title: Clinical and CT imaging features of the COVID-19 pneumonia: Focus on pregnant women and children

text: Abstract Background The ongoing outbreak of COVID-19 pneumonia is globally concerning. We aimed to investigate the clinical and CT features in the pregnant women and children with this disease, which have not been well reported. Methods Clinical and CT data of 59 patients with COVID-19 from January 27 to February 14, 2020 were retrospectively reviewed, including 14 laboratory-confirmed non-pregnant adults, 16 laboratory-confirmed and 25 clinically-diagnosed pregnant women, and 4 laboratory-confirmed children. The clinical and CT features were analyzed and compared. Findings Compared with the non-pregnant adults group (n = 14), initial normal body temperature (9 [56%] and 16 [64%]), leukocytosis (8 [50%] and 9 [36%]) and elevated neutrophil ratio (14 [88%] and 20 [80%]), and lymphopenia (9 [56%] and 16 [64%]) were more common in the laboratory-confirmed (n = 16) and clinically-diagnosed (n = 25) pregnant groups. Totally 614 lesions were detected with predominantly peripheral and bilateral distributions in 54 (98%) and 37 (67%) patients, respectively. Pure ground-glass opacity (GGO) was the predominant presence in 94/131 (72%) lesions for the non-pregnant adults. Mixed consolidation and complete consolidation were more common in the laboratory-confirmed (70/161 [43%]) and clinically-diagnosed (153/322 [48%]) pregnant groups than 37/131 (28%) in the non-pregnant adults (P = 0·007, P < 0·001). GGO with reticulation was less common in 9/161 (6%) and 16/322 (5%) lesions for the two pregnant groups than 24/131 (18%) for the non-pregnant adults (P = 0·001, P < 0·001). The pulmonary involvement in children with COVID-19 was mild with a focal GGO or consolidation. Twenty-three patients underwent follow-up CT, revealing progression in 9/13 (69%) at 3 days whereas improvement in 8/10 (80%) at 6–9 days after initial CT scans. Interpretation Atypical clinical findings of pregnant women with COVID-19 could increase the difficulty in initial identification. Consolidation was more common in the pregnant groups. The clinically-diagnosed cases were vulnerable to more pulmonary involvement. CT was the modality of choice for early detection, severity assessment, and timely therapeutic effects evaluation for the cases with epidemic and clinical features of COVID-19 with or without laboratory confirmation. The exposure history and clinical symptoms were more helpful for screening in children versus chest CT.


COVID19 –Nuclear Medicine Departments, be prepared!


title: Essential Oils as Antimicrobial Agents—Myth or Real Alternative?

text: Herbs and the essential oils derived from them have been used from the beginning of human history for different purposes. Their beneficial properties have been applied to mask unpleasant odors, attract the attention of other people, add flavor and aroma properties to prepared dishes, perfumes, and cosmetics, etc. Herbs and essential oils (EOs) have also been used in medicine because of their biological properties, such as larvicidal action, analgesic and anti-inflammatory properties, antioxidant, fungicide, and antitumor activities, and many more. Many EOs exhibit antimicrobial properties, which is extremely important in fields of science and industry, such as medicine, agriculture, or cosmetology. Among the 250 EOs which are commercially available, about a dozen possess high antimicrobial potential. According to available papers and patents, EOs seem to be a potential alternative to synthetic compounds, especially because of the resistance that has been increasingly developed by pathogenic microorganisms. In this review we summarize the latest research studies about the most-active EOs that are known and used because of their antimicrobial properties. Finally, it is noteworthy that the antimicrobial activities of EOs are not preeminent for all strains. Further investigations should, thus, focus on targeting EOs and microorganisms.


title: Putative Inhibitors of SARS-CoV-2 Main Protease from A Library of Marine Natural Products: A Virtual Screening and Molecular Modeling Study

text: The current emergency due to the worldwide spread of the COVID-19 caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a great concern for global public health. Already in the past, the outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle Eastern respiratory syndrome (MERS) in 2012 demonstrates the potential of coronaviruses to cross-species borders and further underlines the importance of identifying new-targeted drugs. An ideal antiviral agent should target essential proteins involved in the lifecycle of SARS-CoV. Currently, some HIV protease inhibitors (i.e., Lopinavir) are proposed for the treatment of COVID-19, although their effectiveness has not yet been assessed. The main protease (M(pro)) provides a highly validated pharmacological target for the discovery and design of inhibitors. We identified potent M(pro) inhibitors employing computational techniques that entail the screening of a Marine Natural Product (MNP) library. MNP library was screened by a hyphenated pharmacophore model, and molecular docking approaches. Molecular dynamics and re-docking further confirmed the results obtained by structure-based techniques and allowed this study to highlight some crucial aspects. Seventeen potential SARS-CoV-2 M(pro) inhibitors have been identified among the natural substances of marine origin. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds could be bioactive is excellent.


title: Deceased Donor Liver Transplantation in India in the COVID-19 Era: Current Scenario and Future Perspectives

text: Abstract Coronavirus Disease 2019 (COVID-19) has been recently declared a global pandemic. As of June 5, 2020, over 75,000 cases have been reported with nearly 2,500 deaths in India alone. COVID-19 has severely impacted deceased donor liver transplant (DDLT) programs throughout the world. Acceptance of deceased liver donors have decreased worldwide due to the unknown risks associated with COVID-19 transmission or post-operative infection in the immediate post-transplant period, along with the risks to the healthcare workers in a multidisciplinary setting. In India, DDLT has come to a standstill in the setting of a national lockdown. Many national guidelines have emerged on how to safely perform transplantation as well on immunosuppressive regimes and care of the post-transplant patients. Here, we take a look at the current situation and summarize the different guidelines and future perspectives of DDLT in India in the COVID-19 era.


title: Immune-epidemiological parameters of the novel coronavirus – a perspective

text: Introduction: At the end of 2019, Wuhan, a city in China with a population of about 11 million, witnessed the outbreak of unusual pneumonia. As of 29 March 2020, the disease has spread to more 199 countries and territories worldwide. The 2019 novel coronavirus, 2019-nCoV, is known as the probable causative agent of the illness. Areas covered: Here, the epidemiological dynamics of the coronavirus disease 2019 (COVID-19) that stand in close relation to distinct immunogenetic characters of the pathogen are discussed, to understand the ability and inability of the immune system in combatting COVID-19. Expert opinion: The elderly population is at increased risk of developing and dying from COVID-19. Comorbidity is present in more than 30% of cases with COVID-19. Except for less than 1% of the total, a chronic condition has been found in all cases that died from COVID-19. Men are more than 1.5 times more likely to die from COVID-19. Evidence links aging to cytokine dysregulation and T-cell repertoire reduction, male population to relatively reduced anti-viral immunity, and COVID-19-related comorbidities to hyper inflammation. The transmission of COVID-19 is influenced by the host-related factors that are known to be associated with immune dysregulation.


title: Control of gene expression by translational recoding

text: Abstract Like all rules, even the genetic code has exceptions: these are generically classified as “translational recoding.” Almost every conceivable mode of recoding has been documented, including signals that redefine translational reading frame and codon assignation. While first described in viruses, it is becoming clear that sequences that program elongating ribosomes to shift translational reading frame are widely used by organisms in all domains of life, thus expanding both the coding capacity of genomes and the modes through which gene expression can be regulated at the posttranscriptional level. Instances of programmed ribosomal frameshifting and stop codon reassignment are opening up new avenues for treatment of numerous inborn errors of metabolism. The implications of these findings on human health are only beginning to emerge.


title: Comparative phylogenomics of pathogenic bacteria by microarray analysis

text: DNA microarrays represent a powerful technology that enables whole-scale comparison of bacterial genomes. This, coupled with new methods to model DNA microarray data, is facilitating the development of robust comparative phylogenomics analyses. Such studies have dramatically increased our ability to differentiate between bacteria, highlighting previously undetected genetic differences and population structures and providing new insight into virulence and evolution of bacterial pathogens. Recent results from such studies have generated insights into the evolution of bacterial pathogens, the levels of diversity and plasticity in the genome of a species, as well as the differences in virulence amongst pathogenic bacteria.


Consideration on TMPRSS2 and the risk of COVID-19 infection in Cushing’s syndrome


Dynamics of B cell subsets within the CNS during viral encephalomyelitis


The immunomodulatory effects of exercise against COVID-19


title: Value of Pharmacy-Based Influenza Surveillance — Ontario, Canada, 2009

text: As part of ongoing efforts by the Public Health Agency of Canada (PHAC) to enhance disease surveillance, a retrospective epidemiologic study was undertaken to investigate the usefulness for influenza surveillance of data on changes in the volume of prescriptions for antiviral medications. The weekly numbers of dispensed prescriptions for the antiviral medications oseltamivir and zanamivir, as a proportion of all dispensed prescriptions, were compared with the numbers of confirmed laboratory reports of influenza A(H1N1) at the local health authority level in Ontario, Canada, during the second wave of the outbreak of pandemic influenza A(H1N1) in 2009. Qualitative and quantitative analyses demonstrated that antiviral prescription dispensing dates were a reasonable proxy for influenza A(H1N1) onset dates at the local health authority level. This report describes the results of those analyses, which indicated that 1) antiviral prescription proportions increased in advance of laboratory reports of influenza and 2) antiviral dispensing data can be available in near real-time. These findings suggest that pharmacy prescription data can provide timely intelligence to help characterize local influenza activity.


title: Efficacité de l’association budésonide/formotérol dans le trouble ventilatoire obstructif survenant après allogreffe de cellules souches hématopoïétiques

text: Prospective evaluation of the efficacy of the combination of budesonide/formoterol in obstructive airway disease after allogeneic hematopoietic stem cell transplantation A. Bergeron, K. Chagnon, S. Feuillet, S. Chevret, A. Tazi Background Although it has not been evaluated prospectively, the usual treatment for obstructive airway disease after allogeneic hematopoietic stem cell transplantation, which is related to graft versus host disease, consists of intensification of systemic immunosuppressive therapy. However, this treatment has a limited efficacy and is associated with a significant number of serious adverse effects, particularly infectious. Alternative treatments are therefore required. Recently, clinical and functional improvement in patients with obstructive airway disease following allogenic hematopoietic stem cell transplantation treated with inhaled combined Budesonide/Formoterol has been retrospectively reported. Methods The present prospective multi-centered, randomised double-blind trial is designed to evaluate the efficacy of the combination of budesonide/formoterol (400/12µg 2 inhalations bid) versus placebo in patients with moderate to severe obstructive airway disease, not requiring initiation or intensification of systemic immunosuppressive therapy for extra thoracic graft versus host disease. The primary outcome will be the improvement of FEV1 at 1 month of treatment. The secondary outcomes will be the clinical and functional pulmonary improvements at 6 months. Expected Results The leading hypothesis is that patients treated with inhaled combined Budesonide/Formoterol will show significant improvement of their clinical symptoms and pulmonary functional testing.


title: Host defense function of the airway epithelium in health and disease: clinical background

text: Respiratory infection is extremely common and a major cause of morbidity and mortality worldwide. The airway epithelium has an important role in host defense against infection and this is illustrated in this review by considering infection by respiratory viruses. In patients with asthma or chronic obstructive pulmonary disease, respiratory viruses are a common trigger of exacerbations. Rhinoviruses (RV) are the most common virus type detected. Knowledge of the immunopathogenesis of such RV‐induced exacerbations remains limited, but information is available from in vitro and from in vivo studies, especially of experimental infection in human volunteers. RV infects and replicates within epithelial cells (EC) of the lower respiratory tract. EC are an important component of the innate‐immune response to RV infection. The interaction between virus and the intracellular signaling pathways of the host cell results in activation of potentially antiviral mechanisms, including type 1 interferons and nitric oxide, and in the producton of cytokines and chemokines [interleukin (IL)‐1β, IL‐6, IL‐8, IL‐11, IL‐16, tumor necrosis factor α, granulocyte macrophage‐colony stimulating factor, growth‐regulated oncogene‐α, epithelial neutrophil‐activating protein‐78, regulated on activation, normal T expressed and secreted, eotaxin 1/2, macrophage‐inflammatory protein‐1α], which influence the subsequent induced innate‐ and specific‐immune response. Although this is beneficial in facilitating clearance of virus from the respiratory tract, the generation of proinflammatory mediators and the recruitment of inflammatory cells result in a degree of immunopathology and may amplify pre‐existing airway inflammation. Further research will be necessary to determine whether modification of EC responses to respiratory virus infection will be of therapeutic benefit.


title: Rhinovirus C targets ciliated airway epithelial cells

text: BACKGROUND: The Rhinovirus C (RV-C), first identified in 2006, produce high symptom burdens in children and asthmatics, however, their primary target host cell in the airways remains unknown. Our primary hypotheses were that RV-C target ciliated airway epithelial cells (AECs), and that cell specificity is determined by restricted and high expression of the only known RV-C cell-entry factor, cadherin related family member 3 (CDHR3). METHODS: RV-C15 (C15) infection in differentiated human bronchial epithelial cell (HBEC) cultures was assessed using immunofluorescent and time-lapse epifluorescent imaging. Morphology of C15-infected differentiated AECs was assessed by immunohistochemistry. RESULTS: C15 produced a scattered pattern of infection, and infected cells were shed from the epithelium. The percentage of cells infected with C15 varied from 1.4 to 14.7% depending on cell culture conditions. Infected cells had increased staining for markers of ciliated cells (acetylated-alpha-tubulin [aat], p < 0.001) but not markers of goblet cells (wheat germ agglutinin or Muc5AC, p = ns). CDHR3 expression was increased on ciliated epithelial cells, but not other epithelial cells (p < 0.01). C15 infection caused a 27.4% reduction of ciliated cells expressing CDHR3 (p < 0.01). During differentiation of AECs, CDHR3 expression progressively increased and correlated with both RV-C binding and replication. CONCLUSIONS: The RV-C only replicate in ciliated AECs in vitro, leading to infected cell shedding. CDHR3 expression positively correlates with RV-C binding and replication, and is largely confined to ciliated AECs. Our data imply that factors regulating differentiation and CDHR3 production may be important determinants of RV-C illness severity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12931-017-0567-0) contains supplementary material, which is available to authorized users.


title: The 19th Rocky Mountain Virology Association Meeting

text: This autumn, 95 scientists and students from the Rocky Mountain area, along with invited speakers from Colorado, California, Montana, Florida, Louisiana, New York, Maryland, and India, attended the 19th annual meeting of the Rocky Mountain Virology Association that was held at the Colorado State University Mountain Campus located in the Rocky Mountains. The two-day gathering featured 30 talks and 13 posters—all of which focused on specific areas of current virology and prion protein research. The keynote presentation reviewed new tools for microbial discovery and diagnostics. This timely discussion described the opportunities new investigators have to expand the field of microbiology into chronic and acute diseases, the pitfalls of sensitive molecular methods for pathogen discovery, and ways in which microbiology help us understand disruptions in the social fabric that pose pandemic threats at least as real as Ebola or influenza. Other areas of interest included host factors that influence virus replication, in-depth analysis of virus transcription and its effect on host gene expression, and multiple discussions of virus pathology, epidemiology as well as new avenues of diagnosis and treatment. The meeting was held at the peak of fall Aspen colors, surrounded by five mountains >11,000 ft (3.3 km), where the secluded campus provided the ideal setting for extended discussions, outdoor exercise and stargazing. On behalf of the Rocky Mountain Virology Association, this report summarizes 43 selected presentations.


title: Epidemiological and phylogenetic analysis of canine kobuviruses in Tangshan, China

text: Canine kobuviruses (CaKoV) have been found in healthy and diarrheic dogs as well as asymptomatic wild carnivores in various countries. In order to investigate the prevalence and evolution of CaKoV in Tangshan, China, 82 dog fecal samples from pet hospitals in Tangshan were subjected to RT-PCR targeting a segment of the 3D gene of CaKoV. Using this method, we identified CaKoV in 14 samples (17.07%, 14/82). Of the CaKoV-positive samples, 78.57% (11/14) and 50% (7/14) were positive for canine parvovirus and canine coronavirus, respectively. The nucleotide sequences of the 14 strains 96.6%–100% identical to each other and 77.6%–99.2% identical to representative sequences from the NCBI GenBank database. We also amplified the 14 VP1 gene sequences and found that they were 93.3%–99.6% identical to each other and 73.3%–97.8% identical to representative sequences from the NCBI GenBank database. Phylogenetic analysis revealed that the 14 CaKoV strains from Tangshan are closely related to those identified in China and Thailand and display less similarity to those found in Africa, the United States, and Europe. Our data suggest that CaKoV circulated in young pet dogs in Tangshan and displays a high co-infection rate with CCoV and CPV. However, the relationship between the three viruses and their roles in the host requires further investigation.


title: COVID-19 in the Greater Mekong Subregion: how resilient are rural households?

text: In this paper we submit some thoughts on the possible implications of the COVID-19 pandemic for rural people in the countries of the Greater Mekong Subregion (GMS). We base our observations and conclusions on our long-term research experience in the region. The paper focuses on the economics of rural households during this crisis period and its aftermath. We conclude that country differences clearly exist due to their different stages of development. However, while rural households belong to the Corona risk groups, they are also resilient to such a shock. We submit that Governments in the GMS should strengthen policies that conserve the safety-net function of rural villages.


title: Human dendritic cell-specific ICAM-3-grabbing non-integrin downstream signaling alleviates renal fibrosis via Raf-1 activation in systemic candidiasis

text: We generated a human dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN) transgenic mouse in which renal tubular epithelial cells expressed DC-SIGN. The transgenic mice were infected with Candida albicans intravenously to study how DC-SIGN expression affected the pathogenesis of systemic candidiasis. We discovered that, while C. albicans infection induced renal fibrosis in both transgenic and littermate control mice, the transgenic mice had significantly lower levels of Acta2, Col1a2, Col3a1, and Col4a1 mRNA transcripts compared to the controls. KIM-1, an emerging biomarker for kidney injury, along with Tnf, Il6, and Tgfb1 transcripts, were lower in infected transgenic mice, and yet, the levels of Il10 remained comparable to the controls. While renal CD45(+) infiltrating cells were the source of Tnf, Il6, and Il10, LTL(+) renal proximal tubular epithelial cells were TGF-β1 producers in both infected transgenic and littermate controls. DC-SIGN-expressing tubular epithelial cells produced less TGF-β1 in response to C. albicans infection. In vivo experiments demonstrated that renal proximal tubular epithelial cell production of TGF-β1 was key to C. albicans-induced renal fibrosis and injury. Infection of transgenic mice induced a marked increase of phosphorylated Raf-1 and p38 in the kidney. However, ERK1/2 and JNK phosphorylation was more pronounced in the infected-littermate controls. Interestingly, treating the infected transgenic mice with a Raf-1 inhibitor increased the levels of the Tgfb1, Kim1, and Acta2 transcripts. These results indicate that DC-SIGN signaling, through activation of Raf-1 and p38 and suppression of JNK and ERK1/2 phosphorylation, reduces TGF-β1 production and C. albicans-induced renal fibrosis. Our study reveals for the first time the effect of DC-SIGN expression on C. albicans-induced renal fibrosis.


title: Reply to “Acute urticaria with pyrexia as the first manifestations of a COVID‐19 infection”: Urticaria‐like lesions in COVID‐19 patients are not really urticaria. A case with clinicopathologic correlation

text: We have read with great attention the article by Van Damme et al. considering urticarial lesions as a coronavirus disease 2019 (COVID‐19) associated skin manifestation(1). They observed two patients with erythemato‐edematous lesions surrounded by whitish halo, thus similar to hives but without additional data on their evolution(1). A previous report of COVID19‐related urticarial lesions had also been first published by Recalcati(2). However, none of these two published articles detailed if the lesions where evanescent, as it is mandatory for urticaria, nor did a pathological study.


title: The role of veterinary epidemiology in combating infectious animal diseases on a global scale: The impact of training and outreach programs

text: Abstract The effectiveness of detection and control of highly contagious animal diseases is dependent on a solid understanding of their nature and implementation of scientifically sound methods by people who are well trained. The implementation of specific detection methods and tools requires training and application in natural as well as field conditions. The aim of this paper is to present the design and implementation of training in disease investigation and basic veterinary epidemiology in selected countries using the Highly Pathogenic Avian Influenza (HPAI) H5N1 Asia strain as a disease detection model. Indonesia, Egypt, Nigeria, Turkey, and Vietnam were each identified as either a priority country where AI was spreading rapidly or a country at risk for infection. In each of these countries, a training program on epidemiological concepts, field investigation methodology, and detection of H5N1 Asia strain cases was conducted. This report includes the impact of these training sessions on national animal health programs, including follow-up activities of animal health officers who went through these training sessions.


title: Applying one health methods to improve cocoa production in Bougainville: A case study

text: Cocoa production is the major contributor to livelihoods for farming families that constitute nearly two-thirds of the population of the Autonomous Region of Bougainville, a Province in Papua New Guinea (PNG). These families, living mostly in subsistence poverty as a result of the Bougainville Civil War (1988–98), have significantly reduced cocoa production. Efforts to rebuild the industry have not been realised, due to known agricultural factors such as labour shortages, pests and diseases, poor support for farmers from trained agricultural extension officers and inefficient cocoa supply chains. But cocoa production involves factors other than agricultural ones. This article describes how we applied One Health methods to design and undertake a 6-year research project in Bougainville to improve cocoa productivity. Maximising the health and wellbeing of farming families and increasing agricultural productivity we argue, requires an in-depth understanding of the non-linear interactions between health, labour, household decision-making, yields and incomes.


title: Editors sound the SARS alarm bells

text: Abstract Mediawatch: Lethal virus outbreaks may help sell newspapers but Bernard Dixon finds that the early response from journalists to the severe acute respiratory syndrome (SARS) has been more informed than in many previous scares with diseases resulting from other dangerous viruses.


title: The effects of ARBs, ACEIs and statins on clinical outcomes of COVID-19 infection among nursing home residents

text: Abstract Objectives Angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB) and HMG-CoA reductase inhibitors (‘statins’) have been hypothesised to impact COVID-19 severity. However, up till now, no studies investigating this association were conducted in the most vulnerable and affected population groups, i.e. older adults residing in nursing homes. The objective of this study has been to explore the association of ACEi/ARB and/or statins with clinical manifestations in COVID-19 infected older adults residing in nursing homes. Design We undertook a retrospective multi-centre cohort study to analyse the association between ACEi/ARB and/or statin use with clinical outcome of COVID-19. The outcomes were 1) serious COVID-19 defined as long-stay hospital admission or death within 14 days of disease onset, and 2) asymptomatic, i.e. no disease symptoms in the whole study-period while still being PCR diagnosed. Setting and participants A total of 154 COVID-19 positive subjects was identified, residing in one of two Belgian nursing homes that experienced similar COVID-19 outbreaks. Measures Logistic regression models were applied with age, sex, functional status, diabetes and hypertension as covariates. Results We found a statistically significant association between statin intake and the absence of symptoms during COVID-19 (OR 2.91; CI 1.27-6.71), which remained statistically significant after adjusting for covariates (OR 2.65; CI 1.13-6.68). Although the effects of statin intake on serious clinical outcome were in the same beneficial direction, these were not statistically significant (OR 0.75; CI 0.24-1.87). There was also no statistically significant association between ACEi/ARB and asymptomatic status (OR 2.72; CI 0.59-25.1) or serious clinical outcome (OR 0.48; CI 0.10-1.97). Conclusions and Implications Our data indicate that statin intake in old, frail adults could be associated with a considerable beneficial effect on COVID-19 clinical symptoms. The role of statins and renin-angiotensin system drugs need to be further explored in larger observational studies as well as randomised clinical trials.


title: Prevalence and predictors of PTSS during COVID-19 outbreak in China hardest-hit areas: Gender differences matter

text: Abstract The outbreak of COVID-19 in China in December 2019 has been identified as a pandemic and a health emergency of global concern. Our objective was to investigate the prevalence and predictors of posttraumatic stress symptoms (PTSS) in China hardest-hit areas during COVID-19 outbreak, especially exploring the gender difference existing in PTSS. One month after the December 2019 COVID-19 outbreak in Wuhan China, we surveyed PTSS and sleep qualities among 285 residents in Wuhan and surrounding cities using the PTSD Checklist for DSM-5 (PCL-5) and 4 items from the Pittsburgh Sleep Quality Index (PSQI). Hierarchical regression analysis and non-parametric test were used to analyze the data. Results indicated that the prevalence of PTSS in China hardest-hit areas a month after the COVID-19 outbreak was 7%. Women reported significant higher PTSS in the domains of re-experiencing, negative alterations in cognition or mood, and hyper-arousal. Participants with better sleep quality or less frequency of early awakenings reported lower PTSS. Professional and effective mental health services should be designed in order to aid the psychological wellbeing of the population in affected areas, especially those living in hardest-hit areas, females and people with poor sleep quality.


title: Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing

text: BACKGROUND: To explore and describe the current literature surrounding bacterial/fungal co-infection in patients with coronavirus infection. METHODS: MEDLINE, EMBASE, and Web of Science were searched using broad based search criteria relating to coronavirus and bacterial co-infection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-COV-2, and other coronavirus) and bacterial/fungal co-infection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal co-infections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-COV-2 even in the absence of co-infection was performed. RESULTS: 1007 abstracts were identified. Eighteen full texts reported bacterial/fungal co-infection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140;61%). 9/18 (50%) studies reported on COVID-19, 5/18 (28%) SARS-1, 1/18 (6%) MERS, and 3/18 (17%) other coronavirus. For COVID-19, 62/806 (8%) patients were reported as experiencing bacterial/fungal co-infection during hospital admission. Secondary analysis demonstrated wide use of broad-spectrum antibacterials, despite a paucity of evidence for bacterial coinfection. On secondary analysis, 1450/2010 (72%) of patients reported received antimicrobial therapy. No antimicrobial stewardship interventions were described. For non-COVID-19 cases bacterial/fungal co-infection was reported in 89/815 (11%) of patients. Broad-spectrum antibiotic use was reported. CONCLUSIONS: Despite frequent prescription of broad-spectrum empirical antimicrobials in patients with coronavirus associated respiratory infections, there is a paucity of data to support the association with respiratory bacterial/fungal co-infection. Generation of prospective evidence to support development of antimicrobial policy and appropriate stewardship interventions specific for the COVID-19 pandemic are urgently required.


title: Development of methods to study the survival of airborne viruses

text: Abstract A number of viruses have been shown to be transmitted by the airborne route. It is the ability of these viruses to retain their infectivity for living hosts which play a key role in their aerial dissemination. Data generated by a number of workers on the airborne survival of viruses varies considerably because laboratory techniques have not been standardized. About 5 yr ago we started studies on the airborne survival of a number of animal and human viruses. This paper describes the methodology developed to study the aerobiology of these viruses. These methods should be useful in the aerobiological work of other viruses.


title: Clinical presentation, diagnosis, treatment and outcome of spinal epidural empyema in four cats (2010 to 2016)

text: This case series reviews previous publications and reports four feline spinal epidural empyema cases that presented with non‐ambulatory thoracolumbar myelopathy. Two cats underwent myelography and two MRI. Bacteria were obtained in three cases, in two from epidural abscesses and from a tail base wound in one; histopathological examination of epidural tissue showed pyogranulomatous changes in the remaining cat. Three cats were treated by surgical decompression plus antimicrobial therapy and one cat was treated medically. All cats showed satisfactory improvement following treatment over a follow‐up period of 3 months. Spinal epidural empyema is a rare condition but all cats in this series had favourable outcomes.


title: Physical properties of polymer composite: Natural rubber glove waste/polystyrene foam waste/cellulose

text: Abstract The polymer composite was prepared from the wastes of natural rubber glove (NRG) and polystyrene foam (PSF) blended with cellulose from sugar cane leaves via the laminate method. The NRG and PSF were firstly dispersed in toluene under continuous stirring. Then, maleic anhydride (MA) was added into the mixture. Effects of blend ratio and of MA content (0.5–15%, w/w) on physical properties of the polymer composite were investigated. The toluene resistance of the polymer blend was improved after adding MA and cellulose. The highest toluene resistance was achieved when using 12% cellulose. The chemical reactions of MA with polymer blend and with composite were confirmed by ATR-FTIR. The hardness of the polymer blend and composite increased as a function of PSF. In addition, their impact strength increased with increasing NRG and cellulose contents.


title: Identification of mouse hepatitis coronavirus A59 nucleocapsid protein phosphorylation sites

text: The coronavirus nucleocapsid (N) is a multifunctional phosphoprotein that encapsidates the genomic RNA into a helical nucleocapsid within the mature virion. The protein also plays roles in viral RNA transcription and/or replication and possibly viral mRNA translation. Phosphorylation is one of the most common post-translation modifications that plays important regulatory roles in modulating protein functions. It has been speculated for sometime that phosphorylation could play an important role in regulation of coronavirus N protein functions. As a first step toward positioning to address this we have identified the amino acids that are phosphorylated on the mouse hepatitis coronavirus (MHV) A59 N protein. High performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was used to identify phosphorylated sites on the N protein from both infected cells and purified extracellular virions. A total of six phosphorylated sites (S162, S170, T177, S389, S424 and T428) were identified on the protein from infected cells. The same six sites were also phosphorylated on the extracellular mature virion N protein. This is the first identification of phosphorylated sites for a group II coronavirus N protein.


title: Antiviral activity of K22 against members of the order Nidovirales

text: Abstract Recently, a novel antiviral compound (K22) that inhibits replication of a broad range of animal and human coronaviruses was reported to interfere with viral RNA synthesis by impairing double-membrane vesicle (DMV) formation (Lundin et al., 2014). Here we assessed potential antiviral activities of K22 against a range of viruses representing two (sub)families of the order Nidovirales, the Arteriviridae (porcine reproductive and respiratory syndrome virus [PRRSV], equine arteritis virus [EAV] and simian hemorrhagic fever virus [SHFV]), and the Torovirinae (equine torovirus [EToV] and White Bream virus [WBV]). Possible effects of K22 on nidovirus replication were studied in suitable cell lines. K22 concentrations significantly decreasing infectious titres of the viruses included in this study ranged from 25 to 50 μM. Reduction of double-stranded RNA intermediates of viral replication in nidovirus-infected cells treated with K22 confirmed the anti-viral potential of K22. Collectively, the data show that K22 has antiviral activity against diverse lineages of nidoviruses, suggesting that the inhibitor targets a critical and conserved step during nidovirus replication.


title: Global Proteomics Analysis of Circulating Extracellular Vesicles Isolated from Lung Transplant Recipients

text: [Image: see text] Lung transplant recipients (LTxRs) with acute rejection (AR) and chronic rejection (bronchiolitis obliterans syndrome [BOS]) induce circulating exosomes known to contain donor human leukocyte antigens and lung-associated self-antigens. Here, we sought to identify proteomic signatures in circulating extracellular vesicles (EVs) that differentiate LTxRs in 4 groups: stable, AR, BOS, or respiratory viral infection (RVI). EVs were isolated from plasma from patients in each group via ultracentrifugation. EV protein cargoes were prepared for shotgun proteomics using liquid chromatography–tandem mass spectrometry. We identified 2 unique proteins for AR, 4 for RVI, 24 for BOS, and 8 for stable LTxRs. Differential analysis of AR, BOS, RVI, and stable proteins identified significantly deregulated proteins (p < 0.05, log(2)(fold change) > ±1) in each condition (31, 2, and 2, respectively). EVs from LTxRs with AR contained proteins involved in immunoglobulin, complement regulation, coagulation, and innate and adaptive immune response pathways. EVs from LTxRs with BOS revealed enriched immunoglobulin receptors and a carboxypeptidase N catalytic chain. EVs from LTxRs with RVI had an enriched macrophage-stimulating factor. We found unique signatures in LTxRs with AR, BOS, and RVI, highlighting complex immune mechanisms underlying lung allograft rejection. Proteomic signatures in LTxRs’ circulating EVs provided insights into immunological mechanisms of graft rejection and RVI.


Virus-spreading procedures


title: Localization of the Lys, Asp, Glu, Leu tetrapeptide receptor to the Golgi complex and the intermediate compartment in mammalian cells

text: The carboxyl-terminal Lys-Asp-Glu-Leu (KDEL), or a closely-related sequence, is important for ER localization of both lumenal as well as type II membrane proteins. This sequence functions as a retrieval signal at post-ER compartment(s), but the exact compartment(s) where the retrieval occurs remains unresolved. With an affinity-purified antibody against the carboxyl-terminal sequence of the mammalian KDEL receptor, we have investigated its subcellular localization using immunogold labeling on thawed cryosections of different tissues, such as mouse spermatids and rat pancreas, as well as HeLa, Vero, NRK, and mouse L cells. We show that rab1 is an excellent marker of the intermediate compartment, and we use this marker, as well as budding profiles of the mouse hepatitis virus (MHV) in cells infected with this virus, to identify this compartment. Our results demonstrate that the KDEL receptor is concentrated in the intermediate compartment, as well as in the Golgi stack. Lower but significant labeling was detected in the rough ER. In general, only small amounts of the receptor were detected on the trans side of the Golgi stack, including the trans- Golgi network (TGN) of normal cells and tissues. However, some stress conditions, such as infection with vaccinia virus or vesicular stomatitis virus, as well as 20 degrees C or 43 degrees C treatment, resulted in a significant shift of the distribution towards the trans- TGN side of the Golgi stack. This shift could be quantified in HeLa cells stably expressing a TGN marker. No significant labeling was detected in structures distal to the TGN under all conditions tested. After GTP gamma S treatment of permeabilized cells, the receptor was detected in the beta-COP-containing buds/vesicles that accumulate after this treatment, suggesting that these vesicles may transport the receptor between compartments. We propose that retrieval of KDEL- containing proteins occurs at multiple post-ER compartments up to the TGN along the exocytotic pathway, and that within this pathway, the amounts of the receptor in different compartments varies according to physiological conditions.


title: Human Bocavirus Prevalence In Children With Acute Gastroenteritis From Rural Communities In The Northen Region Of South Africa

text: Acute gastroenteritis (AGE) is a leading cause of morbidity and mortality in young children worldwide. Human Bocavirus (HBoV) is an emerging virus globally associated with diarrhea. The aim of this study was to demonstrate the prevalence of HBoV genotypes in children (≤5 years) from rural communities in South Africa (SA) suffering from AGE. A total of 141 fecal samples of children ≤5 years with acute gastroenteritis (AGE) were collected from rural Primary Health Care facilities in the Vhembe district of SA between June 2017 and July 2018. Clinical symptoms and demographic data were also recorded. A total of 102 (72%) were outpatients and 39 (28%) were hospitalized patients. Human Bocavirus (HBoV) genotypes were determined using Real-Time Multiplex PCR. DNA extracts of positive samples were confirmed by conventional PCR targeting the NS1 gene. Co-infection with other enteric viruses were determined in HBoV positive samples using Real-Time PCR. HBoV was detected in 8 (5.7%) children with AGE. Children were in the age group between 1-24 months. HBoV1 and HBoV3 genotypes were each detected in 3 (37.5%) stool samples and HBoV2 in 2 (25%) stool samples. Co-infection with other enteric viruses included Rotavirus (37.5%); Adenovirus (37.5%); Norovirus (25%) and Astrovirus (12.5%). HBoV infections could be seen as a potential emerging diarrheal pathogen in South Africa. Further studies are required to understand the role of HBoV infections in children and adults with acute gastroenteritis. Acute gastroenteritis (AGE) is recognized as a major cause for mortality in children ≤5 years of age in Africa and other developing countries. Viruses known to be involved in AGE includes Rotavirus, Norovirus, Astrovirus and Adenovirus and have been reported globally. Recently the Human Bocavirus (HBoV) have been reported in numerous studies globally as a potential cause of diarrhea. In this study, the prevalence and genetic diversity of human Bocavirus in children with AGE from rural communities in Limpopo, South Africa were investigated. In total, 141 stool samples from children ≤ 5 years with AGE were assessed for the presence of HBoV using Real-Time PCR. HBoV were detected in 8 (5.7%) patients and included 3 positive samples for HBoV1 and HBoV3 respectively and 2 positive for HBoV2. No HBoV4 were detected. Among the 8 positive HBoV samples, co-infection with other enteric viruses were found in 7 (87.5%) samples, while mono infection with HBoV alone was detected in 1 (12.5%) patient. HBoV mixed infection with Rotavirus (3/8; 37.5%); Adenovirus (3/8; 37.5%); Norovirus (2/8; 25%) and Astrovirus (1/8; 12.5%) were observed in this study. This study reported for the first time on the prevalence of human Bocavirus in children with AGE from rural communities in South Africa.


Hero clinical pharmacists and the COVID‐19 pandemic: Overworked and overlooked


title: Respiratory Tract Infection and Risk of Hospitalization in Children with Congenital Heart Defects During Season and Off-Season: A Swedish National Study

text: Respiratory tract infections (RTI) are common among young children, and congenital heart defect (CHD) is a risk factor for severe illness and hospitalization. This study aims to assess the relative risk of hospitalization due to RTI in winter and summer seasons for different types of CHD. All children born in Sweden and under the age of two, in 2006–2011, were included. Heart defects were grouped according to type. Hospitalization rates for respiratory syncytial virus (RSV) infection and RTI in general were retrieved from the national inpatient registry. The relative risk of hospitalization was calculated by comparing each subgroup to other types of CHD and otherwise healthy children. The relative risk of hospitalization was increased for all CHD subgroups, and there was a greater increase in risk in summer for the most severe CHD. This included RSV infection, as well as RTI in general. The risk of hospitalization due to RTI is greater for CHD children. Prophylactic treatment with palivizumab, given to prevent severe RSV illness, is only recommended during winter. We argue that information to healthcare staff and parents should include how the risk of severe infectious respiratory tract illnesses, RSV and others, is present all year round for children with CHD.


title: Epidemiological Investigation of the Outbreak of Acute Respiratory Infection caused by Adenovirus Type B55 in a Physical Education School in 2017

text: BACKGROUND: On May 19, 2017, the cluster of 6 acute respiratory infections due to adenovirus in the swimming department of a physical education school (School J) was reported to Korea Centers for Disease Control and Prevention. An epidemiological investigation was conducted to identify the transmission route of the infection and to control the outbreak. MATERIALS AND METHODS: A retrospective cohort study (Study 1) was conducted on students and teachers of the athletic departments using the swimming pool, and a prospective surveillance (Study 2) was conducted on all students and teachers of the School J. A case was defined as any student and school personnel who developed more than two of the following symptoms from April 10 to July 2, 2017: fever, sore throat, cough, rhinorrhea, or headache. Relative risks (RRs) were calculated to compare the attack rates according to potential risk factors. Multivariable logistic regression was performed to identify the risk factors for infection in the outbreak. RESULTS: 47 cases were identified: 33 (55.9%) cases occurred among 59 students and teachers in Study 1 and 14 (3.9%) among 362 students and school personnel in Study 2. There were 18 laboratory confirmed adenovirus infection cases. The common symptoms were headache (71.7%), fever (69.6%), rhinorrhea (63.0%), sputum (56.5%), and sore throat (54.3%). 23.9% of the cases were accompanied with diarrhea and 19.6% with eye congestion. None of the cases developed pneumonia. 32.6% of the cases were hospitalized. In Study 1, attack rate in the swimming department was higher than that in others (RR: 1.90; 95% confidence interval [CI]: 1.01-3.60). In Study 2, being a member of the shooting department (RR: 20.70; 95% CI: 4.90-87.47) and being a first year high school student (RR: 10.95; 95% CI: 2.90-41.33) were identified as risk factors for the infections. Genetic analyses of the adenoviruses showed 100% identical sequence in homology and confirmed the human adenovirus B55 (HAdV-B55). No adenovirus was detected at examining the water and environment of the swimming pool and dormitory. CONCLUSION: The outbreak is inferred to be occurred via propagated transmission among the students in the same athletic department, while the students with symptoms of respiratory infection continued performing school activities without any restrictions. Infection control measures such as early detection of symptoms of respiratory infection and restriction of group activity are necessary to prevent respiratory infection outbreak in the communal living setting.


Comment on “Epidemiological and clinical characteristics of heart transplant recipients during the 2019 coronavirus outbreak in Wuhan, China” by Ren et al


title: Scientific opinion on an alternative method for the hygienic treatment of bovine colostrum through a series of filtration steps

text: An alternative method to the HTST treatment (High Temperature Short Time pasteurisation at 72 °C for at least 15 seconds or equivalent pasteurisation effect achieving a negative reaction to a phosphatase test), approved for the treatment of bovine colostrum (Category 3 material), was assessed. The purpose of the alternative method, based on a series of filtration steps, is the production of Colostrinov, a product whose main ingredient is bovine colostrum, to be used for foal nutrition. Since the filtration techniques used are known to eliminate particles of the size of bacteria, fungi and protozoa from liquids, it is reasonable to assume that the microfiltration process reduces these contaminants to a level at least equivalent to the treatment required by the legislation. Owing to their small size, viruses are not retained by the mechanical effect of the filters but they may be retained by physico‐chemical interactions with the surface of the filter, depending on the surface properties of the viruses and those of the filter, as well as on the properties of the surrounding liquid. From the information provided by the applicant, it cannot be concluded whether or not the microfiltration process reduces the relevant viral contaminants to a level at least equivalent to a single HTST treatment as required by the legislation.


title: Frequent detection of bocavirus DNA in German children with respiratory tract infections

text: BACKGROUND: In a substantial proportion of respiratory tract diseases of suspected infectious origin, the etiology is unknown. Some of these cases may be caused by the recently described human bocavirus (hBoV). The aim of this study was to investigate the frequency and the potential clinical relevance of hBoV in pediatric patients. METHODS: We tested 835 nasopharyngeal aspirates (NPA) obtained between 2002 and 2005 from pediatric in-patients with acute respiratory tract diseases at the University of Würzburg, Germany, for the presence of hBoV DNA. The specificity of positive PCR reactions was confirmed by sequencing. RESULTS: HBoV DNA was found in 87 (10.3 %) of the NPAs. The median age of the infants and children with hBoV infection was 1.8 years (mean age 2.0 years; range 18 days – 8 years). Infections with hBoV were found year-round, though most occurred in the winter months. Coinfections were found in 34 (39.1 %) of the hBoV positive samples. RSV, influenza A, and adenoviruses were most frequently detected as coinfecting agents. Sequence determination of the PCR products in the NP-1 region revealed high identity (99 %) between the nucleotide sequences obtained in different years and in comparison to the Swedish viruses ST1 and ST2. An association of hBoV with a distinct respiratory tract manifestation was not apparent. CONCLUSION: HBoV is frequently found in NPAs of hospitalized infants and children with acute respiratory tract diseases. Proving the clinical relevance of hBoV is challenging, because application of some of Koch's revised postulates is not possible. Because of the high rate of coinfections with hBoV and other respiratory tract pathogens, an association between hBoV and respiratory tract diseases remains unproven.


title: Reasons for the increase in emerging and re-emerging viral infectious diseases

text: Abstract In the past two decades, humans have faced many new viral infectious agents in emerging and re-emerging infectious diseases (EIDs). Many factors contribute to the appearance of EIDs. These factors are complex but can be classified into three different categories: virus factors, human factors, and ecological factors. The factors contributing to the cause of such viral infectious diseases will be systematically reviewed in this article.


title: Propiedades de una escala de preocupación por el COVID-19: Análisis exploratorio en una muestra peruana

text: Abstract Objective: Concern about getting sick could help prevent disease. The aim of this study was to analyze the psychometric properties of a COVID-19 concern scale (EPCov-19). Materials and methods: This is an instrument-based study and information was collected from 224 people of Peruvian nationality in the context of social isolation. The items of the Cancer Concern Scale (CCS) were adapted for this study. Results: A scale with satisfactory psychometric properties was obtained. With a matrix of polychoric correlations, values higher than the standard were obtained in all 6 items (r > 0.3) and the reliability was acceptable (α = 0.866; 95% CI = 0.83 - 0.89). Parallel analysis suggested unidimensionality of the EPCov-19, the variance explained was 79.7% and saturations were higher than 0.4. Goodness-of-fit indices were satisfactory (CFI=0.995; GFI = 0.997; TLI = 0.991; and RMSEA = 0.059, 95% CI = 0.012 - 0.077). Conclusions: This is a valid and reliable instrument for measuring concern about the spread of COVID-19 and can be used in future studies.


title: Structure and function study of paramyxovirus fusion protein heptad repeat peptides

text: Paramyxovirus might adopt a molecular mechanism of membrane fusion similar to that of other class I viruses in which the heptad repeat (HR) regions of fusion protein (F) HR1 and HR2 form a six-helix bundle structure inducing membrane fusion. In this study, we examined the structure and function of HR1 and HR2 from the avian paramyxovirus-2 (APMV-2) F protein. The study showed that APMV-2 HR1 and HR2 formed a stable six-helix bundle. Only a soluble APMV-2 HR2 peptide showed potent and specific virus-cell fusion inhibition activity. Cross-inhibiting activity with APMV-1 (Newcastle disease virus, NDV) was not found. A possible mechanism of membrane fusion inhibition by the paramyxovirus HR2 peptide is discussed.


title: Increased Mortality and Major Complications in Hip Fracture Care During the COVID-19 Pandemic: A New York City Perspective

text: OBJECTIVES: To examine one health system's response to the essential care of its hip fracture population during the COVID-19 pandemic and report on its effect on patient outcomes. DESIGN: Prospective cohort study. SETTING: Seven musculoskeletal care centers within New York City and Long Island. PATIENTS/PARTICIPANTS: One hundred thirty-eight recent and 115 historical hip fracture patients. INTERVENTION: Patients with hip fractures occurring between February 1, 2020, and April 15, 2020, or between February 1, 2019, and April 15, 2019, were prospectively enrolled in an orthopaedic trauma registry and chart reviewed for demographic and hospital quality measures. Patients with recent hip fractures were identified as COVID positive (C+), COVID suspected (Cs), or COVID negative (C−). MAIN OUTCOME MEASUREMENTS: Hospital quality measures, inpatient complications, and mortality rates. RESULTS: Seventeen (12.2%) patients were confirmed C+ by testing, and another 14 (10.1%) were suspected (Cs) of having had the virus but were never tested. The C+ cohort, when compared with Cs and C− cohorts, had an increased mortality rate (35.3% vs. 7.1% vs. 0.9%), increased length of hospital stay, a greater major complication rate, and a greater incidence of ventilator need postoperatively. CONCLUSIONS: COVID-19 had a devastating effect on the care of patients with hip fracture during the pandemic. Although practice patterns generally remained unchanged, treating physicians need to understand the increased morbidity and mortality in patients with hip fracture complicated by COVID-19. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of Levels of Evidence.


title: The molecular dynamics of feline coronaviruses

text: Abstract Feline coronaviruses are widespread and come in different flavors. There are two main serotypes both of which occur in two pathotypes, the avirulent enteric viruses and the virulent, usually fatal peritonitis viruses, the latter in turn occurring either in a ‘wet’ or exudative form or in a ‘dry’ or proliferative form. In this paper a concise overview is given of the molecular features of these viruses. Special attention is given to the genetic dynamics of the viruses as these now allow us to begin to understand the origin of the different phenotypes, in particular the genesis of virulence during persistent infection. As discussed, the surprising new insights obtained over the last few years call for a critical reevaluation of strategies for protection.


title: Rapid multiplex microfiber-based immunoassay for anti-MERS-CoV antibody detection

text: Abstract On-site multiplex biosensors for innate immunity antibodies are ideal tools for monitoring health status of individuals against various diseases. This study introduces a novel antibody immunoassay testing platform incorporating microfiber-based arrays of antigens to capture specific antibodies. The fabrication and setup of the device revolved around electrospun polystyrene (ESPS) microfibers that act as three-dimensional membrane filters, capable of rapid and multifold analyte capture. In particular, the ESPS microfibers were patterned through localized oxygen plasma to create hydrophilic zones that facilitate fluid flows and immobilizations of antigens. The bulk of this robust antibody immunoassay platform could be installed into a compact syringe-driven cassette device, which could perform multiplex antibody immunoassay for antibodies specifically against Middle East respiratory syndrome coronavirus (MERS-CoV) with rapid preparation amounting to a total of 5 min, as well as high sensitivity and specificity for the MERS-CoV down to 200 μg/mL.


title: Current concepts in SARS treatment

text: Abstract The outbreak of severe acute respiratory syndrome (SARS) has drawn enormous attention and caused fear worldwide since early 2003. The disease appears to be under control now; however, the possible return of SARS must be emphasized. Although many clinical experiments have been reported, the treatment of SARS is largely anecdotal, and so far no treatment consensus has been reached. We summarize 14 clinical reports and attempt to assess the effectiveness of various treatment regimens. A combination treatment of steroids and ribavirin was widely used empirically from the outset of the epidemic. In general, the use of steroids for SARS seemed beneficial, but the optimal timing, dosage, and duration of treatment have not yet been determined. On the other hand, ribavirin administration apparently reduced neither the rate of intratracheal intubation nor that of mortality. Moreover, significant toxicity, such as hemolytic anemia, has been attributed to ribavirin. A few preliminary trials and in vitro data suggest the possibility of treating SARS with interferon. Other agents, including the HIV protease inhibitor glycyrrhizin and convalescent plasma, remain to be evaluated.


title: Circulating Levels of IL‐2, IL‐4, TNF‐α, IFN‐γ and C reactive protein Are Not Associated with Severity of COVID‐19 Symptoms

text: As of May 5, 2020, the total number of coronavirus disease 2019 (COVID‐19) cases had reached over 3.5 million worldwide. The outbreak of COVID‐19 has been officially declared as a pandemic by the World Health Organization because of global spread and severity. Accumulating evidence has been showed that patients with severe COVID‐19 have a cytokine storm syndrome. This article is protected by copyright. All rights reserved.


title: Chapter 5 Laboratory Diagnosis of Viral Infections

text: Abstract This chapter describes methods of laboratory diagnosis of viral infections.


title: A Hypothesis on the role of the human immune system in covid-19

text: The COVID-19 pandemic has not spared any continent. The disease has affected more than 7,500,000 individuals globally and killed approximately 450,000 individuals. The disease is caused by a very small virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is an enveloped single-stranded RNA virus with a spike-like structure on its envelope that can interact with the angiotensin-converting enzyme 2 (ACE2) receptor after cleavage. ACE2 receptors are present in the human lungs and other organs. SARS-CoV-2 is a new virus that belongs to the subgenus Sarbecovirus; viruses in this subgenus have spread widely in the previous years and caused outbreaks of severe acute respiratory syndromes.


title: Complete Genome Sequence of Strain SDCV/USA/Illinois121/2014, a Porcine Deltacoronavirus from the United States

text: To investigate the causative agent of swine diarrhea, next-generation sequencing (NGS) was performed on a porcine fecal sample. The NGS reads were assembled, which generated a complete swine Deltacoronavirus genome sequence, that of strain SDCV/USA/Illinois121/2014.


title: Knowledge, Perceptions, and Self-reported Performance of Hand Hygiene Among Registered Nurses at Community-based Hospitals in the Republic of Korea: A Cross-sectional Multi-center Study

text: OBJECTIVES: To assess the nurses’ hand hygiene (HH) knowledge, perception, attitude, and self-reported performance in small- and medium-sized hospitals after Middle East Respiratory Syndrome outbreak. METHODS: The structured questionnaire was adapted from the World Health Organization’s survey. Data were collected between June 26 and July 14, 2017. RESULTS: Nurses showed scores on knowledge (17.6±2.5), perception (69.3±0.8), self-reported HH performance of non-self (86.0±11.0), self-reported performance of self (88.2±11.0), and attitude (50.5±5.5). HH performance rate of non-self was Y(1)=36.678+ 0.555X1 (HH performance rate of self) (adjusted R(2)=0.280, p<0.001). The regression model for performance was Y(4)=18.302+0.247X(41) (peception)+0.232X(42) (attitude)+0.875X(42) (role model); coefficients were significant statistically except attitude, and this model significant statistically (adjusted R(2)=0.191, p<0.001). CONCLUSIONS: Advanced HH education program would be developed and operated continuously. Perception, attitude, role model was found to be a significant predictors of HH performance of self. So these findings could be used in future HH promotion strategies for nurses.


title: Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility

text: BACKGROUND: The novel Middle East respiratory syndrome coronavirus (MERS-CoV) had, as of Aug 8, 2013, caused 111 virologically confirmed or probable human cases of infection worldwide. We analysed epidemiological and genetic data to assess the extent of human infection, the performance of case detection, and the transmission potential of MERS-CoV with and without control measures. METHODS: We assembled a comprehensive database of all confirmed and probable cases from public sources and estimated the incubation period and generation time from case cluster data. Using data of numbers of visitors to the Middle East and their duration of stay, we estimated the number of symptomatic cases in the Middle East. We did independent analyses, looking at the growth in incident clusters, the growth in viral population, the reproduction number of cluster index cases, and cluster sizes to characterise the dynamical properties of the epidemic and the transmission scenario. FINDINGS: The estimated number of symptomatic cases up to Aug 8, 2013, is 940 (95% CI 290–2200), indicating that at least 62% of human symptomatic cases have not been detected. We find that the case-fatality ratio of primary cases detected via routine surveillance (74%; 95% CI 49–91) is biased upwards because of detection bias; the case-fatality ratio of secondary cases was 20% (7–42). Detection of milder cases (or clinical management) seemed to have improved in recent months. Analysis of human clusters indicated that chains of transmission were not self-sustaining when infection control was implemented, but that R in the absence of controls was in the range 0·8–1·3. Three independent data sources provide evidence that R cannot be much above 1, with an upper bound of 1·2–1·5. INTERPRETATION: By showing that a slowly growing epidemic is underway either in human beings or in an animal reservoir, quantification of uncertainty in transmissibility estimates, and provision of the first estimates of the scale of the epidemic and extent of case detection biases, we provide valuable information for more informed risk assessment. FUNDING: Medical Research Council, Bill & Melinda Gates Foundation, EU FP7, and National Institute of General Medical Sciences.


title: A system dynamics approach to scenario analysis for urban passenger transport energy consumption and CO2 emissions: A case study of Beijing

text: Abstract With the accelerating process of urbanization, developing countries are facing growing pressure to pursue energy savings and emission reductions, especially in urban passenger transport. In this paper, we built a Beijing urban passenger transport carbon model, including an economy subsystem, population subsystem, transport subsystem, and energy consumption and CO2 emissions subsystem using System Dynamics. Furthermore, we constructed a variety of policy scenarios based on management experience in Beijing. The analysis showed that priority to the development of public transport (PDPT) could significantly increase the proportion of public transport locally and would be helpful in pursuing energy savings and emission reductions as well. Travel demand management (TDM) had a distinctive effect on energy savings and emission reductions in the short term, while technical progress (TP) was more conducive to realizing emission reduction targets. Administrative rules and regulations management (ARM) had the best overall effect of the individual policies on both energy savings and emission reductions. However, the effect of comprehensive policy (CP) was better than any of the individual policies pursued separately. Furthermore, the optimal implementation sequence of each individual policy in CP was TP→PDPT→TDM→ARM.


Pandemic Bronchoscopy: A Technique to Improve Safety


title: The use of Nanotrap particles for biodefense and emerging infectious disease diagnostics

text: Detection of early infectious disease may be challenging due to the low copy number of organisms present. To overcome this limitation and rapidly measure low concentrations of the pathogen, we developed a novel technology: Nanotrap particles, which are designed to capture, concentrate, and protect biomarkers from complex biofluids. Nanotrap particles are thermoresponsive hydrogels that are capable of antigen capture through the coupling of affinity baits to the particles. Here, we describe recent findings demonstrating that Nanotrap particles are able to capture live infectious virus, viral RNA, and viral proteins. Capture is possible even in complex mixtures such as serum and allows the concentration and protection of these analytes, providing increased performance of downstream assays. The Nanotrap particles are a versatile sample preparation technology that has far reaching implications for biomarker discovery and diagnostic assays.


title: Characterization of Murine Coronavirus Neutralization Epitopes with Phage-Displayed Peptides

text: Abstract Phage-displayed peptide libraries were used to map immunologically relevant epitopes on the surface (S) glycoprotein of a neurotropic murine coronavirus (MHV-A59). Three in vitro virus-neutralizing and in vivo protective mAbs against either continuous or discontinuous epitopes on the S glycoprotein were used to screen 12 different peptide libraries expressed on the pVIII major coat protein of the fd filamentous bacteriophage. Consensus sequences that matched short sequences within the S glycoprotein were identified. The sequence of a tight-binding, mAb-selected peptide suggested the location of a discontinuous epitope within the N-terminal S1 subunit. Several tightly binding phage were amplified and used directly as immunogens in BALB/c and C57BL/6 mice. Partial protection of C57BL/6 mice against a lethal acute virus infection was achieved with a phage preparation that displayed a linear epitope. Protection correlated with the presence of sufficient levels of specific antiviral antibodies recognizing the same immunodominant domain and 13-mer peptide, located within the C-terminal S2 subunit, as the selecting mAb. Thus, the direct use of phage-displayed peptides to evaluate protective antiviral immune responses complements their use to characterize antibody-binding epitopes. This is the first evaluation of protective immunization induced by mAb-selected phage-displayed peptides.


title: Pediatric Crohn's Disease and Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19 Treated with Infliximab

text: Coronavirus disease 2019 (COVID-19) may lead to a severe inflammatory response referred to as a cytokine storm. We describe a case of severe COVID-19 infection in a recently diagnosed pediatric Crohn's disease patient successfully treated with Tumor Necrosis Factor-alpha (TNF-α) blockade. The patient presented with five days of fever, an erythematous maculopapular facial rash, and abdominal pain without respiratory symptoms. SARS-CoV-2 PCR was positive. Despite inpatient treatment for COVID-19 and a perianal abscess, the patient acutely decompensated, with worsening fever, tachycardia, fluid-refractory hypotension, elevation of liver enzymes, and transformation of the rash into purpura extending from the face to the trunk, upper and lower extremities, including the palmar and plantar surfaces of the hands and feet. Cytokine profile revealed rising levels of interleukin (IL)-6, IL-8, and TNF-α, higher than those described in either inflammatory bowel disease (IBD) or severe COVID-19 alone. The patient was treated with infliximab for TNF-α blockade to address both moderately to severely active Crohn's disease and multisystem inflammatory syndrome in children (MIS-C) temporally related to COVID-19. Within hours of infliximab treatment, fever, tachycardia and hypotension resolved. Cytokine profile improved with normalization of TNF-α, a decrease in IL-6, and IL-8 concentrations. This case supports a role for blockade of TNF-α in the treatment of COVID-19 inflammatory cascade. The role of anti-TNF agents in patients with MIS-C temporally related to COVID-19 requires further investigation.


title: Novel Lyssavirus in Natterer’s Bat, Germany

text: A virus isolated from a Natterer’s bat (Myotis nattererii) in Germany was differentiated from other lyssaviruses on the basis of the reaction pattern of a panel of monoclonal antibodies. Phylogenetic analysis supported the assumption that the isolated virus, Bokeloh bat lyssavirus, may represent a new member of the genus Lyssavirus.


title: Olfactory and Gustatory Dysfunction in a COVID-19 Patient with Ankylosing Spondylitis Treated with Etanercept: Case Report

text: The neurologic manifestations concerning coronavirus disease 2019 (COVID-19) are highly penetrated. Anosmia and ageusia are one of the common acute neurologic symptoms, which develop in the early stage of COVID-19. However, it is not reported that how immunosuppressive agents affect these symptoms. We report olfactory and gustatory dysfunctions in a patient with ankylosing spondylitis (AS) treated with etanercept during COVID-19. A 53-year-old female showing AS controlled with tumor necrosis factor-α inhibitor, etanercept, had been diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, presenting cough and rhinorrhea. One month after diagnosis, she complained about hyposmia and hypogeusia two days before the seronegative conversion of SARS-CoV-2, which were confirmed by a neurological examination. We speculate that the etanercept may have delayed the development of olfactory and gustatory dysfunction in the patient.


title: Evaluation of an Adjustable Epidemiologic Information System

text: BACKGROUND: In order to facilitate public health response and to achieve early control of infectious disease epidemics, an adjustable epidemiologic information system (AEIS) was established in the Taiwan public health network in February 2006. METHODOLOGY/PRINCIPAL FINDINGS: The performance of AEIS for the period 2006 through 2008 was evaluated based on a number of response times (RT) and the public health impact. After implementation of the system, the apparent overall shortened RT was mainly due to the shortening of personnel response time (PRT) and the time needed to draft a new questionnaire that incurred as personnel-system interface (PSI); PRT dropped from a fluctuating range of 9.8 ∼28.8 days in the first four months to <10 days in the following months and remained low till 2008 (0.88±1.52 days). The PSIs for newly emerged infectious diseases were 2.6 and 3.4 person-hours for H5N1 in 2007 and chikungunya in 2008, respectively, a much improvement from 1142.5 person-hours for SARS in 2003. The duration of each rubella epidemic cluster was evaluated as public health impact and showed a shortening trend (p = 0.019) that concurred with the shortening of PRT from 64.8±47.3 to 25.2±38.2 hours per cluster (p<0.0001). CONCLUSIONS/SIGNIFICANCE: The first evaluation of the novel instrument AEIS that had been used to assist Taiwan's multi-level government for infectious diseases control demonstrated that it was well integrated into the existing public health infrastructure. It provided flexible tools and computer algorithms with friendly interface for timely data collection, integration, and analysis; as a result, it shortened RTs, filled in gaps of personnel lacking sufficient experiences, created a more efficient flow of response, and identified asymptomatic/mild cases early to minimize further spreading. With further development, AEIS is anticipated to be useful in the application of other acute public health events needing immediate orchestrated data collection and public health actions.


title: A Metagenomic Analysis of Pandemic Influenza A (2009 H1N1) Infection in Patients from North America

text: Although metagenomics has been previously employed for pathogen discovery, its cost and complexity have prevented its use as a practical front-line diagnostic for unknown infectious diseases. Here we demonstrate the utility of two metagenomics-based strategies, a pan-viral microarray (Virochip) and deep sequencing, for the identification and characterization of 2009 pandemic H1N1 influenza A virus. Using nasopharyngeal swabs collected during the earliest stages of the pandemic in Mexico, Canada, and the United States (n = 17), the Virochip was able to detect a novel virus most closely related to swine influenza viruses without a priori information. Deep sequencing yielded reads corresponding to 2009 H1N1 influenza in each sample (percentage of aligned sequences corresponding to 2009 H1N1 ranging from 0.0011% to 10.9%), with up to 97% coverage of the influenza genome in one sample. Detection of 2009 H1N1 by deep sequencing was possible even at titers near the limits of detection for specific RT-PCR, and the percentage of sequence reads was linearly correlated with virus titer. Deep sequencing also provided insights into the upper respiratory microbiota and host gene expression in response to 2009 H1N1 infection. An unbiased analysis combining sequence data from all 17 outbreak samples revealed that 90% of the 2009 H1N1 genome could be assembled de novo without the use of any reference sequence, including assembly of several near full-length genomic segments. These results indicate that a streamlined metagenomics detection strategy can potentially replace the multiple conventional diagnostic tests required to investigate an outbreak of a novel pathogen, and provide a blueprint for comprehensive diagnosis of unexplained acute illnesses or outbreaks in clinical and public health settings.


title: Evaluation of the amplicor HCV test: Experiences after 1 year of routine use in a diagnostic laboratory

text: To evaluate the usefulness of a standardized commercial amplification assay for detection of hepatitis C virus (HCV) RNA, Amplicor® HCV Test (Roche), a total of 1,204 serum samples from 888 patients was examined. Seven out of 443 anti-HCV-negative samples, 638 out of 729 anti-HCV-positive samples and four out of 32 anti-HCV-indeterminate samples tested HCV RNA positive by Amplicor® in initial testing. One false-negative and five false-positive Amplicor® results were found in initial testing, giving an overall sensitivity and specificity of the Amplicor® HCV Test of 99.8% and 99.1%, respectively. Our study confirmed that the Amplicor® HCV Test is a practical, rapid, sensitive and specific assay for detection of HCV RNA. However, the results must be interpreted with some caution and with the patient's anti-HCV status and clinical data in mind.


title: Stress, Nutrition, and Intestinal Immune Responses in Pigs — A Review

text: Modern livestock production became highly intensive and large scaled to increase production efficiency. This production environment could add stressors affecting the health and growth of animals. Major stressors can include environment (air quality and temperature), nutrition, and infection. These stressors can reduce growth performance and alter immune systems at systemic and local levels including the gastrointestinal tract. Heat stress increases the permeability, oxidative stress, and inflammatory responses in the gut. Nutritional stress from fasting, antinutritional compounds, and toxins induces the leakage and destruction of the tight junction proteins in the gut. Fasting is shown to suppress pro-inflammatory cytokines, whereas deoxynivalenol increases the recruitment of intestinal pro-inflammatory cytokines and the level of lymphocytes in the gut. Pathogenic and viral infections such as Enterotoxigenic E. coli (ETEC) and porcine epidemic diarrhea virus can lead to loosening the intestinal epithelial barrier. On the other hand, supplementation of Lactobacillus or Saccharaomyces reduced infectious stress by ETEC. It was noted that major stressors altered the permeability of intestinal barriers and profiles of genes and proteins of pro-inflammatory cytokines and chemokines in mucosal system in pigs. However, it is not sufficient to fully explain the mechanism of the gut immune system in pigs under stress conditions. Correlation and interaction of gut and systemic immune system under major stressors should be better defined to overcome aforementioned obstacles.


title: SARS-CoV-2 and Cancer: are they really partners in crime ?

text: Abstract The outbreak of the SARS-CoV-2 pandemic has overwhelmed health care systems in many countries. The clinical presentation of the SARS-CoV-2 varies between a subclinical or flu-like syndrome to that of severe pneumonia with multi-organ failure and death. Initial reports have suggested that cancer patients may have a higher susceptibility to get infected by the SARS-CoV-2 virus but current evidence remains poor as it is biased by important confounders. Patients with ongoing or recent cancer treatment for advanced active disease, metastatic solid tumors and hematological malignancies are at higher risk of developing severe COVID-19 respiratory disease that requires hospitalization and have a poorer disease outcome compared to individuals without cancer. However it is not clear whether these are independent risk factors, or mainly driven by male gender, age, obesity, performance status, uncontrolled diabetes, cardiovascular disease and various other medical conditions. These often have a greater influence on the probability to die due to SARS-CoV-2 then cancer. Delayed diagnosis and suboptimal cancer management due to the pandemic results in disease upstaging and has considerable impact cancer on specific death rates. Surgery during the peak of the pandemic seems to increase mortality, but there is no convincing evidence that adjuvant systemic cancer therapy and radiotherapy are contraindicated, implicating that cancer treatment can be provided safely after individual risk/benefit assessment and some adaptive measures. Underlying immunosuppression, elevated cytokine levels, altered expression of the angiotensin converting enzyme (ACE-2) and TMPRSS2, and a prothrombotic status may fuel the effects of a SARS-CoV-2 in some cancer patients, but have the potential to be used as biomarkers for severe disease and therapeutic targets. The rapidly expanding literature on COVID-19 should be interpreted with care as it is often hampered by methodological and statistical flaws.


Final 2012 Reports of Nationally Notifiable Infectious Diseases


title: Sequence analysis of the spike gene of Porcine epidemic diarrhea virus isolated from South China during 2011–2015

text: The spike gene of porcine epidemic diarrhea virus (PEDV) was sequenced from 55 South China field strains isolated from pigs with symptoms of diarrhea. The sequences were compared within the set of field strains as well as with reference strains available in GenBank. Within the 55 South China PEDV field strains, the deduced amino acid sequence identities ranged from 93.8% to 99.9 % and ranged from 90.7% to 99.5% when compared with the foreign reference strains in GenBank. Our phylogenetic analysis showed that 10 of the 55 South China PEDV strains belonged to G1b and 45 belonged to G2b.


title: SARS-Coronavirus-2 Nsp13 Possesses NTPase and RNA Helicase Activities That Can Be Inhibited by Bismuth Salts

text: The ongoing outbreak of Coronavirus Disease 2019 (COVID-19) has become a global public health emergency. SARS-coronavirus-2 (SARS-CoV-2), the causative pathogen of COVID-19, is a positive-sense single-stranded RNA virus belonging to the family Coronaviridae. For RNA viruses, virus-encoded RNA helicases have long been recognized to play pivotal roles during viral life cycles by facilitating the correct folding and replication of viral RNAs. Here, our studies show that SARS-CoV-2-encoded nonstructural protein 13 (nsp13) possesses the nucleoside triphosphate hydrolase (NTPase) and RNA helicase activities that can hydrolyze all types of NTPs and unwind RNA helices dependently of the presence of NTP, and further characterize the biochemical characteristics of these two enzymatic activities associated with SARS-CoV-2 nsp13. Moreover, we found that some bismuth salts could effectively inhibit both the NTPase and RNA helicase activities of SARS-CoV-2 nsp13 in a dose-dependent manner. Thus, our findings demonstrate the NTPase and helicase activities of SARS-CoV-2 nsp13, which may play an important role in SARS-CoV-2 replication and serve as a target for antivirals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-020-00242-1) contains supplementary material, which is available to authorized users.


title: Epidemiological Observations on the Association Between Anosmia and COVID-19 Infection: Analysis of Data From a Self-Assessment Web Application

text: BACKGROUND: We developed a self-assessment and participatory surveillance web application for coronavirus disease (COVID-19), which was launched in France in March 2020. OBJECTIVE: Our objective was to determine if self-reported symptoms could help monitor the dynamics of the COVID-19 outbreak in France. METHODS: Users were asked questions about underlying conditions, sociodemographic status, zip code, and COVID-19 symptoms. Depending on the symptoms reported and the presence of coexisting disorders, users were told to either stay at home, contact a general practitioner (GP), or call an emergency phone number. Data regarding COVID-19–related hospitalizations were retrieved from the Ministry of Health. RESULTS: As of March 29, 2020, the application was opened 4,126,789 times; 3,799,535 electronic questionnaires were filled out; and 2,477,174 users had at least one symptom. In total, 34.8% (n=1,322,361) reported no symptoms. The remaining users were directed to self-monitoring (n=858,878, 22.6%), GP visit or teleconsultation (n=1,033,922, 27.2%), or an emergency phone call (n=584,374, 15.4%). Emergency warning signs were reported by 39.1% of participants with anosmia, a loss of the sense of smell (n=127,586) versus 22.7% of participants without anosmia (n=1,597,289). Anosmia and fever and/or cough were correlated with hospitalizations for COVID-19 (Spearman correlation coefficients=0.87 and 0.82, respectively; P<.001 for both). CONCLUSIONS: This study suggests that anosmia may be strongly associated with COVID-19 and its severity. Despite a lack of medical assessment and virological confirmation, self-checking application data could be a relevant tool to monitor outbreak trends. TRIAL REGISTRATION: ClinicalTrials.gov NCT04331171; https://clinicaltrials.gov/ct2/show/NCT04331171


title: Research trends on bats in China: A twenty-first century review

text: In this century, China has sustained unparalleled economic development, leading to exponentially growing investments in scientific research. Yet, the demand for research-funding is large and tracing the current knowledge is a key step to define priority research topics. In this same span, studies on bats in China have uncovered an overlooked diversity and revealed novelties in bats’ evolutionary history and life-history aspects. All this 21st-century knowledge, however, is scattered and a large part is concealed from most of the international scientific community in Mandarin-language articles. Here, we summarize the post-millennium (2000–2017) research on bats in China and point out trends and future directions based on neglected topics, groups, and regions. In addition, we provide an up-to-date list of bat species in China. We retrieved 594 publications related to bats in China, nearly half were written in Mandarin. At least 147 bat species are present in China, which places it among the most bat-rich countries in the world. There was a significant positive trend on the number of publications, from 12.5 annual average in 2000–2005 to 46.5 in recent years, reflecting the Chinese economic-scientific development in this century. We found marked taxonomic and spatial biases. Half of the studies in this century focused on Rhinolophus, Myotis, and Hipposideros, and the southern and eastern provinces were the most studied. Systematic/taxonomy and Ecology were the predominant topics post-millennium, whereas only 10 articles have clear conservation-driven goals. Our review shows that the majority of studies were focused on the least concern, cave-dweller species, and on bat-rich provinces. Future projects should address the effects of human-modified landscapes on bat community to define proper conservation actions. We discuss some priority actions and projects that will help to enhance bat protection in China.


title: A complex COVID-19 case with rheumatoid arthritis treated with tocilizumab

text: Recurrences of COVID-19 were observed in a patient with long-term usage of hydroxychloroquine, leflunomide, and glucocorticoids due to her 30-year history of rheumatoid arthritis (RA). Tocilizumab was applied and intended to target both COVID-19 and RA. However, disease of this patient aggravated after usage of tocilizumab. After the discussion of a multiple disciplinary team (MDT) including rheumatologists, antimicrobial treatments were applied to target the potential opportunistic infections (Pneumocystis jirovecii and Aspergillus fumigatus), which were authenticated several days later via high throughput sequencing. As an important cytokine in immune responses, IL-6 can be a double-edged sword: interference in the IL-6-IL-6 receptor signaling may save patients from cytokine release storm (CRS), but can also weaken the anti-infectious immunity, particularly in rheumatic patients, who may have received a long-term treatment with immunosuppressive/modulatory agents. Thus, we suggest careful considerations before and close monitoring in the administration of tocilizumab in rheumatic patients with COVID-19. Besides tocilizumab, several disease-modifying antirheumatic drugs (DMARDs) can also be applied in the treatment of COVID-19. Therefore, we also reviewed and discussed the application of these DMARDs in COVID-19 condition. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10067-020-05234-w) contains supplementary material, which is available to authorized users.


Novel Coronavirus (COVID-19): Leveraging Telemedicine to Optimize Care While Minimizing Exposures and Viral Transmission


title: A Strategic Vaccine Facility for the UK

text: This paper describes a proposed Strategic Vaccine Facility (SVF) to provide a capability to the UK to deal with new and emerging disease threats. It would underpin the vaccine manufacturing industry by developing expertise and technology to enable rapid manufacture of small batches of vaccines for emergency use against agents, such as bioterrorist agents and emerging diseases. It would have a rare ability to work with dangerous pathogens under containment, allowing the production of inactivated and live vaccines, which would be difficult in a conventional plant. The facility's output will include vaccine candidates and manufacturing protocols for transfer to industry, small vaccine batches for emergency use or clinical trials, and vaccine reference standards. It would also be available for manufacturing small batches of experimental and public health vaccines for the UK and the developing world, allowing clinical trials to be undertaken against key diseases.


title: Adequacy of public health communications on H7N9 and MERS in Singapore: insights from a community based cross-sectional study

text: BACKGROUND: Singapore remains vulnerable to worldwide epidemics due to high air traffic with other countries This study aims to measure the public’s awareness of the Middle East Respiratory Syndrome (MERS) and Avian Influenza A (H7N9), identify population groups who are uninformed or misinformed about the diseases, understand their choice of outbreak information source, and assess the effectiveness of communication channels in Singapore. METHODS: A cross-sectional study, comprising of face-to-face interviews, was conducted between June and December 2013 to assess the public’s awareness and knowledge of MERS and H7N9, including their choice of information source. Respondents were randomly selected and recruited from 3 existing cohort studies. An opportunistic sampling approach was also used to recruit new participants or members in the same household through referrals from existing participants. RESULTS: Out of 2969 participants, 53.2% and 79.4% were not aware of H7N9 and MERS respectively. Participants who were older and better educated were most likely to hear about the diseases. The mean total knowledge score was 9.2 (S.D ± 2.3) out of 20, and 5.9 (S.D ± 1.2) out of 10 for H7N9 and MERS respectively. Participants who were Chinese, more educated and older had better knowledge of the diseases. Television and radio were the primary sources of outbreak information regardless of socio-demographic factors. CONCLUSION: Heightening education of infectious outbreaks through appropriate media to the young and less educated could increase awareness.


title: Middle East Respiratory Syndrome Coronavirus during Pregnancy, Abu Dhabi, United Arab Emirates, 2013

text: As of June 19, 2015, the World Health Organization had received 1,338 notifications of laboratory-confirmed infection with Middle East respiratory syndrome coronavirus (MERS-CoV). Little is known about the course of or treatment for MERS-CoV in pregnant women. We report a fatal case of MERS-CoV in a pregnant woman administered combination ribavirin–peginterferon-α therapy.


title: Seasonality of Suicidal Behavior

text: A seasonal suicide peak in spring is highly replicated, but its specific cause is unknown. We reviewed the literature on suicide risk factors which can be associated with seasonal variation of suicide rates, assessing published articles from 1979 to 2011. Such risk factors include environmental determinants, including physical, chemical, and biological factors. We also summarized the influence of potential demographic and clinical characteristics such as age, gender, month of birth, socioeconomic status, methods of prior suicide attempt, and comorbid psychiatric and medical diseases. Comprehensive evaluation of risk factors which could be linked to the seasonal variation in suicide is important, not only to identify the major driving force for the seasonality of suicide, but also could lead to better suicide prevention in general.


title: Detection of Influenza Virus Infection Using Two PCR Methods

text: Rapid, accurate, and cost-effective methods to identify the cause of respiratory tract infections are needed to maximize clinical benefit. Outpatients with acute respiratory illness were tested for influenza using a singleplex reverse transcriptase polymerase chain reaction (SRT-PCR) method. A multiplex RT-PCR (MRT-PCR) method tested for influenza and 17 other viruses and was compared with SRT-PCR using chi-square tests. Among 935 patients, 335 (36%) tested positive for influenza A and influenza B using SRT-PCR. Using MRT-PCR, 320 (34.2%) tested positive for influenza A and influenza B. This study supports MRT-PCR as a comparable method for detecting influenza among patients seeking outpatient care for acute respiratory illnesses.


title: Directed Evolution of a Yeast-Displayed HIV-1 SOSIP gp140 Spike Protein toward Improved Expression and Affinity for Conformational Antibodies

text: Design of an envelope-based immunogen capable of inducing a broadly neutralizing antibody response is thought to be key to the development of a protective HIV-1 vaccine. However, the broad diversity of viral variants and a limited ability to produce native envelope have hampered such design efforts. Here we describe adaptation of the yeast display system and use of a combinatorial protein engineering approach to permit directed evolution of HIV envelope variants. Because the intrinsic instability and complexity of this trimeric glycoprotein has greatly impeded the development of immunogens that properly represent the structure of native envelope, this platform addresses an essential need for methodologies with the capacity to rapidly engineer HIV spike proteins towards improved homogeneity, stability, and presentation of neutralizing epitopes. We report for the first time the display of a designed SOSIP gp140 on yeast, and the in vitro evolution of derivatives with greatly improved expression and binding to conformation-dependent antibodies. These efforts represent an initial and critical step toward the ability to rapidly engineer HIV-1 envelope immunogens via directed evolution.


title: Binding affinities of 438 HLA proteins to complete proteomes of seven pandemic viruses and distributions of strongest and weakest HLA peptide binders in populations worldwide

text: We report detailed peptide‐binding affinities between 438 HLA Class I and Class II proteins and complete proteomes of seven pandemic human viruses, including coronaviruses, influenza viruses and HIV‐1. We contrast these affinities with HLA allele frequencies across hundreds of human populations worldwide. Statistical modelling shows that peptide‐binding affinities classified into four distinct categories depend on the HLA locus but that the type of virus is only a weak predictor, except in the case of HIV‐1. Among the strong HLA binders (IC(50) ≤ 50), we uncovered 16 alleles (the top ones being A*02:02, B*15:03 and DRB1*01:02) binding more than 1% of peptides derived from all viruses, 9 (top ones including HLA‐A*68:01, B*15:25, C*03:02 and DRB1*07:01) binding all viruses except HIV‐1, and 15 (top ones A*02:01 and C*14:02) only binding coronaviruses. The frequencies of strongest and weakest HLA peptide binders differ significantly among populations from different geographic regions. In particular, Indigenous peoples of America show both higher frequencies of strongest and lower frequencies of weakest HLA binders. As many HLA proteins are found to be strong binders of peptides derived from distinct viral families, and are hence promiscuous (or generalist), we discuss this result in relation to possible signatures of natural selection on HLA promiscuous alleles due to past pathogenic infections. Our findings are highly relevant for both evolutionary genetics and the development of vaccine therapies. However they should not lead to forget that individual resistance and vulnerability to diseases go beyond the sole HLA allelic affinity and depend on multiple, complex and often unknown biological, environmental and other variables.