title: Synthesis of N-methyl-d-ribopyranuronamide nucleosides

text: Abstract The synthesis of N-methyl-d-ribopyranuronamide nucleosides is described. The key route is the rearrangement of a 1,2-O-isopropylidene protected furanose sugar with a carboxamide function in the 4-position to a ribopyranuronamide ring. The Lewis acid catalyzed condensation of adenine and thymine nucleobases with the per-O-acetylated N-methyl-d-ribopyranuronamide sugar is used to give the target nucleosides as a mixture of the α and β anomers. The mixture was separated and the final compounds were obtained by deacetylation in basic conditions.


title: PCR sequencing of the spike genes of geographically and chronologically distinct human coronaviruses 229E

text: Abstract A reverse transcription nested PCR (RT-PCR) sequencing methodology was developed and used to generate sequence data from the spike genes of three geographically and chronologically distinct human coronaviruses 229E. These three coronaviruses were isolated originally from the USA in the 1960s (human coronavirus 229E strain ATCC VR-74), the UK in the 1990s (human coronavirus 229E LRI 281) and Ghana (human coronavirus 229E A162). Upon translation and alignment with the published spike protein sequence of human coronavirus 229E ‘LP’ (isolated in the UK in the 1970s), it was found that variation within the translated protein sequences was rather limited. In particular, minimal variation was observed between the translated spike protein sequence of human coronaviruses 229E LP and ATCC VR-74 (1/1012 amino acid differences), whilst most variation was observed between the translated spike protein sequence of human coronaviruses 229E LP and A162 (47/1012 amino acid changes). Further, the translated spike protein sequence of human coronavirus 229E A162 showed three clusters of amino acid changes, situated within the 5′ half of the translated spike protein sequence.


title: Hantavirus Immunology of Rodent Reservoirs: Current Status and Future Directions

text: Hantaviruses are hosted by rodents, insectivores and bats. Several rodent-borne hantaviruses cause two diseases that share many features in humans, hemorrhagic fever with renal syndrome in Eurasia or hantavirus cardiopulmonary syndrome in the Americas. It is thought that the immune response plays a significant contributory role in these diseases. However, in reservoir hosts that have been closely examined, little or no pathology occurs and infection is persistent despite evidence of adaptive immune responses. Because most hantavirus reservoirs are not model organisms, it is difficult to conduct meaningful experiments that might shed light on how the viruses evade sterilizing immune responses and why immunopathology does not occur. Despite these limitations, recent advances in instrumentation and bioinformatics will have a dramatic impact on understanding reservoir host responses to hantaviruses by employing a systems biology approach to identify important pathways that mediate virus/reservoir relationships.


title: Latin American healthcare systems in times of pandemic

text: The COVID‐ 19 pandemic is a critical test for the already overburdened and mostly underfunded public healthcare systems of Latin America. In a region that suffers from severe inequalities, public healthcare systems are the only source of medical care for a large sector of the population who work in the informal economy or are unemployed. State‐run hospitals and clinics are already overstressed by continuous demand for treatment of vector‐borne diseases and community‐acquired infections as well as high rates of non‐communicable diseases. Ideological misconceptions and denial among Latin America’s political leaders prevented timely preparations for the pandemic and added to chronic governance problems. As ethical expertise in Latin America focuses on research ethics, few hospitals in the region have functioning clinical ethics committees or clinical ethics policy, forcing healthcare personnel to make excruciating treatment decisions in an environment dominated by material scarcity and public distrust. This essay examines the emergence of COVID‐19 in Latin America and the serious challenge that it poses for Latin America's public healthcare systems.


Lernen in der Krise


PS3-04 Cytokine induction during coronavirus entry


title: Differential Immune Responses to Hemorrhagic Fever-Causing Arenaviruses

text: The family Arenaviridae contains several pathogens of major clinical importance. The Old World (OW) arenavirus Lassa virus is endemic in West Africa and is estimated to cause up to 300,000 infections each year. The New World (NW) arenaviruses Junín and Machupo periodically cause hemorrhagic fever outbreaks in South America. While these arenaviruses are highly pathogenic in humans, recent evidence indicates that pathogenic OW and NW arenaviruses interact with the host immune system differently, which may have differential impacts on viral pathogenesis. Severe Lassa fever cases are characterized by profound immunosuppression. In contrast, pathogenic NW arenavirus infections are accompanied by elevated levels of Type I interferon and pro-inflammatory cytokines. This review aims to summarize recent findings about interactions of these pathogenic arenaviruses with the innate immune machinery and the subsequent effects on adaptive immunity, which may inform the development of vaccines and therapeutics against arenavirus infections.


Pistes urgentes dans le traitement de l’infection par le COVID-19 : cibler l’inflammation en aval pour prévenir un syndrome catastrophique


Pandemic H1N1 2009 in Neonates


title: Risk factors of weaning diarrhea in puppies housed in breeding kennels

text: Abstract Diarrhea represents one of the most frequent disorders in dogs. In puppies, degradation of feces quality is associated with a reduced daily weight gain and an increased risk of death. Prevention of diarrhea in puppies requires a global approach encompassing enteropathogens, environment and management practices especially when housed in groups. The purpose of this study was to determine prevalence of enteropathogens in puppies in breeding kennels and to identify risk factors of diarrhea. Two hundred and sixty six puppies (between 5 and 14weeks of age) from 29 French breeding kennels were included. For each kennel, data about environment, management of the kennel and puppies’ characteristics (age, sex and breed) were collected. For each puppy, fecal consistency and fecal excretion of enteropathogens (viruses and parasites) was evaluated. At least one enteropathogen was identified in 77.1% of puppies and 24.8% of puppies presented abnormal feces. The main risk factor of weaning diarrhea was fecal excretion of canine parvovirus type 2 (odds ratio=5; confidence interval 95%: 1.7–14.7). A targeted sanitary and medical prophylaxis against canine parvovirus type 2 should be implemented to decrease risk of weaning diarrhea.


title: COVID-19 and myocarditis: What do we know so far?

text: COVID-19 has been declared a global pandemic by the World Health Organization and is responsible for hundreds of thousands of deaths worldwide. COVID-19 is caused by SARS-CoV-2, and common clinical symptoms include fever, cough, sore throat, headache, and fatigue. Myocardial injury is relatively common in COVID-19, accounting for 7-23% of cases, and is associated with a higher morbidity and mortality. There is a discrepancy in the literature about myocarditis as the etiology of myocardial injury in COVID-19; although many anecdotal reports of myocarditis have been noted, there are only a handful of case reports in the literature about myocarditis related to COVID-19. This review summarizes the most up-to-date literature around the association between COVID-19 and myocarditis and gives clinicians a practical framework about the clinical manifestations, diagnostic tools and treatment options currently available. Importantly, this review will heighten suspicion for myocarditis as an etiology of myocardial injury in COVID-19 patients, therefore improving clinical outcomes and encouraging shared clinical decision-making. This will also open the door for further research to build around this review. Emergent treatment options for COVID-19 are in clinical trials and may be of benefit to COVID-19 patients with myocarditis in addition to current guideline-based recommendations.


title: Self-contamination during doffing of personal protective equipment by healthcare workers to prevent Ebola transmission

text: BACKGROUND: Healthcare workers (HCWs) use personal protective equipment (PPE) in Ebola virus disease (EVD) situations. However, preventing the contamination of HCWs and the environment during PPE removal crucially requires improved strategies. This study aimed to compare the efficacy of three PPE ensembles, namely, Hospital Authority (HA) Standard Ebola PPE set (PPE1), Dupont Tyvek Model, style 1422A (PPE2), and HA isolation gown for routine patient care and performing aerosol-generating procedures (PPE3) to prevent EVD transmission by measuring the degree of contamination of HCWs and the environment. METHODS: A total of 59 participants randomly performed PPE donning and doffing. The trial consisted of PPE donning, applying fluorescent solution on the PPE surface, PPE doffing of participants, and estimation of the degree of contamination as indicated by the number of fluorescent stains on the working clothes and environment. Protocol deviations during PPE donning and doffing were monitored. RESULTS: PPE2 and PPE3 presented higher contamination risks than PPE1. Environmental contaminations such as those originating from rubbish bin covers, chairs, faucets, and sinks were detected. Procedure deviations were observed during PPE donning and doffing, with PPE1 presenting the lowest overall deviation rate (%) among the three PPE ensembles (p < 0.05). CONCLUSION: Contamination of the subjects’ working clothes and surrounding environment occurred frequently during PPE doffing. Procedure deviations were observed during PPE donning and doffing. Although PPE1 presented a lower contamination risk than PPE2 and PPE3 during doffing and protocol deviations, the design of PPE1 can still be further improved. Future directions should focus on designing a high-coverage-area PPE with simple ergonomic features and on evaluating the doffing procedure to minimise the risk of recontamination. Regular training for users should be emphasised to minimise protocol deviations, and in turn, guarantee the best protection to HCWs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13756-018-0433-y) contains supplementary material, which is available to authorized users.


title: Indigowood root extract protects hematopoietic cells, reduces tissue damage and modulates inflammatory cytokines after total-body irradiation: Does Indirubin play a role in radioprotection?

text: Abstract Radix of Isatis indigotica (indigowood root, IR) has been used in traditional medicine for its potential anti-inflammatory effect. The purpose of this study is to investigate the radioprotective effects of radiation caused damages in hematopoietic system and normal tissues in mice. A total of 57 BALB/c mice were randomized into six treatment groups: control, IR treatment (0.195, 0.585 and 1.170g/kg, p.o. daily), L-glutamine (0.520g/kg) and sham group. All mice except the sham group were irradiated and then administered for one week. The radioprotective effect on hematopoietic system, serum cytokines, and intestinal toxicity was studied. Protective effects on spleen and thymus are found in IR-treated groups. IR assisted in restoration of leukocytopenia after whole mice irradiation with significant reduction of serum TNF-α, IL-1β, and IL-6. These enhancements of hematopoietic effects are due to an increase in the serum G-CSF concentration in IR treated groups. In histopathological assessment, significant improvement of intestine toxicity is observed in high-dose IR and L-glutamine group. Evidences show that IR has potentials to be a radioprotector, especially in recovery of hematopoietic system, reduction of inflammatory cytokines and intestinal toxicity. Indirubin may play a crucial role, but the underlying mechanism is not very clear and warrants further studies.


title: Has the virus of multiple sclerosis been isolated?

text: There have been many attempts to isolate infectious agents from patients with multiple sclerosis (MS), and many viruses have been incriminated at one time or another over the past few decades. However, in every case further research has disproved the original claim. Thus, we cautiously report on the isolation of four antigenically related agents from the cerebrospinal fluid (CSF) of three patients with MS and one patient with amyotrophic lateral sclerosis. The patients yielding the isolates from their CSF possessed neutralizing antibodies to the virus in their blood, in contrast to several other virus-free patients with chronic central nervous system (CNS) diseases studied at the same time. The virus could not be isolated from 27 patients who were not suffering from chronic disease of the CNS. The agent has not yet been adequately characterized, but it deserves further attention because it seems to be a hitherto unknown virus, difficult to isolate and difficult to work with in the laboratory. Its isolation from the four patients mentioned above (and subsequently in several other MS patients) warrants further investigation of its potential role in MS and other progressive diseases of the CNS.


title: Comparison of different samples for 2019 novel coronavirus detection by nucleic acid amplification tests

text: Abstract A severe respiratory ongoing outbreak of pneumonia associated with 2019 novel coronavirus was recently emerged in China. Here, we reported the epidemiological, clinical, laboratory and radiological characteristics of 19 suspect cases. We compared the positive ratio of 2019-nCoV nucleic acid amplification test from different samples including oropharyngeal swab, blood, urine and stool with 3different Fluorescent RT-PCR kits. Nine out of the 19 patients were detected 2019-nCoV infection using oropharyngeal swab samples, and the virus nucleic acid was also detected in eight of these nine patients using stool samples. None of positive results was identified in the blood and urine samples. Thses three different kits got the same result for each sample and the positive ratio of nucleic acid detection for 2019-nCoV was only 47.4% in the suspect patients. Therefore, it is possible that the really infected patients have been missed by using nucleic acid detection only. It might be better to make a diagnosis combining the Computed Tomography scans and the nucleic acid detection together.


title: Loss of Apelin Augments Angiotensin II-Induced Cardiac Dysfunction and Pathological Remodeling

text: Apelin is an inotropic and cardioprotective peptide that exhibits beneficial effects through activation of the APJ receptor in the pathology of cardiovascular diseases. Apelin induces the expression of angiotensin-converting enzyme 2 (ACE2) in failing hearts, thereby improving heart function in an angiotensin 1–7-dependent manner. Whether apelin antagonizes the over-activation of the renin–angiotensin system in the heart remains elusive. In this study we show that the detrimental effects of angiotensin II (Ang II) were exacerbated in the hearts of aged apelin-gene-deficient mice. Ang II-mediated cardiac dysfunction and hypertrophy were augmented in apelin knockout mice. The loss of apelin increased the ratio of angiotensin-converting enzyme (ACE) to ACE2 expression in the Ang II-stressed hearts, and Ang II-induced cardiac fibrosis was markedly enhanced in apelin knockout mice. mRNA expression of pro-fibrotic genes, such as transforming growth-factor beta (TGF-β) signaling, were significantly upregulated in apelin knockout hearts. Consistently, treatment with the ACE-inhibitor Captopril decreased cardiac contractility in apelin knockout mice. In vitro, apelin ameliorated Ang II-induced TGF-β expression in primary cardiomyocytes, accompanied with reduced hypertrophy. These results provide direct evidence that endogenous apelin plays a crucial role in suppressing Ang II-induced cardiac dysfunction and pathological remodeling.


Designing of improved drugs for COVID-19: Crystal structure of SARS-CoV-2 main protease M(pro)


title: Antimicrobial activity of Chinese medicine herbs against common bacteria in oral biofilm. A pilot study

text: Abstract Twenty traditional Chinese medicines (TCM) were evaluated for their antimicrobial activity against four common oral bacteria. TCMs were tested for sensitivity against Streptococcus mitis, Streptococcus sanguis, Streptococcus mutans and Porphyromonas gingivalis. Aliquots of suspension of each bacterial species were inoculated onto a horse blood agar plate with TCMs soaked separately on 6mm paper disks. The plates were incubated for 48h anaerobically and the mean diameters of growth inhibition of three different areas obtained. 0.2% (w/v) chlorhexidine was used as a positive control. Broth microdilution assay was used to determine minimum inhibitory concentration and minimum bactericidal concentration. Fructus armeniaca mume was effective against all four bacteria. Thirteen TCMs demonstrated antimicrobial activity against Porphyromonas gingivalis, including Cortex magnoliae officinalis, Cortex phellodendri, Flos caryophylli, Flos lonicerae japonicae, Fructus armeniaca mume, Fructus forsythiae suspensae, Herba cum radice violae yedoensitis, Herba menthae haplocalycis, Pericarpium granati, Radix et rhizoma rhei, Radix gentianae, Ramulus cinnamomi cassia and Rhizoma cimicifugae. Cortex phellodendri showed antimicrobial activity against Streptococcus mutans, while Radix et rhizoma rhei was effective against Streptococcus mitis and Streptococcus sanguis. Fructus armeniaca mume had inhibitory effects against Streptococcus mitis, Streptococcus sanguis, Streptococcus mutans and Porphyromonas gingivalis in vitro.


title: Hajj-associated viral respiratory infections: A systematic review

text: Summary Respiratory tract infections (RTI) are the most common infections transmitted between Hajj pilgrims. The aim of this systematic review was to determine the prevalence of virus carriage potentially responsible for RTI among pilgrims before and after participating in the Hajj. A systematic search for relevant literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. 31 studies were identified. Severe Acute Respiratory Syndrome coronavirus and Middle East Respiratory Syndrome coronavirus (MERS) were never isolated in Hajj pilgrims. The viruses most commonly isolated from symptomatic patients during the Hajj by PCR were rhinovirus (5.9–48.8% prevalence), followed by influenza virus (4.5–13.9%) and non-MERS coronaviruses (2.7–13.2%) with most infections due to coronavirus 229E; other viruses were less frequently isolated. Several viruses including influenza A, rhinovirus, and non-MERS coronaviruses had low carriage rates among arriving pilgrims and a statistically significant increase in their carriage rate was observed, following participation in the Hajj. Further research is needed to assess the role of viruses in the pathogenesis of respiratory symptoms and their potential role in the severity of the symptoms.


title: Protecting healthcare staff from severe acute respiratory syndrome: filtration capacity of multiple surgical masks

text: Summary Guidelines issued by the Centers for Disease Control and Prevention and the World Health Organisation state that healthcare workers should wear N95 masks or higher-level protection during all contact with suspected severe acute respiratory syndrome (SARS). In areas where N95 masks are not available, multiple layers of surgical masks have been tried to prevent transmission of SARS. The in vivo filtration capacity of a single surgical mask is known to be poor. However, the filtration capacity of a combination of masks is unknown. This was a crossover trial of one, two, three and five surgical masks in six volunteers to determine the in vivo filtration efficiency of wearing more than one surgical mask. We used a Portacount to measure the difference in ambient particle counts inside and outside the masks. The best combination of five surgical masks scored a fit factor of 13.7, which is well below the minimum level of 100 required for a half face respirator. Multiple surgical masks filter ambient particles poorly. They should not be used as a substitute for N95 masks unless there is no alternative.


title: Cell attenuated porcine epidemic diarrhea virus strain Zhejiang08 provides effective immune protection attributed to dendritic cell stimulation

text: Since 2010, the porcine epidemic diarrhea coronavirus (PEDV) has caused significant damage to the global pork industry. However, classical PEDV vaccine strains only provide limited protection against emerging strains. In this study, we successfully isolated and attenuated the PEDV epidemic strain Zhejiang08, which was characterized by good cell adaptation and high-titer production 48 h post infection in Vero E6 cells. The attenuated virus induced a high level of virus-specific neutralizing antibodies until 120 days after immunization in piglets and provided complete protection when challenged with an emerging virus strain on day 14 post immunization. Moreover, the capability to activate dendritic cells (DCs) of this isolate was identified. Higher expression levels of IL-12 and IFN-γ were recorded in DCs after treatment with Zhejiang08 for 24 h. Furthermore, genome sequencing and phylogenetic analysis revealed high homology between the main antigen epitopes of Zhejiang08 and PEDV pandemic isolates following 2011. Combining the glycosylation site prediction results and their distribution within the spatial structure of the S protein, led to the conclusion that the observed more effective host immune response of Zhejiang08 compared to CV777 was possibly associated with a lack of the potential glycosylation site in the 296 amino acids of the S protein. In summary, we illustrated that the attenuated virus represents a promising vaccine candidate.


title: The relationship of serum vitamins A, D, E and LL-37 levels with allergic status, tonsillar virus detection and immune response

text: BACKGROUND: Tonsils have an active role in immune defence and inducing and maintaining tolerance to allergens. Vitamins A, D, and E, and antimicrobial peptide LL-37 may have immunomodulatory effects. We studied how their serum levels were associated with allergy status, intratonsillar/nasopharyngeal virus detection and intratonsillar expression of T cell- and innate immune response-specific cytokines, transcription factors and type I/II/III interferons in patients undergoing tonsillectomy. METHODS: 110 elective tonsillectomy patients participated. Serum levels of vitamins A, 25(OH)D, and E, LL-37 and allergen-specific IgE as well as nasopharyngeal/intratonsillar respiratory viruses were analyzed. The mRNA expression of IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2 and Tbet in tonsils were analyzed by quantitative RT-PCR. RESULTS: The median age of the patients was 16 years (range 3–60), 28% of subjects had atopy, and 57% carried ≥1 respiratory virus in nasopharynx. Detection of viruses decreased by age. Higher vitamin A levels showed borderline significance with less viral detection (P = 0.056). Higher 25(OH)D was associated with less allergic rhinitis and atopy (P < 0.05) and higher vitamin E with less self-reported allergy (P < 0.05). In gene expression analyses, 25(OH)D was associated with higher IL-37, vitamin A with higher IFN-γ and vitamin E with less IL-28 (P < 0.05). LL-37 was associated with less FOXP3, RORC2 and IL-17 in tonsils (P < 0.05). CONCLUSIONS: Vitamin D and E levels were associated with less allergic disorders. Vitamin A was linked to antiviral and vitamin D with anti-inflammatory activity. LL-37 and was linked to T regulatory cell effects.


title: Revitalization of integrated disease surveillance and response in Sierra Leone post Ebola virus disease outbreak

text: BACKGROUND: The Ministry of Health and Sanitation (MOHS) in Sierra Leone partially rolled out the implementation of Integrated Disease Surveillance and Response (IDSR) in 2003. After the Ebola virus disease outbreak in 2014–2015, there was need to strengthen IDSR to ensure prompt detection and response to epidemic-prone diseases. We describe the processes, successes and challenges of revitalizing public health surveillance in a country recovering from a protracted Ebola virus disease outbreak. METHODS: The revitalization process began with adaptation of the revised IDSR guidelines and development of customized guidelines to suit the health care systems in Sierra Leone. Public health experts defined data flow, system operations, case definitions, frequency and channels of reporting and dissemination. Next, phased training of IDSR focal persons in each health facility and the distribution of data collection and reporting tools was done. Monitoring activities included periodic supportive supervision and data quality assessments. Rapid response teams were formed to investigate and respond to disease outbreak alerts in all districts. RESULTS: Submission of reports through the IDSR system began in mid-2015 and by the 35th epidemiologic week, all district health teams were submitting reports. The key performance indicators measuring the functionality of the IDSR system in 2016 and 2017 were achieved (WHO Africa Region target ≥80%); the annual average proportion of timely weekly health facility reports submitted to the next level was 93% in 2016 and 97% in 2017; the proportion of suspected outbreaks and public health events detected through the IDSR system was 96% (n = 87) in 2016 and 100% (n = 85) in 2017. CONCLUSION: With proper planning, phased implementation and adequate investment of resources, it is possible to establish a functional IDSR system in a country recovering from a public health crisis. A functional IDSR system requires well trained workforce, provision of the necessary tools and guidelines, information, communication and technology infrastructure to support data transmission, provision of timely feedback as well as logistical support. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-019-6636-1) contains supplementary material, which is available to authorized users.


title: Mitochondria and viruses

text: Abstract Mitochondria are involved in a variety of cellular metabolic processes, and their functions are regulated by extrinsic and intrinsic stimuli including viruses. Recent studies have shown that mitochondria play a central role in the primary host defense mechanisms against viral infections, and a number of novel viral and mitochondrial proteins are involved in these processes. Some viral proteins localize in mitochondria and interact with mitochondrial proteins to regulate cellular responses. This review summarizes recent findings on the functions and roles of these molecules as well as mitochondrial responses to viral infections.


title: The long‐term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status

text: Background and objective: Severe acute respiratory syndrome (SARS) emerged in 2003 and its long‐term sequelae remain largely unclear. This study examined the long‐term outcome of pulmonary function, exercise capacity, health and work status among SARS survivors. Methods: A prospective cohort study of SARS patients at the Prince of Wales Hospital, Hong Kong was conducted, with serial assessments of lung function, 6MWD and 36 item Short Form General Health Survey at 3, 6, 12, 18 and 24 months after disease onset. The work status was also recorded. Results: Serial assessments were completed by 55 of the 123 (39.9%) subjects, of whom 27 were health‐care workers (HCW). The mean age of the group was 44.4 (SD 13.2) years and 19 (34.5%) were males. At 24 months, 10 (18.2%), 9 (16.4%), 6 (10.9%) and 29 (52.7%) subjects had FEV(1), FVC, TLC and DL(CO) < 80% of predicted values, respectively. The mean (SD) 6MWD increased significantly from 439.0 (89.1) m at 3 months to 460.1 (102.8) m at 6 months (P 0.016) and became steady after 6 months. However, 6MWD and 36 item Short Form General Health Survey scores were lower than the normal population throughout the study. Moreover, 29.6% of HCW and 7.1% of non‐HCW had not returned to work 2 years after illness onset. Conclusions: This 2‐year study of a selected population of SARS survivors, showed significant impairment of DL(CO), exercise capacity and health status persisted, with a more marked adverse impact among HCW.


title: Extremes in Context: A Life-Course Approach to Disaster Mental Health

text: Exposure to disasters has a range of adverse mental-health consequences. This Commentary argues that to understand variation in post-disaster mental health, we must look beyond the disaster itself to other sources of vulnerability throughout the life course, as well as the developmental stage at which the disaster was experienced.


title: Epidemiology of Enterovirus D68 in Ontario

text: In August 2014, children’s hospitals in Kansas City, Missouri and Chicago, Illinois notified the Centers for Disease Control and Prevention (CDC) about increased numbers of pediatric patients hospitalized with severe respiratory illness (SRI). In response to CDC reports, Public Health Ontario Laboratories (PHOL) launched an investigation of patients being tested for enterovirus D-68 (EV-D68) in Ontario, Canada. The purpose of this investigation was to enhance our understanding of EV-D68 epidemiology and clinical features. Data for this study included specimens submitted for EV-D68 testing at PHOL from September 1, 2014 to October 31, 2014. Comparisons were made between patients who tested positive for the virus (cases) and those testing negative (controls). EV-D68 was identified in 153/907 (16.8%) of patients tested. In the logistic regression model adjusting for age, sex, setting and time to specimen collection, individuals younger than 20 years of age were more likely to be diagnosed with EV-D68 compared to those 20 and over, with peak positivity at ages 5–9 years. Cases were not more likely to be hospitalized than controls. Cases were more likely to be identified in September than October (OR 8.07; 95% CI 5.15 to 12.64). Routine viral culture and multiplex PCR were inadequate methods to identify EV-D68 due to poor sensitivity and inability to differentiate EV-D68 from other enterovirus serotypes or rhinovirus. Testing for EV-D68 in Ontario from July to December, 2014 detected the presence of EV-D68 virus among young children during September-October, 2014, with most cases detected in September. There was no difference in hospitalization status between cases and controls. In order to better understand the epidemiology of this virus, surveillance for EV-D68 should include testing of symptomatic individuals from all treatment settings and patient age groups, with collection and analysis of comprehensive clinical and epidemiological data.


title: Blood immune transcriptome analysis of artificially fed dairy calves and naturally suckled beef calves from birth to 7 days of age

text: Neonatal calves possess a very immature and naïve immune system and are reliant on the intake of maternal colostrum for passive transfer of immunoglobulins. Variation in colostrum management of beef and dairy calves is thought to affect early immune development. Therefore, the objective of this study was to examine changes in gene expression and investigate molecular pathways involved in the immune-competence development of neonatal Holstein dairy calves and naturally suckled beef calves using next generation RNA-sequencing during the first week of life. Jugular whole blood samples were collected from Holstein (H) dairy calves (n = 8) artificially fed 5% B.W. colostrum, and from beef calves which were the progenies of Charolais-Limousin (CL; n = 7) and Limousin-Friesian beef suckler cows (LF; n = 7), for subsequent RNA isolation. In dairy calves, there was a surge in pro-inflammatory cytokine gene expression possibly due to the stress of separation from the dam. LF calves exhibited early signs of humoral immune development with observed increases in the expression genes coding for Ig receptors, which was not evident in the other breeds by 7 days of age. Immune and health related DEGs identified as upregulated in beef calves are prospective contender genes for the classification of biomarkers for immune-competence development, and will contribute towards a greater understanding of the development of an immune response in neonatal calves.


title: Novel Coronavirus in Cape Town Informal Settlements: Feasibility of Using Informal Dwelling Outlines to Identify High Risk Areas for COVID-19 Transmission From A Social Distancing Perspective

text: BACKGROUND: The challenges faced by the Global South during the coronavirus disease (COVID-19) pandemic are compounded by the presence of informal settlements, which are typically densely populated and lacking in formalized sanitation infrastructure. Social distancing measures in informal settlements may be difficult to implement due to the density and layout of settlements. This study measures the distance between dwellings in informal settlements in Cape Town to identify the risk of COVID-19 transmission. OBJECTIVE: The aim of this paper is to determine if social distancing measures are achievable in informal settlements in Cape Town, using two settlements as an example. We will first examine the distance between dwellings and their first, second, and third nearest neighbors and then identify clusters of dwellings in which residents would be unable to effectively practice social isolation due to the close proximity of their homes. METHODS: Dwellings in the settlements of Masiphumelele and Klipfontein Glebe were extracted from a geographic information system data set of outlines of all informal dwellings in Cape Town. The distance to each dwelling’s first, second, and third nearest neighbors was calculated for each settlement. A social distance measure of 2 m was used (buffer of 1 m, as dwellings less than 2 m apart are joined) to identify clusters of dwellings that are unable to effectively practice social distancing in each settlement. RESULTS: The distance to each dwelling’s first 3 nearest neighbors illustrates that the settlement of Masiphumelele is constructed in a denser fashion as compared to the Klipfontein Glebe settlement. This implies that implementing social distancing will likely be more challenging in Masiphumelele than in Klipfontein Glebe. However, using a 2-m social distancing measure, it was demonstrated that large portions of Klipfontein Glebe would also be unable to effectively implement social distancing. CONCLUSIONS: Effectively implementing social distancing may be a challenge in informal settlements due to their density. This paper uses dwelling outlines for informal settlements in the city of Cape Town to demonstrate that with a 2 m measure, effective social distancing will be challenging.


title: Apolipoprotein D deficiency is associated to high bone turnover, low bone mass and impaired osteoblastic function in aged female mice

text: Abstract Background Apolipoprotein D (ApoD) is a member of the lipocalin family known to transport small hydrophobic ligands. A major site of ApoD expression in mice is the central nervous system where evidence suggests that it plays a protective role. Gene expression of ApoD was reported in bone-forming osteoblasts but its impact on bone metabolism remains undocumented. Methods We compared basic bone parameters of ApoD −/− (null) and transgenic (tg) mice to wild-type (wt) littermates through microCT and histochemistry, as well as ApoD expression and secretion in osteoblasts under various culture conditions through real-time PCR and immunoblotting. Results ApoD-null females displayed progressive bone loss with aging, resulting in a 50% reduction in trabecular bone volume and a 23% reduction in cortical bone volume by 9months of age. Only cortical bone volume was significantly reduced in ApoD-null males by an average of 24%. Histochemistry indicated significantly higher osteoblast surface and number of osteoclasts in femora from ApoD-null females. ApoD gene expression was confirmed in primary cultures of bone marrow mesenchymal cells (MSC), with higher expression levels in MSC from females compared to males. ApoD-null MSC exhibited impaired proliferation and differentiation potentials. Moreover, exogenous ApoD partially rescued the osteogenic potential of null MSC, which were shown to readily uptake the protein from media. ApoD expression was upregulated under low proliferation conditions, by contact inhibition and osteoblastic differentiation in MC3T3-E1 osteoblast-like cells. Conclusion Our results indicate that ApoD influences bone metabolism in mice in a gender-specific manner, potentially through an auto-/paracrine pathway.


title: Epidemiologic analysis of respiratory viral infections among Singapore military servicemen in 2016

text: BACKGROUND: Respiratory illnesses have been identified as a significant factor leading to lost training time and morbidity among Singapore military recruits. A surveillance programme has been put in place to determine etiological agents responsible for febrile, as well as afebrile respiratory illnesses in a military camp. The goal of the study is to better understand the epidemiology of these diseases and identify potential countermeasures to protect military recruits against them. METHODS: From Jan 2016 - Jan 2017, a total of 2647 respiratory cases were enrolled into the surveillance programme. The cases were further stratified into Febrile Respiratory Illness (FRI, with body temperature > 37.5 °C) or Acute Respiratory Illness (ARI, with body temperature < 37.5 °C). Nasal washes were collected and tested by multiplex PCR to detect 26 different pathogens. RESULTS: One thousand ninety five cases (41% of total cases) met the criteria of FRI in which 932 cases (85% of FRI cases) were screened positive for at least one virus. The most common etiological agents for FRI mono-infection cases were Adenovirus E and Rhinovirus. Recruits infected with H3N2 influenza, Influenza B and Adenovirus E viruses were most likely presented as FRI cases. Notably, H3N2 influenza resulted in the greatest rise in body temperature. The remaining 1552 cases (59% of total cases) met the criteria of ARI in which 1198 cases (77% of ARI cases) were screened positive for at least one virus. The most common etiological agent for ARI mono-infection was Rhinovirus. The distribution pattern for dual infections was different for ARI and FRI cases. Maximum number of pathogens detected in a sample was five for both groups. CONCLUSION: Previous studies on respiratory diseases in military focused largely on FRI cases. With the expanded surveillance to ARI cases, this study allows unbiased evaluation of the impact of respiratory disease pathogens among recruits in a military environment. The results show that several pathogens have a much bigger role in causing respiratory diseases in this cohort. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3040-x) contains supplementary material, which is available to authorized users.


title: A systematic review of MERS-CoV (Middle East Respiratory Syndrome Coronavirus) seroprevalence and viral RNA prevalence in dromedary camels: implications for animal vaccination

text: Human infection with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is driven by recurring dromedary-to-human spill-over events, leading decision-makers to consider dromedary vaccination. Dromedary vaccine candidates in the development pipeline are showing hopeful results, but gaps in our understanding of the epidemiology of MERS-CoV in dromedaries must be addressed to design and evaluate potential vaccination strategies. We systematically reviewed the published literature reporting seroprevalence and/or prevalence of active MERS-CoV infection in dromedary populations from both cross-sectional and longitudinal studies, including 60 studies in our qualitative syntheses. MERS-CoV seroprevalence increased with age up to 80-100% in adult dromedaries supporting geographically wide spread endemicity of MERS-CoV in dromedaries in both the Arabian Peninsula and countries exporting dromedaries from Africa. The high prevalence of active infection measured in juveniles and at sites where dromedary populations mix should guide further investigation – particularly of dromedary movement – and inform vaccination strategy design.


title: Modern Biomolecular Mass Spectrometry and its Role in Studying Virus Structure, Dynamics, and Assembly

text: Over a century since its development, the analytical technique of mass spectrometry is blooming more than ever, and applied in nearly all aspects of the natural and life sciences. In the last two decades mass spectrometry has also become amenable to the analysis of proteins and even intact protein complexes, and thus begun to make a significant impact in the field of structural biology. In this Review, we describe the emerging role of mass spectrometry, with its different technical facets, in structural biology, focusing especially on structural virology. We describe how mass spectrometry has evolved into a tool that can provide unique structural and functional information about viral‐protein and protein‐complex structure, conformation, assembly, and topology, extending to the direct analysis of intact virus capsids of several million Dalton in mass. Mass spectrometry is now used to address important questions in virology ranging from how viruses assemble to how they interact with their host.


title: Chapter 20 Ethics, Legality, and Education in the Practice of Cardiology

text: Advances in diagnostics, drugs, and devices have revolutionized cardiology practice, and improved quality of life of the patients. However, awareness, achievements, and advances in cardiac health care have enhanced the demands and expectations of the community, which lacks awareness about the social, economic, administrative, professional, and technical constraints or limitations of implementation. Being unfamiliar with medical ethics and legal aspects of care, and suboptimal virtues among physicians, have led to patients and the public utilizing legal remedies. In addition, sophistication of medical practice, increasing costs of health care, involvement of insurance systems, increased awareness and high expectations from the community and patients, and increased participation of the media have altered the attitude toward claiming compensation and acquisition of health care delivery among the public. In view of the changing trends of consumers and emerging areas in health care, providers must get accustomed to patient empowerment and come up to their expectations. Interactive programs on these aspects in medical education will help students understand not only the intricacies of medical ethics and the laws and shortcomings of health professionals and/or health systems, but also strengthen their knowledge of ethics and laws to improve their practice. Principles of ethics and legal issues have to be discussed at every stage of medical education. To improve the quality of the physician–patient encounter, we need to develop formal and informal curricula about effective communication skills. This chapter also highlights preventive measures and educational aspects of cardiology practice.


title: 65 years of influenza surveillance by a World Health Organization‐coordinated global network

text: The 1918 devastating influenza pandemic left a lasting impact on influenza experts and the public, and the importance of global influenza surveillance was soon recognized. The World Health Organization (WHO) Global Influenza Surveillance Network (GISN) was founded in 1952 and renamed to Global Influenza Surveillance and Response System in 2011 upon the adoption by the World Health Assembly, of the Pandemic Influenza Preparedness Framework for the Sharing of Influenza Viruses and Access to Vaccines and Other Benefits (“PIP Framework”). The importance of influenza surveillance had been recognized and promoted by experts prior to the years leading up to the establishment of WHO. In the 65 years of its existence, the Network has grown to comprise 143 National Influenza Centers recognized by WHO, 6 WHO Collaborating Centers, 4 Essential Regulatory Laboratories, and 13 H5 Reference Laboratories. The Network has proven its excellence throughout these 65 years, providing detailed information on circulating seasonal influenza viruses, as well as immediate response to the influenza pandemics in 1957, 1968, and 2009, and to threats caused by animal influenza viruses and by zoonotic transmission of coronaviruses. For its central role in global public health, the Network has been highly recognized by its many partners and by international bodies. Several generations of world‐renowned influenza scientists have brought the Network to where it is now and they will take it forward to the future, as influenza will remain a preeminent threat to humans and to animals.


title: Molecular characterization of hepatitis E virus ORF1 gene supports a papain-like cysteine protease (PCP)-domain activity

text: Abstract Hepatitis E Virus (HEV) ORF1 encodes the nonstructural polyprotein wherein a role of PCP-domain in ORF1 proteolysis and/or RNA replication still remains contested. A series of ORF1 mutants of HEV-SAR55 replicon were constructed and tested for viability in S10-3 cells. Six of PCP-‘cysteine’ (C457A, C459A, C471A, C472A, C481A and C483A) and three ‘histidine’ (H443L, H497L and H590L) mutants were lethal. Further, a highly conserved ‘glycine-triad’ (G815-G816-G817) in downstream X-domain, homologous to rubella virus protease-substrate (G1299-G1300-G1301) was identified where two of X-mutants (G816V and G817V) turned lethal. However, all ORF1 sequential nucleotide-mutants conserving the amino acids were viable, which clearly showed post-translational regulation of HEV replication by PCP- and X-domains. Moreover, while vector-expressed ORF1-fusion polyprotein yielded a ∼191kDa band in vitro, it produced ∼78 and ∼35kDa fragments ex vivo. Collectively, the indispensability and functional effects of ‘PCP-catalytic’ and ‘X-substrate’ residues on HEV replication strongly supported a viral protease.


COVID-19 en migrantes y minorías étnicas


title: Comparison of Subcutaneous versus Intravenous Alemtuzumab for Graft-versus-Host Disease Prophylaxis with Fludarabine/Melphalan–Based Conditioning in Matched Unrelated Donor Allogeneic Stem Cell Transplantation

text: Abstract The objective of this study was to compare infusion-related reactions and outcomes of using subcutaneous (subQ) alemtuzumab versus intravenous (i.v.) alemtuzumab as graft-versus-host disease (GVHD) prophylaxis for matched unrelated donor stem cell transplantations. Outcomes include incidence of cytomegalovirus (CMV)/Epstein-Barr (EBV) viremia, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, acute and chronic GVHD, time to engraftment, relapse rate, and survival. We conducted a retrospective study of all adult matched unrelated donor stem cell transplantations patients who received fludarabine/melphalan with subQ or i.v. alemtuzumab in combination with tacrolimus as part of their conditioning for unrelated donor transplantation at New York-Presbyterian/Weill Cornell Medical Center from January 1, 2012 to March 21, 2014. Alemtuzumab was administered at a total cumulative dose of 100 mg (divided over days −7 to −3). Forty-six patients received an unrelated donor stem cell transplantation with fludarabine/melphalan and either subQ (n = 26) or i.v. (n = 20) alemtuzumab in combination with tacrolimus. Within the evaluable population, 130 subQ and 100 i.v. alemtuzumab doses were administered. For the primary outcome, ≥grade 2 infusion-related reactions occurred in 11 (8%) versus 25 (25%) infusions in the subQ and i.v. cohorts, respectively (P = .001). Overall, 12 injections (9%) in the subQ arm versus 26 infusions (26%) in the i.v. arm experienced an infusion-related reaction of any grade (P = .001). There were no significant differences between the subQ and i.v. arms in rates of reactivation of CMV/EBV, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, acute and chronic GVHD, relapse, or survival. Subcutaneous administration of alemtuzumab for GVHD prophylaxis was associated with fewer infusion-related reactions compared with i.v. administration in the SCT setting. Incidences of acute and chronic GVHD were similar between both arms. There was also no difference in reactivation of CMV/EBV viremia, development of CMV disease or post-transplantation lymphoproliferative disorder, fatal infections, relapse, or survival.


The role of CT for Covid-19 patient's management remains poorly defined.


title: The Rationale for Potential Pharmacotherapy of COVID-19

text: On 11 March 2020, the coronavirus disease (COVID-19) was defined by the World Health Organization as a pandemic. Severe acute respiratory syndrome-2 (SARS-CoV-2) is the newly evolving human coronavirus infection that causes COVID-19, and it first appeared in Wuhan, China in December 2019 and spread rapidly all over the world. COVID-19 is being increasingly investigated through virology, epidemiology, and clinical management strategies. There is currently no established consensus on the standard of care in the pharmacological treatment of COVID-19 patients. However, certain medications suggested for other diseases have been shown to be potentially effective for treating this infection, though there has yet to be clear evidence. Therapies include new agents that are currently tested in several clinical trials, in addition to other medications that have been repurposed as antiviral and immune-modulating therapies. Previous high-morbidity human coronavirus epidemics such as the 2003 SARS-CoV and the 2012 Middle East respiratory syndrome coronavirus (MERS-CoV) prompted the identification of compounds that could theoretically be active against the emerging coronavirus SARS-CoV-2. Moreover, advances in molecular biology techniques and computational analysis have allowed for the better recognition of the virus structure and the quicker screening of chemical libraries to suggest potential therapies. This review aims to summarize rationalized pharmacotherapy considerations in COVID-19 patients in order to serve as a tool for health care professionals at the forefront of clinical care during this pandemic. All the reviewed therapies require either additional drug development or randomized large-scale clinical trials to be justified for clinical use.


title: The Potential Role of Th17 Immune Responses in Coronavirus Immunopathology and Vaccine-induced Immune Enhancement

text: Abstract Increasing evidence points to host Th17 inflammatory responses as contributing to the severe lung pathology and mortality of lower respiratory tract infections from coronaviruses. This includes host inflammatory and cytokine responses to COVID-19 caused by the SARS-2 coronavirus (SARS CoV2). From studies conducted in laboratory animals, there are additional concerns about immune enhancement and the role of potential host immunopathology resulting from experimental human COVID-19 vaccines. Here we summarize evidence suggesting there may be partial overlap between the underlying immunopathologic processes linked to both coronavirus infection and vaccination, and a role for Th17 in immune enhancement and eosinophilic pulmonary immunopathology. Such findings help explain the link between viral-vectored coronavirus vaccines and immune enhancement and its reduction through alum adjuvants. Additional research may also clarify links between COVID-19 pulmonary immunopathology and heart disease.


title: Etiology, clinical, and epidemiological characteristics of severe respiratory infection in people living with HIV

text: People living with HIV (PLWH) are more prone to severe respiratory infections. We used the severe acute respiratory infection (SARI) definition to describe the etiology, clinical, and epidemiological characteristics in this population. This was a prospective observational study including PLWH hospitalized with fever and cough. Those with symptom onset up to 10 days were classified as severe acute respiratory infection and 11–30 days as non-severe acute respiratory infection. Blood, urine samples and nasopharyngeal swabs were collected. Data were extracted from patient charts during their hospital stay. Forty-nine patients were included, median CD4 cell count: 80 cells/mm(3), median time since HIV diagnosis and hospital admission: 84 months and 80% were antiretroviral therapy exposed. Twenty-seven patients were classified as SARI. Etiology was identified in 69%, 47% were polymicrobial. Respiratory virus (9 SARI vs. 13 non-SARI), bacteria (5 SARI vs. 4 non-SARI), Mycobacterium tuberculosis (6 SARI group vs. 7 non-SARI group), Pneumocystis jirovecii (4 SARI vs. 1 non-SARI), Cryptococcus neoformans (1 SARI vs. 3 non-SARI), and influenza A (1 SARI vs. 2 non-SARI). Dyspnea was statistically more prevalent in SARI (78% vs. 36%, p = 0.011) but the risk of death was higher in the non-SARI (4% vs. 36%, p = 0.0067). In the severely immunocompromised PLWH, severe acute respiratory infection can be caused by multiple pathogens and codetection is a common feature.


title: Core Outcome Set for Clinical Trials on Coronavirus Disease 2019 (COS-COVID)

text: Abstract Since its outbreak in December 2019, a series of clinical trials on Coronavirus Disease 2019 (COVID-19) have been registered or carried out. However, the significant heterogeneity and less critical outcomes of such trials may be leading to a waste of research resources. This study aimed to develop a core outcome set (COS) for clinical trials on COVID-19 in order to tackle the outcome issues. The study was conducted according to the Core Outcome Measures in Effectiveness Trials (COMET) handbook (version 1.0), a guideline for COS development. A research group was set up that included experts in respiratory and critical medicine, traditional Chinese medicine, evidence-based medicine, clinical pharmacology, and statistics, in addition to medical journal editors. Clinical trial registry websites (chictr.org.cn and clinicaltrials.gov) were searched to retrieve clinical trial protocols and outcomes in order to form an outcome pool. A total of 78 clinical trial protocols on COVID-19 were included and 259 outcomes were collected. After standardization, 132 outcomes were identified within seven different categories, of which 58 were selected to develop a preliminary outcome list for further consensus. After two rounds of Delphi survey and one consensus meeting, the most important outcomes for the different clinical classifications of COVID-19 were identified and determined to constitute the COS for clinical trials on COVID-19 (COS-COVID). The COS-COVID includes one outcome for the mild type (time to 2019-nCoV reverse transcription-polymerase chain reaction (RT-PCR) negativity), four outcomes for the ordinary type (length of hospital stay, composite events, score of clinical symptoms, and time to 2019-nCoV RT-PCR negativity), five outcomes for the severe type (composite events, length of hospital stay, arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2), duration of mechanical ventilation, and time to 2019-nCoV RT-PCR negativity), one outcome for critical type (all-cause mortality), and one outcome for rehabilitation period (pulmonary function). The COS-COVID is currently the most valuable and practical clinical outcome set for the evaluation of intervention effect, and is useful for evidence assessment and decision-making. With a deepening understanding of COVID-19 and application feedback, the COS-COVID should be continuously updated.


Management of Upper Airway Bleeding in COVID‐19 Patients on Extracorporeal Membrane Oxygenation


title: Induction and sequencing of Rousette bat interferon α and β genes

text: Abstract Bats are considered to be natural reservoirs for several viruses of clinical importance, including rabies virus, Nipah virus, and Hendra virus. Type I interferons (IFNs) is an important part of the immune system in the defense against viral infection. To investigate the function of type I IFNs upon viral infection in bats, the nucleic acid, and amino acid sequences of Egyptian Rousette (Rousettus aegyptiacus) IFN-α and -β were characterized. Sequence data indicated that bat IFN-α consists of 562-bp encoded 187-aa, and IFN-β consisted of 558-bp encoded 186-aa. Phylogenetic analysis of the overall identity of IFN-β shared the highest sequence homology with pig IFN-β in both nucleotide and amino acid level. Stimulation of bat primary kidney cells (BPKCs) and bat lung cell lines, Tb-1 Lu, with polyinosinic–polycytidylic acid (poly(I:C)) or exogenous bat type I IFNs resulted in increased type I IFNs mRNA expression in BPKCs, but not in Tb-1 Lu. Characterization of the bat IFN-α and -β genes allows understanding of the immune responses upon stimulation in different tissues, thus providing practical strategies for control and treatment of clinically important diseases. These results are important especially for the virus infection, and suggest that future molecular studies on virus infection experiment of bats in vitro will require careful consideration of the differences of type I IFN expression patterns in different cell types.


title: Psychological support in times of COVID-19: the Essen community-based CoPE concept

text: The SARS CoV-2-virus (COVID-19) pandemic is pushing national and international structures to their limits. Little is known about treatment options to combat the novel virus, but the same applies to the effects of COVID-19 on people’s mental health. In Germany, as in many other countries, governmental actions impact peoples’ individual freedom. These highly necessary actions to slow down the spread of the virus, however, are a burden to the community. We established a structured concept to support psychological burdened people in Essen, which is located in the Ruhr area, a metropolitan region with more than 5.1 million inhabitants in the heart of the federal state North Rhine Westphalia. The psychological burden following the spread of the virus and individual restrictions should not be neglected.


title: Imaging evaluation of COVID-19 in the emergency department

text: PURPOSE: The purpose of this study is to elucidate the chest imaging findings of suspected COVID-19 patients presenting to the emergency department and the relationship with their demographics and RT-PCR testing results. METHODS: Patients presenting to the ED between March 12 and March 28, 2020, with symptoms suspicious for COVID-19 and subsequent CXR and/or CT exam were selected. Patients imaged for other reasons with findings suspicious for COVID-19 were also included. Demographics, laboratory test results, and history were extracted from the medical record. Descriptive statistics were used to explore the relationship between imaging and these factors. RESULTS: A total of 227 patients from the emergency department were analyzed (224 CXRs and 25 CTs). Of the 192 patients with COVID-19 results, 173 (90.1%) had COVID-19 RT-PCR (+). Abnormal imaging (CXR, 85.7% and/or CT, 100%) was noted in 155 (89.6%) of COVID-19 RT-PCR (+) cases. The most common imaging findings were mixed airspace/interstitial opacities (39.8%) on CXR and peripheral GGOs on CT (92%). The most common demographic were African Americans (76.8%). Furthermore, 97.1% of African Americans were RT-PCR (+) compared to 65.8% of Caucasians. CONCLUSION: We found a similar spectrum of thoracic imaging findings in COVID-19 patients as previous studies. The most common demographic were African Americans (76.8%). Furthermore, 97.1% of African Americans were RT-PCR (+) compared to 65.8% of Caucasians. Both CT and CXR can accurately identify COVID-19 pneumonitis in 89.6% of RT-PCR (+) cases, 89.5% of false negatives, and 72.7% of cases with no RT-PCR result. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10140-020-01787-0) contains supplementary material, which is available to authorized users.


title: Comparison of three multiplex PCR assays for detection of respiratory viruses: Anyplex II RV16, AdvanSure RV, and Real‐Q RV

text: BACKGROUND: Due to its great sensitivity, the nucleic acid amplification test (NAAT) is widely used for detection of respiratory viruses (RV). However, few reports have described a direct comparison between multiplex RT‐PCR assays for RV. The objective of this study was to perform a direct comparison of three multiplex RT‐PCR assays for the detection of respiratory viruses. METHODS: A total of 201 respiratory samples (161 nasopharyngeal swab samples and 40 sputum samples) were tested with three commercial RV assays: Seegene Anyplex II RV16 (AP), LG AdvanSure RV (AD), and Biosewoom Real‐Q RV (RQ). The additional tests for the discrepant results were conducted by repeat RV assay or monoplex PCR coupled direct sequencing. Data analysis using percent agreement, kappa, and prevalence‐adjusted and bias‐adjusted kappa (PABAK) values was performed for comparisons among the three RV assays. RESULTS: Of the 201 samples, AP, AD, and RQ detected 105 (52.2%), 99 (49.3%), and 95 (47.3%) positive cases respectively. The overall agreement, kappa, and PABAK values for the three assays ranged between 97%‐98%, 0.76‐0.86, and 0.93‐0.96 respectively. The performance of the three assays was very similar, with 94%‐100% agreement for all comparisons, each virus types. The additional testing of samples showed discrepant results demonstrating that AD assay had the highest rate of concordance with original results. CONCLUSIONS: We suggest that all multiplex assay would be suitable for the detection of for respiratory viruses in clinical setting.


SARS-CoV-2 infection in liver-Author’s reply


Tocilizumab, an anti-IL6 receptor antibody, to treat Covid-19-related respiratory failure: a case report


title: Biosafety Level 3 Laboratory for Autopsies of Patients with Severe Acute Respiratory Syndrome: Principles, Practices, and Prospects

text: Background. During the outbreak of the emergent severe acute respiratory syndrome (SARS) infection, >30% of the ∼8000 infected persons were health care workers. The highly infectious nature of SARS coronavirus (SARS-CoV) compelled our pathologists to consider biosafety issues in the autopsy room and for tissue processing procedures. Methods. A specially designed biosafety level 3 (BSL-3) autopsy laboratory was constructed and divided into a clean area, a semicontaminated area, a contaminated area, and 2 buffer zones. High-efficiency particulate air filters were placed in the air supply and exhaust systems. Laminar air flow was from the clean areas to the less clean areas. The negative pressures of the contaminated, semicontaminated, and clean areas were approximately -50 pa, -25 pa, and -5 pa, respectively. Personal protective equipment, including gas mask, impermeable protective clothing, and 3 layers of gloves worn during autopsies; the equipment was decontaminated before it was allowed to exit the facility. Strict BSL-3 practices were followed. Results. When a given concentration of particulate sarin simulant was introduced into the contaminated area, it could not be detected in either the semicontaminated area or clean area, and particles >0.3 μm in size were not detected in the exhaust air. A total of 16 complete postmortem examinations for probable and suspected SARS were performed during a 2-month period. Of these, 7 reported confirmed cases of SARS. None of the 23 pathologists and technicians who participated in these autopsies was infected with SARS-CoV. Conclusions. Our experience suggests that BSL-3 laboratory operating principles should be among the special requirements for performing autopsies of contaminated bodies and that they can safeguard the clinicians and the environment involved in these procedures.


title: Hospital response to the COVID‐19 outbreak: The experience in Shanghai, China

text: On 20th January 2020, the first COVID-19 case was reported in Shanghai, China. As of 12th March 2020, 344 cases with laboratory-confirmed COVID-19 infection have been detected in Shanghai, of which three died, 321 patients are discharged, 20 patients still receive ongoing treatments (Shanghai Municipal Health Commission, 2020).


title: Health shocks and their long-lasting impact on health behaviors: Evidence from the 2009 H1N1 pandemic in Mexico

text: Abstract Worldwide, the leading causes of death could be avoided with health behaviors that are low-cost but also difficult to adopt. We show that exogenous health shocks could facilitate the adoption of these behaviors and provide long-lasting effects on health outcomes. Specifically, we exploit the spatial and temporal variation of the 2009 H1N1 influenza pandemic in Mexico and show that areas with a higher incidence of H1N1 experienced larger reductions in diarrhea-related cases among young children. These reductions continue even three years after the shock ended. Health improvements and evidence of information seeking via Google searches were consistent with changes in hand washing behaviors. Several robustness checks validate our findings and mechanism.


title: SARS-CoV-2 pneumonia in hospitalized asthmatic patients did not induce severe exacerbation

text: Abstract Background Viral infections are known to exacerbate asthma in adults. Previous studies have found few asthmatics among SARS-CoV-2 pneumonia cases. However, the relationship between SARS-CoV-2 infection and severe asthma exacerbation is not known. Objective We assessed the frequency of asthma exacerbation in asthmatic patients hospitalized for SARS-CoV-2 pneumonia and compared symptoms laboratory and radiological findings in asthmatic and non-asthmatic patients with SARS-CoV-2 pneumonia. Methods We included 106 patients between March 4 and April 6, 2020, who were hospitalized in the Chest Diseases Department of Strasbourg University Hospital; 23 were asthmatics. To assess the patients’ asthma status, three periods were defined: the last month before the onset of COVID-19 symptoms (p1), pre-hospitalization (p2) and during hospitalization (p3). Severe asthma exacerbations were defined according to GINA guidelines during p1 and p2. During p3, we defined severe asthma deterioration as the onset of breathlessness and wheezing requiring systemic corticosteroids and inhaled beta-2-agonist. Results We found no significant difference between asthmatics and non-asthmatics in terms of severity (length of stay, maximal oxygen flow needed, non-invasive ventilation requirement and ICU transfer). 52.2% of the asthmatic patients were Gina 1. One patient had a severe exacerbation during p1, two patients during p2, and five patients were treated with systemic corticosteroids and inhaled beta-2-agonist during p3. Conclusion Our results demonstrate that asthmatic patients appeared not to be at risk for severe SARS-CoV-2 pneumonia. Moreover, SARS-CoV-2 pneumonia did not induce severe asthma exacerbation.


title: Estimating Influenza Vaccine Effectiveness With the Test-Negative Design Using Alternative Control Groups: A Systematic Review and Meta-Analysis

text: One important assumption in case-control studies is that control selection should be independent of exposure. Nevertheless, it has been hypothesized that virus interference might lead to a correlation between receipt of influenza vaccination and increased risk of infection with other respiratory viruses. We investigated whether such a phenomenon might affect a study design commonly used to estimate influenza vaccine effectiveness (VE). We searched publications in MEDLINE, PubMed, and Web of Science. We identified 12 studies using the test-negative design (2011–2017) that reported VE estimates separately derived by 3 alternative control groups: 1) all patients testing negative for influenza (FLU), VE(FLU−); 2) patients who tested positive for other/another respiratory virus (ORV), VE(ORV+); and 3) patients who tested negative for all viruses in the panel (PAN), VE(PAN−). These included VE estimates from 7 countries for all age groups from 2003/2004 to 2013/2014. We observed no difference in vaccination coverage between the ORV-positive and PAN-negative control groups. A total of 63 VE(FLU−) estimates, 62 VE(ORV+) estimates, and 33 VE(PAN−) estimates were extracted. Pooled estimates of the difference in VE (ΔVE) were very similar between groups. In meta-regression, no association was found between the selection of control group and VE estimates. In conclusion, we did not find any differences in VE estimates based on the choice of control group.


title: Chapter 6 Bat Rabies

text: The lyssaviruses are a diverse group of viruses capable of causing rabies, which is an invariably fatal encephalitic disease in both humans and animals. Currently, the lyssavirus genus consists of 12 species with 11 of these distinct species having been isolated from bats. The basis for the apparent geographical segregation of bat lyssavirus infection between the Old and New World is poorly understood. In the New World species of insectivorous, frugivorous, and hematophagous bats, all represent important reservoirs of rabies virus. In contrast, rabies virus has never been detected in Old World bat populations, despite being endemic in terrestrial mammals. Instead, both insectivorous and frugivorous bat species across the Old World appear to act as reservoirs for the non-rabies lyssaviruses. In this chapter, we describe the association of the different lyssaviruses with different bat species across the world, classifying bat species by their feeding behavior.


“Everything is a Mess”: How COVID-19 is Impacting Engagement with HIV Testing Services in Rural Southwestern Uganda


title: Chromatography of complex protein mixtures

text: Abstract This review has shown that a variety of chromatographic techniques are available for fractionating proteins. Fortunately, high-quality columns of every type described in this review are commercially available. Most water-soluble proteins may be eluted from size-exclusion, hydrophobic-interaction, ion-exchange, metal chelate, and bioaffinity columns with ease. When this is the case, high recovery and retention of biological activity are the norm. The exception is reversed-phase chromatography where the organic solvents and acids used in polypeptide elution denature many proteins. When problems do occur, they are generally the result of unique structural features of the protein. Very hydrophobic proteins have presented the biggest problem in that they are difficult to solubilize, particularly with retention of biological activity. It has been found that zwitterionic an non-ionic detergents are the most suitable solubilizing agents, but area has also been used in cases where hydrophobic interacts are not as strong. Unfortunately, there is still an element of trial-and-error in selecting the most suitable solubilizing agent. Heterogeneous glycosylation of proteins also presents a problem. Both neutral and charged monosaccharides can be incorporated into proteins through multiple steps at several sites. Thus, there is the potential in a sample for a large number of glycoprotein species which have the same polypeptide backbone and differing amounts of oligosaccharide. A problem arises when size-exclusion, ion-exchange, hydrophobic-interaction, reversed-phase and bioaffinity systems begin to discriminate between these very similar glycoprotein species. Chromatographic peaks can become very load, due to incomplete fractionation, and the polypeptide chain of interest can be associated with multiple peaks. The separation of glycoproteins requires much more study before logical procedures can be suggested for column selection and operation. Aggregated species are another class of proteins which present occasional problems. Multimeric proteins are adsorbed to sorbents by a series of forces, among which are hydrogen bonding, hydrophobic interactions, and electrostatic forces. These forces are also responsible for the maintenance of quaternary structure in proteins. When the same forces dominate both retention of protein structure and adsorption at the sorbent surface, the quaternary structure of the protein can be disrupted during elution. Very basic proteins also present a problem in some cases. Columns with residual negative charges, such as a silica-based reversed-phase column, adsorb anionic species so strongly that they are difficult to elute. This is the case with ribosomal and nucleoproteins. The solution is to use exhaustively end-capped columns which diminish electrostatic interactions.


title: Does energy and CO2 emissions performance of China benefit from regional integration?

text: Abstract Low energy and carbon efficiency and widespread market segmentation are two stylized facts of China's regional economies. This paper evaluates energy and CO2 emissions performance using a newly developed non-radial directional distance function, and China's regional integration is investigated using a price approach. The study points to evidence that: (1) most provinces do not perform efficiently in terms of energy use and CO2 emissions with performance gaps among regions becoming larger, indicating regional segmentation; (2) magnitude of regional integration has increased dramatically, while China's eastern provinces are less integrated in domestic side due to their convenience to international openness; (3) regional integration has significant and robust positive effects on energy and CO2 emissions performance with over 70% of effects coming from artificial barriers, rather than geographical distance; (4) international openness is also beneficial for promoting energy and CO2 emissions performance, but cannot substitute for regional integration because of China's specialization in energy-intensive manufacturing in the global economy. Based on the empirical findings, we suggest that central government should continue to encourage regional integration given that local governments have incentives to fragment because it is a way of promoting energy and CO2 emissions performance and stimulating economy at the same time.


title: Protein analysis based on molecular beacon probes and biofunctionalized nanoparticles

text: With the completion of the human genome-sequencing project, there has been a resulting change in the focus of studies from genomics to proteomics. By utilizing the inherent advantages of molecular beacon probes and biofunctionalized nanoparticles, a series of novel principles, methods and techniques have been exploited for bioanalytical and biomedical studies. This review mainly discusses the applications of molecular beacon probes and biofunctionalized nanoparticles-based technologies for real-time, in-situ, highly sensitive and highly selective protein analysis, including the nonspecific or specific protein detection and separation, protein/DNA interaction studies, cell surface protein recognition, and antigen-antibody binding process-based bacteria assays. The introduction of molecular beacon probes and biofunctionalized nanoparticles into the protein analysis area would necessarily advance the proteomics research.


title: Nonsteroidal Anti-Inflammatory Drug without Antibiotics for Acute Viral Infection Increases the Empyema Risk in Children: A Matched Case-Control Study

text: Objective To investigate the risk factors of empyema after acute viral infection and to clarify the hypothesized association(s) between empyema and some viruses and/or the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Study design A case-control study was conducted in 15 centers. Cases and controls were enrolled for a source population of children 3-15 years of age with acute viral infections between 2006 and 2009. Results Among 215 empyemas, 83 cases (children with empyema and acute viral infection within the 15 preceding days) were included, and 83 controls (children with acute viral infection) were matched to cases. Considering the intake of any drug within 72 hours after acute viral infection onset and at least 6 consecutive days of antibiotic use and at least 1 day of NSAIDs exposure, the multivariable analysis retained an increased risk of empyema associated with NSAIDs exposure (aOR 2.79, 95% CI 1.4-5.58, P = .004), and a decreased risk associated with antibiotic use (aOR 0.32, 95% CI 0.11-0.97, P = .04). The risk of empyema associated with NSAIDs exposure was greater for children not prescribed an antibiotic and antibiotic intake diminished that risk for children given NSAIDs. Conclusions NSAIDs use during acute viral infection is associated with an increased risk of empyema in children, and antibiotics are associated with a decreased risk. The presence of antibiotic-NSAIDs interaction with this risk is suggested. These findings suggest that NSAIDs should not be recommended as a first-line antipyretic treatment during acute viral infections in children.


title: Obesity, the most common comorbidity in SARS-CoV-2: is leptin the link?

text: Overweight and obesity are major risk factors for diabetes, cardiovascular disease, and lung disease. These diseases are the most commonly reported health conditions that predispose individuals with SARS-CoV-2 infection to require hospitalization including intensive care unit admissions. The innate immune response is the host’s first line of defense against a human coronavirus infection. However, most coronaviruses are armed with one strategy or another to overcome host antiviral defense, and the pathogenicity of the virus is related to its capacity to suppress host immunity. The multifaceted nature of obesity including its effects on immunity can fundamentally alter the pathogenesis of acute respiratory distress syndrome and pneumonia, which are the major causes of death due to SARS-CoV-2 infection. Elevated circulating leptin concentrations are a hallmark of obesity, which is associated with a leptin-resistant state. Leptin is secreted by adipocytes in proportion to body fat and regulates appetite and metabolism through signaling in the hypothalamus. However, leptin also signals through the Jak/STAT and Akt pathways, among others, to modulate T cell number and function. Thus, leptin connects metabolism with the immune response. Therefore, it seems appropriate that its dysregulation would have serious consequences during an infection. We propose that leptin may be the link between obesity and its high prevalence as a comorbidity of the SARS-CoV-2 infection. In this article, we present a synthesis of the mechanisms underpinning susceptibility to respiratory viral infections and the contribution of the immunomodulatory effects of obesity to the outcome.


title: The Development of an AIDS Mucosal Vaccine

text: It is well known that mucosal tissues contain the largest surface area of the human body and are the front line of natural host defense against various pathogens. In fact, more than 80% of infectious disease pathogens probably gain entry into the susceptible human hosts through open mucosal surfaces. Human immunodeficiency virus type one (HIV-1), a mainly sexually transmitted virus, also primarily targets the vaginal and gastrointestinal mucosa as entry sites for viral transmission, seeding, replication and amplification. Since HIV-1 establishes its early replication in vaginal or rectal mucosal tissues, the induction of sufficient mucosal immunity at the initial site of HIV-1 transmission becomes essential for a protective vaccine. However, despite the fact that current conventional vaccine strategies have remained unsuccessful in preventing HIV-1 infection, sufficient financial support and resources have yet to be given to develop a vaccine able to elicit protective mucosal immunity against sexual transmissions. Interestingly, Chinese ancestors invented variolation through intranasal administration about one thousand years ago, which led to the discovery of a successful smallpox vaccine and the final eradication of the disease. It is the hope for all mankind that the development of a mucosal AIDS vaccine will ultimately help control the AIDS pandemic. In order to discover an effective mucosal AIDS vaccine, it is necessary to have a deep understanding of mucosal immunology and to test various mucosal vaccination strategies.


title: Mutation in the cytoplasmic retrieval signal of porcine epidemic diarrhea virus spike (S) protein is responsible for enhanced fusion activity

text: Abstract Murine-adapted porcine epidemic diarrhea virus (PEDV), MK-p10, shows high neurovirulence and increased fusion activity compared with a non-adapted MK strain. MK-p10 S protein had four mutations relative to the original virus S, and one of these (H→R at position 1381, H1381R) in the cytoplasmic tail (CT) was suggested to be responsible for the increased fusion activity. To explore this, we examined fusion activity using recombinant S proteins. We expressed and compared the fusion activity of MK-p10 S, S with the H1381R mutation, S with the three other mutations that were not thought to be involved in high fusion activity, and the original S protein. The MK-p10 and MK-H1381R S proteins induced larger cell fusions than others. We also examined the distribution of these S proteins; the MK-p10 and MK-H1381R S proteins were transported onto the cell surface more efficiently than others. These findings suggest that the H1381R mutation is responsible for enhanced fusion activity, which may be attributed to the efficient transfer of S onto the cell surface. H1381 is a component of the KxHxx motif in the CT region, which is a retrieval signal of the S protein for the endoplasmic reticulum–Golgi intermediate compartment (ERGIC). Loss of this motif could allow for the efficient transfer of S proteins from ERGIC onto the cell surface and subsequent increased fusion activity.


title: Characterization of the cold-sensitive murine hepatitis virus mutants rescued from latently infected cells by cell fusion

text: Abstract Mouse hepatitis virus, a coronavirus, was rescued from latently infected mouse neuroblastoma cells by polyethylene glycol-induced fusion to permissive cells. The isolated viruses grew to equal or higher titers than parental JHM virus at 39° but were restricted in replication at 32° and hence were cold-sensitive mutants. Neither isolate synthesized RNA at the nonpermissive temperature (32°), and temperature shift experiments indicated that the restrictive cold-sensitive step in replication occurred during an early viral function. The isolates were unable to complement each other at 32°. Although coinfection between each mutant and parental JHM virus often resulted in decreased yields of both infecting viruses, interference could not be convincingly demonstrated. Both mutants were more thermostable than parental JHM virus and could be distinguished from each other and from parental JHM virus by their thermal inactivation kinetics. The isolates were obtained from single cell clones and therefore presumed to be homogeneous; however, thermal inactivation of one (S-3JHM) indicated the possible existence of a second population. Subclones of virus prepared from each isolate were also found to be thermally stable and to retain the cold sensitive defect. No indication of a second population of S-3JHM virus was detected.


title: SIRT1 Activating compounds reduce oxidative stress mediated neuronal loss in viral induced CNS demyelinating disease

text: BACKGROUND: Multiple sclerosis (MS) is characterized by central nervous system inflammation and demyelination, and increasing evidence demonstrates significant neuronal damage also occurs and is associated with permanent functional impairment. Current MS therapies have limited ability to prevent neuronal damage, suggesting additional neuroprotective therapies are needed. Compounds that activate the NAD(+)-dependent SIRT1 deacetylase prevent neuronal loss in an autoimmune-mediated MS model, but the mechanism of this effect is unknown, and it is unclear whether SIRT1 activating compounds exert similar effects in demyelinating disease induced by other etiologies. We measured neuronal loss in C57BL/6 mice inoculated with a neurotropic strain of mouse hepatitis virus, MHV-A59, that induces an MS-like disease. RESULTS: Oral treatment with the SIRT1 activating compound SRTAW04 significantly increased SIRT1 activity within optic nerves and prevented neuronal loss during optic neuritis, an inflammatory demyelinating optic nerve lesion that occurs in MS and its animal models. MHV-A59 induced neuronal loss was associated with reactive oxygen species (ROS) accumulation, and SRTAW04 treatment significantly reduced ROS levels while promoting increased expression of enzymes involved in mitochondrial function and reduction of ROS. SRTAW04 exerted similar protective effects in EAE spinal cords, with decreased demyelination. CONCLUSIONS: Results demonstrate that SIRT1 activating compounds prevent neuronal loss in viral-induced demyelinating disease similar to their effects in autoimmune-mediated disease. One mechanism of this neuroprotective effect involves increasing mitochondrial biogenesis with reduction of oxidative stress. SIRT1 activators represent a potential neuroprotective therapy for MS. Understanding common mechanisms of these effects in distinct disease models will help identify targets for more specific therapies.


Infectious diseases: a call for manuscripts in an interdisciplinary era


title: Interferon-β-1a Inhibition of Severe Acute Respiratory Syndrome–Coronavirus 2 In Vitro When Administered After Virus Infection

text: The ongoing coronavirus disease 2019 pandemic has forced the clinical and scientific community to try drug repurposing of existing antiviral agents as a quick option against severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2). Under this scenario, interferon (IFN) β-1a, whose antiviral potential is already known, and which is a drug currently used in the clinical management of multiple sclerosis, may represent as a potential candidate. In this report, we demonstrate that IFN-β-1a was highly effective in inhibiting in vitro SARS-CoV-2 replication at clinically achievable concentration when administered after virus infection.


title: A baculovirus dual expression system-based vaccine confers complete protection against lethal challenge with H9N2 avian influenza virus in mice

text: BACKGROUND: Avian influenza viruses of H9N2 subtype have become highly prevalent in avian species. Although these viruses generally cause only mild to moderate disease, they can infect a wide variety of species, including chickens, quail, turkeys, ducks, geese, pheasant, partridge, and pigeon, even transmitted to mammalian species, including humans, accelerating the efforts to devise protective strategies against them. RESULTS: The results showed that stronger immune responses were induced in a mouse model immunized with BV-Dual-HA than in those vaccinated with a DNA vaccine encoding the same antigen. Moreover, complete protection against lethal challenge with H9N2 virus was observed in mice. CONCLUSION: BV-Dual-HA could be utilized as a vaccine candidate against H9N2 virus infection.


title: Baculovirus Surface Display of Immunogenic Proteins for Vaccine Development

text: Vaccination is an efficient way to prevent the occurrence of many infectious diseases in humans. To date, several viral vectors have been utilized for the generation of vaccines. Among them, baculovirus—categorized as a nonhuman viral vector—has been used in wider applications. Its versatile features, like large cloning capacity, nonreplicative nature in mammalian cells, and broad tissue tropism, hold it at an excellent position among vaccine vectors. In addition to ease and safety during swift production, recent key improvements to existing baculovirus vectors (such as inclusion of hybrid promoters, immunostimulatory elements, etc.) have led to significant improvements in immunogenicity and efficacy of surface-displayed antigens. Furthermore, some promising preclinical results have been reported that mirror the scope and practicality of baculovirus as a vaccine vector for human applications in the near future. Herein, this review provides an overview of the induced immune responses by baculovirus surface-displayed vaccines against influenza and other infectious diseases in animal models, and highlights the strategies applied to enhance the protective immune responses against the displayed antigens.


Is COVID-19-related Guillain-Barré Syndrome Different?


title: Synthesis, anti-varicella-zoster virus and anti-cytomegalovirus activity of quinazoline-2,4-diones containing isoxazolidine and phosphonate substructures

text: Cycloadditions of N-substituted C-(diethoxyphosphoryl)nitrones to N-allylated quinazoline-2,4-diones functionalized at N3 with substituted benzoyl or benzyl groups proceeded with moderate to good diastereoselectivities (d.e. 28–68%). The synthesized isoxazolidine phosphonates were assessed for the antiviral activity against a broad range of DNA and RNA viruses. Compounds trans-13c, cis-13c/trans-13c (86:14), cis-15b/trans-15b (87:13) and trans-15d/cis-15d (95:5) exhibited the highest activity toward both TK(+) and TK(−) VZV strains (mean EC(50) values in the range of 3.0–8.7 μM). The EC(50)'s for isoxazolidines trans-12a, cis-12a, cis-13a, trans-13d, cis-15a/trans-15a (50:50) ranged between 6.9 and 8.5 μM for VZV TK(+) strain and between 10.7 and 13.2 μM for VZV TK(–) strain. The isoxazolidine phosphonates cis-15/trans-15 having benzyl substituents both at N3 of the quinazoline-2,4-dione skeleton and at N2 of the isoxazolidine ring displayed some anti-cytomegalovirus potency but at the same time showed significant cytostatic activity for human embryonic lung fibroblasts (used to carry out the antiviral assays) as well as for other cell lines (i.e. CEM, L1210, HeLa and HMEC-1).


title: National outreach of telepalliative medicine volunteers for a New York City safety net system COVID-19 pandemic response

text: The COVID-19 surge in New York City created an increased demand for palliative care (PC) services. In staff-limited settings such as safety net systems, and amid growing reports of healthcare worker illness, leveraging help from less-affected areas around the country may provide an untapped source of support. A national social media outreach effort recruited 413 telepalliative medicine volunteers (TPMV). After expedited credentialing and onboarding of 67 TPMV, a 2-week pilot was initiated in partnership with five public health hospitals without any previous existing telehealth structure. The volunteers completed 109 PC consults in the pilot period. Survey feedback from TPMV and on-site PC providers was largely positive, with areas of improvement identified around electronic health record navigation and continuity of care. This was a successful, proof of concept, quality improvement initiative leveraging TPMV from across the nation for a PC pandemic response in a safety net system.


title: COVID-19 pandemic: every day feels like a weekday to most

text: The COVID-19 outbreak has clear clinical and economic impacts, but also affects behaviors e.g. through social distancing, and may increase stress and anxiety. However, while case numbers are tracked daily, we know little about the psychological effects of the outbreak on individuals in the moment. Here we examine the psychological and behavioral shifts over the initial stages of the outbreak in the United States in an observational longitudinal study. Through GPS phone data we find that homestay is increasing, while being at work dropped precipitously. Using regular real-time experiential surveys we observe an overall increase in stress and mood levels which is similar in size to the weekend vs. weekday differences. As there is a significant difference between weekday and weekend mood and stress levels, this is an important decrease in wellbeing. For some, especially those affected by job loss, the mental health impact is severe.


title: Fragment-based discovery of a new family of non-peptidic small-molecule cyclophilin inhibitors with potent antiviral activities

text: Cyclophilins are peptidyl-prolyl cis/trans isomerases (PPIase) that catalyse the interconversion of the peptide bond at proline residues. Several cyclophilins play a pivotal role in the life cycle of a number of viruses. The existing cyclophilin inhibitors, all derived from cyclosporine A or sanglifehrin A, have disadvantages, including their size, potential for side effects unrelated to cyclophilin inhibition and drug–drug interactions, unclear antiviral spectrum and manufacturing issues. Here we use a fragment-based drug discovery approach using nucleic magnetic resonance, X-ray crystallography and structure-based compound optimization to generate a new family of non-peptidic, small-molecule cyclophilin inhibitors with potent in vitro PPIase inhibitory activity and antiviral activity against hepatitis C virus, human immunodeficiency virus and coronaviruses. This family of compounds has the potential for broad-spectrum, high-barrier-to-resistance treatment of viral infections.


title: Opportunities and Challenges for Biosensors and Nanoscale Analytical Tools for Pandemics: COVID-19

text: [Image: see text] Biosensors and nanoscale analytical tools have shown huge growth in literature in the past 20 years, with a large number of reports on the topic of ‘ultrasensitive’, ‘cost-effective’, and ‘early detection’ tools with a potential of ‘mass-production’ cited on the web of science. Yet none of these tools are commercially available in the market or practically viable for mass production and use in pandemic diseases such as coronavirus disease 2019 (COVID-19). In this context, we review the technological challenges and opportunities of current bio/chemical sensors and analytical tools by critically analyzing the bottlenecks which have hindered the implementation of advanced sensing technologies in pandemic diseases. We also describe in brief COVID-19 by comparing it with other pandemic strains such as that of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) for the identification of features that enable biosensing. Moreover, we discuss visualization and characterization tools that can potentially be used not only for sensing applications but also to assist in speeding up the drug discovery and vaccine development process. Furthermore, we discuss the emerging monitoring mechanism, namely wastewater-based epidemiology, for early warning of the outbreak, focusing on sensors for rapid and on-site analysis of SARS-CoV2 in sewage. To conclude, we provide holistic insights into challenges associated with the quick translation of sensing technologies, policies, ethical issues, technology adoption, and an overall outlook of the role of the sensing technologies in pandemics.


title: Marmota himalayana in the Qinghai–Tibetan plateau as a special host for bi-segmented and unsegmented picobirnaviruses

text: Wildlife has been considered the main source of novel viruses causing emerging infectious diseases. Marmota himalayana is endemic to the Qinghai–Tibetan Plateau, China. Here, based on a high-throughput method using Illumina RNA sequencing, we studied the RNA virome of M. himalayana and discovered multiple novel viruses, especially picobirnaviruses (PBVs), which have a bi-segmented genome and belong to the family Picobirnaviridae. A total of 63% of the viral contigs corresponded to PBVs, comprising 274 segment 1 and 56 segment 2 sequences. Unexpectedly, four unsegmented PBV genomes were also detected and confirmed by PCR and resequencing. According to the phylogenetic analysis, the following nine PBV assortment types are proposed: C1:GI, C2:GIV, C4:GI, C4:GV, C5:GI, C7:GI, C8:GIV, C8:GV and C8:GII. We hypothesize a model of segmentation for the PBV genome, mediated by a 6-bp direct repeat sequence, GAAAGG. The model is supported by detection of the segmentation-associated sequence GAAAGG not only in the 5′ untranslated regions of segment 1 (221 in 289) and segment 2 (57 in 80) of bi-segmented PBVs but also in the 5′ untranslated regions and junction sequences between the capsid and RdRp genes of unsegmented PBVs. Therefore, with RNA sequencing, we found an unexpected biodiversity of PBVs in M. himalayana, indicating that M. himalayana is a special host for PBVs. We also proposed a putative model of how bi-segmented PBVs could be converted into unsegmented PBVs, which sheds new light on the processes of RNA virus genome evolution.


title: A dynamic compartmental model for the Middle East respiratory syndrome outbreak in the Republic of Korea: A retrospective analysis on control interventions and superspreading events

text: Abstract The 2015 Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea has provided an opportunity to improve our understanding of the spread of MERS linked to healthcare settings. Here we designed a dynamic transmission model to analyze the MERS outbreak in the Republic of Korea based on confirmed cases reported during the period May 20–July 4, 2015. Our model explicitly incorporates superspreading events and time-dependent transmission and isolation rates. Our model was able to provide a good fit to the trajectory of the outbreak and was useful to analyze the role of hypothetical control scenarios. Specifically, we assessed the impact of the timing of control measures, especially associated with a reduction of the transmission rate and diagnostic delays on outbreak size and duration. Early interventions within 1week after the epidemic onset, for instance, including the initial government announcement to the public about the list of hospitals exposed to MERS coronavirus (MERS-CoV), show a promising means to reduce the size ( > 71 % ) and duration ( > 35 % ) of the MERS epidemic. Finally, we also present results of an uncertainty analysis focused on the role of superspreading events.