title: Severe COVID-19, Another Piece in the Puzzle of the Hyperferritinemic Syndrome. An Immunomodulatory Perspective to Alleviate the Storm

text: The coronavirus disease 2019 (COVID-19), an acute respiratory disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has been declared as a worldwide public health emergency. Interestingly, severe COVID-19 is characterized by fever, hyperferritinemia, and a hyper-inflammatory process with a massive release of pro-inflammatory cytokines, which may be responsible for the high rate of mortality. These findings may advocate for a similarity between severe COVID-19 and some challenging rheumatic diseases, such as adult onset Still's disease, secondary hemophagocytic lymphohistiocytosis, and catastrophic anti-phospholipid syndrome, which have been included in the “hyperferritinemic syndrome” category. Furthermore, as performed in these hyper-inflammatory states, severe COVID-19 may benefit from immunomodulatory therapies.


title: Prostasomes: Their Characterisation: Implications for Human Reproduction: Prostasomes and Human Reproduction

text: The prostate is a principal accessory genital gland that is vital for normal fertility. Epithelial cells lining the prostate acini release in a defined fashion (exocytosis) organellar nanosized structures named prostasomes. They are involved in the protection of sperm cells against immune response in the female reproductive tract by modulating the complement system and by inhibiting monocyte and neutrophil phagocytosis and lymphocyte proliferation. The immunomodulatory function most probably involves small non-coding RNAs present in prostasomes. Prostasomes have also been proposed to regulate the timing of sperm cell capacitation and induction of the acrosome reaction, since they are rich in various transferable bioactive molecules (e.g. receptors and enzymes) that promote the fertilising ability of sperm cells. Antigenicity of sperm cells has been well documented and implicated in involuntary immunological infertility of human couples, and antisperm antibodies (ASA) occur in several body fluids. The propensity of sperm cells to carry attached prostasomes suggests that they are a new category of sperm antigens. Circulating human ASA recognise prostasomes, and among 12 identified prostasomal antigens, prolactin- inducible protein (95 %) and clusterin (85 %) were immunodominant at the expense of the other 10 that were sporadically occurring.


Sedation of Mechanically Ventilated COVID-19 Patients: Challenges and Special Considerations


title: Virological and clinical cure in COVID‐19 patients treated with hydroxychloroquine: A systematic review and meta‐analysis

text: Following the demonstration of the efficacy of hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 in vitro, many trials started to evaluate its efficacy in clinical settings. However, no systematic review and meta‐analysis have addressed the issue of the safety and efficacy of hydroxychloroquine (HCQ) in coronavirus disease 2019. We conducted a systematic review and meta‐analysis with the objectives of evaluation of safety and efficacy of HCQ alone or in combination in terms of “time to clinical cure,” “virological cure,” “death or clinical worsening of disease,” “radiological progression,” and safety. RevMan was used for meta‐analysis. We searched 16 literature databases out of which seven studies (n = 1358) were included in the systematic review. In terms of clinical cure, two studies reported possible benefit in “time to body temperature normalization” and one study reported less “cough days” in the HCQ arm. Treatment with HCQ resulted in less number of cases showing the radiological progression of lung disease (odds ratio [OR], 0.31, 95% confidence interval [CI], 0.11‐0.9). No difference was observed in virological cure (OR, 2.37, 95% CI, 0.13‐44.53), death or clinical worsening of disease (OR, 1.37, 95% CI, 1.37‐21.97), and safety (OR, 2.19, 95% CI, 0.59‐8.18), when compared with the control/conventional treatment. Five studies reported either the safety or efficacy of HCQ + azithromycin. Although seems safe and effective, more data are required for a definitive conclusion. HCQ seems to be promising in terms of less number of cases with radiological progression with a comparable safety profile to control/conventional treatment. We need more data to come to a definite conclusion.


Pandemic airway management: A cognitive aid to increase safety and team cohesion during intubation, donning, and doffing


Changes in Care Delivery for Patients with Heart Failure During the COVID-19 Pandemic: Results of a Multicenter Survey


title: Anesthetic concerns for pediatric patients in the era of COVID‐19

text: After a novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), was reported in China in December 2019, the disease quickly reached pandemic level. On January 30, 2020, the World Health Organization (WHO) declared that the SARS‐CoV‐2 outbreak constituted a Public Health Emergency of International Concern. The caseload has increased exponentially, with WHO reporting 182 000 global cases by March 17, 2020, and over 2.6 million by 23 April. The clinical situation is complex, with children presenting different clinical features compared to adults. Several articles with recommendations on the anesthetic management of adult patients with COVID‐19 have been published, but no specific recommendations for pediatric anesthesiologists have been made yet. This article addresses specific concerns for the anesthetic management of the pediatric population with COVID‐19.


title: A community study of clinical traits and risk factors for human metapneumovirus and respiratory syncytial virus infection during the first year of life

text: Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are important respiratory pathogens with similar symptomatology. The aim of this prospective birth cohort study was to identify risk factors for an hMPV or RSV infection during the first year of life in unselected healthy children. We followed 217 children from birth to 1 year of age. Nasal swabs and symptom diaries were collected monthly. Anti-hMPV and anti-RSV IgG antibodies by age 1 year were detected by ELISA, and nasal swabs were analysed for hMPV and RSV by RT-PCR. Logistic regression was used for risk factor analysis. Anti-hMPV IgG was found in 38 children (17.5%), and anti-RSV IgG in 172 children (79%). Risk factors for being anti-hMPV IgG-positive were: (1) being born in the spring (OR = 2.36; 95% CI:1.06–5.27), and (2) having older siblings (OR = 3.82; 95% CI:1.75–8.34). Risk factors for being anti-RSV IgG-positive were: (1) gestational age <38 weeks (OR = 3.39; 95% CI:1.42–8.05), (2) increasing paternal age (OR = 1.85 per 5 yrs; 95% CI:1.28–2.68), and (3) wall-to-wall carpeting (OR = 3.15; 95% CI:1.29–7.68). Being born in the spring was associated with decreased odds of being anti-RSV IgG-positive (OR = 0.27, 95% CI:0.09–0.85). Risk factors for RSV hospitalisation (n = 11) were: (1) older siblings (OR = 4.49; 95% CI: 1.08–18.73) and (2) smoking in the household (OR = 5.06; 95% CI: 1.36–18.76). Exclusive breastfeeding for the first 14 days of life protected against hospitalisation (OR = 0.21; 95% CI:0.06–0.79). In conclusion, this study identifies risk factors for mild and asymptomatic hMPV infections in infancy.


Developing Bioinformatic Resources for Coronaviruses


title: MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity

text: Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of zoonotic infection. Although MERS-CoV infection is ubiquitous in dromedaries across Africa as well as in the Arabian Peninsula, zoonotic disease appears confined to the Arabian Peninsula. MERS-CoVs from Africa have hitherto been poorly studied. We genetically and phenotypically characterized MERS-CoV from dromedaries sampled in Morocco, Burkina Faso, Nigeria, and Ethiopia. Viruses from Africa (clade C) are phylogenetically distinct from contemporary viruses from the Arabian Peninsula (clades A and B) but remain antigenically similar in microneutralization tests. Viruses from West (Nigeria, Burkina Faso) and North (Morocco) Africa form a subclade, C1, that shares clade-defining genetic signatures including deletions in the accessory gene ORF4b. Compared with human and camel MERS-CoV from Saudi Arabia, virus isolates from Burkina Faso (BF785) and Nigeria (Nig1657) had lower virus replication competence in Calu-3 cells and in ex vivo cultures of human bronchus and lung. BF785 replicated to lower titer in lungs of human DPP4-transduced mice. A reverse genetics-derived recombinant MERS-CoV (EMC) lacking ORF4b elicited higher type I and III IFN responses than the isogenic EMC virus in Calu-3 cells. However, ORF4b deletions may not be the major determinant of the reduced replication competence of BF785 and Nig1657. Genetic and phenotypic differences in West African viruses may be relevant to zoonotic potential. There is an urgent need for studies of MERS-CoV at the animal–human interface.


title: Time Course of Lung Changes On Chest CT During Recovery From 2019 Novel Coronavirus (COVID-19) Pneumonia

text: BACKGROUND: Chest CT is used to assess the severity of lung involvement in COVID-19 pneumonia. PURPOSE: To determine the change in chest CT findings associated with COVID-19 pneumonia from initial diagnosis until patient recovery. MATERIALS AND METHODS: This retrospective review included patients with RT-PCR confirmed COVID-19 infection presenting between 12 January 2020 to 6 February 2020. Patients with severe respiratory distress and/ or oxygen requirement at any time during the disease course were excluded. Repeat Chest CT was obtained at approximately 4 day intervals. The total CT score was the sum of lung involvement (5 lobes, score 1-5 for each lobe, range, 0 none, 25 maximum) was determined. RESULTS: Twenty one patients (6 males and 15 females, age 25-63 years) with confirmed COVID-19 pneumonia were evaluated. These patients under went a total of 82 pulmonary CT scans with a mean interval of 4±1 days (range: 1-8 days). All patients were discharged after a mean hospitalized period of 17±4 days (range: 11-26 days). Maximum lung involved peaked at approximately 10 days (with the calculated total CT score of 6) from the onset of initial symptoms (R2=0.25), p<0.001). Based on quartiles of patients from day 0 to day 26 involvement, 4 stages of lung CT were defined: Stage 1 (0-4 days): ground glass opacities (GGO) in 18/24 (75%) patients with the total CT score of 2±2; (2)Stage-2 (5-8d days): increased crazy-paving pattern 9/17 patients (53%) with a increase in total CT score (6±4, p=0.002); (3) Stage-3 (9-13days): consolidation 19/21 (91%) patients with the peak of total CT score (7±4); (4) Stage-4 (≥14 days): gradual resolution of consolidation 15/20 (75%) patients with a decreased total CT score (6±4) without crazy-paving pattern. CONCLUSION: In patients recovering from COVID-19 pneumonia (without severe respiratory distress during the disease course), lung abnormalities on chest CT showed greatest severity approximately 10 days after initial onset of symptoms.


Corrigendum to ‘COVID-19 in forensic medicine unit personnel: Observation from Thailand’ Journal of Forensic and Legal Medicine, Volume 72 (May 2020) Article Number: 101964


title: A parainfluenza-3 outbreak in a SCT unit: sepsis with multi-organ failure and multiple co-pathogens are associated with increased mortality

text: The estimated frequency of parainfluenza virus 3 (PIV-3) infections following haematopoietic SCT (HSCT) is 2–7%, whereas reported mortality ranges from 18 to 33%. We report a retrospective outcome analysis following an outbreak of PIV-3 infection in our transplant unit. A total of 16 HSCT patients developed PIV-3 infection. All patients had upper respiratory tract infection, whereas lower respiratory tract infection occurred in 8 patients. Overall, 13 patients were treated with aerosolised Ribavirin (2 g t.d.s. for 5 days) and i.v. Ig (0.5 g/kg) as per standard protocol. One patient refused treatment, whereas two patients with full immune reconstitution were not treated. Overall mortality was 62.5%. Sepsis with multi-organ failure and the presence of pulmonary co-pathogens were both significantly associated with PIV-3-related mortality. Our series confirms that high mortality is associated with PIV-3 infection in HSCT recipients. In patients who develop PIV-3 infection, despite strict enforcement of infection control policies, the best strategy might be careful risk assessment, with effective broad-spectrum anti-microbials in those who are at risk of secondary infection.


title: Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection

text: Influenza A virus (IAV) causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection.


title: The SARS-CoV-2 Vaccine Pipeline: an Overview

text: PURPOSE OF REVIEW: The goal of this review is to provide a timely overview on efforts to develop a vaccine for the 2019 novel coronavirus SARS-CoV-2, the causative agent of coronavirus disease (COVID-19). RECENT FINDINGS: Previous research efforts to develop a severe acute respiratory syndrome coronavirus (SARS-CoV) vaccine in the years following the 2003 pandemic have opened the door for investigators to design vaccine concepts and approaches for the COVID-19 epidemic in China. Both SARS-CoV and SARS-CoV-2 exhibit a high degree of genetic similarity and bind to the same host cell ACE2 receptor. Based on previous experience with SARS-CoV vaccines, it is expected that all COVID-19 vaccines will require careful safety evaluations for immunopotentiation that could lead to increased infectivity or eosinophilic infiltration. Besides this, a COVID-19 vaccine target product profile must address vaccinating at-risk human populations including frontline healthcare workers, individuals over the age of 60, and those with underlying and debilitating chronic conditions. Among the vaccine technologies under evaluation are whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines. SUMMARY: Each current vaccine strategy has distinct advantages and disadvantages. Therefore, it is paramount that multiple strategies be advanced quickly and then evaluated for safety and efficacy. Ultimately, the safety studies to minimize undesired immunopotentiation will become the most significant bottleneck in terms of time.


title: Domain-based asymmetry in expectations of the future

text: Abstract We examine how prior outcomes can influence expectations about unrelated future events. Consistent with the affect literature, we first predict that prior outcomes will yield more optimistic expectations when the outcomes are positively, rather than negatively, valenced. We then predict that the impact of prior outcomes will depend on not only the valence, but also the domain of prior outcomes. Specifically, we draw from Prospect theory to predict that the impact of prior outcomes on future expectations will be greater in the domain of losses than in the domain of gains. Two lottery-based experiments demonstrate that this effect is robust across different starting and ending wealth states, and a third experiment shows that these differences in expectations also translate into differences in risk preferences.


title: Analysis of the swine tracheobronchial lymph node transcriptomic response to infection with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus

text: BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen of swine worldwide. Emergence in 2006 of a novel highly pathogenic PRRSV (HP-PRRSV) isolate in China necessitated a comparative investigation into the host transcriptome response in tracheobronchial lymph nodes (TBLN) 13 days post-infection with HP-PRRSV rJXwn06, PRRSV strain VR-2332 or sham inocula. RNA from each was prepared for next-generation sequencing. Amplified library constructs were directly sequenced and a list of sequence transcripts and counts was generated using an RNAseq analysis pipeline to determine differential gene expression. Transcripts were annotated and relative abundance was calculated based upon the number of times a given transcript was represented in the library. RESULTS: Major changes in transcript abundance occurred in response to infection with either PRRSV strain, each with over 630 differentially expressed transcripts. The largest increase in transcript level for either virus versus sham-inoculated controls were three serum amyloid A2 acute-phase isoforms. However, the degree of up or down-regulation of transcripts following infection with HP-PRRSV rJXwn06 was greater than transcript changes observed with US PRRSV VR-2332. Also, of 632 significantly altered transcripts within the HP-PRRSV rJXwn06 library 55 were up-regulated and 69 were down-regulated more than 3-fold, whilst in the US PRRSV VR-2332 library only 4 transcripts were up-regulated and 116 were down-regulated more than 3-fold. CONCLUSIONS: The magnitude of differentially expressed gene profiles detected in HP-PRRSV rJXwn06 infected pigs as compared to VR-2332 infected pigs was consistent with the increased pathogenicity of the HP-PRRSV in vivo.


title: Gap between tourism planning and implementation: A case of China

text: Abstract In tourism literature, a phenomenon is identified, and considered ubiquitous in planning exercise. Namely, a gap occurs between planning and implementation once the planned approach to tourism development is adopted. Such a phenomenon is not rare to find in China, where tourism has become increasingly important for the country's economy. This paper presents a research that attempts to examine the causes of the gap in a Chinese context, in order to offer insights about what possible countermeasures should be sought. A case study is adopted for the examination which focuses on the 3-year implementation of 2001–2020 Guniujiang Guanyintang Tourism Development Master Plan. These seven major causes are detected: flaws of master planning, planner's inadequate background survey and analysis, planner's inaccurate anticipation, planner's lack of practical experience, practitioner's misunderstanding, divergence of views between practitioner and planner, pitfalls of private investment and imbalance of development between regions of China.


title: Les principales maladies du porc

text: Résumé Plusieurs pathologies autrefois mortelles au sein des élevages porcins ont disparu de notre territoire, mais de nombreuses maladies polysystémiques subsistent. Si l’antibiothérapie s’avère parfois efficace, la vaccination permet de prévenir un certain nombre de pathologies alors qu’il n’existe aucun traitement préventif ni curatif pour d’autres. Par ailleurs, tous les organes du porc sont susceptibles d’être la cible d’agents pathogènes. Là encore, des vaccins et des traitements antibiotiques sont disponibles. Summary Several pathologies which were once mortal within pig farms have disappeared from our territory, numerous polysystemic diseases remain. If antibiotherapy is sometimes effective, vaccination can prevent a certain number of pathologies while there is no preventive of curative treatment for others. Moreover, all the pig's organs are susceptible to being targeted by pathogenic agents. Here again, vaccines and antibiotic treatments are available.


title: Viral-bacterial synergy in otitis media: Implications for management

text: Despite the extensive use of broad-spectrum antibiotics, poor clinical response to the treatment of acute otitis media is common. Evidence derived from numerous studies during the past two decades supports a crucial role for respiratory viruses in the etiology and pathogenesis of acute otitis media, and recent studies indicate that viruses may also have a profound adverse effect on the resolution of this disease. Viruses seem to interact with bacteria and enhance the local inflammatory process in the middle ear. Effective adjuvant therapies are needed to improve outcome in children with otitis media. Increasing knowledge of the role of viruses, viral-bacterial interaction, and host inflammatory mechanisms in otitis media may lead to major improvements in the management of this disease.


title: Epidemic Assistance by the Centers for Disease Control and Prevention: Role of the Epidemic Intelligence Service, 1946–2005

text: Since 1946, the Centers for Disease Control and Prevention has responded to urgent requests from US states, federal agencies, and international organizations through epidemic-assistance investigations (Epi-Aids). The authors describe the first 60 years of Epi-Aids, breadth of problems addressed, evolution of methodologies, scope of activities, and impact of investigations on population health. They reviewed Epi-Aid reports and EIS Bulletins, contacted current and former Epidemic Intelligence Service staff, and systematically searched the PubMed and Web of Science databases. They abstracted information on dates, location, staff involved, health problems, methods, and impacts of investigations according to a preplanned protocol. They assessed the methods presented as well as the quality of reports. During 1946–2005, a total of 4,484 investigations of health events were initiated by 2,815 Epidemic Intelligence Service officers. In the early years, the majority were in response to infectious agents, although environmental problems emerged. Investigations in subsequent years focused on occupational conditions, birth defects, reproductive health, tobacco use, cancer, violence, legal debate, and terrorism. These Epi-Aids heralded expansion of the agency's mission and presented new methods in statistics and epidemiology. Recommendations from Epi-Aids led to policy implementation, evaluation, or modification. Epi-Aids provide the Centers for Disease Control and Prevention with the agility to respond rapidly to public health crises.


title: Early Vaccination of Chickens Induces Suboptimal Immunity Against Infectious Bronchitis Virus.

text: Infectious bronchitis virus (IBV) is highly prevalent in broiler chickens despite extensive vaccination commonly conducted early after hatch. The effects of early vaccination on immune responses were further investigated in chickens primed at increasing ages, followed by booster vaccination with an attenuated Arkansas (Ark) Delmarva Poultry Industry-type vaccine. Results show that vaccination on day 1 of age elicits significantly lower systemic and mucosal antibody responses compared with vaccination at later time points in the life of the chicken. The increase of IBV antibodies in serum from secondary responses after booster vaccination was more dramatic and significantly higher when measured by an Ark spike subunit 1 protein ELISA compared with measuring by non-Ark serotype whole-virus ELISA, which underlines the immunogenic importance of the virus spike at inducing antibodies. However, the levels achieved following boosting did not differ significantly between ages of priming. Thus, it seems that the booster vaccination mitigated the differences detected after prime immunization. In contrast to the continued rise of systemic antibodies after booster vaccination, the levels of mucosal IBV-specific immunoglobulin A decreased after booster vaccination. The recruitment or expansion of cluster of differentiation (CD)4+, CD8+, and CD4+/CD8+ T-cell populations in different immune effector sites was increased with age, but remained unaltered by IBV vaccination. In contrast, peripheral blood CD4+ cells showed a significant increase in IBV-vaccinated chickens compared with nonvaccinated age-matched controls both after primary and booster immunization. The results of the current study confirm that IBV vaccination on the day of hatch induces suboptimal IBV immune responses both in the systemic and mucosal compartments. This routine practice may be contributing to the immunologic escape of the virus and increased persistence of vaccine virus in vaccinated chickens. However, booster vaccination seems to overcome poor initial responses.


title: Vulnerabilities in coronavirus glycan shields despite extensive glycosylation

text: Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential. Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein. Coronavirus S proteins are extensively glycosylated, encoding around 66–87 N-linked glycosylation sites per trimeric spike. Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs. We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes. Overall, our data reveal how organisation of glycosylation across class I viral fusion proteins influence not only individual glycan compositions but also the immunological pressure across the protein surface.


title: Rationing Limited Health Care Resources in the COVID‐19 Era and Beyond: Ethical Considerations Regarding Older Adults

text: COVID‐19 continues to impact older adults disproportionately with respect to serious consequences ranging from severe illness and hospitalization to increased mortality risk. Concurrently, concerns about potential shortages of healthcare professionals and health supplies to address these issues have focused attention on how these resources are ultimately allocated and used. Some strategies, for example, misguidedly use age as an arbitrary criterion, which disfavors older adults in resource allocation decisions. This is a companion manuscript to the American Geriatrics Society (AGS) position statement, “Resource Allocation Strategies and Age‐Related Considerations in the COVID‐19 Era and Beyond.” It is intended to inform stakeholders including hospitals, health systems, and policymakers about ethical considerations that should be considered when developing strategies for allocation of scarce resources during an emergency involving older adults. This review presents the legal and ethical background for the position statement and discusses the following issues that informed the development of the AGS positions: (1) age as a determining factor; (2) age as a tiebreaker; (3) criteria with a differential impact on older adults; (4) individual choices and advance directives; (5) racial/ethnic disparities and resource allocation; and (6) scoring systems and their impact on older adults. It also considers the role of advance directives as expressions of individual preferences in pandemics.


title: Chemical Modifications of Nucleic Acid Aptamers for Therapeutic Purposes

text: Nucleic acid aptamers have minimal immunogenicity, high chemical synthesis production, low cost and high chemical stability when compared with antibodies. However, the susceptibility to nuclease degradation, rapid excretion through renal filtration and insufficient binding affinity hindered their development as drug candidates for therapeutic applications. In this review, we will discuss methods to conquer these challenges and highlight recent developments of chemical modifications and technological advances that may enable early aptamers to be translated into clinical therapeutics.


title: Development of Point-of-Care Biosensors for COVID-19

text: Coronavirus disease 2019 (COVID-19) outbreak has become a global pandemic. The deleterious effects of coronavirus have prompted the development of diagnostic tools to manage the spread of disease. While conventional technologies such as quantitative real time polymerase chain reaction (qRT-PCR) have been broadly used to detect COVID-19, they are time-consuming, labor-intensive and are unavailable in remote settings. Point-of-care (POC) biosensors, including chip-based and paper-based biosensors are typically low-cost and user-friendly, which offer tremendous potential for rapid medical diagnosis. This mini review article discusses the recent advances in POC biosensors for COVID-19. First, the development of POC biosensors which are made of polydimethylsiloxane (PDMS), papers, and other flexible materials such as textile, film, and carbon nanosheets are reviewed. The advantages of each biosensors along with the commercially available COVID-19 biosensors are highlighted. Lastly, the existing challenges and future perspectives of developing robust POC biosensors to rapidly identify and manage the spread of COVID-19 are briefly discussed.


title: Activation of the DNA Damage Response by RNA Viruses

text: RNA viruses are a genetically diverse group of pathogens that are responsible for some of the most prevalent and lethal human diseases. Numerous viruses introduce DNA damage and genetic instability in host cells during their lifecycles and some species also manipulate components of the DNA damage response (DDR), a complex and sophisticated series of cellular pathways that have evolved to detect and repair DNA lesions. Activation and manipulation of the DDR by DNA viruses has been extensively studied. It is apparent, however, that many RNA viruses can also induce significant DNA damage, even in cases where viral replication takes place exclusively in the cytoplasm. DNA damage can contribute to the pathogenesis of RNA viruses through the triggering of apoptosis, stimulation of inflammatory immune responses and the introduction of deleterious mutations that can increase the risk of tumorigenesis. In addition, activation of DDR pathways can contribute positively to replication of viral RNA genomes. Elucidation of the interactions between RNA viruses and the DDR has provided important insights into modulation of host cell functions by these pathogens. This review summarises the current literature regarding activation and manipulation of the DDR by several medically important RNA viruses.


Pricing vaccines and drugs in Europe: worth differentiating?


title: Combined analysis of cell growth and apoptosis-regulating proteins in HPVs associated anogenital tumors

text: BACKGROUND: The clinical course of human papillomavirus (HPV) associated with Bowenoid papulosis and condyloma acuminatum of anogenital tumors are still unknown. Here we evaluated molecules that are relevant to cellular proliferation and regulation of apoptosis in HPV associated anogenital tumors. METHODS: We investigated the levels of telomerase activity, and inhibitor of apoptosis proteins (IAPs) family (c-IAP1, c-IAP2, XIAP) and c-Myc mRNA expression levels in 20 specimens of Bowenoid papulosis and 36 specimens of condyloma acuminatum in anogenital areas. Overall, phosphorylated (p-) AKT, p-ribosomal protein S6 (S6) and p-4E-binding protein 1 (4EBP1) expression levels were examined by immunohistochemistry in anogenital tumors both with and without positive telomerase activity. RESULTS: Positive telomerase activity was detected in 41.7% of Bowenoid papulosis and 27.3% of condyloma acuminatum compared to normal skin (p < 0.001). In contrast, the expression levels of Bowenoid papulosis indicated that c-IAP1, c-IAP2 and XIAP mRNA were significantly upregulated compared to those in both condyloma acuminatum samples (p < 0.001, p < 0.001, p = 0.022, respectively) and normal skin (p < 0.001, p = 0.002, p = 0.034, respectively). Overall, 30% of Bowenoid papulosis with high risk HPV strongly promoted IAPs family and c-Myc but condyloma acuminatum did not significantly activate those genes. Immunohistochemically, p-Akt and p-S6 expressions were associated with positive telomerase activity but not with p-4EBP1 expression. CONCLUSION: Combined analysis of the IAPs family, c-Myc mRNA expression, telomerase activity levels and p-Akt/p-S6 expressions may provide clinically relevant molecular markers in HPV associated anogenital tumors.


title: Earth observation for public health: Biodiversity change and emerging disease surveillance

text: Abstract One Health is an emerging concept in the health sciences that approaches human, animal and environmental health from a single framework. This policy approach is grounded in the knowledge that approximately 70 percent of emerging diseases in humans originate from other species, and that this species crossover is precipitated by stresses to environmental systems such as habitat change and biodiversity loss. Remote sensing tools apply well to this approach due to the multitude of variables that can be measured across borders in real-time. This paper explores the challenges and opportunities of using satellite remote sensing to monitor biodiversity loss in real time, with a goal of predictive surveillance for emerging disease events. Key findings include that (1) certain emerging disease events are preceded by biodiversity changes that can be observed from space; (2) refining quantitative assessments of biodiversity loss is a critical next step; and (3) biodiversity loss as observed from space merits inclusion in emerging disease surveillance programs as a complement to in situ and epidemiological surveillance data.


title: Imaging features and mechanisms of novel coronavirus pneumonia (COVID-19): Study Protocol Clinical Trial (SPIRIT Compliant)

text: INTRODUCTION: A novel coronavirus, tentatively designated as 2019 Novel Coronavirus (2019-nCoV), now called severe acute respiratory syndrome coronavirus 2, emerged in Wuhan, China, at the end of 2019 and which continues to expand. On February 11, 2020, the World Health Organization (WHO) named the disease coronavirus disease 2019 (COVID-19). On February 28, WHO increased our assessment of the risk of spread and the risk of impact of COVID-19 to very high at a global level. The COVID-19 poses significant threats to international health. Computed tomography (CT) has been an important imaging modality in assisting in the diagnosis and management of patients withCOVID-19. Some retrospective imaging studies have reported chest CT findings of COVID-19 in the past 2 months, suggesting that several CT findings may be characteristic. To our knowledge, there has been no prospective multicentre imaging study of COVID-19 to date. We proposed a hypothesis: There are some specific CT features on Chest CT of COVID-19 patients. And the mechanism of these CT features is explicable based on pathological findings. OBJECTIVE: To investigate the specific CT features of COVID-19 and the formation mechanism of these CT features. METHOD: This study is a prospective multicenter observational study. We will recruit 100 patients with COVID-19 at 55 hospitals. All patients undergo chest CT examination with the same scan protocol. The distribution and morphology of lesions on chest CT, clinical data will be recorded. A number of patients will be pathologically examined after permission is granted. The data of these three aspects will be analyzed synthetically. DISCUSSION: This study will help us to identify the chest CT features of COVID-19 and its mechanism. ETHICS AND DISSEMINATION: This retrospective study was approved by the Biomedical Research Ethics Committee of West China Hospital of Sichuan University (No. 2020–140). Written informed consent will be obtained from all study participants prior to enrollment in the study. To protect privacy of participants, all private information were kept anonymous. The results will be published in a peer-reviewed journal and will be disseminated electronically and in print regardless of results.


title: China's model to combat the COVID-19 epidemic: a public health emergency governance approach

text: The outbreak of Coronavirus Disease 2019 (COVID-19) is of global health concern. It is a serious public health emergency for the entire world, threatening human life and public health security. To address the epidemic, it is necessary not only to take good prevention and treatment measures, but also to have effective and targeted public health emergency governance. That said, reports focusing on governance are scant. In this commentary, we summarize China’s model to combat the COVID-19 epidemic from a public health emergency governance approach. Stemmed from goals and values, a number of mechanisms are put forward, which include: a whole-of-government response and accountability, setting up a multi-sectoral cooperation platform, swiftly scaling up epidemic emergency capacity, whole-of-society actions with engagement of social organizations, and engaging citizens in the epidemic prevention and control. As the epidemic continues to evolve, other countries might learn from China to build their own, context-specific models for better outcomes.


title: First Case of 2019 Novel Coronavirus in the United States

text: An outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient’s initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.


title: Preparation for and organization during a major incident

text: Major incidents during the recent past have reinforced the value that the NHS and other agencies have invested into the comprehensive Emergency, Preparedness, Resilience and Response framework. This gives a detailed structure of the role of the NHS in any type of major incident from man-made disaster to pandemic flu. This has required preparation of communication, transport, security, military and healthcare systems. Also included is how the response to the incident is handled at a local level and for different levels of response. Examples of how this has played out are described. Specialist training at the higher and advanced level for trainees is established so that victims are triaged at the scene and received by consultants with appropriate training. Hospitals, ambulance services and intensive care units across the country can use networks to ensure not only rapid access to Major Trauma Centres but also to highly sophisticated skills when advanced life support is required. The NHS response to major incidents has been shown to be effective and successful.


Scoping the perplexing effect of the COVID pandemic in Nepal, and the appraisal for precautionary measures from its lurking aftermath


title: Repositioning salicylanilide anthelmintic drugs to treat adenovirus infections

text: The repositioning of drugs already approved by regulatory agencies for other indications is an emerging alternative for the development of new antimicrobial therapies. The repositioning process involves lower risks and costs than the de novo development of novel antimicrobial drugs. Currently, infections by adenovirus show a steady increment with a high clinical impact in immunosuppressed and immunocompetent patients. The lack of a safe and efficacious drug to treat these infections supports the search for new antiviral drugs. Here we evaluated the anti-adenovirus activity of niclosanide, oxyclozanide, and rafoxanide, three salicylanilide anthelmintic drugs. Also, we carried out the cytotoxicity evaluation and partial characterization of the mechanism of action of these drugs. The salicylanilide anthelmintic drugs showed significant anti-adenovirus activity at low micromolar concentrations with little cytotoxicity. Moreover, our mechanistic assays suggest differences in the way the drugs exert anti-adenovirus activity. Niclosamide and rafoxanide target transport of the HAdV particle from the endosome to the nuclear envelope, whilst oxyclozanide specifically targets adenovirus immediately early gene E1A transcription. Data suggests that the studied salicylanilide anthelmintic drugs could be suitable for further clinical evaluation for the development of new antiviral drugs to treat infections by adenovirus in immunosuppressed patients and in immunocompetent individuals with community-acquired pneumonia.


The COVID-19 MS Coalition—accelerating diagnostics, prognostics, and treatment


title: Recognizing Right Ventricular Dysfunction in COVID-19 Related Respiratory Illness

text: COVID-19, coronavirus, Right ventricular failure, Heart failure, Acute cor pulmonale, Shock, ARDS


title: An empirical analysis of the non-linear impacts of ICT-trade openness on renewable energy transition, energy efficiency, clean cooking fuel access and environmental sustainability in South Asia

text: Energy security and environmental sustainability have become an integral policy agenda worldwide whereby the global economic growth policies are being restructured to ensure the reliability of energy supply and safeguard environmental well-being as well. However, technological inefficiency is one of the major hindrances in attaining these over-arching goals. Hence, this paper probed into the non-linear impacts of ICT trade on the prospects of undergoing renewable energy transition, improving energy use efficiencies, enhancing access to cleaner cooking fuels, and mitigating carbon dioxide emissions across selected South Asian economies: Bangladesh, India, Pakistan, Sri Lanka, Nepal, and Maldives. The results from the econometric analyses reveal that ICT trade directly increases renewable energy consumption, enhances renewable energy shares, reduces intensity of energy use, facilitates adoption of cleaner cooking fuels, and reduces carbon-dioxide emissions. Moreover, ICT trade also indirectly mitigates carbon-dioxide emissions through boosting renewable energy consumption levels, improving energy efficiencies, and enhancing cleaner cooking fuel access. Hence, these results, in a nutshell, portray the significance of reducing the barriers to ICT trade with respect to ensuring energy security and environmental sustainability across South Asia. Therefore, it is ideal for the government to gradually lessen the trade barriers to boost the volumes of cross-border flows of green ICT commodities. Besides, it is also recommended to attract foreign direct investments for the potential development of the respective ICT sectors of the South Asian economies.


title: The prevalence, origin, and prevention of six human coronaviruses

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title: Virus hazards from food, water and other contaminated environments

text: Numerous viruses of human or animal origin can spread in the environment and infect people via water and food, mostly through ingestion and occasionally through skin contact. These viruses are released into the environment by various routes including water run-offs and aerosols. Furthermore, zoonotic viruses may infect humans exposed to contaminated surface waters. Foodstuffs of animal origin can be contaminated, and their consumption may cause human infection if the viruses are not inactivated during food processing. Molecular epidemiology and surveillance of environmental samples are necessary to elucidate the public health hazards associated with exposure to environmental viruses. Whereas monitoring of viral nucleic acids by PCR methods is relatively straightforward and well documented, detection of infectious virus particles is technically more demanding and not always possible (e.g. human norovirus or hepatitis E virus). The human pathogenic viruses that are most relevant in this context are nonenveloped and belong to the families of the Caliciviridae, Adenoviridae, Hepeviridae, Picornaviridae and Reoviridae. Sampling methods and strategies, first-choice detection methods and evaluation criteria are reviewed.


title: The 4 D’s of Pellagra and Progress

text: Nicotinamide homeostasis is a candidate common denominator to explain smooth transitions, whether demographic, epidemiological or economic. This ‘NAD world’, dependent on hydrogen-based energy, is not widely recognised as it is neither measured nor viewed from a sufficiently multi-genomic or historical perspective. Reviewing the importance of meat and nicotinamide balances during our co-evolution, recent history suggests that populations only modernise and age well with low fertility on a suitably balanced diet. Imbalances on the low meat side lead to an excess of infectious disease, short lives and boom-bust demographics. On the high side, meat has led to an excess of degenerative, allergic and metabolic disease and low fertility. A ‘Goldilocks’ diet derived from mixed and sustainable farming (preserving the topsoil) allows for high intellectual capital, height and good health with controlled population growth resulting in economic growth and prosperity. Implementing meat equity worldwide could lead to progress for future generations on ‘spaceship’ earth by establishing control over population quality, thermostat and biodiversity, if it is not already too late.


Self-harm and COVID-19 Pandemic: An emerging concern – A report of 2 cases from India


title: COVID-19’s disasters are perilous than Global Financial Crisis: A rumor or fact?

text: This investigation employed the Asymmetric Power GARCH model and found that COVID-19 substantially harms the US and Japan's market returns. Moreover, COVID-19 has influenced the variance of the US, Germany, and Italy's stock markets more than the Global Financial Crises (GFC). However, GFC indicated a more significant impact on the financial volatility of the Nikkei 225 index and SSEC than COVID-19. The study confirmed the leverage effect for the S&P 500, Nasdaq Composite Index, DAX 30, Nikkei 225, FTSE MIB, and SSEC. The analysis authenticated that the health crisis that befell due to COVID-19 have imperatively originated the financial crisis globally; however, the Asian markets still make available better prospects for portfolio optimization.


title: Anticipating the impact of the COVID-19 pandemic on TB patients and TB control programmes

text: The COVID-19 pandemic has currently overtaken every other health issue throughout the world. There are numerous ways in which this will impact existing public health issues. Here we reflect on the interactions between COVID-19 and tuberculosis (TB), which still ranks as the leading cause of death from a single infectious disease globally. There may be grave consequences for existing and undiagnosed TB patients globally, particularly in low and middle income countries (LMICs) where TB is endemic and health services poorly equipped. TB control programmes will be strained due to diversion of resources, and an inevitable loss of health system focus, such that some activities cannot or will not be prioritised. This is likely to lead to a reduction in quality of TB care and worse outcomes. Further, TB patients often have underlying co-morbidities and lung damage that may make them prone to more severe COVID-19. The symptoms of TB and COVID-19 can be similar, with for example cough and fever. Not only can this create diagnostic confusion, but it could worsen the stigmatization of TB patients especially in LMICs, given the fear of COVID-19. Children with TB are a vulnerable group especially likely to suffer as part of the “collateral damage”. There will be a confounding of symptoms and epidemiological data through co-infection, as happens already with TB–HIV, and this will require unpicking. Lessons for COVID-19 could be learned from the vast experience of running global TB control programmes, while the astonishingly rapid and relatively well co-ordinated response to COVID-19 demonstrates how existing programmes could be significantly improved.


title: Evaluation and application of reverse transcription loop‐mediated isothermal amplification for detection of noroviruses

text: A one‐step reverse transcription loop‐mediated isothermal amplification (RT‐LAMP) assay for the detection of norovirus (NV) was developed. In order to design primer sets for the detection of a wide range of NVs, NVs were categorized into three groups, that is, genogroup I (GI), prevalent GII, and minor GII; three sets of primers were developed for each group. Clinical specimens of patients suffering from enteric RNA viruses, such as NV, group A and C rotavirus, and sapovirus were examined using these primer sets. Various genotypes of NVs were detected in clinical specimens from patients infected with NV where no false positive reaction was observed with other enteric RNA viruses. Additionally, 88 samples of acute gastroenteritis outbreaks were analyzed by an RT‐LAMP assay and compared with the results of routine RT‐PCR. The results of the RT‐LAMP assay corresponded well to that of RT‐PCR. These findings suggest the practical application of the RT‐LAMP assay for the detection of NVs in clinical specimens. Consequently, the RT‐LAMP system and conventional detection kits (NVGI and NVGII detection kits; Eiken Chemical Co., Ltd., Japan) were compared. The detection rate of the prevalent and minor GII primer sets was similar to that of the conventional NVGII kit, while the detection rate of the GI primer set is different because it can detect several genotypes better than the conventional NVGI kit. This is an initial report that the RT‐LAMP system is able to detect NVs in clinical specimens within a wide range. J. Med. Virol. 79:326–334, 2007. © 2007 Wiley‐Liss, Inc.


title: 1 Tropical Lung Diseases

text: Abstract Lung disease is common in the tropics; lower respiratory tract infections are a major cause of mortality, especially in children under 5 years of age. The World Health Organization has launched strategies to tackle this killer of children. Infections, including tuberculosis and drug-resistant tuberculosis, find vulnerable hosts in the tropics where human immunodeficiency virus co-infection is widespread, especially in India and sub-Saharan Africa. Parasitic infections can cause pulmonary manifestations (e.g., pleural effusion and cavitary lesions). Blood and pulmonary eosinophilia are common in such infections. Non-communicable lung disease such as chronic obstructive pulmonary disease and lung cancer associated with tobacco use, contribute to mortality, particularly where there is poor access to health structures.


title: Mode of neutralization of lactate dehydrogenase-elevating virus by polyclonal and monoclonal antibodies

text: Neutralization of the infectivity of [(3)H]uridine-labeled lactate dehydrogenase-elevating virus (LDV) by polyclonal mouse or rabbit antibodies to the envelope glycoprotein of LDV, VP-3, or by neutralizing monoclonal antibodies (mAb) that recognize a different epitope on VP-3 than the polyclonal antibodies correlated with an increase in the sedimentation rate of LDV from 230 S to ≧270 S. Incubation of LDV with normal mouse plasma or nonneutralizing mAbs to LDV VP-3 had no effect on its sedimentation rate. Similarly, incubation of a neutralization escape variant of LDV with the mAb used in its selection had no effect on its sedimentation rate, whereas neutralization of this variant by polyclonal mouse or rabbit anti-VP 3 antibodies increased the sedimentation rate. Neutralization of LDV infectivity was only observed at high antibody/virion ratios and often was followed by loss of the viral RNA. The results suggest that neutralization of LDV infectivity results from binding of multiple antibody molecules that recognize specific epitopes on the viral envelope glycoprotein and ultimately leads to disintegration of the virions.


title: Student engagement in a public health initiative in response to COVID‐19

text: In face of the current pandemic, universities are closing worldwide. In Brazil, as elsewhere, academic activities have been suspended in response to the Ministry of Health's recommendations to socially distance. This created risk of suboptimally utilizing the great potential students have to contribute to the COVID-19 response.


title: The role of angiotensin-converting enzyme 2 in coronaviruses/influenza viruses and cardiovascular disease

text: Angiotensin-converting enzyme 2 (ACE2) has emerged as a key regulator of the renin–angiotensin system in cardiovascular (CV) disease and plays a pivotal role in infections by coronaviruses and influenza viruses. The present review is primarily focused on the findings to indicate the role of ACE2 in the relationship of coronaviruses and influenza viruses to CV disease. It is postulated that the risk of coronavirus or influenza virus infection is high, at least partly due to high ACE2 expression in populations with a high CV risk. Coronavirus and influenza virus vaccine usage in high CV risk populations could be a potential strategy to prevent both CV disease and coronavirus/influenza virus infections.


title: Free-floating carsharing users’ willingness-to-pay/accept for logistics management mechanisms

text: The spatio-temporal flexibility of free-floating carsharing (FFCS) fleets leads to vehicle stock imbalances across the network. One set of strategies for managing fleet distribution involves incentivising users to participate in relocating the vehicles. The objective of this study is to establish FFCS customers’ preferences for each of four incentivisation mechanisms: 1) vehicle delivery, 2) paid relocation, and 3–4) incentivisation for alternate vehicle pick-up and drop-off locations. Survey data (n = 311; collected Sept. 2017) from FFCS users in Vancouver and Washington D.C. are employed to quantify willingness-to-pay/accept (WTP/WTA) for these mechanisms. We find that a majority of respondents report positive attitudes (“definitely” or “possibly” willing to use) toward each of the four incentivisation mechanisms, with alternate drop-off the highest (57%) and paid relocation the lowest (40%). Regression analysis finds that user experiences using FFCS are generally stronger predictors of WTP/WTA than socio-demographic features, with (intuitively) the frequency of FFCS unavailability the strongest predictor. Age is the strongest socio-demographic predictor, with the WTP for vehicle delivery increasing and the size of required incentives for alternate pick-up/drop-off locations decreasing with age. Finally, we performed k-means cluster analysis of respondents based on the times-of-week that they report experiencing difficulty finding an available FFCS vehicle, and identified four distinct segments of users. However, we found generally weak relationships between WTP/WTA and the specific time-of-week periods that unavailability is experienced.


title: Genetic Manipulation of Human Intestinal Enteroids Demonstrates the Necessity of a Functional Fucosyltransferase 2 Gene for Secretor-Dependent Human Norovirus Infection

text: Human noroviruses (HuNoVs) are the leading cause of nonbacterial gastroenteritis worldwide. Histo-blood group antigen (HBGA) expression is an important susceptibility factor for HuNoV infection based on controlled human infection models and epidemiologic studies that show an association of secretor status with infection caused by several genotypes. The fucosyltransferase 2 gene (FUT2) affects HBGA expression in intestinal epithelial cells; secretors express a functional FUT2 enzyme, while nonsecretors lack this enzyme and are highly resistant to infection and gastroenteritis caused by many HuNoV strains. These epidemiologic associations are confirmed by infections in stem cell-derived human intestinal enteroid (HIE) cultures. GII.4 HuNoV does not replicate in HIE cultures derived from nonsecretor individuals, while HIEs from secretors are permissive to infection. However, whether FUT2 expression alone is critical for infection remains unproven, since routinely used secretor-positive transformed cell lines are resistant to HuNoV replication. To evaluate the role of FUT2 in HuNoV replication, we used CRISPR or overexpression to genetically manipulate FUT2 gene function to produce isogenic HIE lines with or without FUT2 expression. We show that FUT2 expression alone affects both HuNoV binding to the HIE cell surface and susceptibility to HuNoV infection. These findings indicate that initial binding to a molecule(s) glycosylated by FUT2 is critical for HuNoV infection and that the HuNoV receptor is present in nonsecretor HIEs. In addition to HuNoV studies, these isogenic HIE lines will be useful tools to study other enteric microbes where infection and/or disease outcome is associated with secretor status.


title: Virus detection by transmission electron microscopy: Still useful for diagnosis and a plus for biosafety

text: Transmission electron microscopy (TEM) is the only imaging technique allowing the direct visualization of viruses, due to its nanometer‐scale resolution. Between the 1960s and 1990s, TEM contributed to the discovery of many types of viruses and served as a diagnostic tool for identifying viruses directly in biological samples, either in suspension or in sections of tissues or mammalian cells grown in vitro in contact with clinical samples. The diagnosis of viral infections improved considerably during the 1990s, with the advent of highly sensitive techniques, such as enzyme‐linked immunosorbent assay (ELISA) and PCR, rendering TEM obsolete for this purpose. However, the last 20 years have demonstrated the utility of this technique in particular situations, due to its “catch‐all” nature, making diagnosis possible through visualization of the virus, without the need of prior assumptions about the infectious agent sought. Thus, in several major outbreaks in which molecular techniques failed to identify the infectious agent, TEM provided the answer. TEM is also still occasionally used in routine diagnosis to characterize infections not diagnosed by molecular assays. It is also used to check the microbiological safety of biological products. Many biopharmaceuticals are produced in animal cells that might contain little‐known, difficult‐to‐detect viruses. In this context, the “catch‐all” properties of TEM make it possible to document the presence of viruses or virus‐like particles in these products.


title: Conducting Exposure and Response Prevention Treatment for Contamination Fears During COVID-19: The Behavioral Immune System Impact on Clinician Approaches to Treatment

text: The coronavirus disease 2019 (COVID-19) pandemic sparked significant anxiety regarding viral rates and means of transmission. Heightened concerns about contamination have prompted new hygienic strategies to vigilantly guard against infection, including hand washing immediately after touching foreign objects or suspected contaminants. This has presented a critical challenge for the delivery of exposure and response prevention (ERP) therapy to individuals with contamination fears due to Obsessive Compulsive Disorder (OCD), as providers must manage not only their clients’ attitudes and reactions but their own as well. In this investigation, self-identified anxiety and OCD treatment specialists (N = 139) provided demographic information, including their anxiety and OCD caseloads, and completed measures related to intolerance of uncertainty (IUS-SF; Carlton et al., 2007), beliefs about exposure therapy (TBES; Deacon et al., 2013), and emotional reactions to physical sensations (The Chills; Maruskin et al., 2012). We tested the hypothesis that intolerance of uncertainty and activation of the behavioral immune system (BIS; Schaller & Park, 2011), a mechanism theoretically activated by the prominent emergence of pathogens to protect against illness would predict attitudes toward exposure. The Chills Scale was used to assess BIS activation, a broad assessment of vasoconstriction responses associated with different emotional reactions, and includes a subscale (coldness) that evaluates vasoconstriction associated with defense against pathogens. Both coldness and OCD caseload, but not anxiety caseload or subscales of intolerance of uncertainty, emerged as significant predictors of clinicians’ beliefs about exposure; increases in OCD caseload were also related to decreases in negative beliefs about exposure. Findings are useful in determining methods for aiding clinicians in developing effective approaches to contamination fears during and post-pandemic that include addressing their own BIS-related concerns and mapping out means for social behavioral norms associated with engaging in exposure treatment.


Health and safety considerations for hotel cleaners during Covid-19


title: Silibinin and SARS-CoV-2: Dual Targeting of Host Cytokine Storm and Virus Replication Machinery for Clinical Management of COVID-19 Patients.

text: COVID-19, the illness caused by infection with the novel coronavirus SARS-CoV-2, is a rapidly spreading global pandemic in urgent need of effective treatments. Here we present a comprehensive examination of the host- and virus-targeted functions of the flavonolignan silibinin, a potential drug candidate against COVID-19/SARS-CoV-2. As a direct inhibitor of STAT3-a master checkpoint regulator of inflammatory cytokine signaling and immune response-silibinin might be expected to phenotypically integrate the mechanisms of action of IL-6-targeted monoclonal antibodies and pan-JAK1/2 inhibitors to limit the cytokine storm and T-cell lymphopenia in the clinical setting of severe COVID-19. As a computationally predicted, remdesivir-like inhibitor of RNA-dependent RNA polymerase (RdRp)-the central component of the replication/transcription machinery of SARS-CoV-2-silibinin is expected to reduce viral load and impede delayed interferon responses. The dual ability of silibinin to target both the host cytokine storm and the virus replication machinery provides a strong rationale for the clinical testing of silibinin against the COVID-19 global public health emergency. A randomized, open-label, phase II multicentric clinical trial (SIL-COVID19) will evaluate the therapeutic efficacy of silibinin in the prevention of acute respiratory distress syndrome in moderate-to-severe COVID-19-positive onco-hematological patients at the Catalan Institute of Oncology in Catalonia, Spain.


title: The TRAPP Complex: Insights into its Architecture and Function

text: Vesicle-mediated transport is a process carried out by virtually every cell and is required for the proper targeting and secretion of proteins. As such, there are numerous players involved to ensure that the proteins are properly localized. Overall, transport requires vesicle budding, recognition of the vesicle by the target membrane and fusion of the vesicle with the target membrane resulting in delivery of its contents. The initial interaction between the vesicle and the target membrane has been referred to as tethering. Because this is the first contact between the two membranes, tethering is critical to ensuring that specificity is achieved. It is therefore not surprising that there are numerous ‘tethering factors’ involved ranging from multisubunit complexes, coiled-coil proteins and Rab guanosine triphosphatases. Of the multisubunit tethering complexes, one of the best studied at the molecular level is the evolutionarily conserved TRAPP complex. There are two forms of this complex: TRAPP I and TRAPP II. In yeast, these complexes function in a number of processes including endoplasmic reticulum-to-Golgi transport (TRAPP I) and an ill-defined step at the trans Golgi (TRAPP II). Because the complex was first reported in 1998 (1), there has been a decade of studies that have clarified some aspects of its function but have also raised further questions. In this review, we will discuss recent advances in our understanding of yeast and mammalian TRAPP at the structural and functional levels and its role in disease while trying to resolve some apparent discrepancies and highlighting areas for future study.


title: Does the human immune system ever really become “senescent”?

text: Like all somatic tissues, the human immune system changes with age. This is believed to result in an increased frequency of, and susceptibility to, infectious disease and to contribute to a wide range of non-communicable age-associated diseases in later life, especially cancer, cardiovascular disease, and autoimmunity. The majority of studies addressing immune ageing has been cross-sectional, but limited longitudinal studies are contributing to a better understanding of age-associated changes, as opposed to differences, and their clinical relevance. However, intriguing differences are emerging that implicate highly context-dependent immune ageing processes, mitigating against current generalisations concerning human immunosenescence and indicating the necessity for detailed comparisons of different populations, even those that would appear quite similar at first glance.


title: Clinical implications of aminotransferase elevation in hospitalised infants aged 8‐90 days with respiratory virus detection

text: BACKGROUND: Fever and respiratory symptoms are the major causes of hospitalisation in infants aged 90 days or less. Respiratory viruses (RVs) are detected by multiplex reverse transcriptase‐polymerase chain reaction (mRT‐PCR) in up to 70% of infants tested in this population. Aminotransferase elevation is not uncommon in RV infections, and repeat laboratory investigations are frequent due to concerns regarding the occurrence of hepatic disease. METHODS: This retrospective observational cohort study included 271 infants aged 8‐90 days, with positive RV mRT‐PCR results. Data were obtained on demographics, laboratory results and final diagnoses of hepatobiliary disease. RESULTS: Fever (73.1%) and/or respiratory symptoms (75.6%) were the major presentations among the hospitalised infants. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels were elevated in 62 (22.9%) of the 271 infants. Twenty‐four of these 62 infants had their first follow‐up, and 19 (79.2%) showed persistent elevation. All 10 (100%) infants who had their second follow‐up showed persistently elevated aminotransferase levels. Eventually, none of the 10 infants were diagnosed with hepatic disease during the median follow‐up of 10 days (range 3‐232 days). Among the RVs of interest, parainfluenza virus type 1 was significantly associated with aminotransferase elevation (odds ratio: 2.95; 95% confidence interval [CI]: 1.11‐7.83). CONCLUSIONS: RV‐related non‐specific hepatitis is occasionally observed in infants aged 8‐90 days, and ALT elevation is the most common abnormality. However, a final diagnosis of primary hepatobiliary disease appears to be rare. Therefore, regular follow‐ups and targeted testing may be recommended in this specific population.


title: Risk Factors of Streptococcus suis Infection in Vietnam. A Case-Control Study

text: BACKGROUND: Streptococcus suis infection, an emerging zoonosis, is an increasing public health problem across South East Asia and the most common cause of acute bacterial meningitis in adults in Vietnam. Little is known of the risk factors underlying the disease. METHODS AND FINDINGS: A case-control study with appropriate hospital and matched community controls for each patient was conducted between May 2006 and June 2009. Potential risk factors were assessed using a standardized questionnaire and investigation of throat and rectal S. suis carriage in cases, controls and their pigs, using real-time PCR and culture of swab samples. We recruited 101 cases of S. suis meningitis, 303 hospital controls and 300 community controls. By multivariate analysis, risk factors identified for S. suis infection as compared to either control group included eating “high risk” dishes, including such dishes as undercooked pig blood and pig intestine (OR(1) = 2.22; 95%CI = [1.15–4.28] and OR(2) = 4.44; 95%CI = [2.15–9.15]), occupations related to pigs (OR(1) = 3.84; 95%CI = [1.32–11.11] and OR(2) = 5.52; 95%CI = [1.49–20.39]), and exposures to pigs or pork in the presence of skin injuries (OR(1) = 7.48; 95%CI = [1.97–28.44] and OR(2) = 15.96; 95%CI = [2.97–85.72]). S. suis specific DNA was detected in rectal and throat swabs of 6 patients and was cultured from 2 rectal samples, but was not detected in such samples of 1522 healthy individuals or patients without S. suis infection. CONCLUSIONS: This case control study, the largest prospective epidemiological assessment of this disease, has identified the most important risk factors associated with S. suis bacterial meningitis to be eating ‘high risk’ dishes popular in parts of Asia, occupational exposure to pigs and pig products, and preparation of pork in the presence of skin lesions. These risk factors can be addressed in public health campaigns aimed at preventing S. suis infection.


title: Creating a Resilient Research Program – Lessons Learned from a Palliative Care Research Lab

text: Conducting palliative care research can be personally and professionally challenging. While limitations in funding and training opportunities are well-described, a less recognized barrier to successful palliative care research is creating a sustainable and resilient team. In this special report, we describe the experience and lessons-learned in a single palliative care research lab. In the first few years of the program, 75% of staff quit, citing burnout and the emotional tolls of their work. To address our sustainability, we translated resilience theory to practice. First, we identified and operationalized shared mission and values. Next, we conducted a resilience resource needs assessment for both individual team-members and the larger team as a whole, and created a workshop based curriculum to address unmet personal and professional support needs. Finally, we changed our leadership approach to foster psychological safety and shared mission. Since then, no team-member has left and the program has thrived. As the demand for rigorous palliative care research grows, we hope this report will provide perspective and ideas to other established and emerging palliative care research programs.


title: The impact of COVID‐19 on heart failure hospitalization and management: report from a Heart Failure Unit in London during the peak of the pandemic

text: AIMS: To examine the impact of COVID‐19 on acute heart failure (AHF) hospitalization rates, clinical characteristics and management of patients admitted to a tertiary Heart Failure Unit in London during the peak of the pandemic. METHODS AND RESULTS: Data from King's College Hospital, London, reported to the National Heart Failure Audit for England and Wales, between 2nd March – 19(th) April 2020 were compared both to a pre‐COVID cohort and the corresponding time periods in 2017‐2019 with respect to absolute hospitalization rates. Furthermore, we performed detailed comparison of patients hospitalized during the COVID‐19 pandemic and patients presenting in the same period in 2019 with respect to clinical characteristics and management during the index admission. A significantly lower admission rate for AHF was observed during the study period compared to all other included time periods. Patients admitted during the COVID‐19 pandemic had higher rates of NYHA III or IV symptoms (96% vs. 77%, p=0.03) and severe peripheral oedema (39% vs. 14%, p=0.01). We did not observe any differences in inpatient management, including place of care and pharmacological management of heart failure with reduced ejection fraction (HFrEF) CONCLUSION: Incident AHF hospitalization significantly declined in our centre during the COVID‐19 pandemic, but hospitalized patients had more severe symptoms at admission. Further studies are needed to investigate whether the incidence of AHF declined or patients did not present to hospital while the national lockdown and social distancing restrictions were in place. From a public health perspective, it is imperative to ascertain whether this will be associated with worse long‐term outcomes. This article is protected by copyright. All rights reserved.


title: An update on SARS-CoV-2/COVID-19 with particular reference to its clinical pathology, pathogenesis, immunopathology and mitigation strategies

text: Coronavirus Disease 2019 (COVID-19), emerged in early December 2019 in China and became a pandemic situation worldwide by its rapid spread to nearly 190 countries. Bats are considered as the reservoir host, and the search of a probable intermediate host is still going on. The severe form of the infection is associated with death is mainly reported in older and immune-compromised patients with pre-existing disease history. Death in severe cases is attributed to respiratory failure associated with hyperinflammation. Cytokine storm syndrome associated with inflammation in response to SARS-CoV-2 infection is considered as the leading cause of mortality in COVID-19 patients. COVID-19 patients have thus higher levels of many proinflammatory cytokines and chemokines. The blood lab profile of the COVID-19 patients exhibits lymphopenia, leukopenia, thrombocytopenia, and RNAaemia, along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection in pregnant women does not lead to fetus mortality, unlike other zoonotic coronaviruses such as SARS-CoV and MERS-CoV, and there is, to date, no evidence of intrauterine transmission to neonates. Rapid diagnostics have been developed, and significant efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapy, internationally, health care authorities are recommending the adoption of effective community mitigation measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-CoV-2/COVID-19 clinical pathology, pathogenesis, and immunopathology, along with recent research developments.


title: Sharing Information on COVID-19: the ethical challenges in the Malaysian setting

text: The COVID-19 pandemic has raised challenges in dealing with information sharing by the public and the authorities. There are two categories of information sharing on social media that are believed to be potentially problematic and unethical: the sharing of personal information of patients and the sharing of fake news or false information. We present a discussion on how the response to the COVID-19 pandemic in Malaysia can be ethically handled in terms of information sharing. It is recommended that the public should cultivate the basic skills to evaluate information and determine its validity. On the other hand, the authorities should refrain from placing the blame on patients to avoid them from being stigmatized. It is crucial that all parties are aware of their ethical duty to ensure only ethical and valid information gets shared on social media.


title: Therapeutic applications of nucleic acid aptamers in microbial infections

text: Today, the treatment of bacterial infections is a major challenge, due to growing rate of multidrug-resistant bacteria, complication of treatment and increased healthcare costs. Moreover, new treatments for bacterial infections are limited. Oligonucleotide aptamers are single stranded DNAs or RNAs with target-selective high-affinity feature, which considered as nucleic acid-based affinity ligands, replacing monoclonal antibodies. The aptamer-based systems have been found to be talented tools in the treatment of microbial infections, regarding their promising anti-biofilm and antimicrobial activities; they can reduce or inhibit the effects of bacterial toxins, and inhibit pathogen invasion to immune cell, as well as they can be used in drug delivery systems. The focus of this review is on the therapeutic applications of aptamers in infections. In this regard, an introduction of infections and related challenges were presented, first. Then, aptamer definition and selection, with a brief history of aptamers development against various pathogens and toxins were reviewed. Diverse strategies of aptamer application in drug delivery, as well as, the effect of aptamers on the immune system, as the main natural agents of human defense against pathogens, were also discussed. Finally, the future trends in clinical applications of this technology were discussed.


title: Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan

text: A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses. However, the external subdomain of Spike’s receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses. Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection.


SARS: Political Pathology of the First Post‐Westphalian Pathogen


title: Crystallization and preliminary crystallographic study of Feline infectious peritonitis virus main protease in complex with an inhibitor

text: Feline infectious peritonitis virus (FIPV) causes a lethal systemic granulomatous disease in wild and domestic cats around the world. Currently, no effective vaccines or drugs have been developed against it. As a member of the genus Alphacoronavirus, FIPV encodes two polyprotein precursors required for genome replication and transcription. Each polyprotein undergoes extensive proteolytic processing, resulting in functional subunits. This process is mainly mediated by its genome-encoded main protease, which is an attractive target for antiviral drug design. In this study, the main protease of FIPV in complex with a Michael acceptor-type inhibitor was crystallized. The complex crystals diffracted to 2.5 Å resolution and belonged to space group I422, with unit-cell parameters a = 112.3, b = 112.3, c = 102.1 Å. There is one molecule per asymmetric unit.


Proposition for an international DNR symbol printable on patients’ wristbands and usable in hospital, nursing and retirement homes with the aim to avoid unwanted CPR in patients with a DNR status


title: Detection of SARS-CoV-2 RNA in fecal specimens of patients with confirmed COVID-19: a meta-analysis

text: INTRODUCTION: Recent studies showed that SARS-CoV-2 RNA may be found in fecal specimens of COVID-19 patients, but the sample size is limited. This systematic review and meta-analysis examined the detection rate of SARS-CoV-2 RNA in fecal specimens of these patients according to their clinical characteristics. METHODS: MEDLINE, Embase, Scopus, and three Chinese biomedical databases were searched up to 25 March, 2020 with no language restriction. We included original observational studies that reported the detection rate of SARS-CoV-2 RNA in fecal specimens of COVID-19 patients. Two separate reviewers conducted the review. Metaprop was adopted to conduct a meta-analysis of prevalence with variances stabilized by Freeman-Tukey Double Arcsine Transformation. A random-effects model was used. Heterogeneity across different studies was computed using Cochran's Q test and chi square statistics. RESULTS: From 17 studies, the pooled detection rate of fecal SARS-CoV-2 RNA was 43.7% (95% CI 32.6%-55.0%) and 33.7% (95% C.I. 33.7%, 95% C.I. 20.1%-48.8%) by patient and number of specimens as a unit count, respectively. Female individuals (59.6% vs. 53.5%), those who presented with gastrointestinal symptoms (77.1% vs. 57.7%), and patients with more severe disease (68.3% vs. 34.6%) tended to have a higher detection rate. DISCUSSION: A significant proportion of COVID-19 patients carry SARS-CoV-2 in their intestinal tract. Feces being a self-collected specimen bears a potential to improve case identification in community, especially for young children where proper respiratory sampling at home is difficult. Specific infection control strategies focusing on spread via fecal contamination and faulty toilet drainage are urgently needed.


title: A stable trypsin inhibitor from Chinese dull black soybeans with potentially exploitable activities

text: Abstract A dimeric 40-kDa Kunitz-type trypsin inhibitor was isolated from seeds of the Chinese black soybean Glycine max cv. ‘Dull Black’. The purification protocol comprised ion exchange chromatography on Q-Sepharose, SP-Sepharose, and Mono Q, and gel filtration on Superdex 75. The trypsin inhibitor inhibited chymotrypsin, albeit to a lesser extent than it inhibited trypsin. Its trypsin-inhibitory activity was unaffected after exposure to pH 1–14, or to temperatures up to 80°C. The trypsin inhibitor was inhibited by dithiothreitol in a dose-dependent (from 2.5 to 50mM) and a time-dependent (from 5 to 120min) manner. Besides inhibiting serine proteases, the trypsin inhibitor demonstrated additional biological activities including stimulation of nitric oxide production by macrophages. It inhibited HIV-1 reverse transcriptase, cell-free translation and proliferation of liver cancer cells and breast cancer cells, with an IC50 value 9.4, 14, 39 and 70μM, respectively. However, it did not exhibit antifungal, antibacterial or mitogenic activity.


title: Isolation and Characterization of a Kunitz-Type Trypsin Inhibitor with Antiproliferative Activity from Gymnocladus Chinensis (Yunnan Bean) Seeds

text: A 20-kDa Kunitz-type trypsin inhibitor was isolated from Gymnocladus chinensis (Yunnan bean) seeds. The isolation procedure involved ion exchange chromatography on diethylaminoethyl cellulose (DEAE-cellulose), affinity chromatography on Affi-gel blue gel, ion exchange chromatography on sulfopropyl sepharose (SP-sepharose), and gel filtration by FPLC on Superdex 75. The trypsin inhibitor was adsorbed on DEAE-cellulose, unadsorbed on Affi-gel blue gel, and adsorbed on SP-Sepharose. It dose-dependently inhibited trypsin with an IC(50) value of 0.4 μM. Dithiothreitol reduced its trypsin inhibitory activity, suggesting that an intact disulfide bond is indispensable to the activity. It suppressed [methyl-(3)H] thymidine incorporation by leukemia L1210 cells and lymphoma MBL2 cells with an IC(50) value of 4.7 and 9.4 μM, respectively. There was no effect on human immunodeficiency virus(4)-1 reverse transcriptase activity and fungal growth when the trypsin inhibitor was tested up to 100 μM.


title: Yeast and the AIDS Virus: The Odd Couple

text: Despite being simple eukaryotic organisms, the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe have been widely used as a model to study human pathologies and the replication of human, animal, and plant viruses, as well as the function of individual viral proteins. The complete genome of S. cerevisiae was the first of eukaryotic origin to be sequenced and contains about 6,000 genes. More than 75% of the genes have an assigned function, while more than 40% share conserved sequences with known or predicted human genes. This strong homology has allowed the function of human orthologs to be unveiled starting from the data obtained in yeast. RNA plant viruses were the first to be studied in yeast. In this paper, we focus on the use of the yeast model to study the function of the proteins of human immunodeficiency virus type 1 (HIV-1) and the search for its cellular partners. This human retrovirus is the cause of AIDS. The WHO estimates that there are 33.4 million people worldwide living with HIV/AIDS, with 2.7 million new HIV infections per year and 2.0 million annual deaths due to AIDS. Current therapy is able to control the disease but there is no permanent cure or a vaccine. By using yeast, it is possible to dissect the function of some HIV-1 proteins and discover new cellular factors common to this simple cell and humans that may become potential therapeutic targets, leading to a long-lasting treatment for AIDS.


title: Virus and tumor microenvironment induced ER stress and unfolded protein response: from complexity to therapeutics

text: Endoplasmic reticulum (ER) stress can be activated by various pathological and physiological conditions including the unfolded protein response (UPR) to restore homeostasis. The UPR signaling pathways initiated by double-stranded RNA-activated protein kinase (PKR) like ER kinase (PERK), inositol requiring enzyme 1 α (IRE1α), and activating transcription factor 6 (ATF6) are vital for tumor growth, aggressiveness, microenvironment remodeling, and resistance to cancer therapeutics. This review focuses on the role of ER stress and activity of UPR signaling pathways involved in tumor formation and uncontrolled cell proliferation during various cancers and viral malignancies.


title: Global networks and global change-induced tipping points

text: The existence of “tipping points” in human–environmental systems at multiple scales—such as abrupt negative changes in coral reef ecosystems, “runaway” climate change, and interacting nonlinear “planetary boundaries”—is often viewed as a substantial challenge for governance due to their inherent uncertainty, potential for rapid and large system change, and possible cascading effects on human well-being. Despite an increased scholarly and policy interest in the dynamics of these perceived “tipping points,” institutional and governance scholars have yet to make progress on how to analyze in which ways state and non-state actors attempt to anticipate, respond, and prevent the transgression of “tipping points” at large scales. In this article, we use three cases of global network responses to what we denote as global change-induced “tipping points”—ocean acidification, fisheries collapse, and infectious disease outbreaks. Based on the commonalities in several research streams, we develop four working propositions: information processing and early warning, multilevel and multinetwork responses, diversity in response capacity, and the balance between efficiency and legitimacy. We conclude by proposing a simple framework for the analysis of the interplay between perceived global change-induced “tipping points,” global networks, and international institutions.


Prioritizing infants in a time of Bacille Calmette–Guérin vaccine shortage caused by premature expectations against COVID-19


title: The Clinical Significance of FilmArray Respiratory Panel in Diagnosing Community-Acquired Pneumonia

text: AIM: FilmArray Respiratory Panel (FilmArray RP) test is an emerging diagnostic method in fast detecting multiple respiratory pathogens; the methodology and clinical significance of FilmArray RP in community-acquired pneumonia (CAP) diagnosis were evaluated in this study. METHODS: Specimens from 74 patients with CAP were analyzed and compared using FilmArray RP, traditional multiple PCR assay, bacterial (or fungal) culture, and serological detection. RESULTS: FilmArray RP and multiplex PCR showed 100% coincidence rate in detecting coronaviruses 229E, OC43, HKU1, and NL63, human metapneumovirus, influenza A and B, and parainfluenza viruses (PIV1, PIV2, and PIV4). There were 15 viral specimens tested as disagreement positive results. FilmArray RP had higher detection rate in detecting dual viral and Mycoplasma pneumoniae infection. The positive bacteria (or fungi) were found in 25 specimens. CONCLUSIONS: This study demonstrated the capability of FilmArray RP for simultaneous detection of broad-spectrum respiratory pathogens and potential use in facilitating better patient care.


title: Diversity and role of cave-dwelling hematophagous insects in pathogen transmission in the Afrotropical region

text: The progressive anthropization of caves for food resources or economic purposes increases human exposure to pathogens that naturally infect cave-dwelling animals. The presence of wild or domestic animals in the immediate surroundings of caves also may contribute to increasing the risk of emergence of such pathogens. Some zoonotic pathogens are transmitted through direct contact, but many others require arthropod vectors, such as blood-feeding insects. In Africa, hematophagous insects often play a key role in the epidemiology of many pathogens; however, their ecology in cave habitats remains poorly known. During the last decades, several investigations carried out in Afrotropical caves suggested the medical and veterinary importance particularly of insect taxa of the Diptera order. Therefore, the role of some of these insects as vectors of pathogens that infect cave-dwelling vertebrates has been studied. The present review summarizes these findings, brings insights into the diversity of cave-dwelling hematophagous Diptera and their involvement in pathogen transmission, and finally discusses new challenges and future research directions.


title: Origins of Enterovirus Replication Organelles Established by Whole-Cell Electron Microscopy

text: Enterovirus genome replication occurs at virus-induced structures derived from cellular membranes and lipids. However, the origin of these replication organelles (ROs) remains uncertain. Ultrastructural evidence of the membrane donor is lacking, suggesting that the sites of its transition into ROs are rare or fleeting. To overcome this challenge, we combined live-cell imaging and serial block-face scanning electron microscopy of whole cells to capture emerging enterovirus ROs. The first foci of fluorescently labeled viral protein correlated with ROs connected to the endoplasmic reticulum (ER) and preceded the appearance of ROs stemming from the trans-Golgi network. Whole-cell data sets further revealed striking contact regions between ROs and lipid droplets that may represent a route for lipid shuttling to facilitate RO proliferation and genome replication. Our data provide direct evidence that enteroviruses use ER and then Golgi membranes to initiate RO formation, demonstrating the remarkable flexibility with which enteroviruses usurp cellular organelles.


The Acute Effects of the COVID-19 Pandemic on Insomnia and Psychological Symptoms


title: Multi-omic network signatures of disease

text: To better understand dynamic disease processes, integrated multi-omic methods are needed, yet comparing different types of omic data remains difficult. Integrative solutions benefit experimenters by eliminating potential biases that come with single omic analysis. We have developed the methods needed to explore whether a relationship exists between co-expression network models built from transcriptomic and proteomic data types, and whether this relationship can be used to improve the disease signature discovery process. A naïve, correlation based method is utilized for comparison. Using publicly available infectious disease time series data, we analyzed the related co-expression structure of the transcriptome and proteome in response to SARS-CoV infection in mice. Transcript and peptide expression data was filtered using quality scores and subset by taking the intersection on mapped Entrez IDs. Using this data set, independent co-expression networks were built. The networks were integrated by constructing a bipartite module graph based on module member overlap, module summary correlation, and correlation to phenotypes of interest. Compared to the module level results, the naïve approach is hindered by a lack of correlation across data types, less significant enrichment results, and little functional overlap across data types. Our module graph approach avoids these problems, resulting in an integrated omic signature of disease progression, which allows prioritization across data types for down-stream experiment planning. Integrated modules exhibited related functional enrichments and could suggest novel interactions in response to infection. These disease and platform-independent methods can be used to realize the full potential of multi-omic network signatures. The data (experiment SM001) are publically available through the NIAID Systems Virology (https://www.systemsvirology.org) and PNNL (http://omics.pnl.gov) web portals. Phenotype data is found in the supplementary information. The ProCoNA package is available as part of Bioconductor 2.13.


title: Ezrin Interacts with the SARS Coronavirus Spike Protein and Restrains Infection at the Entry Stage

text: BACKGROUND: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. METHODOLOGY/PRINCIPAL FINDINGS: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S-pseudotyped particles and potentiated S-dependent membrane fusion. CONCLUSIONS/SIGNIFICANCE: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.


title: General thoracic surgery services across Asia during the 2020 COVID-19 pandemic

text: The COVID-19 pandemic of 2020 posed an historic challenge to healthcare systems around the world. Besides mounting a massive response to the viral outbreak, healthcare systems needed to consider provision of clinical services to other patients in need. Surgical services for patients with thoracic disease were maintained to different degrees across various regions of Asia, ranging from significant reductions to near-normal service. Key determinants of robust thoracic surgery service provision included: preexisting plans for an epidemic response, aggressive early action to “flatten the curve”, ability to dedicate resources separately to COVID-19 and routine clinical services, prioritization of thoracic surgery, and the volume of COVID-19 cases in that region. The lessons learned can apply to other regions during this pandemic, and to the world, in preparation for the next one.


Mask‐induced contact dermatitis in handling COVID‐19 outbreak


title: 应用多肽芯片研究非小细胞肺癌患者血清中的EGFR自身抗体

text: BACKGROUND AND OBJECTIVE: Autoantibodies as new tumor markers may play an important role in the early diagnosis and evaluating the prognosis of lung cancer. In this study, we detect epidermal growth factor receptor (EGFR) autoantibodies using peptide array and screen the epitopes which are recognized by EGFR autoantibodies. METHODS: Peptide array covering the extracellular domain of EGFR protein was synthesized by a synthesizer (ASPSL) made by Intavis company. EGFR autoantibodies in the serums of non-small cell lung cancer patients was detected using peptide array. RESULTS: Six of 20 patients were found to have EGFR autoantibodis. The positive rate is 30%. Nine high frequency spots were found in the 6 positive patients and 8 high frequency spots clustered in the Ⅲ and Ⅳ domains. CONCLUSION: These findings will offer new clues for the futher studies of EGFR and EGFR autoantibodies.


title: Molecular detection and characterization of human gyroviruses identified in the ferret fecal virome

text: The recently described novel gyroviruses may infect chickens and/or humans; however, their pathogenic potential is unknown. In our metagenomic investigation, we detected many of the novel gyroviruses in the fecal viromes of ferrets with lymph node and organ enlargement. The complete genomic sequences of selected gyrovirus strains showed 90.7-99.4 % similarity to homologous reference gyrovirus strains. This study did not demonstrate an association between gyrovirus shedding from ferrets and the observed background disease; however, it provides evidence for genetic diversity among gyroviruses and raises the possibility that pet ferrets may transmit gyroviruses to heterologous hosts, e.g., humans.