title: Asymptomatic novel coronavirus pneumonia patient outside Wuhan: The value of CT images in the course of the disease

text: Abstract The purpose of this case report is to describe the imaging and associated clinical features of an asymptomatic novel coronavirus pneumonia (COVID-19) patient outside Wuhan, China. The principle findings are that in this patient with laboratory-confirmed COVID-19, CT findings preceded symptoms and included bilateral pleural effusions, previously not reported in association with COVID-19. The role of this case report is promotion of potential recognition amongst radiologists of this new disease, which has been declared a global health emergency by the World Health Organization (WHO).


title: Exogenous avian leukosis virus-induced activation of the ERK/AP1 pathway is required for virus replication and correlates with virus-induced tumorigenesis

text: A proteomics approach was used to reveal the up-regulated proteins involved in the targeted mitogen-activated protein kinase (MAPK) signal transduction pathway in DF-1 cells after ALV subgroup J (ALV-J) infection. Next, we found that ALV-J CHN06 strain infection of DF-1 cells correlated with extracellular signal-regulated kinase 2 (ERK2) activation, which was mainly induced within 15 min, a very early stage of infection, and at a late infection stage, from 108 h to 132 h post-infection. Infection with other ALV subgroup (A/B) strains also triggered ERK/MAPK activation. Moreover, when activating ERK2, ALV subgroups A, B and J simultaneously induced the phosphorylation of c-Jun, an AP1 family member and p38 activation but had no obvious effect on JNK activation at either 15 min or 120 h. Interestingly, only PD98059 inhibited the ALV-induced c-Jun phosphorylation while SP600125 or SB203580 had no influence on c-Jun activation. Furthermore, the viral gp85 and gag proteins were found to contribute to ERK2/AP1 activation. Additionally, the specific ERK inhibitor, PD980509, significantly suppressed ALV replication, as evidenced by extremely low levels of ALV promoter activity and ALV-J protein expression. In vivo analysis of ERK2 activation in tumor cells derived from ALV-J-infected chicken demonstrated a strong correlation between ERK/MAPK activation and virus-associated tumorigenesis.


Evidence for Quasi Species in Severe Acute Respiratory Syndrome-associated Coronavirus Deletion Mutants


title: Molecular characterization and biological activity of bovine interferon-omega3

text: Abstract Bovine interferon-omega3 (BoIFN-ω3) gene was amplified from bovine liver genomic DNA, which encodes a 195-amino acid protein containing a 23-amino acid signal peptide. Analysis of the molecular characteristics revealed that BoIFN-ω3 evolving from IFN-ω, contained four cysteine residues and five alpha helices, showing that BoIFN-ω3 presented the typical molecular characteristics of type I interferon. BoIFN-ω3 exhibited antiviral and antiproliferative activities, which exerted a protective effect against VSV in several mammalian cell lines, as well as against BEV, IBRV, and BVDV in MDBK cell. Moreover, BoIFN-ω3 was shown to be highly sensitive to trypsin, but remaining stable despite changes in pH and temperature. Additionally, BoIFN-ω3 induced the transcription of Mx1, ISG15, and ISG56 genes, as well as the expression of Mx1 protein in a time-dependent manner. These findings will be useful to further study BoIFN-ω in host's defence against infectious diseases, particularly viral infections. Furthermore, results will facilitate further research on the bovine interferon family.


title: Disaster Preparedness, Triage, and Surge Capacity for Hospital Definitive Care Areas: Optimizing Outcomes when Demands Exceed Resources

text: Disaster planning must anticipate how demands imposed by a disaster reconcile with the capacity of the treating facility. Resources must be organized before an event so that they are optimally used to treat as many victims as possible, as well as to avoid overwhelming available resources.


title: The phylogenomics of evolving virus virulence

text: How virulence evolves after a virus jumps to a new host species is central to disease emergence. Our current understanding of virulence evolution is based on insights drawn from two perspectives that have developed largely independently: long-standing evolutionary theory based on limited real data examples that often lack a genomic basis, and experimental studies of virulence-determining mutations using cell culture or animal models. A more comprehensive understanding of virulence mutations and their evolution can be achieved by bridging the gap between these two research pathways through the phylogenomic analysis of virus genome sequence data as a guide to experimental study.


title: Bat and pig IFN-induced transmembrane protein 3 restrict cell entry by influenza virus and lyssaviruses

text: IFN-induced transmembrane protein 3 (IFITM3) is a restriction factor that blocks cytosolic entry of numerous viruses that utilize acidic endosomal entry pathways. In humans and mice, IFITM3 limits influenza-induced morbidity and mortality. Although many IFITM3-sensitive viruses are zoonotic, whether IFITMs function as antiviral restriction factors in mammalian species other than humans and mice is unknown. Here, IFITM3 orthologues in the microbat (Myotis myotis) and pig (Sus scrofa domesticus) were identified using rapid amplification of cDNA ends. Amino acid residues known to be important for IFITM3 function were conserved in the pig and microbat orthologues. Ectopically expressed pig and microbat IFITM3 co-localized with transferrin (early endosomes) and CD63 (late endosomes/multivesicular bodies). Pig and microbat IFITM3 restricted cell entry mediated by multiple influenza haemagglutinin subtypes and lyssavirus glycoproteins. Expression of pig or microbat IFITM3 in A549 cells reduced influenza virus yields and nucleoprotein expression. Conversely, small interfering RNA knockdown of IFITM3 in pig NPTr cells and primary microbat cells enhanced virus replication, demonstrating that these genes are functional in their species of origin at endogenous levels. In summary, we showed that IFITMs function as potent broad-spectrum antiviral effectors in two mammals – pigs and bats – identified as major reservoirs for emerging viruses.


title: Aufgaben der Weaning-Zentren im Pandemiefall COVID-19: Unterstützende Handlungsempfehlung zur Sicherstellung dringend benötigter Intensivkapazitäten am Beispiel des Berlin-Brandenburger POST-SAVE-Konzepts

text: The enormous increase in patients with severe respiratory distress due to the COVID-19 pandemic outbreak requires a systematic approach to optimize ventilated patient at risk flow. A standardised algorithm called „SAVE“ was developed to distribute patients with COVID-19 respiratory distress syndrome requiring invasive ventilation. This program is established by now in Berlin. An instrumental bottleneck of this approach is the vacant slot assignment in the intensive care unit to guarantee constant patient flow. The transfer of the patients after acute care treatment is needed urgently to facilitate the weaning process. In a next step we developed a triage algorithm to identify patients at SAVE intensive care units with potential to wean and transfer to weaning institutions – we called POST SAVE. This manuscript highlights the algorithms including the use of a standardised digital evaluation tool, the use of trained navigators to facilitate the communication between SAVE intensive care units and weaning institutions and the establishment of a prospective data registry for patient assignment and reevaluation of the weaning potential in the future.


Human Bocavirus in Hospitalized Children, South Africa


title: More than smell – COVID-19 is associated with severe impairment of smell, taste, and chemesthesis

text: Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation and initial results of a multi-lingual, international questionnaire to assess self-reported quantity and quality of perception in three distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, 8 other, ages 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± SD), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell, but also affects taste and chemesthesis. The multimodal impact of COVID-19 and lack of perceived nasal obstruction suggest that SARS-CoV-2 infection may disrupt sensory-neural mechanisms.


title: Dynamic changes in circulating T follicular helper cell composition predict neutralising antibody responses after yellow fever vaccination

text: OBJECTIVES: T follicular helper (Tfh) cells are the principal T helper cell subset that provides help to B cells for potent antibody responses against various pathogens. In this study, we took advantage of the live‐attenuated yellow fever virus (YFV) vaccine strain, YF‐17D, as a model system for studying human antiviral immune responses in vivo following exposure to an acute primary virus challenge under safe and highly controlled conditions, to comprehensively analyse the dynamics of circulating Tfh (cTfh) cells. METHODS: We tracked and analysed the response of cTfh and other T and B cell subsets in peripheral blood of healthy volunteers by flow cytometry over the course of 4 weeks after YF‐17D vaccination. RESULTS: Using surface staining of cell activation markers to track YFV‐specific T cells, we found increasing cTfh cell frequencies starting at day 3 and peaking around 2 weeks after YF‐17D vaccination. This kinetic was confirmed in a subgroup of donors using MHC multimer staining for four known MHC class II epitopes of YF‐17D. The subset composition of cTfh cells changed dynamically during the course of the immune response and was dominated by the cTfh1‐polarised subpopulation. Importantly, frequencies of cTfh1 cells correlated with the strength of the neutralising antibody response, whereas frequencies of cTfh17 cells were inversely correlated. CONCLUSION: In summary, we describe detailed cTfh kinetics during YF‐17D vaccination. Our results suggest that cTfh expansion and polarisation can serve as a prognostic marker for vaccine success. These insights may be leveraged in the future to improve current vaccine design and strategies.


title: COVID-19 pandemic: a viewpoint from Asia

text: The expansion of severe acute respiratory syndrome (SARS) coronavirus 2 (SARSCoV-2) has now procured on epidemic percentages, affecting more than 190 nations in a matter of weeks. A widespread SARSCoV-2 contagion begun in Wuhan, Hubei Province, China, and circulate through China and beyond in December 2019. The containment events in China have lessened new instances by more than 90%, but this diminution is not the case to a different place. European countries like Italy and Spain have been the most affected. In Asia, the COVID-19 brings a catastrophe where after China mainland, countries like Iran and South Korea have been affected. There is now severe apprehension concerning the Asian health care system’s ability to effectually counter to the necessities of patients who are infected and need rigorous precaution for COVID-19. The patient’s ratio in special care reported in Iran has perpetually been between 6 and 8% who are rapidly infected. As about South Korea, the ratio is 3% and 4% who are rapidly infected. This analysis emphasizes the epidemiology of COVID-19, its effects in the Asia continent, and active case study of COVID-19 including the distinct countries.


Control of measles encephalitis in the rat by CD4+ T-cell


title: Acyclonucleosides: Part 2. diseco-Nucleosides* * Part 1 is in Volume 67 and Part 3 is in Volume 69.

text: This chapter is the second of a sequence of three chapters that appears in successive volumes of this series dealing with the chemistry of acyclonucleosides. The first chapter appeared in the previous volume [97AHC391] and dealt with seco-nucleosides (one bond disconnection). This chapter deals with diseco-nucleosides (two bond disconnections). The final chapter of this series will deal with tri-, tetra-, and pentaseco-nucleosides, as well as contain an appendix of the literature that appeared after the three chapters were prepared.


title: A Preliminary Study of Pneumonia Etiology Among Hospitalized Children in Kenya

text: Background. Pneumonia is the leading cause of childhood death in the developing world. Higher-quality etiological data are required to reduce this mortality burden. Methods. We conducted a case-control study of pneumonia etiology among children aged 1–59 months in rural Kenya. Case patients were hospitalized with World Health Organization–defined severe pneumonia (SP) or very severe pneumonia (VSP); controls were outpatient children without pneumonia. We collected blood for culture, induced sputum for culture and multiplex polymerase chain reaction (PCR), and obtained oropharyngeal swab specimens for multiplex PCR from case patients, and serum for serology and nasopharyngeal swab specimens for multiplex PCR from case patients and controls. Results. Of 984 eligible case patients, 810 (84%) were enrolled in the study; 232 (29%) had VSP. Blood cultures were positive in 52 of 749 case patients (7%). A predominant potential pathogen was identified in sputum culture in 70 of 417 case patients (17%). A respiratory virus was detected by PCR from nasopharyngeal swab specimens in 486 of 805 case patients (60%) and 172 of 369 controls (47%). Only respiratory syncytial virus (RSV) showed a statistically significant association between virus detection in the nasopharynx and pneumonia hospitalization (odds ratio, 12.5; 95% confidence interval, 3.1–51.5). Among 257 case patients in whom all specimens (excluding serum specimens) were collected, bacteria were identified in 24 (9%), viruses in 137 (53%), mixed viral and bacterial infection in 39 (15%), and no pathogen in 57 (22%); bacterial causes outnumbered viral causes when the results of the case-control analysis were considered. Conclusions. A potential etiology was detected in >75% of children admitted with SP or VSP. Except for RSV, the case-control analysis did not detect an association between viral detection in the nasopharynx and hospitalization for pneumonia.


title: Identification of porcine epidemic diarrhea virus variant with a large spike gene deletion from a clinical swine sample in the United States

text: Two genetically different porcine epidemic diarrhea virus (PEDV) strains have been identified in the USA: US prototype (also called non-S INDEL) and S INDEL PEDVs. In February 2017, a PEDV variant (USA/OK10240-8/2017) was identified in a rectal swab from a sow farm in Oklahoma, USA. Complete genome sequence analyses indicated this PEDV variant was genetically similar to US non-S INDEL strain but had a continuous 600-nt (200-aa) deletion in the N-terminal domain of the spike gene compared to non-S INDEL PEDVs. This is the first report of detecting PEDV bearing large spike gene deletion in clinical swine samples in the USA.


title: Proteomics analysis of differentially expressed proteins in chicken trachea and kidney after infection with the highly virulent and attenuated coronavirus infectious bronchitis virus in vivo

text: BACKGROUND: Infectious bronchitis virus (IBV) is first to be discovered coronavirus which is probably endemic in all regions with intensive impact on poultry production. In this study, we used two-dimensional gel electrophoresis (2-DE) and two-dimensional fluorescence difference gel electrophoresis (2-DIGE), coupled with matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS), to explore the global proteome profiles of trachea and kidney tissues from chicken at different stages infected in vivo with the highly virulent ck/CH/LDL/97I P(5 )strain of infectious bronchitis virus (IBV) and the embryo-passaged, attenuated ck/CH/LDL/97I P(115 )strain. RESULTS: Fifty-eight differentially expressed proteins were identified. Results demonstrated that some proteins which had functions in cytoskeleton organization, anti-oxidative stress, and stress response, showed different change patterns in abundance from chicken infected with the highly virulent ck/CH/LDL/97I P(5 )strain and those given the embryo-passaged, attenuated P(115 )stain. In addition, the dynamic transcriptional alterations of 12 selected proteins were analyzed by the real-time RT-PCR, and western blot analysis confirmed the change in abundance of heat shock proteins (HSP) beta-1, annexin A2, and annexin A5. CONCLUSIONS: The proteomic alterations described here may suggest that these changes to protein expression correlate with IBV virus' virulence in chicken, hence provides valuable insights into the interactions of IBV with its host and may also assist with investigations of the pathogenesis of IBV and other coronavirus infections.


title: Torovirus

text: Toroviruses are single-stranded RNA viruses with a peplomer-bearing envelope that have been associated with enteric disease in cattle and possibly humans. Toroviruses appear to occur worldwide, and torovirus-like particles in fecal preparations have been reported from Europe, the Americas, Asia, New Zealand, and South Africa. These viruses have a unique C-shape or open torus morphology in the extracellular environment. There are four recognized species in the genus Torovirus (family Coronaviridae, order Nidovirales): Equine torovirus, Bovine torovirus, Human torovirus, and Porcine torovirus. Among them there is little genetic divergence (20–40%). Antigenic cross-reactivity has revealed a relationship between equine torovirus (EToV), bovine torovirus (BToV), and human torovirus (HToV). The torovirus genome contains six open reading frames (ORFs), which are transcribed as a 3′ co-terminal nested set of four mRNAs. ORF1a and -1b encode the replicase, and ORFs 2–5 encode the spike (S), membrane (M), hemagglutinin-esterase (HE), and nucleocapsid (N) proteins, respectively. EToV is apathogenic, and the only torovirus that has been grown in vitro. All BToV strains are pathogenic, causing diarrhea in experimentally or naturally infected calves. HToVs have been associated with gastroenteritis and diarrhea in children, as well as with nosocomial infections in infants with necrotizing enterocolitis.


title: Leading on the Edge of Insanity

text: COVID-19 has officially consumed every nurse leader's time and efforts. The purpose of this article is to share early learnings from the West Coast of the United States, where the first US case was cared for. In this article, I describe the emerging principles allowing us to respond to an unprecedented crisis: prevent, protect, and control. By the time this crisis is over, I do not doubt that we will have additional science and experience to support our frontline nurses and our nurse leaders. That said, I felt it was important to share our expertise in real time for others to benefit from. I would also point out that writing about what you are feeling is cathartic—I encourage my colleagues to join me in writing about what you are experiencing.


Characterization of Persistent SARS-CoV Infection in Vero E6 Cells


title: Unconditional care in academic emergency departments

text: Recent news stories have explicitly stated that patients with symptoms of COVID‐19 were “turned away” from emergency departments. This commentary addresses these serious allegations, with an attempt to provide the perspective of academic emergency departments (EDs) around the Nation. The overarching point we wish to make is that academic EDs never deny emergency care to any person.


title: Snakebite envenoming from an Ecohealth perspective

text: Snakebite envenomings occur in complex ecological, social, economic, cultural, and political contexts. Hence, the understanding of this public health issue demands systemic and holistic approaches. Ecohealth constitutes a valuable paradigm to study snakebites, as it emphasizes on the close linkages between ecosystems, society, and health. This essay highlights some of the areas in the field of snakebite envenoming that could greatly benefit from an Ecohealth approach based on trans-disciplinary research, systems thinking, and the involvement of stakeholders at many levels. Ecohealth focuses not only on the generation of knowledge through research, but also in the translation of knowledge into actions.


title: The Novel Cyclophilin Inhibitor CPI-431-32 Concurrently Blocks HCV and HIV-1 Infections via a Similar Mechanism of Action

text: HCV-related liver disease is the main cause of morbidity and mortality of HCV/HIV-1 co-infected patients. Despite the recent advent of anti-HCV direct acting antivirals (DAAs), the treatment of HCV/HIV-1 co-infected patients remains a challenge, as these patients are refractory to most therapies and develop liver fibrosis, cirrhosis and liver cancer more often than HCV mono-infected patients. Until the present study, there was no suitable in vitro assay to test the inhibitory activity of drugs on HCV/HIV-1 co-infection. Here we developed a novel in vitro “co-infection” model where HCV and HIV-1 concurrently replicate in their respective main host target cells—human hepatocytes and CD4+ T-lymphocytes. Using this co-culture model, we demonstrate that cyclophilin inhibitors (CypI), including a novel cyclosporin A (CsA) analog, CPI-431-32, simultaneously inhibits replication of both HCV and HIV-1 when added pre- and post-infection. In contrast, the HIV-1 protease inhibitor nelfinavir or the HCV NS5A inhibitor daclatasvir only blocks the replication of a single virus in the “co-infection” system. CPI-431-32 efficiently inhibits HCV and HIV-1 variants, which are normally resistant to DAAs. CPI-431-32 is slightly, but consistently more efficacious than the most advanced clinically tested CypI—alisporivir (ALV)—at interrupting an established HCV/HIV-1 co-infection. The superior antiviral efficacy of CPI-431-32 over ALV correlates with its higher potency inhibition of cyclophilin A (CypA) isomerase activity and at preventing HCV NS5A-CypA and HIV-1 capsid-CypA interactions known to be vital for replication of the respective viruses. Moreover, we obtained evidence that CPI-431-32 prevents the cloaking of both the HIV-1 and HCV genomes from cellular sensors. Based on these results, CPI-431-32 has the potential, as a single agent or in combination with DAAs, to inhibit both HCV and HIV-1 infections.


title: Polymerase-chain reaction/electrospray ionization-mass spectrometry for the detection of bacteria and fungi in bronchoalveolar lavage fluids: a prospective observational study

text: Abstract PLEX-ID uses polymerase chain reaction-electrospray ionization/mass spectrometry for rapid identification of infectious agents in clinical samples. We evaluated its concordance with our centre's standard methods (SM) for bacterial and fungal detection in bronchoalveolar lavage (BAL) fluid in a prospective observational cohort study. The primary outcome was concordance (%) between SM and PLEX-ID. Secondary outcomes included concordance when excluding commensal oral flora, detection of resistance genes, and PLEX-ID's potential impact on clinical management, as determined by two independent reviewers. Included were 101 specimens from 94 patients. BALs were performed primarily for suspected pneumonia (76/101, 75%) and lung transplant work-ups (12/101, 12%). Most specimens yielded at least one organism by either method (92/101, 91%). Among all microorganisms detected (n = 218), 83% and 17% were bacterial and fungal, respectively. Overall concordance between SM and PLEX-ID was 45% (45/101). Concordance increased to 66% (67/101) when discordance for commensal flora was excluded. PLEX-ID failed to detect 21% of all 183 SM-identified organisms, while SM did not identify 28% of the 191 PLEX-ID-identified organisms (p <0.001). There was low concordance for mecA detection. Two infectious-disease specialists' analyses concluded that in most of the 31 discordant, non-commensal cases, PLEX-ID results would have had little or no impact on patient management; in eight cases, however, PLEX-ID would have led to ‘wrong decision-making’. The tested version of PLEX-ID concurred weakly with standard methods in the detection of bacteria and fungi in BAL specimens, and is not likely to be useful as a standalone tool for microbiological diagnosis in suspected respiratory infections.


title: Home gardening and urban agriculture for advancing food and nutritional security in response to the COVID-19 pandemic

text: Despite a 2.3% increase in world cereal production in 2019 over 2018, the number of people facing severe food insecurity may double from 135 million in January 2020 to 265 million by the end of 2020. The problem of food and nutritional insecurity is severe in urban centers, where the global population is projected to increase (%/year) by 1.84, 1.63, and 1.44 between 2015 to 2020, 2020 to 2025, and 2025 to 2030, and it will increase overall from 54% in 2016 to 60% by 2030. The number of megacities (>10 million people) will increase from 34 in 2015 to 41 by 2030. The COVID-19 pandemic has aggravated food insecurity in urban centers because of the disruption in the food supply chain, aggravation of the physical and economic barriers that restrict access to food, and the catastrophic increase in food waste because of labor shortages. Thus, there is a need to adopt more resilient food systems, reduce food waste, and strengthen local food production. Enhancing availability at the household and community levels through home gardening and urban agriculture is an important strategy. Food production within the cities include small land farming in households, local community gardens, indoor and rooftop gardens, vertical farming, etc. Home gardening can play an important role in advancing food and nutritional security during and after the COVD-19 pandemic, while also strengthening the provisioning of numerous ecosystem services (i.e., plant biodiversity, microclimate, water runoff, water quality, human health). However, risks of soil contamination by heavy metals must be addressed.


title: Etiology of Childhood Pneumonia: What We Know, and What We Need to Know!: Based on 5th Dr. IC Verma Excellence Oration Award

text: Childhood community acquired pneumonia continues to be an important clinical problem at the individual, institutional and community levels. Determination of microbial etiology is critical to develop evidence-based management (therapeutic and prophylactic) decisions. For decades, the approach to this relied on culture of lung aspirate specimens obtained from children with radiographically confirmed pneumonia, before administering antibiotics. Such studies revealed the major bacteria associated with pneumonia, prompting the World Health Organization to develop a highly sensitive clinical definition of pneumonia and advocate empiric antibiotic therapy; in order to save lives (focusing on community settings lacking resources for diagnostic tests). However, it spawned research studies conducted in/from/by institutions enrolling children with the relatively non-specific WHO definition of pneumonia. Specificity got further compromised by abandoning lung aspiration and using naso/oro pharyngeal specimens; even in children who had received antibiotics. This led to the recovery of viruses more often than bacteria. The use of highly sensitive molecular based diagnostics (especially PCR) facilitated the detection of multiple organisms (bacteria, viruses, atypical organisms and even fungal species); making it difficult to attribute etiology in individual cases. This challenge was sought to be addressed through the multi-site PERCH Study (Pneumonia Etiology Research for Child Health), designed as a case-control study to conclusively determine the etiology of pneumonia. However, despite a slew of publications, the answer to the central question of etiology has not emerged so far. Since none of the PERCH Study sites was located in India, the Community Acquired Pneumonia Etiology Study (CAPES) was conducted at Chandigarh. This turned out to be the largest single-centre pneumonia etiology study, and generated a wealth of data. This article summarizes the current challenges in pneumonia etiology research; outlines the key observations from the PERCH and CAPES projects, as well as other important studies; and suggests a way forward for pneumonia etiology research in the current era.


Could Chloroquine /Hydroxychloroquine Be Harmful in Coronavirus Disease 2019 (COVID-19) Treatment?


title: IL-22 Plays a Critical Role in Maintaining Epithelial Integrity During Pulmonary Infection

text: Pulmonary infection is a leading cause of hospitalization in world. Lung damage due to infection and host mediated pathology can have life threatening consequences. Factors that limit lung injury and/or promote epithelial barrier function and repair are highly desirable as immunomodulatory therapeutics. Over the last decade, interleukin−22 has been shown to have pulmonary epithelial protective functions at the mucosal immune interface with bacterial and viral pathogens. This article summarizes recent findings in this area and provides perspective regarding the role of IL-22 in mucosal host defense.


title: COVID-19 e hospitalizações por SRAG no Brasil: uma comparação até a 12ª semana epidemiológica de 2020/ COVID-19 y las hospitalizaciones por el SRAG en Brasil: una comparación hasta la 12ª semana epidemiológica de 2020/ COVID-19 and hospitalizations for SARI in Brazil: a comparison up to the 12th epidemiological week of 2020

text: Resumo: A vigilância de síndrome respiratória aguda grave (SRAG) no Brasil visa a caracterizar a circulação dos vírus Influenza A e B em casos hospitalizados e óbitos, tendo sido ampliada em 2012 para incluir outros vírus respiratórios. A COVID-19 foi detectada no Brasil pela primeira vez na 9ª semana epidemiológica de 2020 e o teste para o vírus SARS-CoV-2 foi incluído no protocolo de vigilância a partir da 12ª semana epidemiológica. O objetivo deste estudo foi investigar o padrão de hospitalizações por SRAG no país após a entrada do SARS-CoV-2, comparando o perfil temporal, etário e de resultados laboratoriais com os anos de 2010 a 2019. Em 2020, a hospitalização por SRAG, contabilizada desde a data do primeiro caso de COVID-19 confirmado até a 12ª semana, superou o observado, no mesmo período, em cada um dos 10 anos anteriores. A faixa etária acima de 60 anos foi a mais acometida, em nível acima do histórico. Houve um aumento considerável de testes laboratoriais negativos, sugerindo a circulação de um vírus diferente dos presentes no painel. Concluímos que o aumento das hospitalizações por SRAG, a falta de informação específica sobre o agente etiológico e a predominância de casos entre idosos, no mesmo período de tempo em que cresce o número de casos novos de COVID-19, é coerente com a hipótese de que os casos graves da doença já estejam sendo detectados pela vigilância de SRAG com sobrecarga para o sistema de saúde. A inclusão da testagem para SARS-CoV-2 no protocolo de vigilância de SRAG e sua efetiva implementação são de grande importância para acompanhar a evolução dos casos graves da doença no país.


title: Keynote presentation at the eight international congress of behavioral medicine Mainz, Germany August 25–28, 2004: The pittsburgh common cold studies: Psychosocial predictors of susceptibility to respiratory infectious illness

text: This article provides a selected overview of 20 years of research on the role of psychosocial factors in susceptibility to upper respiratory infections. We present evidence from our laboratory that psychological stress is associated with increased risk for developing respiratory illness for persons intentionally exposed to a common cold virus, that the longer the duration of the stressor the greater the risk, and that stress association with susceptibility may be mediated by stress-induced disruption of the regulation of proinflammatory cytokines. We further provide evidence that social relationships (social integration and social support) are also associated with risk for respiratory illness: Social integration is associated with reduced risk irrespective of stress level and social support protects persons from the pathogenic influences of stress. Finally, we report recent evidence that lower levels of early childhood socio-economic status (SES) are associated with greater risk of viral-induced illness during adulthood, independent of adult SES.


title: Influenza vaccination and respiratory virus interference among Department of Defense personnel during the 2017–2018 influenza season

text: PURPOSE: Receiving influenza vaccination may increase the risk of other respiratory viruses, a phenomenon known as virus interference. Test-negative study designs are often utilized to calculate influenza vaccine effectiveness. The virus interference phenomenon goes against the basic assumption of the test-negative vaccine effectiveness study that vaccination does not change the risk of infection with other respiratory illness, thus potentially biasing vaccine effectiveness results in the positive direction. This study aimed to investigate virus interference by comparing respiratory virus status among Department of Defense personnel based on their influenza vaccination status. Furthermore, individual respiratory viruses and their association with influenza vaccination were examined. RESULTS: We compared vaccination status of 2880 people with non-influenza respiratory viruses to 3240 people with pan-negative results. Comparing vaccinated to non-vaccinated patients, the adjusted odds ratio for non-flu viruses was 0.97 (95% confidence interval (CI): 0.86, 1.09; p = 0.60). Additionally, the vaccination status of 3349 cases of influenza were compared to three different control groups: all controls (N = 6120), non-influenza positive controls (N = 2880), and pan-negative controls (N = 3240). The adjusted ORs for the comparisons among the three control groups did not vary much (range: 0.46–0.51). CONCLUSIONS: Receipt of influenza vaccination was not associated with virus interference among our population. Examining virus interference by specific respiratory viruses showed mixed results. Vaccine derived virus interference was significantly associated with coronavirus and human metapneumovirus; however, significant protection with vaccination was associated not only with most influenza viruses, but also parainfluenza, RSV, and non-influenza virus coinfections.


title: Discovery and Prevalence of Divergent RNA Viruses in European Field Voles and Rabbits

text: The advent of unbiased metagenomic virus discovery has revolutionized studies of virus biodiversity and evolution. Despite this, our knowledge of the virosphere, including in mammalian species, remains limited. We used unbiased metagenomic sequencing to identify RNA viruses in European field voles and rabbits. Accordingly, we identified a number of novel RNA viruses including astrovirus, rotavirus A, picorna-like virus and a narmovirus (paramyxovirus). In addition, we identified a sobemovirus and a novel luteovirus that likely originated from the rabbit diet. These newly discovered viruses were often divergent from those previously described. The novel astrovirus was most closely related to a virus sampled from the rodent-eating European roller bird (Coracias garrulous). PCR screening revealed that the novel narmovirus in the UK field vole had a prevalence of approximately 4%, and shared common ancestry with other rodent narmoviruses sampled globally. Two novel rotavirus A sequences were detected in a UK field vole and a French rabbit, the latter with a prevalence of 5%. Finally, a highly divergent picorna-like virus found in the gut of the French rabbit virus was only ~35% similar to an arilivirus at the amino acid level, suggesting the presence of a novel viral genus within the Picornaviridae.


title: Human bocavirus: Current knowledge and future challenges

text: Human bocavirus (HBoV) is a parvovirus isolated about a decade ago and found worldwide in both respiratory samples, mainly from early life and children of 6-24 mo of age with acute respiratory infection, and in stool samples, from patients with gastroenteritis. Since then, other viruses related to the first HBoV isolate (HBoV1), namely HBoV2, HBoV3 and HBoV4, have been detected principally in human faeces. HBoVs are small non-enveloped single-stranded DNA viruses of about 5300 nucleotides, consisting of three open reading frames encoding the first two the non-structural protein 1 (NS1) and nuclear phosphoprotein (NP1) and the third the viral capsid proteins 1 and 2 (VP1 and VP2). HBoV pathogenicity remains to be fully clarified mainly due to the lack of animal models for the difficulties in replicating the virus in in vitro cell cultures, and the fact that HBoV infection is frequently accompanied by at least another viral and/or bacterial respiratory and/or gastroenteric pathogen infection. Current diagnostic methods to support HBoV detection include polymerase chain reaction, real-time PCR, enzyme-linked immunosorbent assay and enzyme immunoassay using recombinant VP2 or virus-like particle capsid proteins, although sequence-independent amplification techniques combined with next-generation sequencing platforms promise rapid and simultaneous detection of the pathogens in the future. This review presents the current knowledge on HBoV genotypes with emphasis on taxonomy, phylogenetic relationship and genomic analysis, biology, epidemiology, pathogenesis and diagnostic methods. The emerging discussion on HBoVs as true pathogen or innocent bystander is also emphasized.


title: Novel Papillomaviruses in Free-Ranging Iberian Bats: No Virus–Host Co-evolution, No Strict Host Specificity, and Hints for Recombination

text: Papillomaviruses (PVs) are widespread pathogens. However, the extent of PV infections in bats remains largely unknown. This work represents the first comprehensive study of PVs in Iberian bats. We identified four novel PVs in the mucosa of free-ranging Eptesicus serotinus (EserPV1, EserPV2, and EserPV3) and Rhinolophus ferrumequinum (RferPV1) individuals and analyzed their phylogenetic relationships within the viral family. We further assessed their prevalence in different populations of E. serotinus and its close relative E. isabellinus. Although it is frequent to read that PVs co-evolve with their host, that PVs are highly species-specific, and that PVs do not usually recombine, our results suggest otherwise. First, strict virus–host co-evolution is rejected by the existence of five, distantly related bat PV lineages and by the lack of congruence between bats and bat PVs phylogenies. Second, the ability of EserPV2 and EserPV3 to infect two different bat species (E. serotinus and E. isabellinus) argues against strict host specificity. Finally, the description of a second noncoding region in the RferPV1 genome reinforces the view of an increased susceptibility to recombination in the E2-L2 genomic region. These findings prompt the question of whether the prevailing paradigms regarding PVs evolution should be reconsidered.


title: Nursing homes and COVID‐19: We can and should do better

text: The COVID-19 pandemic is providing us with many painful lessons particularly the vulnerability of individuals living with chronic conditions and the need for preparedness, coordination, and monitoring. Long-term care facilities, including nursing homes, skilled nursing facilities, and assisted living facilities, provide care for some of the most vulnerable populations in society, including older people and those with chronic medical conditions. In the United Kingdom, there are about 17,000 people living in nursing and residential care homes and 200,000 Australians live or stay in residential aged care on any given day.


title: Research Progress of Coronavirus Based on Bibliometric Analysis

text: Background: COVID-19 has become one of the most serious global epidemics in the 21st Century. This study aims to explore the distribution of research capabilities of countries, institutions, and researchers, and the hotspots and frontiers of coronavirus research in the past two decades. In it, references for funding support of urgent projects and international cooperation among research institutions are provided. Method: the Web of Science core collection database was used to retrieve the documents related to coronavirus published from 2003 to 2020. Citespace.5.6.R2, VOSviewer1.6.12, and Excel 2016 were used for bibliometric analysis. Results: 11,036 documents were retrieved, of which China and the United States have contributed the most coronavirus studies, Hong Kong University being the top contributor. Regarding journals, the Journal of Virology has contributed the most, while in terms of researchers, Yuen Kwok Yung has made the most contributions. The proportion of documents published by international cooperation has been rising for decades. Vaccines for SARS-CoV-2 are under development, and clinical trials of several drugs are ongoing. Conclusions: international cooperation is an important way to accelerate research progress and achieve success. Developing corresponding vaccines and drugs are the current hotspots and research directions.


title: Cardiovascular Disease Novel Coronavirus and the Search for Investigational Therapies

text: PURPOSE: The primary purpose of the current study was to investigate and summarize the registered trials that listed COVID-19 as the primary condition. METHODS: We performed a search on ClinicalTrials.gov using the independent search terms COVID-19, SARS, and SARS COV2, and then downloaded the data file on March 23, 2020. All trials were downloaded to a csv file and searched for appropriateness. RESULTS: Fifty-six of 124 (45.2%) registered trials were listed as recruiting. The majority (85, 68.5%) classified their study as interventional, 37 (29.8%) classified as observational and one (0.8%) each classified their study as either expanded access:individual patients | treatment IND/Protocol or expanded access:intermediate-size population | treatment IND/Protocol. There were 67 (54.0%) of the trials that listed drug as the type of study. Immunological and antiviral trials were the greatest, representing approximately 30% and 21%, respectively. When immunological and antiviral drugs were used alone or in combination, they represented 41.9% and 34.4%, respectively. Anti-malarial agents are represented in 7.5% of trials. Approximately 14% of trials involved Traditional Chinese Medicine. The aforementioned study agents used solely or in combination represented approximately 80% of therapeutic approaches to COVID19. CONCLUSION: There was a large and quick response on ClinicalTrials.gov to the COVID-19 outbreak. Many of the registered trials are currently recruiting new patients, while some will begin in the near future. Specific potential experimental therapies, including dosing and monitoring, might be found by reviewing content. Within clinicaltrials.gov, patients, family members, health care professionals and researchers can search and find ongoing and future trials for COVID-19.


title: Detecting Emerging Diseases in Farm Animals through Clinical Observations

text: Predicting emerging diseases is among the most difficult challenges facing researchers and health managers. We present available approaches and tools to detect emerging diseases in animals based on clinical observations of farm animals by veterinarians. Three information systems are described and discussed: Veterinary Practitioner Aided Disease Surveillance in New Zealand, the Rapid Syndrome Validation Project—Animal in the United States, and "émergences" in France. These systems are based on syndromic surveillance with the notification of every case or of specific clinical syndromes or on the notification of atypical clinical cases. Data are entered by field veterinarians into forms available through Internet-accessible devices. Beyond challenges of implementing new information systems, minimizing economic and health effects from emerging diseases in animals requires strong synergies across a group of field partners, in research, and in international animal and public health customs and practices.


title: COVID‐19: what if the brain had a role in causing the deaths?

text: In the last few weeks Italy first, and then several other countries across the world, have been swept up by the deadly wave of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the illness named COVID-19, from the acronym CO (corona) VI (virus) D (disease) and 19 (year of the virus identification). The medical community is working day and night to assist affected people and experts in communicable diseases are striving in multiple ways to understand the progression of events leading to the lethal respiratory syndrome.


title: Development and evaluation of recombinase-aided amplification assays incorporating competitive internal controls for detection of human adenovirus serotypes 3 and 7

text: BACKGROUND: Human adenoviruses are a common group of viruses that cause acute infectious diseases. Human adenovirus (HAdV) 3 and HAdV 7 cause major outbreaks of severe pneumonia. A reliable and practical method for HAdV typing in clinical laboratories is lacking. A simple, rapid and accurate molecular typing method for HAdV may facilitate clinical diagnosis and epidemiological control. METHODS: We developed and evaluated duplex real-time recombinase-aided amplification (RAA) assays incorporating competitive internal controls for detection of HAdV 3 and HAdV 7, respectively. The assays were performed in a one-step in a single tube reaction at 39° for 20 min. RESULTS: The analytical sensitivities of the duplex RAA assays for HAdV 3 and HAdV 7 were 5.0 and 14.8 copies per reaction, respectively (at 95% probability by probit regression analysis). No cross-reaction was observed with other types of HAdV or other common respiratory viruses. The duplex RAA assays were used to detect 152 previously-defined HAdV-positive samples. These results agreed with those obtained using a published triplex quantitative real-time PCR protocol. CONCLUSIONS: We provide the first report of internally-controlled duplex RAA assays for the detection of HAdV 3 and HAdV 7. These assays effectively reduce the rate of false negative results and may be valuable for detection of HAdV 3 and HAdV 7 in clinical laboratories, especially in resource-poor settings.


title: Critical Assessment of the Important Residues Involved in the Dimerization and Catalysis of MERS Coronavirus Main Protease

text: BACKGROUND: A highly pathogenic human coronavirus (CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in Jeddah and other places in Saudi Arabia, and has quickly spread to European and Asian countries since September 2012. Up to the 1(st) October 2015 it has infected at least 1593 people with a global fatality rate of about 35%. Studies to understand the virus are necessary and urgent. In the present study, MERS-CoV main protease (M(pro)) is expressed; the dimerization of the protein and its relationship to catalysis are investigated. METHODS AND RESULTS: The crystal structure of MERS-CoV M(pro) indicates that it shares a similar scaffold to that of other coronaviral M(pro) and consists of chymotrypsin-like domains I and II and a helical domain III of five helices. Analytical ultracentrifugation analysis demonstrated that MERS-CoV M(pro) undergoes a monomer to dimer conversion in the presence of a peptide substrate. Glu169 is a key residue and plays a dual role in both dimerization and catalysis. The mutagenesis of other residues found on the dimerization interface indicate that dimerization of MERS-CoV M(pro) is required for its catalytic activity. One mutation, M298R, resulted in a stable dimer with a higher level of proteolytic activity than the wild-type enzyme. CONCLUSIONS: MERS-CoV M(pro) shows substrate-induced dimerization and potent proteolytic activity. A critical assessment of the residues important to these processes provides insights into the correlation between dimerization and catalysis within the coronaviral M(pro) family.


title: Surgical mask filter and fit performance

text: BACKGROUND: Surgical masks have been used since the early 1900s to minimize infection of surgical wounds from wearer-generated bacteria. There is ongoing debate, however, whether surgical masks can meet the expectations of respiratory protection devices. The goal of this study was to evaluate the filter performance and facial fit of a sample of surgical masks. METHODS: Filter penetration was measured for at least 3 replicates of 9 surgical masks using monodisperse latex sphere aerosols (0.895, 2.0, and 3.1 μm) at 6 L/min and 0.075-μm sodium chloride particles at 84 L/min. Facial fit was measured on 20 subjects for the 5 masks with lowest particle penetration, using both qualitative and quantitative fit tests. RESULTS: Masks typically used in dental settings collected particles with significantly lower efficiency than those typically used in hospital settings. All subjects failed the unassisted qualitative fit test on the first exercise (normal breathing). Eighteen subjects failed the assisted qualitative fit tests; 60% failed on the first exercise. Quantitative fit factors ranged from 2.5 to 9.6. CONCLUSION: None of these surgical masks exhibited adequate filter performance and facial fit characteristics to be considered respiratory protection devices.


title: Respiratory Infections with Particular Emphasis on Influenza Virus Activity in Persons Over 14 Years of Age in the Epidemic Season 2016/2017 in Poland

text: Influenza viruses cause respiratory infections every epidemic season regardless of the patient’s age. The aim of this study was to determine the activity of respiratory viruses in the epidemic season 2016/2017 in Poland, with particular emphasis on influenza viruses among people aged over 14. There were 2982 clinical samples taken from patients from four age groups: 15–25, 26–44, 45–64, and ≥ 65 years tested under the Sentinel and non-Sentinel surveillance programs. The presence of influenza viruses was confirmed in more than 40% of cases, the predominant type was influenza A virus unsubtyped, followed by subtype A/H3N2/. The results for the four age groups indicate that the highest number of confirmed respiratory viruses was recorded in individuals ≥65 years of age, slightly less, in the decreasing order, in the age groups 45–64 years, 15–25 years, and 26–44 years. Influenza type B infections were observed only in sporadic cases. Given the epidemiological data, epidemic season 2016/2017 was characterized by similar dynamics compared to the previous season in Poland and also in most of the European countries. More than 4 million cases and suspected cases of influenza and influenza-like viruses have been reported in Poland, more than 16,000 hospitalizations, and 25 deaths, of which 20 cases occurred among people ≥65 years of age in the epidemic season 2016/2017.


title: Persistence of Low-Pathogenic Avian Influenza H5N7 and H7N1 Subtypes in House Flies (Diptera: Muscidae)

text: Avian influenza caused by avian influenza virus (AIV) has a negative impact on poultry production. Low-pathogenic AIV (LPAIV) is naturally present in wild birds, and the introduction of the virus into domestic poultry is assumed to occur through contact with wild birds and by human activity, including the movement of live and dead poultry, and fomites such as clothing and vehicles. At present, the possible role of insects in the spread of AIV is dubious. The objective of the present work was to investigate the potential transmission of LPAIV by persistence of the virus in the alimentary tract of house flies, Musca domestica L. (Diptera: Muscidae). Flies were fed three virus concentrations of two AIV strains and then incubated at different temperatures for up to 24 h. The persistence of the two virus strains in the flies declined with increasing incubation temperatures and incubation periods. Similarly, increased virus uptake by the flies increased the persistence of virus. Persistence of infective AIV in flies differed significantly between the two virus strains. The laboratory experiments of the present study indicate that the house fly can be a potential carrier of AIV.


Coronavirus Vaccine-Associated Lung Immunopathology-What Is The Significance?


title: COVID-19 Infection Diagnosis: Potential Impact of Isothermal Amplification Technology to Reduce Community Transmission of SARS-CoV-2

text: The current coronavirus disease 2019 (COVID-19) pandemic is largely driven by community transmission, after 2019 novel Coronavirus (2019-nCoV or SARS-CoV-2) crosses the borders. To stop the spread, rapid testing is required at community clinics and hospitals. These rapid tests should be comparable with the standard PCR technology. Isothermal amplification technology provides an excellent alternative that is highly amenable to resource limited settings, where expertise and infrastructure to support PCR are not available. In this review, we provide a brief description of isothermal amplification technology, its potential and the gaps that need to be considered for SARS-CoV-2 detection. Among this emerging technology, loop-mediated amplification (LAMP), recombinase polymerase amplification (RPA) and Nicking enzyme-assisted reaction (NEAR) technologies have been identified as potential platforms that could be implemented at community level, without samples referral to a centralized laboratory and prolonged turnaround time associated with the standard COVID-19 RT-PCR test. LAMP, for example, has recently been shown to be comparable with PCR and could be performed in less than 30 min by non-laboratory staff, without RNA extractions commonly associated with PCR. Interestingly, NEAR (ID NOW™ COVID-19 (Abbott, IL, USA) was able to detect the virus in 5 min. More so, isothermal platforms are cost effective and could easily be scaled up to resource limited settings. Diagnostics developers, scientific community and commercial companies could consider this alternative method to help stop the spread of COVID-19.


“Sorry ICU, I’m an Ophthalmologist!”


Therapeutic approach to skin reactions caused by personal protective equipment (PPE) during COVID‐19 pandemic: An experience from a tertiary hospital in Granada, Spain


title: Analysis of SARS-CoV-2 RNA-dependent RNA polymerase as a potential therapeutic drug target using a computational approach

text: BACKGROUND: The Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) outbreak originating in Wuhan, China, has raised global health concerns and the pandemic has now been reported on all inhabited continents. Hitherto, no antiviral drug is available to combat this viral outbreak. METHODS: Keeping in mind the urgency of the situation, the current study was designed to devise new strategies for drug discovery and/or repositioning against SARS-CoV-2. In the current study, RNA-dependent RNA polymerase (RdRp), which regulates viral replication, is proposed as a potential therapeutic target to inhibit viral infection. RESULTS: Evolutionary studies of whole-genome sequences of SARS-CoV-2 represent high similarity (> 90%) with other SARS viruses. Targeting the RdRp active sites, ASP760 and ASP761, by antiviral drugs could be a potential therapeutic option for inhibition of coronavirus RdRp, and thus viral replication. Target-based virtual screening and molecular docking results show that the antiviral Galidesivir and its structurally similar compounds have shown promise against SARS-CoV-2. CONCLUSIONS: The anti-polymerase drugs predicted here—CID123624208 and CID11687749—may be considered for in vitro and in vivo clinical trials.


title: Nouvelles stratégies pour la conception de molécules antivirales

text: Résumé La recherche antivirale est une discipline encore récente et le nombre de molécules disponibles pour lutter contre les infections virales demeure insuffisant. Pourtant, tant les pathologies causées par des virus endémiques ou émergents que l’existence de résistance de certains virus aux antiviraux rendent indispensables une recherche constante de nouvelles molécules antivirales. Parallèlement à la mise au point des molécules traditionnelles tels que les analogues nucléosidiques, dont l’efficacité n’est plus à démontrer, l’industrie pharmaceutique se tourne aujourd’hui vers de nouvelles solutions antivirales telles que les peptides, qui constituent un nouveau champ d’exploration pour la thérapie. Les progrès importants et récents de disciplines comme la génomique, la protéomique ou la biologie structurale ont permis d’améliorer notre connaissance fondamentale du monde viral. Ces progrès peuvent être mis à profit pour créer de façon rationnelle de nouveaux médicaments plus sélectifs et plus efficaces. L’identification et la mise au point de ces molécules nécessitent l’utilisation de techniques récentes comme le criblage à haut-débit de banques de composés combinatoires où l’utilisation de nouveaux outils bioinformatiques. Cette revue a pour but de présenter certaines méthodes récentes de mise au point de molécules antivirales. Summary Antiviral research is a recent discipline and the number of molecules available to fight against viral infections remains still insufficient. However, both diseases caused by emerging endemic viruses and the existence of resistance from some viruses against antiviral make necessary a constant search for new antiviral drugs. Parallel to the development of traditional molecules such as nucleoside analogues, whose effectiveness is well demonstrated, pharmaceutical industry is now turning to new solutions such as antiviral peptides, which constitute a new exploration field in therapy. The recent progress in disciplines such as genomics, proteomics and structural biology have improved our fundamental understanding of the viral world. These advances can be used to efficiently create new drugs more selective and more effective. Identification and development of these molecules require the use of newer techniques such as high-throughput screening of combinatorial compound libraries and the use of new bioinformatics tools. This review aims to present some recent methods for the development of antiviral molecules.


title: Pulmonary Diseases and Corticosteroids

text: Steroids (corticosteroids) are anti-inflammatory drugs. Corticosteroids are used in many pulmonary conditions. Corticosteroids have a proven beneficial role in asthma, croup (Laryngotracheobronchitis), decreasing the risk and severity of respiratory distress syndrome (RDS), allergic bronchopulmonary aspergillosis, interstitial lung disease, hemangioma of trachea, Pulmonary eosinophillic disorders. Role of corticosteroids is controversial in many conditions e.g. idiopathic pulmonary hemosiderosis, bronchiolitis, hypersensitivity pneumonitis, hyperplasia of thymus, bronchiolitis, acute respiratory distress syndrome, aspiration syndromes, atypical pneumonias, laryngeal diphtheria, AIDS, SARS, sarcoidosis, meconium aspiration syndrome (MAS), pulmonary haemorrhage, bronchitis, bronchiolitis obliterans with organizing pneumonia in JRA, histiocytosis, á-1 antitrypsin deficiency, bordtella pertusis, pulmonary involvement in histiocytosis. However these are used empirically in many of these conditions despite lack of clear evidence in favour. There is concern about their side effects, especially on growth. Systemic steroids are associated with significant adverse effects. Pulmonary conditions have a strategic advantage that inhaled corticosteroids are useful in many of these. Although inhaled preparations of corticosteroids have been developed to maximise effective treatment of lung diseases characterised by inflammation and reduce the frequency of harmful effects, these have not been eliminated. There are situations where only systemic steroids are useful. Clinicians must weigh the benefits against the potential detrimental effects. It is recommended that standard protocols for use of steroids available in literature should be followed, always keeping a watch on the potential hazards of prolonged use.


title: Cattle with increased severity of bovine respiratory disease complex exhibit decreased capacity to protect against histone cytotoxicity(,)

text: Bovine respiratory disease complex (BRDC) is the leading cause of morbidity and mortality in feedlot cattle. Significant inflammation and lesions are often observed in lungs of infected cattle. During acute inflammatory responses, histones contribute to mortality in rodents and humans and serum proteins can protect against histone-induced cytotoxicity. We hypothesized that cattle experiencing chronic or fatal cases of BRDC have reduced ability to protect against cytotoxic effects of histones. Serum samples were collected from 66 bull calves at the time of normal feedlot processing procedures. Animals were retrospectively assigned to groups consisting of calves never treated for BRDC (control [CONT]; n = 10), calves treated with antimicrobials once for BRDC (1T; n = 16), calves treated twice for BRDC (2T; n = 13), calves treated 3 times for BRDC (3T; n = 14), or calves treated 4 times for BRDC (4T; n = 13). Samples were also collected each time animals received antimicrobial treatment; animals within a group were further sorted by calves that recovered and calves that died to test histone cytotoxicity. Bovine kidney cells were cultured in duplicate in 96-well plates and exposed to 0 or 50 μg/mL of total histones for 18 h with 1% serum from each animal. Cell viability was assessed by the addition of resazurin for 6 h followed by fluorescent quantification. Fluorescent values from serum alone were subtracted from values obtained for histone treatment for each animal. Serum from CONT, 1T, and 2T at initial processing all exhibited a similar (P > 0.10) response to histone treatment with fluorescent values of –312 ± 557, –1,059 ± 441, and –975 ± 489, respectively. However, 3T and 4T demonstrated an impaired capacity (P < 0.05) to protect against histones (–2,778 ± 471 and –3,026 ± 489) at initial processing when compared to the other groups. When sorted by mortality within group, calves that were treated twice and recovered (–847 ± 331) demonstrated a greater (P < 0.05) protective capacity than calves that were treated twice and died (–2,264 ± 412), indicating that calves that contract BRDC and ultimately die might have reduced protective capacity against histone cytotoxicity. Results suggest that calves that require multiple treatments for BRDC have reduced ability to protect against cytotoxicity of histones. Understanding the primary mechanism responsible for protecting against histone cytotoxicity could lead to improved identification of animals susceptible to severe cases of BRDC, improved focus and use of available resources, or better treatments for severe cases of BRDC.


title: Comparative Epidemiology of Human Infections with Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome Coronaviruses among Healthcare Personnel

text: The largest nosocomial outbreak of Middle East respiratory syndrome (MERS) occurred in South Korea in 2015. Health Care Personnel (HCP) are at high risk of acquiring MERS-Coronavirus (MERS-CoV) infections, similar to the severe acute respiratory syndrome (SARS)-Coronavirus (SARS-CoV) infections first identified in 2003. This study described the similarities and differences in epidemiological and clinical characteristics of 183 confirmed global MERS cases and 98 SARS cases in Taiwan associated with HCP. The epidemiological findings showed that the mean age of MERS-HCP and total MERS cases were 40 (24~74) and 49 (2~90) years, respectively, much older than those in SARS [SARS-HCP: 35 (21~68) years, p = 0.006; total SARS: 42 (0~94) years, p = 0.0002]. The case fatality rates (CFR) was much lower in MERS-HCP [7.03% (9/128)] or SARS-HCP [12.24% (12/98)] than the MERS-non-HCP [36.96% (34/92), p<0.001] or SARS-non-HCP [24.50% (61/249), p<0.001], however, no difference was found between MERS-HCP and SARS-HCP [p = 0.181]. In terms of clinical period, the days from onset to death [13 (4~17) vs 14.5 (0~52), p = 0.045] and to discharge [11 (5~24) vs 24 (0~74), p = 0.010] and be hospitalized days [9.5 (3~22) vs 22 (0~69), p = 0.040] were much shorter in MERS-HCP than SARS-HCP. Similarly, days from onset to confirmation were shorter in MERS-HCP than MERS-non-HCP [6 (1~14) vs 10 (1~21), p = 0.044]. In conclusion, the severity of MERS-HCP and SARS-HCP was lower than that of MERS-non-HCP and SARS-non-HCP due to younger age and early confirmation in HCP groups. However, no statistical difference was found in MERS-HCP and SARS-HCP. Thus, prevention of nosocomial infections involving both novel Coronavirus is crucially important to protect HCP.


title: A mouse-adapted SARS-CoV-2 model for the evaluation of COVID-19 medical countermeasures

text: Coronaviruses are prone to emergence into new host species most recently evidenced by SARS-CoV-2, the causative agent of the COVID-19 pandemic. Small animal models that recapitulate SARS-CoV-2 disease are desperately needed to rapidly evaluate medical countermeasures (MCMs). SARS-CoV-2 cannot infect wildtype laboratory mice due to inefficient interactions between the viral spike (S) protein and the murine ortholog of the human receptor, ACE2. We used reverse genetics to remodel the S and mACE2 binding interface resulting in a recombinant virus (SARS-CoV-2 MA) that could utilize mACE2 for entry. SARS-CoV-2 MA replicated in both the upper and lower airways of both young adult and aged BALB/c mice. Importantly, disease was more severe in aged mice, and showed more clinically relevant phenotypes than those seen in hACE2 transgenic mice. We then demonstrated the utility of this model through vaccine challenge studies in immune competent mice with native expression of mACE2. Lastly, we show that clinical candidate interferon (IFN) lambda-1a can potently inhibit SARS-CoV-2 replication in primary human airway epithelial cells in vitro, and both prophylactic and therapeutic administration diminished replication in mice. Our mouse-adapted SARS-CoV-2 model demonstrates age-related disease pathogenesis and supports the clinical use of IFN lambda-1a treatment in human COVID-19 infections.


title: Antibody Quality and Protection from Lethal Ebola Virus Challenge in Nonhuman Primates Immunized with Rabies Virus Based Bivalent Vaccine

text: We have previously described the generation of a novel Ebola virus (EBOV) vaccine platform based on (a) replication-competent rabies virus (RABV), (b) replication-deficient RABV, or (c) chemically inactivated RABV expressing EBOV glycoprotein (GP). Mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated RABV/EBOV vaccines. Here, we evaluated these vaccines in nonhuman primates. Our results indicate that all three vaccines do induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced antibodies against EBOV GP differ in their target, affinity, or the isotype. Our results show that IgG1-biased humoral responses as well as high levels of GP-specific antibodies were beneficial for the control of EBOV infection after immunization. These results further support the concept that a successful EBOV vaccine needs to induce strong antibodies against EBOV. We also showed that a dual vaccine against RABV and filoviruses is achievable; therefore addressing concerns for the marketability of this urgently needed vaccine.


Chinese pharmacists’ rapid response to the COVID-19 outbreak


title: Oligonucleotide fingerprints of antigenically related bovine coronavirus and human coronavirus OC43

text: Virion RNAs from the bovine enteric coronavirus and the human respiratory coronavirus OC43 were compared by one dimensional gel electrophoresis and by oligonucleotide fingerprinting. For each virus, approximately 55 per cent of the RNA migrated as a 6.8 Md species, 10 per cent as a 0.68 Md species, and 15 per cent as heterogeneous small molecular weight RNA. A sequence homology of greater than 96 per cent was observed between the 6.8 Md species from the two viruses. The 0.68 Md RNA is apparently an intravirion, subgenomic, polyadenylated molecule based on RNAse studies, oligo (dT)-cellulose chromatography, and hybridization to a cDNA clone of the 3′ terminal 1.19 Kb region of the bovine coronavirus genome.


title: Evaluating Transmission Heterogeneity and Super-Spreading Event of COVID-19 in a Metropolis of China

text: COVID-19 caused rapid mass infection worldwide. Understanding its transmission characteristics, including heterogeneity and the emergence of super spreading events (SSEs) where certain individuals infect large numbers of secondary cases, is of vital importance for prediction and intervention of future epidemics. Here, we collected information of all infected cases (135 cases) between 21 January and 26 February 2020 from official public sources in Tianjin, a metropolis of China, and grouped them into 43 transmission chains with the largest chain of 45 cases and the longest chain of four generations. Utilizing a heterogeneous transmission model based on branching process along with a negative binomial offspring distribution, we estimated the reproductive number R and the dispersion parameter k (lower value indicating higher heterogeneity) to be 0.67 (95% CI: 0.54–0.84) and 0.25 (95% CI: 0.13–0.88), respectively. A super-spreader causing six infections was identified in Tianjin. In addition, our simulation allowing for heterogeneity showed that the outbreak in Tianjin would have caused 165 infections and sustained for 7.56 generations on average if no control measures had been taken by local government since 28 January. Our results highlighted more efforts are needed to verify the transmission heterogeneity of COVID-19 in other populations and its contributing factors.


title: SARS‐CoV nucleocapsid protein binds to hUbc9, a ubiquitin conjugating enzyme of the sumoylation system

text: SARS‐CoV is a newly identified coronavirus (CoV) that causes severe acute respiratory syndrome (SARS). The SARS‐CoV nucleocapsid (N) protein is an important structural and functional protein. To identify cellular proteins that interact with the SARS‐CoV N protein and to elucidate the possible involvement of N protein in SARS‐CoV pathogenesis, a human lymphocyte cDNA library was screened using a yeast two‐hybrid system assay. hUbc9, a ubiquitin conjugating enzyme of sumoylation system, was found to interact specifically with the N protein, implying the post‐translational sumoylation of the N protein. Mapping studies localized the critical N sequences for this interaction to amino acids 170–210, which includes the SR‐rich motif. However, the consensus motif of sumoylation GK(62)EE in the N protein is not responsible for binding to hUbc9. Mutations of hUbc9 at the enzyme active site C93A or C93S severely impair the interaction with the N protein. The two proteins were also shown to colocalize in the cytoplasm of the transfected 293T cells. This is the first report demonstrating the interaction of hUbc9 with a structural protein of plus‐strand RNA viruses, indicating a new drug target for SARS‐CoV. J. Med. Virol. 78:1365–1373, 2006. © 2006 Wiley‐Liss, Inc.


title: A Functional Role for ADAM10 in Human Immunodeficiency Virus Type-1 Replication

text: BACKGROUND: Gene trap insertional mutagenesis was used as a high-throughput approach to discover cellular genes participating in viral infection by screening libraries of cells selected for survival from lytic infection with a variety of viruses. Cells harboring a disrupted ADAM10 (A Disintegrin and Metalloprotease 10) allele survived reovirus infection, and subsequently ADAM10 was shown by RNA interference to be important for replication of HIV-1. RESULTS: Silencing ADAM10 expression with small interfering RNA (siRNA) 48 hours before infection significantly inhibited HIV-1 replication in primary human monocyte-derived macrophages and in CD4(+ )cell lines. In agreement, ADAM10 over-expression significantly increased HIV-1 replication. ADAM10 down-regulation did not inhibit viral reverse transcription, indicating that viral entry and uncoating are also independent of ADAM10 expression. Integration of HIV-1 cDNA was reduced in ADAM10 down-regulated cells; however, concomitant 2-LTR circle formation was not detected, suggesting that HIV-1 does not enter the nucleus. Further, ADAM10 silencing inhibited downstream reporter gene expression and viral protein translation. Interestingly, we found that while the metalloprotease domain of ADAM10 is not required for HIV-1 replication, ADAM15 and γ-secretase (which proteolytically release the extracellular and intracellular domains of ADAM10 from the plasma membrane, respectively) do support productive infection. CONCLUSIONS: We propose that ADAM10 facilitates replication at the level of nuclear trafficking. Collectively, our data support a model whereby ADAM10 is cleaved by ADAM15 and γ-secretase and that the ADAM10 intracellular domain directly facilitates HIV-1 nuclear trafficking. Thus, ADAM10 represents a novel cellular target class for development of antiretroviral drugs.


title: A new simple method of handmade face shield using A4‐size OHP sheet, during the COVID‐19 pandemic

text: Due to the outbreak of COVID‐19, many healthcare providers face the problem of lack of personal protective equipment (PPE) including face shields.(1‐3) However, we need to protect ourselves using standard PPE and continue to perform necessary endoscopic procedures. Skamnelos et. al reported a method to handmake face shields by attaching a sponge and an elastic band to an A4‐size OHP transparent sheet.(4) Yet, preparing such materials in large numbers can be difficult. To solve this problem, we present an alternate, easy method to make face shields with low‐cost materials along with the A4‐size OHP transparent sheet.


title: Concomitant Infection with COVID-19 and Mycoplasma Pneumoniae

text: In late 2019, cases of atypical pneumonia caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were first reported in Wuhan, China. The disease was officially called coronavirus disease 2019 (COVID-19) and has been declared a pandemic disease by the World Health Organization (WHO). The clinical symptoms may include fever, cough, fatigue, headache, and diarrhea. The radiographic features comprise various presentations, including ground-glass opacities, tiny nodules, and consolidation. However, some atypical pathogens related to community-acquired pneumonia (CAP) may share similar presentations. They may be difficult to distinguish according to the clinical presentation and radiographic findings. Recently, there have been several reports reminding physicians to heed the possibility of co-infection with other pathogens in patients diagnosed with COVID-19. We report a COVID-19 patient co-infected with Mycoplasma pneumoniae who recovered well after combination therapy. We propose that all COVID-19 patients should undergo a meticulous screening routine to ensure that they receive adequate treatments.


title: Spatial and temporal epidemiological analysis in the Big Data era

text: Abstract Concurrent with global economic development in the last 50 years, the opportunities for the spread of existing diseases and emergence of new infectious pathogens, have increased substantially. The activities associated with the enormously intensified global connectivity have resulted in large amounts of data being generated, which in turn provides opportunities for generating knowledge that will allow more effective management of animal and human health risks. This so-called Big Data has, more recently, been accompanied by the Internet of Things which highlights the increasing presence of a wide range of sensors, interconnected via the Internet. Analysis of this data needs to exploit its complexity, accommodate variation in data quality and should take advantage of its spatial and temporal dimensions, where available. Apart from the development of hardware technologies and networking/communication infrastructure, it is necessary to develop appropriate data management tools that make this data accessible for analysis. This includes relational databases, geographical information systems and most recently, cloud-based data storage such as Hadoop distributed file systems. While the development in analytical methodologies has not quite caught up with the data deluge, important advances have been made in a number of areas, including spatial and temporal data analysis where the spectrum of analytical methods ranges from visualisation and exploratory analysis, to modelling. While there used to be a primary focus on statistical science in terms of methodological development for data analysis, the newly emerged discipline of data science is a reflection of the challenges presented by the need to integrate diverse data sources and exploit them using novel data- and knowledge-driven modelling methods while simultaneously recognising the value of quantitative as well as qualitative analytical approaches. Machine learning regression methods, which are more robust and can handle large datasets faster than classical regression approaches, are now also used to analyse spatial and spatio-temporal data. Multi-criteria decision analysis methods have gained greater acceptance, due in part, to the need to increasingly combine data from diverse sources including published scientific information and expert opinion in an attempt to fill important knowledge gaps. The opportunities for more effective prevention, detection and control of animal health threats arising from these developments are immense, but not without risks given the different types, and much higher frequency, of biases associated with these data.


title: RNA editing in the phosphoprotein gene of the human parainfluenza virus type 3

text: Abstract RNA editing of the human parainfluenza virus type 3 (HPIV3) phosphoprotein (P) gene was found to occur for the accession of an alternate discontinuous cistron. Editing occurred within a purine-rich sequence (AAUUAAAAAAGGGGG) found at the mRNA nucleotides 791–805. This sequence resembles an HPIV3 consensus transcription termination sequence and is located at the 5′-end of the putative D protein coding sequences. Editing at an alternate site (AAUUGGAAAGGAAAGG), mRNA nucleotides 1121–1136, for accession of a conserved V cistron, which is present in a number of paramyxovirus P genes, was not found to occur in HPIV3. In contrast with many other paramyxoviruses, editing was indiscriminate with the insertion of 1–12 additional G residues not present in the gene template. RNA editing was found to occur in both in vivo (HPIV3 infected cells) and in vitro (purified nucleocapsid complexes) synthesized mRNAs. Further, the in vitro prepared mRNA was edited regardless of whether the nucleocapsid complexes were transcribed in the presence or absence of uninfected human lung carcinoma (HLC) cell lysates. These results support the notion that RNA editing appears to be exclusively a function of viral proteins.


Recently published article by Dr Tang and colleagues on ''Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia'' highlighted that disseminated intravascular coagulation is common severe respiratory failure patients with Covid 191 . Novel Coronavirus (Covid-19) infection leading to pneumonia and severe acute respiratory distress syndrome (ARDS) was first reported in Wuhan, Hubei Province, China and has subsequently spread to almost all other countries in the world. On 11/03/2020, WHO declared the Covid-19 outbreak a global pandemic.


title: An evaluation of contaminated complete feed as a vehicle for porcine epidemic diarrhea virus infection of naïve pigs following consumption via natural feeding behavior: proof of concept

text: BACKGROUND: Since its initial detection in May 2013, porcine epidemic diarrhea virus (PEDV) has spread rapidly throughout the US swine industry. Initially, contaminated feed was proposed as a risk factor for PEDV; however, data were not available to support this theory. Here we provide proof of concept of this risk by describing a novel means for recovering PEDV-contaminated complete feed material from commercial swine sites and conducting an in vivo experiment to prove its infectivity. RESULTS: For on-farm detection of PEDV RNA in feed, paint rollers were used to collect material from at-risk feed bins from 3 clinically affected breeding herds. This material was tested by PCR and determined to be positive for PEDV-RNA (Ct = 19.50-22.20 range). To test infectivity, this material was pooled (Ct = 20.65) and a Treatment group of 3-week old PEDV-naïve piglets were allowed to consume it via natural feeding behavior. For the purpose of a Positive control, piglets were allowed to ingest feed spiked with stock PEDV (Ct = 18.23) while the negative control group received PEDV-free feed. Clinical signs of PEDV infection (vomiting and diarrhea) and viral shedding were observed in both the Positive control and Treatment group’ post-consumption with virus and microscopic lesions detected in intestinal samples No evidence of infection was observed in the Negative controls. CONCLUSIONS: These data provide proof of concept that contaminated complete feed can serve as a vehicle for PEDV infection of naïve pigs using natural feeding behavior.


title: Retention strategies in longitudinal cohort studies: a systematic review and meta-analysis

text: BACKGROUND: Participant retention strategies that minimise attrition in longitudinal cohort studies have evolved considerably in recent years. This study aimed to assess, via systematic review and meta-analysis, the effectiveness of both traditional strategies and contemporary innovations for retention adopted by longitudinal cohort studies in the past decade. METHODS: Health research databases were searched for retention strategies used within longitudinal cohort studies published in the 10-years prior, with 143 eligible longitudinal cohort studies identified (141 articles; sample size range: 30 to 61,895). Details on retention strategies and rates, research designs, and participant demographics were extracted. Meta-analyses of retained proportions were performed to examine the association between cohort retention rate and individual and thematically grouped retention strategies. RESULTS: Results identified 95 retention strategies, broadly classed as either: barrier-reduction, community-building, follow-up/reminder, or tracing strategies. Forty-four of these strategies had not been identified in previous reviews. Meta-regressions indicated that studies using barrier-reduction strategies retained 10% more of their sample (95%CI [0.13 to 1.08]; p = .01); however, studies using follow-up/reminder strategies lost an additional 10% of their sample (95%CI [− 1.19 to − 0.21]; p = .02). The overall number of strategies employed was not associated with retention. CONCLUSIONS: Employing a larger number of retention strategies may not be associated with improved retention in longitudinal cohort studies, contrary to earlier narrative reviews. Results suggest that strategies that aim to reduce participant burden (e.g., flexibility in data collection methods) might be most effective in maximising cohort retention. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12874-018-0586-7) contains supplementary material, which is available to authorized users.


title: When half of the population died: the epidemic of hemorrhagic fevers of 1576 in Mexico

text: During the 16th century, Mexico suffered a demographic catastrophe with few parallels in world's history. In 1519, the year of the arrival of the Spaniards, the population in Mexico was estimated to be between 15 and 30 million inhabitants. Eighty-one years later, in 1600, only two million remained. Epidemics (smallpox, measles, mumps), together with war, and famine have been considered to be the main causes of this enormous population loss. However, re-evaluation of historical data suggests that approximately 60–70% of the death toll was caused by a series of epidemics of hemorrhagic fevers of unknown origin. In order to estimate the impact of the 1576 epidemic of hemorrhagic fevers on the population we analyzed the historical record and data from the 1570 and 1580 censuses of 157 districts. The results identified several remarkable aspects of this epidemic: First, overall, the population loss for these 157 districts was 51.36%. Second, there was a clear ethnic preference of the disease, the Spanish population was minimally affected whereas native population had high mortality rate. Third, the outbreak originated in the valleys of central Mexico whence it evolved as an expansive wave. Fourth, a positive correlation between altitude and mortality in central Mexico was found. Fifth, a specific climatic sequence of events was associated with the initiation and dissemination of the hemorrhagic fevers. Although the last epidemic of hemorrhagic fevers in Mexico ended in 1815, many questions remain to be answered. Perhaps the most relevant ones are whether there is a possible reemergence of the hemorrhagic fevers and how vulnerable we are to the disease.


title: Comparison of the antiviral effect of solid-state copper and silver compounds

text: Abstract Antiviral activities of insoluble solid-state and soluble ionic copper and silver compounds were evaluated against influenza A virus (A/PR8/H1N1) possessing a viral envelope and bacteriophage Qβ lacking an envelope. The viral solutions were exposed on glass samples uniformly loaded with copper and silver compounds. Exposure to solid-state cuprous oxide (Cu2O) efficiently inactivated both influenza A virus and bacteriophage Qβ, whereas solid-state cupric oxide (CuO) and silver sulfide (Ag2S) showed little antiviral activity. Copper ions from copper chloride (CuCl2) had little effect on the activity of bacteriophage Qβ in spite of the fact that copper ions strongly inactivate influenza A in previous studies. Silver ions from silver nitrate (AgNO3) and silver(I) oxide (Ag2O) in solution showed strong inactivation of influenza A and weak inactivation of bacteriophage Qβ. We also investigated the influence of the compounds on the function of two influenza viral proteins, hemagglutinin and neuraminidase. Silver ions from AgNO3 and Ag2O remarkably decreased enzymatic activity of neuraminidase through the breakage of disulfide (SS) bonds, corresponding to the selective inactivation of influenza A virus. By contrast, exposure to Cu2O markedly reduced the activity of hemagglutinin rather than neuraminidase. These findings suggest that solid-state Cu2O disrupts host cell recognition by denaturing protein structures on viral surfaces, leading to the inactivation of viruses regardless of the presence of a viral envelope.


title: View of Pakistani Residents toward Coronavirus Disease (COVID-19) during a Rapid Outbreak: A Rapid Online Survey

text: Background: Coronavirus disease (COVID-19) is a deadly disease that is affecting most of the countries worldwide. Public understanding, including knowledge about signs and symptoms, mode of transmission, and hygiene of COVID-19, is vital for designing effective control strategies during a public health crisis. The current study is aimed at investigating the public’s perspective about COVID-19, including their knowledge, attitude, and practices. Methods: A rapid online survey comprising 22 items was administered during the rapid outbreak of COVID-19 in Pakistan. Questions were focused on the prevention, transmission, clinical features, and control of COVID-19. In addition, the attitudes and practices of the participants were explored. Descriptive statistics, Mann–Whitney tests, Kruskal–Wallis tests, and regression analysis were carried out during data analysis. Results: A total of 1257 respondents participated in this study. Most of the respondents had good knowledge (good = 64.8%, average = 30.5%, poor = 4.7%) of COVID-19. Gender, marital status, education, and residence were observed to have a significant association with the knowledge score. A vast majority of the survey respondents (77.0%) believed that COVID-19 would be controlled successfully in Pakistan. The practices of wearing a mask (85.8%) and handwashing (88.1%) were common among the participants. Conclusion: The participants demonstrated good knowledge and reasonable attitudes and practices toward most aspects of the COVID-19 outbreak. Improvements in certain areas could be made by mass-level education.


title: Why we need more coronavirus tests than we think we need

text: James J. Cochran on the importance of testing a random sample


title: Bioactive Peptides: Synthesis, Properties, and Applications in the Packaging and Preservation of Food

text: Abstract: Bioactive peptides are protein fragments which have a positive impact on the functions and conditions of living beings. Peptides have shown several useful properties for human health, including antimicrobial, antifungal, antiviral, and antitumor activities. These compounds are produced by almost all species of life. However, they are produced in limited quantities in nature. As a result, researchers have tried to synthesize bioactive peptides to study their properties and applications in various areas. Among their applications in food preservation, peptides have been incorporated into packaging materials. This review begins with a brief description of the methods used for the synthesis, purification, and characterization of peptides. Also, the main bioproperties and mechanisms of action of peptides are discussed. Finally, some applications of peptides are presented, especially their use in active packaging, their effects on the polymeric matrix, and peptide migration.


title: Psychological Intervention and COVID-19: What We Know So Far and What We Can Do

text: The coronavirus COVID-19 and the global pandemic has already had a substantial disruptive impact on society, posing major challenges to the provision of mental health services in a time of crisis, and carrying the spectre of an increased burden to mental health, both in terms of existing psychiatric disorder, and emerging psychological distress from the pandemic. In this paper we provide a framework for understanding the key challenges for psychologically informed mental health care during and beyond the pandemic. We identify three groups that can benefit from psychological approaches to mental health, and/or interventions relating to COVID-19. These are (i) healthcare workers engaged in frontline response to the pandemic and their patients; (ii) individuals who will experience the emergence of new mental health distress as a function of being diagnosed with COVID-19, or losing family and loved ones to the illness, or the psychological effects of prolonged social distancing; and (iii) individuals with existing mental health conditions who are either diagnosed with COVID-19 or whose experience of social distancing exacerbates existing vulnerabilities. Drawing on existing literature and our own experience of adapting treatments to the crisis we suggest a number of salient points to consider in identifying risks and offering support to all three groups. We also offer a number of practical and technical considerations for working psychotherapeutically with existing patients where COVID-19 restrictions have forced a move to online or technologically mediated delivery of psychological interventions.


title: Impact of the COVID-19 pandemic on the organisation of stroke care. Madrid Stroke Care Plan

text: Abstract Introduction The overload of the healthcare system and the organisational changes made in response to the COVID-19 pandemic may be having an impact on acute stroke care in the Region of Madrid. Methods We conducted a survey with sections addressing hospital characteristics, changes in infrastructure and resources, code stroke clinical pathways, diagnostic testing, rehabilitation, and outpatient care. We performed a descriptive analysis of results according to the level of complexity of stroke care (availability of stroke units and mechanical thrombectomy). Results The survey was completed by 22 of the 26 hospitals in the Madrid Regional Health System that attend adult emergencies, between 16 and 27 April 2020. Ninety-five percent of hospitals had reallocated neurologists to care for patients with COVID-19. The numbers of neurology ward beds were reduced in 89.4% of hospitals; emergency department stroke care pathways were modified in 81%, with specific pathways for suspected SARS-CoV2 infection established in 50% of hospitals; and SARS-CoV2-positive patients with acute stroke were not admitted to neurology wards in 42%. Twenty four hour on-site availability of mechanical thrombectomy was improved in 10 hospitals, which resulted in a reduction in the number of secondary hospital transfers. The admission of patients with transient ischaemic attack or minor stroke was avoided in 45% of hospitals, and follow-up through telephone consultations was implemented in 100%. Conclusions The organisational changes made in response to the SARS-Co2 pandemic in hospitals in the Region of Madrid have modified the allocation of neurology department staff and infrastructure, stroke units and stroke care pathways, diagnostic testing, hospital admissions, and outpatient follow-up.


title: Human bocavirus in hospitalized children under 5 years with acute respiratory infection, São Paulo, Brazil, 2010

text: The aims of this study were to investigate the human bocavirus (HBoV) frequency and genotypes in hospitalized children <5 years presenting acute respiratory infections (ARI) within the São Paulo metropolitan area. Nasopharyngeal samples from 300 patients, previously screened for common respiratory viruses, were tested by qPCR for the NSP1 and NP-1 genes. The VP1/2 gene in positive samples was then amplified by PCR and sequenced. A total of 49 positive HBoV cases (16.3%; mean Ct value of 34.41) were detected with the mean age being 18.1 months (range 1 month to 5 years) and the median age being 1 year of age. Children aged between 0 and 12 months had higher detection rates of HBoV (69.4%; 34/49; mean Ct = 34.45) than children from other age groups (30.6%; 15/49; mean Ct = 34.34). No significant differences were observed between HBoV Ct levels and clinical illness. The occurrence was more frequently associated with fall (38.8%; 19/49) and spring (36.7%; 18/49). All 12 sequenced isolates were identified as HBoV-1, displaying minor genetic variation compared to the Swedish reference strains ST1 and ST2 (99.1–99.7% nt). The sole identification of HBoV-1 supports the hypothesis that this particular genotype is strongly related to ARI, and contributes to the role of this virus in the aetiology of respiratory diseases.


title: The Impact of COVID-19 pandemic upon Stability and Sequential Irregularity of Equity and Cryptocurrency Markets

text: We explore the evolution of the informational efficiency in 45 cryptocurrency markets and 16 international stock markets before and during COVID-19 pandemic. The measures of Largest Lyapunov Exponent (LLE) based on the Rosenstein's method and Approximate Entropy (ApEn), which are robust to small samples, are applied to price time series in order to estimate degrees of stability and irregularity in cryptocurrency and international stock markets. The amount of regularity infers on the unpredictability of fluctuations. The t-test and F-test are performed on estimated LLE and ApEn. In total, 36 statistical tests are performed to check for differences between time periods (pre- versus during COVID-19 pandemic samples) on the one hand, as well as check for differences between markets (cryptocurrencies versus stocks), on the other hand. During the COVID-19 pandemic period it was found that (a) the level of stability in cryptocurrency markets has significantly diminished while the irregularity level significantly augmented, (b) the level of stability in international equity markets has not changed but gained more irregularity, (c) cryptocurrencies became more volatile, (d) the variability in stability and irregularity in equities has not been affected, (e) cryptocurrency and stock markets exhibit a similar degree of stability in price dynamics, whilst finally (f) cryptocurrency exhibit a low level of regularity compared to international equity markets. We find that cryptos showed more instability and more irregularity during the COVID-19 pandemic compared to international stock markets. Thus, from an informational efficiency perspective, investing in digital assets during big crises as the COVID-19 pandemic, could be considered riskier as opposed to equities.


COVID‐19: are frontline surgical staff ready for this?


Tobacco Use Patterns in Five Countries During the COVID-19 Lockdown