. Cases of SARS-CoV-2 infection quickly grew by several thousand per day. Less than 100 days later, the World Health Organization declared that the rapidly spreading viral outbreak had become a global pandemic. Coronavirus disease 2019 (COVID-19) is typically associated with fever and respiratory symptoms. It often progresses to severe respiratory distress and multi-organ failure which carry a high mortality rate. Older patients or those with medical comorbidities are at greater risk for severe disease. Inflammation, pulmonary edema and an over-reactive immune response can lead to hypoxia, respiratory distress and lung damage. Mesenchymal stromal/stem cells (MSCs) possess potent and broad-ranging immunomodulatory activities. Multiple in vivo studies in animal models and ex vivo human lung models have demonstrated the MSC’s impressive capacity to inhibit lung damage, reduce inflammation, dampen immune responses and aid with alveolar fluid clearance. Additionally, MSCs produce molecules that are antimicrobial and reduce pain. Upon administration by the intravenous route, the cells travel directly to the lungs where the majority are sequestered, a great benefit for the treatment of pulmonary disease. The in vivo safety of local and intravenous administration of MSCs has been demonstrated in multiple human clinical trials, including studies of acute respiratory distress syndrome (ARDS). Recently, the application of MSCs in the context of ongoing COVID-19 disease and other viral respiratory illnesses has demonstrated reduced patient mortality and, in some cases, improved long-term pulmonary function. Adipose-derived stem cells (ASC), an abundant type of MSC, are proposed as a therapeutic option for the treatment of COVID-19 in order to reduce morbidity and mortality. Additionally, when proven to be safe and effective, ASC treatments may reduce the demand on critical hospital resources. The ongoing COVID-19 outbreak has resulted in significant healthcare and socioeconomic burdens across the globe. There is a desperate need for safe and effective treatments. Cellular based therapies hold great promise for the treatment of COVID-19. This literature summary reviews the scientific rationale and need for clinical studies of adipose-derived stem cells and other types of mesenchymal stem cells in the treatment of patients who suffer with COVID-19.


title: The role of phosphatidylinositol 4-kinases and phosphatidylinositol 4-phosphate during viral replication

text: Abstract Phosphoinositides (PI) are phospholipids that mediate signaling cascades in the cell by binding to effector proteins. Reversible phosphorylation of the inositol ring at positions 3, 4 and 5 results in the synthesis of seven different phosphoinositides. Each phosphoinositide has a unique subcellular distribution with a predominant localization in subsets of membranes. These lipids play a major role in recruiting and regulating the function of proteins at membrane interfaces [1]. Several bacteria and viruses modulate and exploit the host PI metabolism to ensure efficient replication and survival. Here, we focus on the roles of cellular phosphatidylinositol 4-phosphate (PI4P) and phosphatidylinositol 4-kinases (PI4Ks) during the replication cycle of various viruses. It has been well documented that phosphatidylinositol 4-kinase IIIβ (PI4KIIIβ, EC 2.7.1.67) is indispensable for viral RNA replication of several picornaviruses. Two recruitment strategies were reported: (i) binding and modulation of GBF1/Arf1 to enhance recruitment of PI4KIIIβ and (ii) interaction with ACBD3 for recruitment of PI4KIIIβ. PI4KIII has also been demonstrated to be crucial for hepatitis C virus (HCV) replication. PI4KIII appears to be directly recruited and activated by HCV NS5A protein to the replication complexes. In contrast to picornaviruses, it is still debated whether the α or the β isoform is the most important. PI4KIII can be explored as a target for inhibition of viral replication. The challenge will be to develop highly selective inhibitors for PI4KIIIα and/or β and to avoid off-target toxicity.


title: A fatal case associated with respiratory syncytial virus infection in a young child

text: BACKGROUND: Respiratory syncytial virus (RSV) is the most common viral cause of pediatric bronchiolitis and pneumonia worldwide. Risk factors for high mortality and prolonged morbidity after RSV infection include premature birth, bronchopulmonary dysplasia, congenital heart disease, and Down syndrome. However, some previously healthy, full-term children who are infected with RSV also require hospitalization and even experience severe sequelae or death. CASE PRESENTATION: In this report, we present the case of an RSV-associated death of a child who was born at full-term and developed normally up to the age of 2 years old. Cardiopulmonary arrest occurred within 3 days after the onset of symptoms, which included cough and high fever. Complete brain edema was prominent, and encephalopathy was developing. Viral antigen detection and microbiome analyses of oral swab and nasopharyngeal aspirate specimens verified an RSV infection, while bacterial culture of blood specimens yielded negative results. The RSV strain detected in this patient was subtyped as RSVB9, and no mutation was found in the six antigenic sites for targeted drugs or vaccines. CONCLUSIONS: The patient had a severe infection associated with RSV, which was very likely the cause of her central nervous system infection and acute neurological complications.


title: Bat-Origin Coronaviruses Expand Their Host Range to Pigs

text: Infections with bat-origin coronaviruses have caused severe illness in humans by ‘host jump’. Recently, novel bat-origin coronaviruses were found in pigs. The large number of mutations on the receptor-binding domain allowed the viruses to infect the new host, posing a potential threat to both agriculture and public health.


title: Low pathogenic avian influenza virus infection increases the staining intensity of KUL01+ cells including macrophages yet decrease of the staining intensity of KUL01+ cells using clodronate liposomes did not affect the viral genome loads in chickens

text: Abstract The effect of depletion of macrophages using clodronate liposomes as well as macrophage response following viral infections have been studied in various mouse-virus infection models, but they have not been extensively studied in chickens relevant to virus infections. When we infected day 6 chickens with H4N6 low pathogenic avian influenza virus (LPAIV), we observed that H4N6 LPAIV infection increased the staining intensity of KUL01+ cells in trachea, lungs and duodenum of chickens at 3 days post-infection. Then, we used clodronate liposomes intra-abdominally in 5 day-old chickens and found significant reduction of staining intensity of KUL01+ cells in trachea and duodenum but not in lungs at 4 days post-treatment. When we infected the clodronate liposome and PBS liposome treated chickens with H4N6 LPAIV intra-nasally at day 6, we found no effect on H4N6 LPAIV genome loads in trachea, lungs and duodenum of chickens. This study indicates that although KUL01+ cell intensity are increased in respiratory and gastrointestinal tissues in chickens following H4N6 LPAIV infection, the decrease of KUL01+ cell intensity using clodronate liposomes did not change the H4N6 LPAIV genome loads in any of the examined tissues suggesting that KUL01+ cells may not be critical during H4N6 LPAIV infection in chicken.


A Case of Long-term Excretion and Subclinical Infection With Middle East Respiratory Syndrome Coronavirus in a Healthcare Worker


title: SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection

text: Autophagy is an essential cellular process affecting virus infections and other diseases and Beclin1 (BECN1) is one of its key regulators. Here, we identified S-phase kinase-associated protein 2 (SKP2) as E3 ligase that executes lysine-48-linked poly-ubiquitination of BECN1, thus promoting its proteasomal degradation. SKP2 activity is regulated by phosphorylation in a hetero-complex involving FKBP51, PHLPP, AKT1, and BECN1. Genetic or pharmacological inhibition of SKP2 decreases BECN1 ubiquitination, decreases BECN1 degradation and enhances autophagic flux. Middle East respiratory syndrome coronavirus (MERS-CoV) multiplication results in reduced BECN1 levels and blocks the fusion of autophagosomes and lysosomes. Inhibitors of SKP2 not only enhance autophagy but also reduce the replication of MERS-CoV up to 28,000-fold. The SKP2-BECN1 link constitutes a promising target for host-directed antiviral drugs and possibly other autophagy-sensitive conditions.


title: Radix Bupleuri: A Review of Traditional Uses, Botany, Phytochemistry, Pharmacology, and Toxicology

text: Radix Bupleuri (Chaihu) has been used as a traditional medicine for more than 2000 years in China, Japan, Korea, and other Asian countries. Phytochemical studies demonstrated that this plant contains essential oils, triterpenoid saponins, polyacetylenes, flavonoids, lignans, fatty acids, and sterols. Crude extracts and pure compounds isolated from Radix Bupleuri exhibited various biological activities, such as anti-inflammatory, anticancer, antipyretic, antimicrobial, antiviral, hepatoprotective, neuroprotective, and immunomodulatory effects. However, Radix Bupleuri could also lead to hepatotoxicity, particularly in high doses and with long-term use. Pharmacokinetic studies have demonstrated that the major bioactive compounds (saikosaponins a, b(2), c, and d) were absorbed rapidly in rats after oral administration of the extract of Radix Bupleuri. This review aims to comprehensively summarize the traditional uses, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics of Radix Bupleuri reported to date with an emphasis on its biological properties and mechanisms of action.


title: Rapid production of antigen-specific monoclonal antibodies from a variety of animals

text: BACKGROUND: Although a variety of animals have been used to produce polyclonal antibodies against antigens, the production of antigen-specific monoclonal antibodies from animals remains challenging. RESULTS: We propose a simple and rapid strategy to produce monoclonal antibodies from a variety of animals. By staining lymph node cells with an antibody against immunoglobulin and a fluorescent dye specific for the endoplasmic reticulum, plasma/plasmablast cells were identified without using a series of antibodies against lineage markers. By using a fluorescently labeled antigen as a tag for a complementary cell surface immunoglobulin, antigen-specific plasma/plasmablast cells were sorted from the rest of the cell population by fluorescence-activated cell sorting. Amplification of cognate pairs of immunoglobulin heavy and light chain genes followed by DNA transfection into 293FT cells resulted in the highly efficient production of antigen-specific monoclonal antibodies from a variety of immunized animals. CONCLUSIONS: Our technology eliminates the need for both cell propagation and screening processes, offering a significant advantage over hybridoma and display strategies.


title: Knowledge and Information Sources About COVID-19 Among University Students in Jordan: A Cross-Sectional Study

text: Background: Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide, and it was officially declared to be a pandemic by the World Health Organization (WHO) on March 11, 2020. Most countries over the entire globe have reported some COVID-19 cases. The current study aimed to assess student knowledge about COVID-19 at different Jordanian universities and determine where they sourced their information. Methods:A cross-sectional study was conducted among 2,083 undergraduate or postgraduate students from different governmental and private universities during the initial stage of the disease in Jordan (March 19–21, 2020) using a validated, structured, self-administered, online questionnaire. The survey was structured to assess their knowledge about viral sources, incubation period, mortality rate, transmission, symptoms and complications as well as the source of information about COVID-19. Results:Overall, 56.5% of the respondents showed good knowledge and almost 40.5% showed moderate knowledge. On the other hand, 3.0% of the participants showed poor knowledge about COVID-19. The average knowledge score of students was 80.1%, which is considered to be within the scale of good knowledge. Both the college of study and educational level significantly (P < 0.05) associated with student knowledge. Students who majored in medical sciences showed the highest mean score of 82.8%, with 69.0% displaying a good knowledge level. Postgraduate students had significantly higher knowledge scores compared to undergraduate students. The majority of students used the internet, social media and mass media as sources of information about COVID-19. Scientific websites and articles were used more commonly by medical and postgraduate students. Conclusions:The COVID-19 pandemic is a major challenge to the health of the world population; therefore, these results assessing students' knowledge provide an important baseline for planning required educational interventions such as contact tracing and self-quarantine. These results may also help public health authorities by engaging communities in implementation of protective health measures, including positive hygienic practices such as hand washing to reduce the risk of COVID-19.


title: A Comparative Study of Chest Computed Tomography Features in Young and Older Adults With Corona Virus Disease (COVID-19)

text: To analyze the most common computed tomography (CT) findings of pneumonia caused by new coronavirus in younger patients (60 and younger) and older adults (older than 60). MATERIALS AND METHODS: The chest CT images of 72 symptomatic patients with corona virus disease (COVID-19) were analyzed retrospectively, including 44 younger patients (47.5±8.7 y old) and 28 older patients (68.4±6.0 y old). CT findings including density (pure ground-glass opacities, ground-glass opacities with consolidation, consolidation), the number of lobes involved, lesion distribution, and the main accompanying signs were analyzed and compared. RESULTS: Characteristic CT findings included the lobes of bilateral lung extensively involved, ground-glass opacity and ground-glass opacity with consolidation in the peripheral area, sometimes accompanied by interlobular septal thickening, and subpleural line and pleural thickening. Compared with the younger group, the proportion of extensive involvement of lung lobes was higher in the elderly group (71.4% vs. 36.4%, P=0.009), and subpleural line and pleural thickening were more likely to occur (50.0% vs. 25.0%, and 71.4% vs. 40.9%, P=0.030 and 0.011, respectively). CONCLUSION: Elderly and younger patients with corona virus disease have some common CT features, but older patients are more likely to have extensive lung lobe involvement, and subpleural line and pleural thickening. These differentiated characteristics may be related to the progress and prognosis of the disease.


Reply to Siniorakis et al., “COVID-19 Interference with Renin-Angiotensin System in the Context of Heart Failure”


title: Respiratory Syncytial Virus and Other Noninfluenza Respiratory Viruses in Older Adults

text: Respiratory viral infections may cause serious complications for older adults, including residents of long-term care facilities (LTCFs). While influenza is the most common cause of viral respiratory infections among older adults, several other respiratory viruses also cause significant morbidity and mortality, most notably respiratory syncytial virus. Other noninfluenza respiratory viral pathogens include human metapneumovirus, parainfluenza virus, rhinovirus, coronavirus, and adenovirus. All of these may cause outbreaks among LTCF residents. Recently developed rapid diagnostic molecular tests may clarify the epidemiology of these viruses and have potential, through early identification, to limit the severity of outbreaks among older adults living in LTCFs.


title: Morphological anomalies of circulating blood cells in COVID‐19

text: In patients with COIVD-19, in the early aggravation phase before treatment, observation of peripheral blood film shows the presence of pronounced morhological anomalies of the granulocyte series. One week after the start of treatment, such anomalies subside, and an increasing proportion of reactive lymphocytes dominates. This article is protected by copyright. All rights reserved.


title: Pathogenic priming likely contributes to serious and critical illness and mortality in COVID-19 via autoimmunity

text: Abstract Homology between human and viral proteins is an established factor in viral- or vaccine-induced autoimmunity. Failure of SARS and MERS vaccines in animal trials involved pathogenesis consistent with an immunological priming that could involve autoimmunity in lung tissues due to previous exposure to the SARS and MERS spike protein. Exposure pathogenesis to SARS-CoV-2 in COVID-19 likely will lead to similar outcomes. Immunogenic peptides in viruses or bacteria that match human proteins are good candidates for pathogenic priming peptides (similar to the more diffuse idea of “immune enhancement”). Here I provide an assessment of potential for human pathogenesis via autoimmunity via exposure, via infection or injection. SAR-CoV-2 spike proteins, and all other SARS-CoV-2 proteins, immunogenic epitopes in each SARS-CoV-2 protein were compared to human proteins in search of high local homologous matching. Only one immunogenic epitope in a SARS-CoV-2 had no homology to human proteins. If all of the parts of the epitopes that are homologous to human proteins are excluded from consideration due to risk of pathogenic priming, the remaining immunogenic parts of the epitopes may be still immunogenic and remain as potentially viable candidates for vaccine development. Mapping of the genes encoding human protein matches to pathways point to targets that could explain the observed presentation of symptoms in COVID-19 disease. It also strongly points to a large number of opportunities for expected disturbances in the immune system itself, targeting elements of MHC Class I and Class II antigen presentation, PD-1 signaling, cross-presentation of soluble exogenous antigens and the ER-Phagosome pathway. Translational consequences of these findings are explored.


title: A recombinant Lactobacillus plantarum strain expressing the spike protein of SARS-CoV-2

text: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic in the past four months and causes respiratory disease in humans of almost all ages. Although several drugs have been announced to be partially effective treatments for this disease, no approved vaccine is available. Here, we described the construction of a recombinant Lactobacillus plantarum strain expressing the SARS-CoV-2 spike protein. The results showed that the spike gene with optimized codons could be efficiently expressed on the surface of recombinant L. plantarum and exhibited high antigenicity. The highest protein yield was obtained under the following conditions: cells were induced with 50 ng/mL SppIP at 37 °C for 6–10 h. The recombinant spike (S) protein was stable under normal conditions and at 50 °C, pH = 1.5, or a high salt concentration. Recombinant L. plantarum may provide a promising food-grade oral vaccine candidate against SARS-CoV-2 infection.


title: COVID-19: Financial Stress Test for Academic Medical Centers

text: The coronavirus pandemic (COVID-19) is having profound effects on the lives and well-being of the world’s population. All levels of the nation’s public health and health care delivery systems are rapidly adjusting to secure the health infrastructure to manage the pandemic in the United States. As the nation’s safety net health care systems, academic medical centers (AMCs) are vital clinical and academic resources in managing the pandemic. COVID-19 may also risk the financial underpinnings of AMCs because their cost structures are high, and they may have incurred large amounts of debt over the last decade as they expanded their clinical operations and facilities. This Invited Commentary reviews existing data on AMC debt levels; summarizes relief provided in the Coronavirus Aid, Relief, and Economic Security Act; and suggests policy options to help mitigate risk.


title: Bat research takes wing

text: In the field and in the lab, scientists across the globe are working to better understand the biology of the bat


title: Mental health and capacity laws in Northern Ireland and the COVID-19 pandemic: Examining powers, procedures and protections under emergency legislation

text: This article examines the changes made to mental health and capacity laws in Northern Ireland through temporary emergency legislation, known as the Coronavirus Act 2020. The purpose of the legislation was to respond to the emergency situation created by the COVID-19 pandemic, in particular the increase pressure placed on health services in the United Kingdom. An overview is provided of the government's rationale for the changes to Northern Ireland mental health and capacity laws, as well as exploring how they are likely to be operationalised in practice. Consideration is also given as to how such changes may impact upon existing human rights protections for persons assessed as lacking mental capacity. It is argued that it is important that regular parliamentary oversight is maintained in relation to the potential impact and consequences of such changes during the period they are in force. This should be done in order to assess whether they remain a necessary, proportionate and least restrictive response to the challenges faced in managing mental health and capacity issues in Northern Ireland during this public health emergency.


title: Moving pathogen genomics out of the lab and into the clinic: what will it take?

text: Pathogen genomic analysis is a potentially transformative new approach to the clinical and public-health management of infectious diseases. Health systems investing in this technology will need to build infrastructure and develop policies that ensure genomic information can be generated, shared and acted upon in a timely manner.


title: SARS corona virus peptides recognized by antibodies in the sera of convalescent cases

text: Abstract We synthesized on cellulose membranes 4942 ten-amino-acid peptides which included all of the sequences predicted for the severe acute respiratory syndrome (SARS) corona virus. We probed these membranes with four pairs of acute and convalescent sera from recovered SARS cases. We correlated positively reacting peptides with the in vitro SARS-CoV neutralizing activity of the samples. We found that convalescent sera with high neutralizing activity recognized exclusively only a limited number of peptides on the membranes. This suggests that antibodies against the epitopes represented by these peptides could be responsible for much of the SARS-CoV neutralizing activity. The findings have implications for monitoring humoral responses to SARS-CoV as well as for developing a successful SARS vaccine.


title: Platelet activation suppresses HIV-1 infection of T cells

text: BACKGROUND: Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. RESULTS: We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. CONCLUSIONS: Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.


SARS safety and science


title: Insufficiency in airway interferon activation defines clinical severity to infant RSV infection

text: Respiratory syncytial virus (RSV) is the leading cause of severe respiratory disease in infants. Other than age at the time of infection, the causes and correlates of severe illness in infants lacking known risk factors are poorly defined. We recruited a cohort of confirmed RSV-infected infants and simultaneously assayed the presence of resident airway microbiota and the molecular status of their airways using a novel method. Rigorous statistical analyses identified a molecular airway gene expression signature of severe illness dominated by excessive chemokine expression. Global 16S rRNA sequencing confirmed an association between H. influenzae and clinical severity. Interestingly, adjusting for H. influenzae in our gene expression analysis revealed an association between severity and airway lymphocyte accumulation. Exploring the relationship between airway gene expression and the time of onset of clinical symptoms revealed a robust, acute activation of interferon (IFN) signaling, which was absent in subjects with severe illness. Finally, we explored the relationship between IFN activity, airway gene expression and productive RSV infection using a novel in vitro model of bona fide pediatric human airway epithelial cells. Interestingly, blocking IFN signaling, but not IFN ligand production, in these cells leads to increased viral infection. Our data reveal that acute airway interferon responses are physiologically relevant in the context of infant RSV infection and may be a target for therapeutic intervention. Additionally, the airway gene expression signature we define may be useful as a biomarker for efficacy of intervention responses.


title: Nonstructural proteins NS7b and NS8 are likely to be phylogenetically associated with evolution of 2019-nCoV

text: Abstract The seventh novel human infecting Betacoronavirus that causes pneumonia (2019 novel coronavirus, 2019-nCoV) originated in Wuhan, China. The evolutionary relationship between 2019-nCoV and the other human respiratory illness-causing coronavirus is not closely related. We sought to characterize the relationship of the translated proteins of 2019-nCoV with other species of Orthocoronavirinae. A phylogenetic tree was constructed from the genome sequences. A cluster tree was developed from the profiles retrieved from the presence and absence of homologs of ten 2019-nCoV proteins. The combined data were used to characterize the relationship of the translated proteins of 2019-nCoV to other species of Orthocoronavirinae. Our analysis reliably suggests that 2019-nCoV is most closely related to BatCoV RaTG13 and belongs to subgenus Sarbecovirus of Betacoronavirus, together with SARS coronavirus and Bat-SARS-like coronavirus. The phylogenetic profiling cluster of homolog proteins of one annotated 2019-nCoV protein against other genome sequences revealed two clades of ten 2019-nCoV proteins. Clade 1 consisted of a group of conserved proteins in Orthocoronavirinae comprising Orf1ab polyprotein, Nucleocapsid protein, Spike glycoprotein, and Membrane protein. Clade 2 comprised six proteins exclusive to Sarbecovirus and Hibecovirus. Two of six Clade 2 nonstructural proteins, NS7b and NS8, were exclusively conserved among 2019-nCoV, BetaCoV_RaTG, and BatSARS-like Cov. NS7b and NS8 have previously been shown to affect immune response signaling in the SARS-CoV experimental model. Thus, we speculated that knowledge of the functional changes in the NS7b and NS8 proteins during evolution may provide important information to explore the human infective property of 2019-nCoV.


title: Horses as a Crucial Part of One Health

text: One Health (OH) is a crucial concept, where the interference between humans, animals and the environment matters. This review article focusses on the role of horses in maintaining the health of humans and the environment. Horses’ impact on environmental health includes their influence on soil and the biodiversity of animal and plant species. Nevertheless, the effect of horses is not usually linear and several factors like plant–animal coevolutionary history, climate and animal density play significant roles. The long history of the relationship between horses and humans is shaped by the service of horses in wars or even in mines. Moreover, horses were essential in developing the first antidote to cure diphtheria. Nowadays, horses do have an influential role in animal assisted therapy, in supporting livelihoods in low income countries and as a leisure partner. Horses are of relevance in the spillover of zoonotic and emerging diseases from wildlife to human (e.g., Hendra Virus), and in non-communicable diseases (e.g., post-traumatic osteoarthritis in horses and back pain in horse riders). Furthermore, many risk factors—such as climate change and antimicrobial resistance—threaten the health of both horses and humans. Finally, the horse is a valuable factor in sustaining the health of humans and the environment, and must be incorporated in any roadmap to achieve OH.


title: The clinical characteristic of eight patients of COVID‐19 with positive RT‐PCR test after discharge

text: Corona virus disease 2019 (COVID‐19) was caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). The phenomenon of positive real time reverse transcription polymerase chain reaction (RT‐PCR) result of SARS‐CoV‐2 in recovered patients had occurred and the research about these patients was rare. In our study, we did a retrospective review of medical records from COVID‐19 patients admitted to one ward of Tongji Hospital of Hua Zhong University of Science and Technology from 10 February to 13 April 2020. From 10 February to 13 April 2020, there were 108 patients of COVID‐19 admitted in the one ward of Tongji Hospital. Among them, eight cases were readmission patients because the RT‐PCR result of SARS‐CoV‐2 was positive again after discharge. On the second admission, they had no symptoms and their chest computed tomography was almost normal. Data from laboratory tests of the readmission patients showed that all eight patients had normal white blood cell count, lymphocyte count. The inflammatory factors like procalcitonin and interleukin 6 were normal. After treatment, two patients met the standard and were discharged. The other six patients were still in the hospital because their RT‐PCR of SARS‐CoV‐2 did not get three consecutive negative results and the course of two patients had persisted more than 90 days. We still needed to be alert that these patients could infect other people as a source of infection, and we also needed to be alert that these patients become chronic virus carriers. It also aroused our concern about the discharge standard of COVID‐19.


title: Epidemiologie und Kontrollmaßnahmen bei COVID-19

text: The Coronavirus Disease Pandemic 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2), started in December 2019 in China. SARS-CoV-2 is easily transmitted by droplet infection. After an incubation period of 1–14 days, COVID-19 shows a mild course in 80 % of observed cases and a severe course in 20 %, with a lethality rate of 0.3–5.8 %. Elderly people and people with underlying diseases have a higher risk of severe courses with mandatory ventilation. So far there are neither effective drugs nor vaccinations available, so only public health interventions such as physical distancing and hygiene measures on the one hand and targeted testing followed by isolation and quarantine measures on the other hand are available. China has shown that maximum use of these measures can control the epidemic. The further course and also the consequences for the global economy cannot be clearly predicted at present.


title: Kinetics of Cytokine mRNA Expression in the Central Nervous System Following Lethal and Nonlethal Coronavirus-Induced Acute Encephalomyelitis

text: Abstract The potential role(s) of cytokines in the reduction of infectious virus and persistent viral infection in the central nervous system was examined by determining the kinetics of cytokine mRNA expression following infection with the neurotropic JHM strain of mouse hepatitis virus. Mice were infected with an antibody escape variant which produces a nonlethal encephalomyelitis and compared to a clonal virus population which produces a fulminant fatal encephalomyelitis. Infection with both viruses induced the accumulation of mRNAs associated with Th1- and Th2-type cytokines, including IFN-γ, IL-4, and IL-10. Peak mRNA accumulations were coincident with the clearance of virus and there was no obvious differences between lethally and nonlethally infected mice. TNF-α mRNA was induced more rapidly in lethally infected mice compared to mice undergoing a nonfatal encephalomyelitis. Rapid transient increases in the mRNAs encoding IL-12, iNOS, IL-1α, IL-1β, and IL-6 occurred following infection. Nonlethal infections were associated with increased IL-12, IL-1β, and earlier expression of IL-6, while lethal infections were associated with increased iNOS and IL-1α mRNA. These data suggest a rapid but differential response within the central nervous system cells to infection by different JHMV variants. However, neither the accumulation nor kinetics of induction provide evidence to distinguish lethal infections from nonlethal infections leading to a persistent infection. Accumulation of both Th1 and Th2 cytokines in the central nervous system of JHMV-infected mice is consistent with the participation of both cytokines and cell immune effectors during resolution of acute viral-induced encephalomyelitis.


title: 8 Green synthesis of polysaccharide-based inorganic nanoparticles and biomedical aspects

text: Abstract Biologically mediated inorganic nanoparticles (NPs) are considered as a green, cheap, and environmental-friendly materials, which connect the nanotechnology and biomedical sciences. Metallic NPs such as gold and silver NPs, synthesized using natural materials are an important branch of inorganic NPs with catalytic functionalities and a diverse range of biomedical applications such as antimicrobial application. Polysaccharides are excellent candidates to stabilize and control the size of NPs during the synthesis process. These polymers possess multiple binding sites, which facilitate attachment to the metal surface. As a result, polysaccharides can effectively create an organic-inorganic network of the metal NPs and confer a significant protection against aggregation and chemical modifications. This chapter discusses the methods of the preparation of polysaccharide-mediated NPs and reviews various types and diverse applications for these novel materials.


title: Empiric treatment of ambulatory community-acquired pneumonia: always include treatment for atypical agents

text: There are no data from proper studies to answer whether it is necessary to include antibiotics that are active against atypical pneumonia agents as part of the empiric therapy of CAP. Until such data are available, clinical judgment and severity of the pneumonic illness are the best guides to empiric antimicrobial therapy.


title: Molecular characterization of a puromycin‐insensitive leucyl‐specific aminopeptidase, PILS‐AP

text: The family M1 of Zn‐dependent aminopeptidases comprises members of closely related enzymes which are known to be involved in a variety of physiologically important processes. On the basis of two highly conserved peptide motifs, we have identified a new member of this family by PCR amplification and cDNA‐library screening. The longest ORF encodes a protein of 930 residues. It contains the HEXXH(X)18E Zn‐binding motif and displays high homology to the other M1 family members except for its N‐terminus for which a signal sequence of 20 residues can be predicted. This interpretation was supported by expressing fusion proteins formed with green fluorescent protein which localized to intracellular vesicles in COS‐7 and BHK cells. Northern‐blot analysis revealed ubiquitous expression of a major 3.1‐kb transcript. For enzymatic studies, the complete protein was expressed in Sf 9 insect cells. When aminoacyl β‐naphthylamides were used as substrates, efficient hydrolysis was only observed for Leu (and to a lesser extent Met). The activity was inhibited by chelators of bivalent cations and by other known aminopeptidase inhibitors, but surprisingly puromycin was without effect. This newly identified puromycin‐insensitive leucyl‐specific aminopeptidase is a signal‐sequence‐bearing member of family M1 and may be another example of the small subset of substrate‐specific peptidases.


title: Some remarks on protein attribute prediction and pseudo amino acid composition

text: Abstract With the accomplishment of human genome sequencing, the number of sequence-known proteins has increased explosively. In contrast, the pace is much slower in determining their biological attributes. As a consequence, the gap between sequence-known proteins and attribute-known proteins has become increasingly large. The unbalanced situation, which has critically limited our ability to timely utilize the newly discovered proteins for basic research and drug development, has called for developing computational methods or high-throughput automated tools for fast and reliably identifying various attributes of uncharacterized proteins based on their sequence information alone. Actually, during the last two decades or so, many methods in this regard have been established in hope to bridge such a gap. In the course of developing these methods, the following things were often needed to consider: (1) benchmark dataset construction, (2) protein sample formulation, (3) operating algorithm (or engine), (4) anticipated accuracy, and (5) web-server establishment. In this review, we are to discuss each of the five procedures, with a special focus on the introduction of pseudo amino acid composition (PseAAC), its different modes and applications as well as its recent development, particularly in how to use the general formulation of PseAAC to reflect the core and essential features that are deeply hidden in complicated protein sequences.


title: Comparison among nasopharyngeal swab, nasal wash, and oropharyngeal swab for respiratory virus detection in adults with acute pharyngitis

text: BACKGROUND: Acute pharyngitis is frequently seen in primary care. Acute viral pharyngitis may be easily misdiagnosed as acute bacterial pharyngitis. Laboratory-confirmed diagnosis of respiratory viruses is recommended. The purpose of this study was to compare the sensitivities among oropharyngeal swab (OPS), nasopharyngeal swab (NPS), and nasal wash (NW) in adults with acute pharyngitis. METHODS: OPS, NPS, and NW were obtained from each participant with acute pharyngitis. The specimens were tested for 15 respiratory viruses by TaqMan real-time polymerase chain reaction. A sample was considered to be a true positive if any of the specimens was positive. The sensitivities among samples were compared by chi-square test or Fisher’s exact test, as appropriate. RESULTS: One hundred three triple samples collected consecutively by OPS, NPS, and NW were obtained. In 73 patients, one or more viruses were detected by any of the three methods. Among all viruses, the sensitivity of NPS was significantly higher than that of NW (74% vs. 49%, respectively; p < 0.01) and OPS (74% vs. 49%, respectively; p < 0.01). CONCLUSIONS: Flocked NPS collection may be the most effective alternative to NW and OPS for detection of respiratory viruses in adults with acute pharyngitis using TaqMan real-time polymerase chain reaction.


title: Influenza A(H1N1)pdm09 virus infection in Norwegian swine herds 2009/10: The risk of human to swine transmission

text: Abstract Influenza A viruses cause respiratory infection in humans and pigs, and some serotypes can be transmitted between these species. The emergence of influenza A(H1N1)pdm09 virus infections in the spring of 2009 quickly led to a worldwide pandemic in humans, with subsequent introduction of the virus to pig populations. Following a widespread infection in the human population in Norway, influenza A(H1N1)pdm09 virus was introduced to the influenza A naïve Norwegian pig population, and within a few months pigs in more than one third of Norwegian swine herds had antibodies against the virus. A cross-sectional study was performed on all swine nucleus and multiplier herds in Norway to analyze risk factors for introduction of infection, and the preventive effects of recommended biosecurity practices. A surveillance program provided information on infection status of the study herds, and a questionnaire was administered to all 118 nucleus and multiplier herds to collect information on herd variables. The surveillance program revealed that pigs in 42% of the herds had antibodies against influenza A(H1N1)pdm09 virus. The incidence of serologically positive pigs was similar in both multiplier herds (41%) and closed nucleus herds (43%). Multivariable logistic regression showed that presence of farm staff with influenza-like illness (ILI) (OR=4.15, CI 1.5–11.4, p =0.005) and herd size (OR=1.01, CI 1–1.02, p =0.009) were risk factors for infection. The rapid and widespread seroconversion for antibodies against influenza A(H1N1)pdm09 virus in the Norwegian pig population can be explained by the emergence of a novel virus that is readily transmitted between people and swine in a largely susceptible population of humans, and an entirely naïve population of pigs.


title: Gradual Increase of High Mobility Group Protein B1 in the Lungs after the Onset of Acute Exacerbation of Idiopathic Pulmonary Fibrosis

text: The pathogenesis of acute exacerbation of idiopathic pulmonary fibrosis (IPF) remains to be elucidated. To evaluate the roles of inflammatory mediators in acute exacerbation, the concentrations of high mobility group protein B1 (HMGB1), a chief mediator of acute lung injury, and 18 inflammatory cytokines were measured in the bronchoalveolar lavage fluid, serially sampled from seven IPF patients after the onset of acute exacerbation. HMGB1 gradually increased in the alveolar fluid after the onset of acute exacerbation, in positive correlation with monocytes chemotactic protein-1 (MCP-1), a potent fibrogenic mediator. In the lung tissues of eight IPF patients autopsied after acute exacerbation, intense cytoplasmic staining for HMGB1 was observed in the alveolar epithelial cells in alveolar capillary augmented lesions, where the capillary endothelial cells remarkably reduced the expression of thrombomodulin, an intrinsic antagonist of HMGB1. These results suggest pathogenic roles for HMGB1 and MCP-1 in the late phase of acute exacerbation of IPF.


title: Noroviruses subvert the core stress granule component G3BP1 to promote viral VPg-dependent translation

text: Knowledge of the host factors required for norovirus replication has been hindered by the challenges associated with culturing human noroviruses. We have combined proteomic analysis of the viral translation and replication complexes with a CRISPR screen, to identify host factors required for norovirus infection. The core stress granule component G3BP1 was identified as a host factor essential for efficient human and murine norovirus infection, demonstrating a conserved function across theNorovirusgenus. Furthermore, we show that G3BP1 functions in the novel paradigm of viral VPg-dependent translation initiation, contributing to the assembly of translation complexes on the VPg-linked viral positive sense RNA genome by facilitating 40S recruitment. Our data suggest that G3BP1 functions by providing viral RNA a competitive advantage over capped cellular RNAs, uncovering a novel function for G3BP1 in the life cycle of positive sense RNA viruses and identifying the first host factor with pan-norovirus pro-viral activity.


title: Antigen Presentation and the Ubiquitin‐Proteasome System in Host–Pathogen Interactions

text: Abstract Relatively small genomes and high replication rates allow viruses and bacteria to accumulate mutations. This continuously presents the host immune system with new challenges. On the other side of the trenches, an increasingly well‐adjusted host immune response, shaped by coevolutionary history, makes a pathogen's life a rather complicated endeavor. It is, therefore, no surprise that pathogens either escape detection or modulate the host immune response, often by redirecting normal cellular pathways to their advantage. For the purpose of this chapter, we focus mainly on the manipulation of the class I and class II major histocompatibility complex (MHC) antigen presentation pathways and the ubiquitin (Ub)‐proteasome system by both viral and bacterial pathogens. First, we describe the general features of antigen presentation pathways and the Ub‐proteasome system and then address how they are manipulated by pathogens. We discuss the many human cytomegalovirus (HCMV)‐encoded immunomodulatory genes that interfere with antigen presentation (immunoevasins) and focus on the HCMV immunoevasins US2 and US11, which induce the degradation of class I MHC heavy chains by the proteasome by catalyzing their export from the endoplasmic reticulum (ER)‐membrane into the cytosol, a process termed ER dislocation. US2‐ and US11‐mediated subversion of ER dislocation ensures proteasomal degradation of class I MHC molecules and presumably allows HCMV to avoid recognition by cytotoxic T cells, whilst providing insight into general aspects of ER‐associated degradation (ERAD) which is used by eukaryotic cells to purge their ER of defective proteins. We discuss the similarities and differences between the distinct pathways co‐opted by US2 and US11 for dislocation and degradation of human class I MHC molecules and also a putatively distinct pathway utilized by the murine herpes virus (MHV)‐68 mK3 immunoevasin for ER dislocation of murine class I MHC. We speculate on the implications of the three pathogen‐exploited dislocation pathways to cellular ER quality control. Moreover, we discuss the ubiquitin (Ub)‐proteasome system and its position at the core of antigen presentation as proteolysis and intracellular trafficking rely heavily on Ub‐dependent processes. We add a few examples of manipulation of the Ub‐proteasome system by pathogens in the context of the immune system and such diverse aspects of the host–pathogen relationship as virus budding, bacterial chromosome integration, and programmed cell death, to name a few. Finally, we speculate on newly found pathogen‐encoded deubiquitinating enzymes (DUBs) and their putative roles in modulation of host–pathogen interactions.


title: Pattern recognition receptors in companion and farm animals – The key to unlocking the door to animal disease?

text: Abstract The innate immune system is essential for host defence and is responsible for early detection of potentially pathogenic microorganisms. Upon recognition of microbes by innate immune cells, such as macrophages and dendritic cells, diverse signalling pathways are activated that combine to define inflammatory responses that direct sterilisation of the threat and/or orchestrate development of the adaptive immune response. Innate immune signalling must be carefully controlled and regulation comes in part from interactions between activating and inhibiting signalling receptors. In recent years, an increasing number of pattern recognition receptors (PRRs), including C-type lectin receptors and Toll-like receptors (TLRs), has been described that participate in innate recognition of microbes, especially through the so called pathogen-associated molecular patterns (PAMPs). Recent studies demonstrate strong interactions between signalling through these receptors. Whereas useful models to study these receptors in great detail in the murine and human system are now emerging, relatively little is known regarding these receptors in companion and farm animals. In this review, current knowledge regarding these receptors in species of veterinary relevance is summarised.


title: Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains

text: The envelope spike (S) proteins of MERS-CoV and SARS-CoV determine the virus host tropism and entry into host cells, and constitute a promising target for the development of prophylactics and therapeutics. Here, we present high-resolution structures of the trimeric MERS-CoV and SARS-CoV S proteins in its pre-fusion conformation by single particle cryo-electron microscopy. The overall structures resemble that from other coronaviruses including HKU1, MHV and NL63 reported recently, with the exception of the receptor binding domain (RBD). We captured two states of the RBD with receptor binding region either buried (lying state) or exposed (standing state), demonstrating an inherently flexible RBD readily recognized by the receptor. Further sequence conservation analysis of six human-infecting coronaviruses revealed that the fusion peptide, HR1 region and the central helix are potential targets for eliciting broadly neutralizing antibodies.


Major reconstructive surgery and the COVID-19 lockdown – is the dust settling?


title: Performance of a multiplexed serological microarray for the detection of antibodies against central nervous system pathogens

text: Abstract Central nervous system (CNS) infections have multiple potential causative agents for which simultaneous pathogen screening can provide a useful tool. This study evaluated a multiplexed microarray for the simultaneous detection of antibodies against CNS pathogens. The performance of selected microarray antigens for the detection of IgG antibodies against herpes simplex virus 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), adenovirus, Mycoplasma pneumoniae and Borrelia burgdorferi sensu lato, was evaluated using serum sample panels tested with reference assays used in a routine diagnostic laboratory. The microarray sensitivity for HSV-1, HSV-2, VZV, adenovirus and M. pneumonia ranged from 77% to 100%, and the specificity ranged from 74% to 97%. Very variable sensitivities and specificities were found for borrelial antigens of three different VlsE protein IR(6) peptide variants (IR6p1, IR6p2, IR6p4) and three recombinant decorin binding proteins A (DbpA; DbpAIa, DbpA91, DbpAG40). For single antigens, good specificity was shown for antigens of IR6p4 and DbpAIa (96%), while DbpA91, IR6p1 and IR6p2 were moderately specific (88–92%). The analytical sensitivity of the microarray was dependent on the borrelial IgG concentration of the specimen. The overall performance and technical features of the platform showed that the platform supports both recombinant proteins, whole viruses and peptides as antigens. This study showed diagnostic potential for all six CNS pathogens, including Borrelia burgdorferi sensu lato, using glutaraldehyde based microarray, and further highlighted the importance of careful antigen selection and the requirement for the use of multiple borrelial antigens in order to increase specificity without a major lack of sensitivity.


title: The COVID-19 pandemic will have a long-lasting impact on the quality of cirrhosis care

text: Summary The coronavirus disease 2019 (COVID-19) pandemic has shattered the meticulously developed processes by which we delivered quality care for patients with cirrhosis. Care has been transformed by the crisis, but enduring lessons have been learned. In this article, we review how COVID-19 will impact cirrhosis care. We describe how this impact unfolds over 3 waves; i) an intense period with prioritized high-acuity care with delayed elective procedures and routine care during physical distancing, ii) a challenging ‘return to normal’ following the end of physical distancing, with increased emergent decompensations, morbidity, and systems of care overwhelmed by the backlog of deferred care, and iii) a protracted period of suboptimal outcomes characterized by missed diagnoses, progressive disease and loss to follow-up. We outline the concrete steps required to preserve the quality of care provided to patients with cirrhosis. This includes an intensification of the preventative care provided to patients with compensated cirrhosis, proactive chronic disease management, robust telehealth programs, and a reorganization of care delivery to provide a full service of care with flexible clinical staffing. Managing the pandemic of a serious chronic disease in the midst of a global infectious pandemic is challenging. It is incumbent upon the entire healthcare establishment to be strong enough to weather the storm. Change is needed.


title: Neurological Manifestations of COVID‐19: A systematic review and current update

text: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), was first identified in December of 2019 in the city of Wuhan, China. Since the outbreak, various reports detail its symptoms and outcomes, primarily focusing on respiratory complications. However, reports are emerging of the virus’ effects systemically, including that of the nervous system. A review of all current published literature was conducted, and we report that headache and anosmia were common neurological manifestations of SARS‐CoV‐2. Less common symptoms include seizure, stroke and isolated cases of Guillain‐Barre syndrome. Further research is now warranted to precisely determine the relationship between those patients developing neurological sequelae, their clinical state and any subsequent morbidity and mortality.


title: Urgent need for evaluating agonists of Angiotensin-(1-7)/ Mas receptor axis for treatment of patients with COVID-19

text: Abstract ACE2 being a receptor of entry of SARS-CoV-2 into the host cells, its upregulation has been implicated in increasing susceptibility of individuals to the infections. Clinical picture of COVID-19 suggests a role ACE2 blockade, rather than its overexpression, in causing the pathogenesis. ACE2 blockade results in increased Angiotensin II activity with simultaneous hampering of functions of Angiotensin-(1-7)/MasR axis. Acute respiratory distress due to interstitial pulmonary fibrosis, cardiomyopathy and shock reported in COVID-19 patients can be explained by imbalanced Angiotensin II and Angiotensin-(1-7) activities. Failure of Angiotensin II type 1 receptor blockers to control severity of SARS-CoV-2 infections indicates importance of simultaneous induction of Angiotensin-(1-7)/MasR axis for correcting pathological conditions in COVID-19 through its anti-fibrotic, anti-inflammatory, vasodilatory and cardioprotective roles. MasR agonists have also shown organ protective effects in a number of animal studies. Unfortunately, these agonists have not been tested in clinical studies. Their urgent evaluation in seriously ill COVID-19 patients is urgently warranted to reduce mortality due to the infections.


Emerging zoonoses: A one health challenge


title: Diarrhoea in the growing pig – a comparison of clinical, morphological and microbial findings between animals from good and poor performance herds

text: Abstract Diarrhoea among growing pigs (8–13 weeks old) is a significant problem in many herds. Nine herds with poor performance and diarrhoea among growing pigs were selected on the basis of their piglet mean age at a body weight of 25kg, compared to the overall mean age in Swedish herds. In addition, four herds with good average performance and no problems with diarrhoea were selected. Pigs were necropsied and samples for histology and microbiology were collected. Based on the necropsy findings, the pigs from the good performing herds were all judged to be healthy. The presence of Brachyspira pilosicoli and Lawsonia intracellularis was significantly correlated to poor performing herds and the results indicate that these microbes are main pathogens involved in enteric diseases among Swedish grower pigs. In addition, concomitant infections with other presumptive pathogens were commonly found.


title: 6.08 Indoor Microbiome and Airborne Pathogens

text: Abstract Individuals spend a majority of their time in indoor or built environments (BEs), where they are exposed to a diverse community of co-existing microorganisms. These microorganisms constitute the BE microbiome. While predominantly consisting of commensal microorganisms, the BE microbiome also contains pathogens that may be transmitted to and between indoor occupants. Therefore, characterization of the BE microbiome and understanding how different factors affect the BE microbiome will enable building scientists to assess health risks associated with indoor microbial exposure and manipulate BE conditions to maximize the health and well-being of occupants. We provide an overview of various aspects of the BE microbiome, including the importance of understanding the indoor microbiome from ecological and clinical perspectives, the history behind BE microbiome research, current laboratory, statistical, and bioinformatic methodologies and considerations in BE microbiome research, the different BE microbiome components and factors that shape this microbiome, the risks of pathogen transmission within BEs, and future directions in BE microbiome research. Some of the most recent and cutting-edge research works are described here, with the aim of providing a comprehensive and up-to-date account of the key findings within the field of indoor microbiology.


title: Thrombocytopenia Is Associated with Acute Respiratory Distress Syndrome Mortality: An International Study

text: BACKGROUND: Early detection of the Acute Respiratory Distress Syndrome (ARDS) has the potential to improvethe prognosis of critically ill patients admitted to the intensive care unit (ICU). However, no reliable biomarkers are currently available for accurate early detection of ARDS in patients with predisposing conditions. OBJECTIVES: This study examined risk factors and biomarkers for ARDS development and mortality in two prospective cohort studies. METHODS: We examined clinical risk factors for ARDS in a cohort of 178 patients in Beijing, China who were admitted to the ICU and were at high risk for ARDS. Identified biomarkers were then replicated in a second cohort of1,878 patients in Boston, USA. RESULTS: Of 178 patients recruited from participating hospitals in Beijing, 75 developed ARDS. After multivariate adjustment, sepsis (odds ratio [OR]:5.58, 95% CI: 1.70–18.3), pulmonary injury (OR: 3.22; 95% CI: 1.60–6.47), and thrombocytopenia, defined as platelet count <80×10(3)/µL, (OR: 2.67; 95% CI: 1.27–5.62)were significantly associated with increased risk of developing ARDS. Thrombocytopenia was also associated with increased mortality in patients who developed ARDS (adjusted hazard ratio [AHR]: 1.38, 95% CI: 1.07–1.57) but not in those who did not develop ARDS(AHR: 1.25, 95% CI: 0.96–1.62). The presence of both thrombocytopenia and ARDS substantially increased 60-daymortality. Sensitivity analyses showed that a platelet count of <100×10(3)/µLin combination with ARDS provide the highest prognostic value for mortality. These associations were replicated in the cohort of US patients. CONCLUSIONS: This study of ICU patients in both China and US showed that thrombocytopenia is associated with an increased risk of ARDS and platelet count in combination with ARDS had a high predictive value for patient mortality.


title: The effects of transplacental porcine circovirus type 2 infection on porcine epidemic diarrhoea virus-induced enteritis in preweaning piglets

text: Abstract The effects of transplacental porcine circovirus type 2 (PCV2) infection on porcine epidemic diarrhoea virus (PEDV)-induced enteritis were examined in neonatal piglets. Six pregnant sows were randomly allocated to an infected (n =3) or control group (n =3). Three pregnant sows were inoculated intranasally with 6mL of tissue culture fluid containing 1.2×105 tissue culture infective doses 50% (TCID50)/mL of PCV2 strain SNUVR000470 three weeks before the expected farrowing date. Three control pregnant sows were similarly exposed to uninfected cell culture supernatants. Thirty piglets from PCV2-infected sows were randomly assigned to two groups (A and B) of 15 piglets each. Another 30 piglets from noninfected sows were randomly assigned to two groups (C and D) of 15 piglets each. The piglets in groups A and C were dosed orally at three days of age with 2mL of virus stock (1×106.5 TCID50/mL) of the PEDV strain, SNUVR971496, at the third passage. The mean villous height and crypt depth (VH:CD) ratio in PEDV-infected piglets from PCV2-infected sows (group A) were significantly different from those of the PEDV-infected piglets from PCV2 negative sows (group C) at 36, 48, and 72h post-inoculation (hpi) (P <0.05). In PEDV-infected piglets from PCV2-infected sows (group A), significantly more PEDV nucleic acid was detected in the jejunal tissues (P <0.05) at 24hpi than in the same tissues of the PEDV-infected piglets from PCV2 negative sows (group C). Thereafter, at 36, 48, 60, and 70hpi significantly more PEDV nucleic acid (P <0.05) was detected in the jejunal tissues of the PEDV-infected piglets from PCV2 negative sows (group C) than those of the PEDV-infected piglets from the PCV2-infected sows (group A). It is concluded that the clinical course of PEDV disease was markedly affected by transplacental infection of PCV2.


title: Fragment Molecular Orbital Based Interaction Analyses on COVID-19 Main Protease − Inhibitor N3 Complex (PDB ID: 6LU7)

text: [Image: see text] The worldwide spread of COVID-19 (new coronavirus found in 2019) is an emergent issue to be tackled. In fact, a great amount of works in various fields have been made in a rather short period. Here, we report a fragment molecular orbital (FMO) based interaction analysis on a complex between the SARS-CoV-2 main protease (Mpro) and its peptide-like inhibitor N3 (PDB ID: 6LU7). The target inhibitor molecule was segmented into five fragments in order to capture site specific interactions with amino acid residues of the protease. The interaction energies were decomposed into several contributions, and then the characteristics of hydrogen bonding and dispersion stabilization were made clear. Furthermore, the hydration effect was incorporated by the Poisson–Boltzmann (PB) scheme. From the present FMO study, His41, His163, His164, and Glu166 were found to be the most important amino acid residues of Mpro in interacting with the inhibitor, mainly due to hydrogen bonding. A guideline for optimizations of the inhibitor molecule was suggested as well based on the FMO analysis.


title: Detection of respiratory viruses and bacteria in children using a twenty-two target reverse-transcription real-time PCR (RT-qPCR) panel

text: BACKGROUND: Rapid detection of the wide range of viruses and bacteria that cause respiratory infection in children is important for patient care and antibiotic stewardship. We therefore designed and evaluated a ready-to-use 22 target respiratory infection reverse-transcription real-time polymerase chain reaction (RT-qPCR) panel to determine if this would improve detection of these agents at our pediatric hospital. METHODS: RT-qPCR assays for twenty-two target organisms were dried-down in individual wells of 96 well plates and saved at room temperature. Targets included 18 respiratory viruses and 4 bacteria. After automated nucleic acid extraction of nasopharyngeal aspirate (NPA) samples, rapid qPCR was performed. RT-qPCR results were compared with those obtained by the testing methods used at our hospital laboratories. RESULTS: One hundred fifty-nine pediatric NPA samples were tested with the RT-qPCR panel. One or more respiratory pathogens were detected in 132/159 (83%) samples. This was significantly higher than the detection rate of standard methods (94/159, 59%) (P<0.001). This difference was mainly due to improved RT-qPCR detection of rhinoviruses, parainfluenza viruses, bocavirus, and coronaviruses. The panel internal control assay performance remained stable at room temperature storage over a two-month testing period. CONCLUSION: The RT-qPCR panel was able to identify pathogens in a high proportion of respiratory samples. The panel detected more positive specimens than the methods in use at our hospital. The pre-made panel format was easy to use and rapid, with results available in approximately 90 minutes. We now plan to determine if use of this panel improves patient care and antibiotic stewardship.


title: Crisis prevention and management by infection control nurses during the Middle East respiratory coronavirus outbreak in Korea

text: A Middle East respiratory coronavirus (MERS-CoV) outbreak occurred in Korea between June 20 and July 28, 2015. A total of 186 patients were confirmed as being infected with MERS-CoV, 36 of whom died. Infection control nurses referred to hospital guidelines to address the screening and isolation needs of patients and instigated a variety of infection control activities to prevent MERS-CoV transmission at the frontlines of patient care. Their concerted effort is believed to have been instrumental in ending the outbreak.


title: Manifestaciones hepáticas y repercusion en el paciente cirrótico de covid-19

text: Resumen El coronavirus SARS-CoV-2, un nuevo coronavirus, es responsable de la enfermedad infecciosa por coronavirus 19 (COVID-19). A nivel global, esta pandemia va en crecimiento y pudiera afectar al 50-60% de la población mundial en los siguientes meses. Si bien es una enfermedad cuya manifestación más severa es la neumonía atípica y sepsis, recientemente se ha descrito que el tracto digestivo y en particular el hígado puede verse afectados por el SARS-COV2. Así pues, el objetivo del presente trabajo es revisar la literatura disponible al respecto y emitir algunas recomendaciones del papel que el COVID-19 ejerce sobre el hígado en la salud y la enfermedad. La incidencia de lesión hepática asociada específicamente a COVID-19 varía de 14.8-53%. La mayoría de las series de casos han reportado alteración en ALT y AST, elevación de bilirrubinas totales y albúmina sérica baja. La afectación hepática se asociado a casos más graves de COVID-19. Por otra parte, se reconoce que la cirrosis hepática es un estado de disfunción inmune que comprende inmunodeficiencia e inflamación sistémica, lo cual hace razonable que estos pacientes sean más susceptibles a la infección por SARS-COV-2. Las recomendaciones para estos pacientes además de las medidas generales para la población (aislamiento social, lavado de manos) incluyen el apoyo social, médico y psicológico durante el periodo de estancia en el domicilio para evitar transgresiones a la terapia. Es recomendable orientar a los pacientes a mantenerse informados de los cambios en recomendaciones y políticas sociales. Abstract The novel SARS-CoV-2 coronavirus is responsible for the infectious disease caused by coronavirus 19 (COVID-19). The current pandemic is growing worldwide and could affect 50-60% of the world population in the months to come. The most severe disease manifestations are atypical pneumonia and sepsis, but the gastrointestinal tract, particularly the liver, has recently been reported to be affected by SARS-COV2. Therefore, the aim of the present work was to review the literature available on the topic and provide information about COVID-19, in both healthy and diseased livers, and issue recommendations. The incidence of liver injury specifically associated with COVID-19 varies from 14.8-53%. The majority of case series have reported altered ALT and AST, elevated total bilirubin, and low serum albumin and liver compromise has been associated with the most severe cases of COVID-19. Cirrhosis of the liver has a recognized immune dysfunction status that includes immunodeficiency and systemic inflammation, making it reasonable for those patients to be more susceptible to SARS-COV-2 infection. The recommendations for those patients, in addition to the general measures of physical distancing and handwashing for all persons, include social, medical, and psychologic support during the period of home quarantine to prevent lapses in treatment. Patients should be made aware that they need to keep abreast of changes in recommendations and social policies.


title: Other Viral Pneumonias Coronavirus, Respiratory Syncytial Virus, Adenovirus, Hantavirus

text: Severe viral pneumonia is an increasing problem among adults. The incidence and number of viruses known to cause pneumonia and respiratory failure have also expanded in recent years. This article provides an overview of severe respiratory disease caused by coronavirus, respiratory syncytial virus, adenovirus, and hantavirus. These emerging pathogens are easily overlooked and timely diagnosis requires a high index of suspicion and confirmation by molecular testing. Management of individual cases is mainly supportive and requires institution of appropriate infection control measures. Vaccines and effective therapeutics for these potentially devastating respiratory viruses are urgently required.


title: Hemorrhagic Stroke in Setting of Severe COVID-19 Infection Requiring Extracorporeal Membrane Oxygenation (ECMO)

text: OBJECTIVE: To highlight the increased risk of hemorrhagic stroke secondary to postulated COVID-19 mediated vasculopathy with concomitant ECMO related bleeding complications. BACKGROUND: COVID-19 has shown to be a systemic illness, not localized to the respiratory tract and lung parenchyma. Stroke is a common neurological complication. In particular, critically ill patients on ECMO are likely at higher risk of developing hemorrhagic stroke. CASE PRESENTATION: 38-year-old man presented with fever, cough, and shortness of breath. Due to severe respiratory failure, he required ECMO support. Subsequently, he was found to have left temporal intraparenchymal hemorrhage. Overall, his clinical course improved, and he was discharged with minimal neurological deficits. CONCLUSION: Although intracranial hemorrhage is a known complication of ECMO, patients with COVID-19 infection may be at a higher risk of cerebrovascular complications due to vasculopathy.


title: Autophagy and mitochondrial alterations in human retinal pigment epithelial cells induced by ethanol: implications of 4-hydroxy-nonenal

text: Retinal pigment epithelium has a crucial role in the physiology and pathophysiology of the retina due to its location and metabolism. Oxidative damage has been demonstrated as a pathogenic mechanism in several retinal diseases, and reactive oxygen species are certainly important by-products of ethanol (EtOH) metabolism. Autophagy has been shown to exert a protective effect in different cellular and animal models. Thus, in our model, EtOH treatment increases autophagy flux, in a concentration-dependent manner. Mitochondrial morphology seems to be clearly altered under EtOH exposure, leading to an apparent increase in mitochondrial fission. An increase in 2′,7′-dichlorofluorescein fluorescence and accumulation of lipid peroxidation products, such as 4-hydroxy-nonenal (4-HNE), among others were confirmed. The characterization of these structures confirmed their nature as aggresomes. Hence, autophagy seems to have a cytoprotective role in ARPE-19 cells under EtOH damage, by degrading fragmented mitochondria and 4-HNE aggresomes. Herein, we describe the central implication of autophagy in human retinal pigment epithelial cells upon oxidative stress induced by EtOH, with possible implications for other conditions and diseases.


Equality, Inclusion, and Diversity in Healthcare During the COVID-19 Pandemic


Integrating behavioral surveillance into emerging infectious disease prevention


title: Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis

text: Abstract Background An outbreak of Novel Coronavirus (COVID -19) in Wuhan, China, the epidemic is more widespread than initially estimated, with cases now confirmed in multiple countries. Aims The aim of the meta-analysis was to assess the prevalence of comorbidities in the COVID-19 infection patients and the risk of underlying diseases in severe patients compared to non-severe patients. Methods A literature search was conducted using the databases PubMed, EMBASE, and Web of sciences until February 25, 2020. Risk ratio (OR) and 95% confidence intervals (CIs) were pooled using random-effects models. Results Eight studies were included in the meta- analysis, including 46248 infected patients. The result showed the most prevalent clinical symptom was fever ( 91 ± 3, 95% CI 86-97% ), followed by cough (67 ± 7, 95% CI 59-76%), fatigue ( 51 ± 0, 95% CI 34-68% ) and dyspnea ( 30 ± 4, 95% CI 21-40%). The most prevalent comorbidity were hypertension (17 ± 7, 95% CI 14-22%) and diabetes ( 8 ± 6, 95% CI 6-11% ), followed by cardiovascular diseases ( 5 ± 4, 95% CI 4-7% ) and respiratory system disease( 2 ± 0, 95% CI 1-3% ). Compared with the Non-severe patient, the pooled odds ratio of hypertension, respiratory system disease, cardiovascular disease in severe patients were (OR 2.36, 95% CI: 1.46-3.83), (OR 2.46, 95% CI: 1.76-3.44) and (OR 3.42, 95% CI: 1.88-6.22)respectively. Conclusion We assessed the prevalence of comorbidities in the COVID-19 infection patients and found underlying disease, including hypertension, respiratory system disease and cardiovascular, may be a risk factor for severe patients compared with Non-severe patients.


Covid-19 and breastfeeding: what’s the risk?


title: First detection of equine coronavirus (ECoV) in Europe

text: Abstract Equine coronavirus (ECoV) is involved mainly in enteric infections. Following the recent description of ECoV in 2000, this study reports for the first time the presence of ECoV in France and, on a wider scale, in Europe. ECoV was molecularly detected from diarrheic and respiratory specimens. Sequencing and phylogenetic analyses demonstrated that European strains are most closely related to the reference North American strain (ECoV-NC99) than the Asian strain (ECoV-Tokachi09).


title: Immunomodulatory Effects of Kimchi in Chinese Healthy College Students: A Randomized Controlled Trial

text: This study examined the potential immunomodulatory effects of Kimchi, a traditional fermented Korean vegetable, in healthy Chinese college students. The four-week clinical-trial (randomized, open-label, prospective, controlled) was followed by a one week wash-out period. Healthy Chinese college students (over 20 years of age with a body mass index of 18.5-23.0 kg/m(2)) volunteered for this study. Forty-three students were randomly classified into two groups, Kimchi (n = 21, supplemented with 100 g of Kimchi per day) or non-Kimchi (n = 22, supplemented with 100 g of radish per day, control) groups. During the four-week intervention period, students were asked to maintain their usual diet and activity, and instructed not to take any medications, functional food products, or dietary supplements. Anthropometrics, nutritional intake, and blood immune parameters (lymphocyte subsets, cytokines, and immunoglobulins) were measured before and after the four weeks of intervention. Thirty-nine students (19 in the Kimchi group, 20 in the non-Kimchi group) finished the study. After the intervention, no significant changes were observed in lymphocyte subsets (T-cell, B-cell, NK cell), pro-inflammatory cytokines (IL-6, TNF-α), anti-inflammatory cytokines (IL-4 and IL-10), and immunoglobulins (Ig A, G, and M) between groups in either the Kimchi or non-Kimchi. These results suggest that the short-term consumption of Kimchi has no immunomodulatory effects in healthy Chinese college students.


title: Outcomes of hydroxychloroquine usage in United States veterans hospitalized with COVID-19

text: Abstract Background Despite limited and conflicting evidence, hydroxychloroquine, alone or in combination with azithromycin, is widely used in COVID-19 therapy. Methods We performed a retrospective study of electronic health records of patients hospitalized with confirmed SARS-CoV-2 infection in United States Veterans Health Administration medical centers between March 9, 2020 and April 29, 2020. Patients hospitalized within 24 hours of diagnosis were classified based on their exposure to hydroxychloroquine alone (HC) or with azithromycin (HC+AZ) or no HC as treatments. The primary outcomes were mortality and use of mechanical ventilation. Findings A total of 807 patients were evaluated. Compared to the no HC group, after propensity score adjustment for clinical characteristics, the risk of death from any cause was higher in the HC group (adjusted hazard ratio (aHR), 1.83; 95% CI, 1.16 to 2.89; P=0.009) but not in the HC+AZ group (aHR, 1.31; 95% CI, 0.80 to 2.15; P=0.28). Both the propensity score-adjusted risks of mechanical ventilation and death after mechanical ventilation were not significantly different in the HC group (aHR, 1.19; 95% CI, 0.78 to 1.82; P=0.42 and aHR, 2.11; 95% CI, 0.96 to 4.62; P=0.06, respectively) or in the HC+AZ group (aHR, 1.09; 95% CI, 0.72 to 1.66; P=0.69 and aHR, 1.25; 95% CI, 0.59 to 2.68; P=0.56, respectively), compared to the no HC group. Conclusions Among patients hospitalized with COVID-19, this retrospective study did not identify any significant reduction in mortality or in the need for mechanical ventilation with hydroxychloroquine treatment with or without azithromycin. Funding University of Virginia Strategic Investment Fund.


title: Experimental hypersensitivity pneumonitis: role of MCP-1

text: Abstract Inhalation of Saccharopolyspora rectivirgula causes “farmer's lung” disease, a classic example of hypersensitivity pneumonitis (HP). Monocyte chemoattractant protein-1 (MCP-1) is increased in the bronchoalveolar lavage fluid of mice challenged with S rectivirgula, and S rectivirgula induces MCP-1 secretion by alveolar macrophages. We tested the hypothesis that MCP-1 and its receptor CC chemokine receptor-2 (CCR2) are essential to the development of experimental HP by treating mice with MCP-1 antibody and using CCR2−/− mice. Administration of anti–MCP-1 did not change the response to intratracheally administered S rectivirgula. CCR2−/− animals responded in a fashion similar to that of wild-type animals to intratracheally administered.S rectivirgula. To determine the influence of the MCP-1–CCR2 interaction in vitro, we transferred S rectivirgula–cultured spleen cells from S rectivirgula–sensitized mice, to naïve recipients. Later, challenge of the recipients with intratracheal S rectivirgula and examination of both lung histology and bronchoalveolar lavage fluid characteristics were used to determine whether adoptive transfer had occurred. We found that cultured cells from CCR2−/− animals were fully capable of adoptive transfer. We conclude that interaction of MCP-1 with CCR2 is not necessary for the development of pulmonary inflammation in response to intratracheally administered S rectivirgula or cells able to adoptively transfer experimental HP.


title: Integrated Blood Barcode Chips

text: Blood comprises the largest version of the human proteome1. Changes of plasma protein profiles can reflect physiological or pathological conditions associated with many human diseases, making blood the most important fluid for clinical diagnostics2-4. Nevertheless, only a handful of plasma proteins are utilized in routine clinical tests. This is due to a host of reasons, including the intrinsic complexity of the plasma proteome1, the heterogeneity of human diseases and the fast kinetics associated with protein degradation in sampled blood5. Simple technologies that can sensitively sample large numbers of proteins over broad concentration ranges, from small amounts of blood, and within minutes of sample collection, would assist in solving these problems. Herein, we report on an integrated microfluidic system, called the Integrated Blood Barcode Chip (IBBC). It enables on-chip blood separation and the rapid measurement of a panel of plasma proteins from small quantities of blood samples including a fingerprick of whole blood. This platform holds potential for inexpensive, non-invasive, and informative clinical diagnoses, particularly, for point-of-care.


title: Role of healthcare apparel and other healthcare textiles in the transmission of pathogens: a review of the literature

text: Summary Healthcare workers (HCWs) wear uniforms, such as scrubs and lab coats, for several reasons: (1) to identify themselves as hospital personnel to their patients and employers; (2) to display professionalism; and (3) to provide barrier protection for street clothes from unexpected exposures during the work shift. A growing body of evidence suggests that HCWs' apparel is often contaminated with micro-organisms or pathogens that can cause infections or illnesses. While the majority of scrubs and lab coats are still made of the same traditional textiles used to make street clothes, new evidence suggests that current innovative textiles function as an engineering control, minimizing the acquisition, retention and transmission of infectious pathogens by reducing the levels of bioburden and microbial sustainability. This paper summarizes recent literature on the role of apparel worn in healthcare settings in the acquisition and transmission of healthcare-associated pathogens. It proposes solutions or technological interventions that can reduce the risk of transmission of micro-organisms that are associated with the healthcare environment. Healthcare apparel is the emerging frontier in epidemiologically important environmental surfaces.


title: Host and infectivity prediction of Wuhan 2019 novel coronavirus using deep learning algorithm

text: The recent outbreak of pneumonia in Wuhan, China caused by the 2019 Novel Coronavirus (2019-nCoV) emphasizes the importance of detecting novel viruses and predicting their risks of infecting people. In this report, we introduced the VHP (Virus Host Prediction) to predict the potential hosts of viruses using deep learning algorithm. Our prediction suggests that 2019-nCoV has close infectivity with other human coronaviruses, especially the severe acute respiratory syndrome coronavirus (SARS-CoV), Bat SARS-like Coronaviruses and the Middle East respiratory syndrome coronavirus (MERS-CoV). Based on our prediction, compared to the Coronaviruses infecting other vertebrates, bat coronaviruses are assigned with more similar infectivity patterns with 2019-nCoVs. Furthermore, by comparing the infectivity patterns of all viruses hosted on vertebrates, we found mink viruses show a closer infectivity pattern to 2019-nCov. These consequences of infectivity pattern analysis illustrate that bat and mink may be two candidate reservoirs of 2019-nCov.These results warn us to beware of 2019-nCoV and guide us to further explore the properties and reservoir of it. It is of great value to identify whether a newly discovered virus has the risk of infecting human. Guo et al. proposed a virus host prediction method based on deep learning to detect what kind of host a virus can infect with DNA sequence as input. Applied to the Wuhan 2019 Novel Coronavirus, our prediction demonstrated that several vertebrate-infectious coronaviruses have strong potential to infect human. This method will be helpful in future viral analysis and early prevention and control of viral pathogens.


MERS-CoV: the intermediate host identified?