title: Potent Inhibition of Feline Coronaviruses with Peptidyl Compounds Targeting Coronavirus 3C-like Protease

text: Feline coronavirus infection is common among domestic and exotic felid species and usually associated with mild or asymptomatic enteritis; however, feline infectious peritonitis (FIP) is a fatal disease of cats that is caused by systemic infection with a feline infectious peritonitis virus (FIPV), a variant of feline enteric coronavirus (FECV). Currently, there is no specific treatment approved for FIP despite the importance of FIP as the leading infectious cause of death in young cats. During the replication process, coronavirus produces viral polyproteins that are processed into mature proteins by viral proteases, the main protease (3C-like [3CL] protease) and the papain-like protease. Since the cleavages of viral polyproteins are an essential step for virus replication, blockage of viral protease is an attractive target for therapeutic intervention. Previously, we reported the generation of broad-spectrum peptidyl inhibitors against viruses that possess a 3C or 3CL protease. In this study, we further evaluated the antiviral effects of the peptidyl inhibitors against feline coronaviruses, and investigated the interaction between our protease inhibitor and a cathepsin B inhibitor, an entry blocker, against feline coronaviruses in cell culture. Herein we report that our compounds behave as reversible, competitive inhibitors of 3CL protease, potently inhibited the replication of feline coronaviruses (EC(50) in a nanomolar range) and, furthermore, the combination of cathepsin B and 3CL protease inhibitors led to a strong synergistic interaction against feline coronaviruses in cell culture systems.


title: The Large 386-nt Deletion in SARS-Associated Coronavirus: Evidence for Quasispecies?

text: The severe acute respiratory syndrome–associated coronavirus (SARS-CoV) is reported to have deletions of various sizes. Recently, the large 386-nucleotide deletion (L386del) comprising nucleotide positions 27719-28104 and spanning open reading frames 9–11 has been reported in the genomes of some human isolates from Hong Kong. In this study, archived specimens from 71 patients with SARS who were admitted to the New Territory East Cluster Hospitals in Hong Kong were analyzed to determine whether the L386del variant of SARS-CoV was present. There was no clear relationship between the presence of the L386del variant and SARS clinical severity as defined either by the need for intensive-care therapy and/or ventilation or by death. One patient had evidence of both the L386del variant and the wild-type variant in the same clinical specimen, supporting the idea that SARS-CoV exists as a quasispecies in some patients, although the clinical significance of these quasispecies remains unclear


title: Antiphospholipid antibodies in patients with COVID‐19: a relevant observation?

text: BACKGROUND: High incidence of thrombosis in COVID‐19 patients indicates a hypercoagulable state. Hence, exploring the involvement of antiphospholipid antibodies (aPL) in these patients is of interest. OBJECTIVES: To illustrate the incidence of criteria (lupus anticoagulant (LAC), anticardiolipin (aCL) IgG/IgM, antibeta2‐glycoprotein I antibodies (aβ2GPI) IgG/IgM) and non‐criteria (anti‐prothrombin/phosphatidyl serine (aPS/PT), aCL and aβ2GPI IgA) aPL in a consecutive cohort of critically ill SARS‐CoV‐2 patients, their association with thrombosis, antibody profile and titers of aPL. PATIENTS/METHODS: Thirty one consecutive confirmed COVID‐19 patients admitted to the Intensive Care Unit were included. aPL were measured at one time point, with part of the aPL positive patients retested after one month. RESULTS: Sixteen patients were single LAC positive, two triple positive, one double positive, one single aCL and three aCL IgG and LAC positive. Seven out of 9 thrombotic patients had at least one aPL. 16 out of 22 patients without thrombosis were aPL positive, amongst them two triple positives. Nine out of ten retested LAC positive patients were negative on a second occasion, as well as the double positive patient. Seven patients were aPS/PT positive associated to LAC. Three patients were aCL and aβ2GPI IgA positive. CONCLUSION: Our observations support the frequent single LAC positivity during (acute phase) observed in COVID‐19 infection, however not clearly related to thrombotic complications. Triple aPL positivity and high aCL/aβ2GPI titers are rare. Repeat testing suggests aPL to be mostly transient. Further studies and international registration of aPL should improve understanding the role of aPL in thrombotic COVID‐19 patients.


title: An Essential Service Decision Model for ABA Providers During Crisis

text: In the United States, applied behavior analysis (ABA) is broadly recognized as a medically necessary treatment for individuals diagnosed with autism and related disorders (Association of Professional Behavior Analysts, 2020, Guidelines for practicing applied behavior analysis during COVID-19 pandemic, Retrieved from https://cdn.ymaws.com/www.apbahome.net/resource/collection/1FDDBDD2-5CAF-4B2A-AB3F-DAE5E72111BF/APBA_Guidelines_-_Practicing_During_COVID-19_Pandemic_040920.pdf). We argue that this designation should not be called into question in light of a particular disaster and that it is critical to consider that an interruption of services can have long-lasting effects on the treatment of the individual (practitioners are ethically obligated to uphold the continuity of services while doing no harm). This dilemma might be ameliorated by a decision model that considers the prioritization of immediate needs, the vulnerability of clients, and the competency of service providers. Just as the medical field prioritizes immediate needs during crisis situations and defers routine appointments (e.g., physicals, checkups), the ABA field can make similar evidence-based decisions. The purpose of the current article is to provide a decision model for ABA practitioners who find themselves questioning the need for essential service delivery during the current COVID-19 pandemic. The impact of this model goes beyond the needs of this crisis and can be applied to any emergency situation where services are at risk of interruption.


title: Mutation pressure shapes codon usage in the GC-Rich genome of foot-and-mouth disease virus

text: Foot-and-mouth disease (FMD) is economically the most important viral-induced livestock disease worldwide. In this study, we report the results of a survey of codon usage bias of FMD virus (FMDV) representing all seven serotypes (A, O, C, Asia 1, SAT 1, SAT 2, and SAT 3). Correspondence analysis, a commonly used multivariate statistical approach, was carried out to analyze synonymous codon usage bias. The analysis showed that the overall extent of codon usage bias in FMDV is low. Furthermore, the good correlation between the frequency of G + C at the synonymous third position of sense codons (GC(3S)) content at silent sites of each sequence and codon usage bias suggested that mutation pressure rather than natural (translational) selection is the most important determinant of the codon bias observed. In addition, other factors, such as the lengths of open reading frame (ORF) and the hydrophobicity of genes also influence the codon usage variation among the genomes of FMDV in a minor way. The result of phylogenetic analyses based on the relative synonymous codon usage (RSCU) values indicated a few obvious phylogenetic incongruities, which suggest that more FMDV genome diversity may exist in nature than is currently indicated. Our work might give some clues to the features of FMDV genome and some evolutionary information of this virus.


title: Bactericidal behavior of chemically exfoliated boron nitride nanosheets doped with zirconium

text: In this work, boron nitride nanosheets (BNNS) were produced through chemical exfoliation of bulk boron nitride (BN). Furthermore, hydrothermal technique was used to incorporate various concentrations (2.5, 5, 7.5, and 10 wt%) of zirconium (Zr) as a dopant. The prepared undoped and doped BN samples were evaluated for its antimicrobial activity against E. coli and S. aureus. Structural analysis was undertaken using x-ray diffraction which identified the presence of hexagonal BN. FTIR and Raman spectroscopy were utilized to outline IR fingerprint and electronic properties of the synthesized material. Morphological information was obtained through micrographs extracted using field emission scanning electron spectroscope (FESEM) and high resolution transmission electron microscope (HRTEM), while d-spacing was also calculated through HRTEM analysis. Optical properties and emission spectra were examined by applying UV–vis and photoluminescence spectroscope (PL); whereas, band gap analysis was carried out via Tauc plot. Zr-doped BN nanosheets at increasing concentrations (0.5, 1.0 mg/50 μl) revealed enhanced antibacterial activity against E. coli compared to S. aureus (p < 0.05).


title: Estacionalidad de la esquizofrenia: hallazgos de un estudio descriptivo ejecutado en Santa Marta, Colombia

text: Resumen Introducción A partir de múltiples estudios ejecutados alrededor del planeta, se ha concluido la existencia de un efecto estacional en los nacimientos de los pacientes que luego desarrollan esquizofrenia. Por ello se ha propuesto una relación entre la exposición a ciertos agentes infecciosos durante el periodo prenatal y posibles efectos directos sobre el cerebro en desarrollo que luego se expresarán con el cuadro clínico clásico. Objetivo Analizar el comportamiento de los nacimientos de una muestra de individuos esquizofrénicos provenientes de Santa Marta, Colombia. Métodos Estudio descriptivo basado en la revisión de historias clínicas de los pacientes atendidos en una institución psiquiátrica de la ciudad. Discusión Se evidenció un mayor número de nacimientos durante los meses más lluviosos del año, lo que sugiere un probable efecto estacional; sin embargo, la ausencia de los datos de nacimientos de individuos en Santa Marta durante los años estudiados impidió comparar los resultados del estudio con las tasas de nacimiento de la población general. Aun así, estos hallazgos tienen implicaciones para las futuras investigaciones respecto a la estacionalidad de la esquizofrenia en Colombia. No reflejan algún riesgo individual para el desarrollo de la enfermedad, pero sí documentan las características del comportamiento temporal de los nacimientos de la muestra estudiada. Nuevos estudios que obvien las limitaciones del presente deben desarrollarse. Abstract Introduction Multiple studies carried out around the globe have concluded that there is a seasonal effect on the births of patients that will go on to develop schizophrenia later on. A relationship between being exposed to certain infectious agents during the prenatal period and possible direct effects on the developing brain that will later be expressed by the classical clinical picture has been suggested. Objective To analyze the behavior of births in a sample of individuals with schizophrenia from Santa Marta, Colombia. Methods Descriptive study based on the review of clinical histories of the patients seen in a psychiatric institute. Discussion A larger number of births took place during the rainiest months of the year suggesting a possible seasonal effect. However, the lack of data on births in Santa Marta during the years of the study did not allow a comparison between the results of the study and the birth rates of the general population. Even so, these findings have implications for future research regarding seasonality of schizophrenia in Colombia. They do not reflect an individual risk of developing the illness but they do document the characteristics of the temporal behavior of the births in the sample studied. Further studies that overcome the limitations of the present one are needed.


title: A cypovirus VP5 displays the RNA chaperone-like activity that destabilizes RNA helices and accelerates strand annealing

text: For double-stranded RNA (dsRNA) viruses in the family Reoviridae, their inner capsids function as the machinery for viral RNA (vRNA) replication. Unlike other multishelled reoviruses, cypovirus has a single-layered capsid, thereby representing a simplified model for studying vRNA replication of reoviruses. VP5 is one of the three major cypovirus capsid proteins and functions as a clamp protein to stabilize cypovirus capsid. Here, we expressed VP5 from type 5 Helicoverpa armigera cypovirus (HaCPV-5) in a eukaryotic system and determined that this VP5 possesses RNA chaperone-like activity, which destabilizes RNA helices and accelerates strand annealing independent of ATP. Our further characterization of VP5 revealed that its helix-destabilizing activity is RNA specific, lacks directionality and could be inhibited by divalent ions, such as Mg(2+), Mn(2+), Ca(2+) or Zn(2+), to varying degrees. Furthermore, we found that HaCPV-5 VP5 facilitates the replication initiation of an alternative polymerase (i.e. reverse transcriptase) through a panhandle-structured RNA template, which mimics the 5′-3′ cyclization of cypoviral positive-stranded RNA. Given that the replication of negative-stranded vRNA on the positive-stranded vRNA template necessitates the dissociation of the 5′-3′ panhandle, the RNA chaperone activity of VP5 may play a direct role in the initiation of reoviral dsRNA synthesis.


Severe acute respiratory syndrome Coronavirus 2 infection in cancer population: Are patient‐related symptoms helpful to track a harmful invisible?


title: Simulation of twisted wind flows in a boundary layer wind tunnel for pedestrian-level wind tunnel tests

text: Abstract Topography-induced twisted wind flows are frequently observed in Hong Kong due to the abundance existence of mountains. Observed twisted wind profiles are with larger wind twist angles and are confined to the lower 500m of the atmosphere, thus may impose significant effects on both structures and near-ground wind conditions. In order to investigate the influences of twisted wind flows on the pedestrian-level wind environment, two twisted wind profiles were simulated in a boundary layer wind tunnel by using 1.5m tall wooden vanes. The maximum guide angles of vanes were 15° and 30° at the ground level to represent two nominal yaw angles of ‘high’ and ‘extreme’ twisted wind flows. Simulated twisted wind profiles followed the power-law profile and have acceptable longitudinal and lateral turbulence power spectra similar to conventional wind flows. The yaw angle profiles were exponentially decayed with the height but had smaller maximum yaw angles than of the guide vanes. The evaluation of wind conditions near an isolated building and a row of buildings in twisted wind flows has displayed substantially modified flow features such as asymmetric wind speed distributions about the building centre line and reduced wind speeds in the passages between buildings.


title: Behavioral economics in the time of coronavirus: rebellion or “willful ignorance” in the face of “grand challenges”

text: This article considers the curious case of human behavior in the context of the coronavirus pandemic. We have observed that individuals, societies, and nations are exhibiting various irrationalities that are worth studying more closely. Applying the insights and research of reputed behavioral economists to these unprecedented circumstances, we explore possible explanations for individual and collective actions that appear, in many cases, to be highly counterintuitive. In the face of large-scale global issues, that Lazaric (2020) refers to as “grand challenges,” fraught with uncertainties and informational asymmetries, we delve deeper into the complexities of the factors that influence decision-making at various levels as we try to make sense of behavior. We wonder if reasons include the outright rejection of facts or perhaps the unwillingness to even receive information that has the potential adversely affect one’s welfare or self-interests—a tendency that Grossman and Van Der Weele (2017) term “willful ignorance.” We conclude with a few lessons and recommendations that can help understand and motivate behavior.


title: Twitter and Middle East respiratory syndrome, South Korea, 2015: A multi-lingual study

text: Abstract Background Different linguo-cultural communities might react to an outbreak differently. The 2015 South Korean MERS outbreak presented an opportunity for us to compare tweets responding to the same outbreak in different languages. Methods We obtained a 1% sample through Twitter streaming application programming interface from June 1 to 30, 2015. We identified MERS-related tweets with keywords such as ‘MERS’ and its translation in five different languages. We translated non-English tweets into English for statistical comparison. Results We retrieved MERS-related Twitter data in five languages: Korean (N = 21,823), English (N = 4024), Thai (N = 2084), Japanese (N = 1334) and Indonesian (N = 1256). Categories of randomly selected user profiles (p < 0.001) and the top 30 sources of retweets (p < 0.001) differed between the five language corpora. Among the randomly selected user profiles, K-pop fans ranged from 4% in the Korean corpus to 70% in the Thai corpus; media ranged from 0% (Thai) to 14% (Indonesian); political advocates ranged from 0% (Thai) to 19% (Japanese); medical professionals ranged from 0% (Thai) to 7% (English). Among the top 30 sources of retweets for each corpus (150 in total), 70 (46.7%) were media; 29 (19.3%) were K-pop fans; 7 (4.7%) were political; 9 (6%) were medical; and 35 (23.3%) were categorized as ‘Others’. We performed chi-square feature selection and identified the top 20 keywords that were most unique to each corpus. Conclusion Different linguo-cultural communities exist on Twitter and they might react to the same outbreak differently. Understanding audiences' unique Twitter cultures will allow public health agencies to develop appropriate Twitter health communication strategies.


title: The allele 4 of neck region liver-lymph node-specific ICAM-3-grabbing integrin variant is associated with spontaneous clearance of hepatitis C virus and decrease of viral loads

text: L-SIGN is a C-type lectin expressed on liver sinusoidal endothelial cells involved in the capture of hepatitis C virus and trans-infection of adjacent hepatocyte cells. The neck region of L-SIGN is highly polymorphic, with three to nine tandem repeats of 23 residues. This polymorphism is associated with a number of infectious diseases, but has not been explored in HCV. We therefore investigated the impact of L-SIGN neck region length variation on the outcome of HCV infection. We studied 322 subjects, 150 patients with persistent HCV infection, 63 individuals with spontaneous clearance and 109 healthy controls. In healthy subjects, we found a total of nine genotypes, with the 7/7 genotype being the most frequent (33%) followed by the 7/6 (22.9%) and the 7/5 (18.3%). The frequencies of the alleles were as follows: 7-LSIGN (56.4%), 6-LSIGN (20.2%), 5-L-SIGN (18.3%) and 4-L-SIGN (5%). The frequency of the 7/4 genotype was higher in spontaneous resolvers (14.3%) as compared with the persistent group (4%) (OR = 0.25, 95% CI = 0.07–0.82, p 0.022). In addition, we found that 4-L-SIGN was associated with spontaneous resolution of HCV infection (OR = 0.30, 95%CI, 0.12–0.74, p 0.005). Interestingly, patients with 4-L-SIGN had lower viral loads when compared with carriers of the 5 (p 0.001), 6 (p 0.021) and 7-alleles (p 0.048). The results indicate that neck region polymorphism of L-SIGN can influence the outcome of HCV infection and the four-tandem repeat is associated with clearance of HCV infection.


title: Comparison of clinical characteristics of coronavirus disease (COVID-19) and severe acute respiratory syndrome (SARS) as experienced in Taiwan

text: • From our data, we know 2019-nCoV invades more common in male, not likely the SARS that is female predominant. • The 2019-nCoV patients are around 20 years older than the population of SARS. Young adults are susceptible to SARS than the children and elderly. • Hypoalbuminemia are noted in SARS patients, it needs a longer time to study whether the 2019-nCoV possesses the same presentation.


title: The emergence of the Middle East Respiratory Syndrome coronavirus (MERS-CoV)

text: On September 20, 2012, a Saudi Arabian physician reported the isolation of a novel coronavirus from a patient with pneumonia on ProMED-mail. Within a few days the same virus was detected in a Qatari patient receiving intensive care in a London hospital, a situation reminiscent of the role air travel played in the spread of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2002. SARS-CoV originated in China’s Guangdong Province and affected more than 8000 patients in 26 countries before it was contained six months later. Over a year after the emergence of this novel coronavirus—Middle East Respiratory Syndrome coronavirus (MERS-CoV)—it has caused 178 laboratory confirmed cases and 76 deaths The emergence of a second highly pathogenic coronavirus within a decade highlights the importance of a coordinated global response incorporating reservoir surveillance, high-containment capacity with fundamental and applied research programs, and dependable communication pathways to ensure outbreak containment. Here we review the current state of knowledge on the epidemiology, ecology, molecular biology, clinical features and intervention strategies of the novel coronavirus, MERS-CoV.


title: Clinical Therapeutics in Hong Kong

text: Abstract Hong Kong is a compact territory in Southern China that enjoys a high degree of autonomy. Despite its dense population and uneven wealth distribution, infant mortality is low and life expectancy is long. The health service is more hospital and clinic based than community based. This seems cost-effective while professional standards are high and rigorously maintained. Drug registration follows American and European requirements. Hong Kong is a part of the Pharmaceutical Inspection Cooperation Scheme, which brings a high standard of drug regulation. Hong Kong is a good choice for clinical trials because the subjects are Chinese and protocols in English do not need to be translated. There are also 2 well-established clinical trials centers in university hospitals that also run Phase I and clinical pharmacology studies.


title: Experts examine MH consequences of social distancing

text: The practice of social distancing in countries all over the world, resulting in changes in national behavioral patterns and shutdowns of usual day‐to‐day functioning, will undoubtedly have consequences for mental health and well‐being in both the short and long term, according to authors of a JAMA Internal Medicine Viewpoint published online in April.


title: Spatial pattern of severe acute respiratory syndrome in-out flow in 2003 in Mainland China

text: BACKGROUND: Severe acute respiratory syndrome (SARS) spread to 32 countries and regions within a few months in 2003. There were 5327 SARS cases from November 2002 to May 2003 in Mainland China, which involved 29 provinces, resulted in 349 deaths, and directly caused economic losses of $18.3 billion. METHODS: This study used an in-out flow model and flow mapping to visualize and explore the spatial pattern of SARS transmission in different regions. In-out flow is measured by the in-out degree and clustering coefficient of SARS. Flow mapping is an exploratory method of spatial visualization for interaction data. RESULTS: The findings were as follows. (1) SARS in-out flow had a clear hierarchy. It formed two main centers, Guangdong in South China and Beijing in North China, and two secondary centers, Shanxi and Inner Mongolia, both connected to Beijing. (2) “Spring Festival travel” strengthened external flow, but “SARS panic effect” played a more significant role and pushed the external flow to the peak. (3) External flow and its three typical kinds showed obvious spatial heterogeneity, such as self-spreading flow (spatial displacement of SARS cases only within the province or municipality of onset and medical locations); hospitalized flow (spatial displacement of SARS cases that had been seen by a hospital doctor); and migrant flow (spatial displacement of SARS cases among migrant workers). (4) Internal and external flow tended to occur in younger groups, and occupational differentiation was particularly evident. Low-income groups of male migrants aged 19–35 years were the main routes of external flow. CONCLUSIONS: During 2002–2003, SARS in-out flow played an important role in countrywide transmission of the disease in Mainland China. The flow had obvious spatial heterogeneity, which was influenced by migrants’ behavior characteristics. In addition, the Chinese holiday effect led to irregular spread of SARS, but the panic effect was more apparent in the middle and late stages of the epidemic. These findings constitute valuable input to prevent and control future serious infectious diseases like SARS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0721-y) contains supplementary material, which is available to authorized users.


title: Global virus outbreaks: Interferons as 1st responders

text: Abstract Outbreaks of severe virus infections with the potential to cause global pandemics are increasing. In many instances these outbreaks have been newly emerging (SARS coronavirus), re-emerging (Ebola virus, Zika virus) or zoonotic (avian influenza H5N1) virus infections. In the absence of a targeted vaccine or a pathogen-specific antiviral, broad-spectrum antivirals would function to limit virus spread. Given the direct antiviral effects of type I interferons (IFNs) in inhibiting the replication of both DNA and RNA viruses at different stages of their replicative cycles, and the effects of type I IFNs on activating immune cell populations to clear virus infections, IFNs-α/β present as ideal candidate broad-spectrum antivirals.


title: Medical relevance of UK-funded non-human primate research published from January 1997 to July 2012

text: In 2012, the Bateson Review of research using non-human primates (NHPs) recommended the commissioning of a working group to identify and follow-up the results of UK-funded NHP research of potential benefit for human health (Recommendation 4), but the Medical Research Council (MRC) has postponed implementation of the recommendation. Information on results and potential benefits of NHP research therefore remains unavailable. To fill this gap in knowledge, this study identified all published NHP research studies funded by the MRC, Wellcome Trust and Biotechnology and Biological Sciences Research Council (BBSRC) from January 1997 to July 2012 and assessed full texts for medical relevance. In total, 284 papers were identified, of which 51 (18%) involved invasive NHP research, compared to 176 (61%) which used NHP tissue and cell lines, indicating a shift in research emphasis from invasive whole animal to cell-based research. Of these studies, 98 (35%) were medically relevant, of which 22 had potential therapeutic or public health applications. The relatively low proportion of medical studies together with the small number of applied studies raises questions over the level of investment in medical research and the effectiveness of knowledge transfer from basic to applied research. Implementation of the Bateson Review’s Recommendation 4 would address these questions.


27th International Mammalian Genome Conference meeting report


title: Chyloabdomen in a cat with pancreatic carcinoma

text: A 12-year-old spayed female domestic shorthair cat was evaluated for a 3-week history of abdominal distension. Chyloabdomen secondary to pancreatic carcinoma was diagnosed. The cat was palliatively managed using rutin and a low-fat diet. The etiology, diagnosis and management of chyloabdomen are discussed.


title: Neutralisation of SARS-CoV-2 by destruction of the prefusion Spike

text: Summary There are as yet no licenced therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric Spike whose receptor binding domain (RBD) recognises angiotensin-converting enzyme 2 (ACE2), initiating conformational changes that drive membrane fusion. We find that the monoclonal antibody CR3022 binds the RBD tightly, neutralising SARS-CoV-2 and report the crystal structure at 2.4 Å of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilising, CR3022 epitope is inaccessible in the prefusion Spike, suggesting that CR3022 binding facilitates conversion to the fusion-incompetent post-fusion state. Cryo-EM analysis confirms that incubation of Spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope may be useful therapeutically, possibly in synergy with an antibody blocking receptor attachment.


Skill mix alive and well


title: Risk and predictors of in-hospital mortality from COVID-19 in patients with diabetes and cardiovascular disease

text: BACKGROUND: Diabetes mellitus (DM) and cardiovascular disease (CVD) are present in a large number of patients with novel Coronavirus disease 2019 (COVID-19). We aimed to determine the risk and predictors of in-hospital mortality from COVID-19 in patients with DM and CVD. METHODS: This retrospective cohort study included hospitalized patients aged ≥ 18 years with confirmed COVID-19 in Alborz province, Iran, from 20 February 2020 to 25 March 2020. Data on demographic, clinical and outcome (in-hospital mortality) data were obtained from electronic medical records. Self-reported comorbidities were classified into the following groups: “DM” (having DM with or without other comorbidities), “only DM” (having DM without other comorbidities), “CVD” (having CVD with or without other comorbidities), “only CVD” (having CVD without other comorbidities), and “having any comorbidity”. Multivariate logistic regression models were fitted to quantify the risk and predictors of in-hospital mortality from COVID-19 in patients with these comorbidities. RESULTS: Among 2957 patients with COVID-19, 2656 were discharged as cured, and 301 died. In multivariate model, DM (OR: 1.62 (95% CI 1.14–2.30)) and only DM (1.69 (1.05–2.74)) increased the risk of death from COVID-19; but, both CVD and only CVD showed non-significant associations (p > 0.05). Moreover, “having any comorbidities” increased the risk of in-hospital mortality from COVID-19 (OR: 2.66 (95% CI 2.09–3.40)). Significant predictors of mortality from COVID-19 in patients with DM were lymphocyte count, creatinine and C-reactive protein (CRP) level (all P-values < 0.05). CONCLUSIONS: Our findings suggest that diabetic patients have an increased risk of in-hospital mortality following COVID-19; also, lymphocyte count, creatinine and CRP concentrations could be considered as significant predictors for the death of COVID-19 in these patients.


title: Chapter 16 Dengue Virus

text: Abstract Dengue virus (DENV) belongs to the family Flaviviridae, genus Flavivirus. It is a single-stranded positive-sense ribonucleic acid virus with 10,700 bases. The genus Flavivirus includes other arthropod borne viruses such as yellow fever virus, West Nile virus, Zika virus, tick-borne encephalitis virus. It infects ~50–200 million people annually, putting over 3.6 billion people living in tropical regions at risk and causing ~20,000 deaths annually. The expansion of dengue is attributed to factors such as the modern dynamics of climate change, globalization, travel, trade, socioeconomics, settlement, and also viral evolution. There are four antigenically different serotypes of DENV based on the differences in their viral structural and nonstructural proteins. DENV infection causes a spectrum of illness ranging from asymptomatic to dengue fever to severe dengue shock syndrome. Infection with one serotype confers lifelong immunity against that serotype, but heterologus infection leads to severe dengue hemorrhagic fever due to antibody-dependent enhancement. Diagnosis of dengue infections is based mainly on serological detection of either antigen in acute cases or antibodies in both acute and chronic infection. Viral detection and real-time PCR detection though helpful is not feasible in resource poor setup. Treatment of dengue depends on symptomatic management along with fluid resuscitation and may require platelet transfusion. Although vaccine development is in late stages of development, developing a single vaccine against four serotypes often causes serious challenges to researchers; hence, the main stay of prevention is vector control and management.


title: Rapid identification of viruses by a simple indirect immune electron microscopy technique using ferritin-labelled antibodies

text: Abstract A simple indirect immune electron microscopy technique using ferritin-labelled antibodies and negative staining to rapidly visualize and identify human viruses is described. The increased electron density given by the ferritin molecules, which also served as a reliable marker, has greatly facilitated virus detection.


title: SARS-Cov-2 in Spanish Intensive Care: Early Experience with 15-day Survival In Vitoria

text: Abstract Purpose: Community transmission of SARS-CoV-2 was detected in Spain in February 2020, with 216% intensive care unit (ICU) capacity expanded in Vitoria by March 18th, 2020. Methods: We identified patients from the two public hospitals in Vitoria who were admitted to ICU with confirmed infection by SARS-CoV-2. Data reported here were available in March 31th, 2020. Mortality was assessed in those who completed 7-days of ICU stay. Results: We identified 48 patients (27 males) with confirmed SARS-CoV-2. Median [interquartile range (IQR)] age of patients was 63 [51-75] years. Symptoms began a median of 7 [5-12] days before ICU admission. The most common comorbidities identified were obesity (n = 48%), arterial hypertension (n = 44%) and chronic lung disease (n = 37%). All patients were admitted by hypoxemic respiratory failure and none received non-invasive mechanical ventilation. Forty-five (94%) underwent intubation, 3 HFNT, 1 (2%) extracorporeal membrane oxygenation (ECMO) and 22 (49%) required prone position. After 15 days, 14/45 (31%) intubated patients died (13% within one week), 10 (22%) were extubated, and 21/45 (47%) underwent mechanical ventilation. Six patients had documented co-infection. Procalcitonin plasma above 0.5 µg/L was associated with 16% vs. 19% (p = 0.78) risk of death after 7 days. Conclusion: This early experience with SARS-CoV-2 in Spain suggests that a strategy of right oxygenation avoiding non-invasive mechanical ventilation was life-saving. Seven-day mortality in SARS-CoV-2 requiring intubation was lower than 15%, with 80% of patients still requiring mechanical ventilation. After 15 days of ICU admission, half of patients remained intubated, whereas one third died.


title: High-resolution computed tomography finding in 552 patients with symptomatic COVID-19: first report from north of Iran

text: PURPOSE: Due to the emergence of the new coronavirus 2019 and the lack of sufficient information about infected patients, this study was conducted to investigate the chest high-resolution computed tomography (HRCT) findings of patients infected with the new coronavirus 2019. METHODS: This cross-sectional study was performed on COVID-19 patients referred to Medical Imaging Centers of Sari, Mazandaran, Iran, on March 2020 for computed tomography (CT) scan. Symptomatic patients were referred to the Medical Imaging Center for diagnosis confirmation through CT scan. In addition to age and sex, HRCT findings were collected from the picture archiving and communication system (PACS) for further evaluations. RESULTS: Out of 552 patients with mean age of 51.2 ± 14.8 years, the male/female ratio was 1.38 to 1. The most common expressive findings in patients were ground-glass opacity (GGO) (87.3%), peripheral distribution (82.4%), and posterior distribution (81.5%). The most conflicting findings in patients were pleural effusion (7.6%), peribronchovascular distribution (7.6%), and lymphadenopathy (5.1%). The peripheral distribution (p = 0.034), round opacities (p = 0.02), single lobe (p = 0.003), and pleural effusion (p = 0.037) were significant in people under and over 50 years of age. CONCLUSION: In summary, the present study indicated that in addition to GGO, peripheral distribution findings could be a vital diagnostic choice in COVID-19 patients.


title: Nrf2 Expression Modifies Influenza A Entry and Replication in Nasal Epithelial Cells

text: Influenza infection is a major cause of morbidity and mortality worldwide, especially during pandemics outbreaks. Emerging data indicate that phase II antioxidant enzyme pathways could play a role in virus-associated inflammation and immune clearance. While Nrf2-dependent gene expression is known to modify inflammation, a mechanistic role in viral susceptibility and clearance has yet to be elucidated. Therefore, we utilized differentiated human nasal epithelial cells (NEC) and an enzymatic virus-like particle entry assay, to examine the role Nrf2-dependent gene expression has on viral entry and replication. Herein, lentiviral vectors that express Nrf2-specific short hairpin (sh)-RNA effectively decreased both Nrf2 mRNA and Nrf2 protein expression in transduced human NEC from healthy volunteers. Nrf2 knockdown correlated with a significant increase in influenza virus entry and replication. Conversely, supplementation with the potent Nrf2 activators sulforaphane (SFN) and epigallocatechin gallate (EGCG) significantly decreased viral entry and replication. The suppressive effects of EGCG on viral replication were abolished in cells with knocked down Nrf2 expression, suggesting a causal relationship between EGCG-induced activation of Nrf2 and ability to protect against viral infection. Interestingly, the induction of Nrf2 via nutritional supplements SFN and EGCG, increased antiviral mediators/responses; RIG-I, IFN-β, and MxA at baseline in the absence of infection. Our data indicate that there is an inverse relationship between the levels of Nrf2 expression, and viral entry/replication. We also demonstrate that supplementation with Nrf2-activating antioxidants inhibit viral replication in human NEC, which may prove to be an attractive therapeutic intervention. Taken together, these data indicate potential mechanisms by which Nrf2-dependent gene expression regulates susceptibility to influenza in human epithelial cells.


title: Involvement of the different lung compartments in the pathogenesis of pH1N1 influenza virus infection in ferrets

text: Severe cases after pH1N1 infection are consequence of interstitial pneumonia triggered by alveolar viral replication and an exacerbated host immune response, characterized by the up-regulation of pro-inflammatory cytokines and the influx of inflammatory leukocytes to the lungs. Different lung cell populations have been suggested as culprits in the unregulated innate immune responses observed in these cases. This study aims to clarify this question by studying the different induction of innate immune molecules by the distinct lung anatomic compartments (vascular, alveolar and bronchiolar) of ferrets intratracheally infected with a human pH1N1 viral isolate, by means of laser microdissection techniques. The obtained results were then analysed in relation to viral quantification in the different anatomic areas and the histopathological lesions observed. More severe lung lesions were observed at 24 h post infection (hpi) correlating with viral antigen detection in bronchiolar and alveolar epithelial cells. However, high levels of viral RNA were detected in all anatomic compartments throughout infection. Bronchiolar areas were the first source of IFN-α and most pro-inflammatory cytokines, through the activation of RIG-I. In contrast, vascular areas contributed with the highest induction of CCL2 and other pro-inflammatory cytokines, through the activation of TLR3. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0395-0) contains supplementary material, which is available to authorized users.


title: A Simple Platform for the Rapid Development of Antimicrobials

text: Recent infectious outbreaks highlight the need for platform technologies that can be quickly deployed to develop therapeutics needed to contain the outbreak. We present a simple concept for rapid development of new antimicrobials. The goal was to produce in as little as one week thousands of doses of an intervention for a new pathogen. We tested the feasibility of a system based on antimicrobial synbodies. The system involves creating an array of 100 peptides that have been selected for broad capability to bind and/or kill viruses and bacteria. The peptides are pre-screened for low cell toxicity prior to large scale synthesis. Any pathogen is then assayed on the chip to find peptides that bind or kill it. Peptides are combined in pairs as synbodies and further screened for activity and toxicity. The lead synbody can be quickly produced in large scale, with completion of the entire process in one week.


title: The detection of feline coronaviruses in blood samples from cats by mRNA RT-PCR

text: In this study, 26 blood samples were collected from 25 healthy cats and one cat with clinical signs suggestive of feline infectious peritonitis (FIP), namely, fever, weight loss, enlarged abdomen, and ascites. Blood samples were tested for feline coronavirus (FCoV) messenger RNA (mRNA) by an reverse transcriptase-polymerase chain reaction (RT-PCR) assay which has previously been described to have a high specificity in the diagnosis of clinical FIP [Simons AF, Vennema H, Rofina JE, Pol JM, Horzinek MC, Rottier PJM, Egberink HF (2005) A mRNA PCR for the diagnosis of feline infectious peritonitis. Journal of Virological Methods 124, 111–116]. Overall we found 14 (54%) of the cats were positive for FCoV including the cat with clinical disease, but the high rate of positivity among healthy cats suggested a poor specificity for the clinical diagnosis of FIP among these cats. It was observed that the positivity rate was highest in cats aged between 6 months–1 year old. Our findings suggest that FCoVs may be present in the blood samples from healthy cats as well as cats with clinical FIP.


Cardiac Catheterization Laboratory Volume Changes During COVID-19 – Findings from a Cardiovascular Fellows Consortium


title: Related Health Factors of Psychological Distress During the COVID-19 Pandemic in Spain

text: Measures to prevent and contain the COVID-19 health crisis include population confinement, with the consequent isolation and interruption of their usual activities. The aim of the study is to analyse psychological distress during the COVID-19 pandemic. For this, a cross-sectional observational study with a sample of 4180 people over the age of 18 during quarantine was developed. Variables considered were sociodemographic variables, physical symptoms, health conditions, COVID-19 contact history and psychological adjustment. The data were collected through a self-developed questionnaire and the General Health Questionnaire (GHQ-12). Bivariate analyses were performed, including Chi-Squared test and Student’s T-test. Predictive ability was calculated through logistic regression. Results obtained showed a high level of psychological distress (72.0%), with a higher percentage in women and people of lower middle age. Statistically significant differences were found in the variable working situation (χ² = 63.139, p ≤ 0.001, V = 0.123) and living with children under the age of 16 (χ² = 7.393, p = 0.007, V = 0.042). The predictive variables with the highest weight were sex (OR = 1.952, 95% IC = (1.667, 2.286)), presence of symptoms (OR = 1.130, 95% CI = (1.074, 1.190)), and having had close contact with an individual with confirmed COVID-19 (OR = 1.241, 95% CI = (1.026, 1.500)). These results could enrich prevention interventions in public health and, in particular, in mental health in similar pandemic situations.


title: Bedside Focused Cardiac Ultrasound in COVID-19 Infection From the Wuhan Epicenter: The Role of Cardiac Point of Care Ultrasound (POCUS), Limited Transthoracic Echocardiography and Critical Care Echocardiography

text: Abstract Three cases of the application of focused cardiac ultrasound in patients with COVID-19 infection are presented. Cardiac point-of-care ultrasound (POCUS), limited transthoracic echocardiography (TTE), and critical care echocardiography (CCE) were applied in cases of heart failure, pulmonary embolism, and myocarditis with thrombus respectively. The impact upon patient management and the global context of each presentation are discussed.


title: Managing Mass Fatalities during COVID‐19: Lessons for Promoting Community Resilience During Global Pandemics

text: In the United States and around the world, COVID‐19 represents a mass fatality incident, as there are more bodies than can be handled using existing resources. Although the management and disposition of bodies is distressing and heartrending, it is a task that local, state, and federal governments must plan for and respond to collaboratively with the private sector and faith‐based community. When mass fatalities are mismanaged, there are grave emotional and mental health consequences that can delay recovery and undermine community resilience. Using insights from one of the author's mass fatality management research during the 2010 Haiti earthquake, this article explores how mass fatalities are being managed in response to COVID‐19. Based on the researcher's findings a decade ago, it is apparent that many lessons have not been learnt. This article concludes by providing governments with practical lessons on how to manage mass fatalities to facilitate and promote community resilience.


title: Clinical and Psychological Impact of COVID-19 Infection in Adult Patients with Eosinophilic Gastrointestinal Disorders during the SARS-CoV-2 Outbreak

text: Eosinophilic gastrointestinal diseases (EGIDs) are chronic gastrointestinal conditions requiring corticosteroid and immunosuppressive therapy for disease control Patients with EGIDs usually report impaired quality of life We aimed to report the clinical and psychological impact of COVID-19 infection in EGID patients In this prospective web-based study we invited all consecutive EGID patients attending the University Hospital of Salerno (Campania) and Padua (Veneto) to fill an ad hoc COVID-19 survey Moreover, a telemedicine service for direct consultation was organized Data regarding the occurrence and perception of COVID-19 infection as well as clinical information were recorded The study population included 102 EGID patients (mean age 36 6 years, 34 females), of whom 89 had eosinophilic esophagitis, nine had gastroenteritis, and four had colitis No patient was diagnosed with COVID-19 or had recurrence of his/her primary disease All of them were adherent to therapy and preventive measures adoption Most patients were worried because of COVID-19 and social preventing measures but did not consider themselves at major risk or susceptible to COVID-19 or other infections due to their chronic condition or therapy Female gender and low education level were associated to a higher psychological perception of COVID-19 compared to lockdown status or other demographic and clinical factors (p < 0 05) Overall, COVID-19 had a limited clinical impact on patients with EGIDs The degree of education and sex, but not the fact of living in a lockdown area, influenced the perception of SARS-CoV-2 infection


title: Massachusetts coalition launches campaign to preserve bed access

text: A coalition of registered nurses with the Massachusetts Nurses Association (MNA), along with patients, families, advocates and elected officials who have been fighting for the preservation of mental health beds across Western Massachusetts, has launched a new campaign, “Mental Health is Public Health,” to save essential inpatient psychiatric services, according to a March 16 news release. The effort comes as Trinity Health plans to close 74 pediatric and adult psychiatric beds at Providence Behavioral Health Hospital in Holyoke; Baystate Health seeks the closure of all its mental health beds in Greenfield, Palmer and Westfield; and COVID‐19 places additional pressure on already‐strained emergency departments and other hospital services throughout the region. “These proposed closures would devastate an already‐strained mental health system,” said Cindy Chaplin, RN at Providence and co‐chair of the MNA Bargaining Committee. “Right now, we need to maximize capacity in emergency departments and other hospital units, not decrease services. When everyone else in Massachusetts agrees we should be making it easier for patients to get high‐quality mental healthcare, Trinity Health is going in the opposite direction.”


title: Snake Deltavirus Utilizes Envelope Proteins of Different Viruses To Generate Infectious Particles

text: Satellite viruses, most commonly found in plants, rely on helper viruses to complete their replication cycle. The only known example of a human satellite virus is the hepatitis D virus (HDV), and it is generally thought to require hepatitis B virus (HBV) to form infectious particles. Until 2018, HDV was the sole representative of the genus Deltavirus and was thought to have evolved in humans, the only known HDV host. The subsequent identification of HDV-like agents in birds, snakes, fish, amphibians, and invertebrates indicated that the evolutionary history of deltaviruses is likely much longer than previously hypothesized. Interestingly, none of the HDV-like agents were found in coinfection with an HBV-like agent, suggesting that these viruses use different helper virus(es). Here we show, using snake deltavirus (SDeV), that HBV and hepadnaviruses represent only one example of helper viruses for deltaviruses. We cloned the SDeV genome into a mammalian expression plasmid, and by transfection could initiate SDeV replication in cultured snake and mammalian cell lines. By superinfecting persistently SDeV-infected cells with reptarenaviruses and hartmaniviruses, or by transfecting their surface proteins, we could induce production of infectious SDeV particles. Our findings indicate that deltaviruses can likely use a multitude of helper viruses or even viral glycoproteins to form infectious particles. This suggests that persistent infections, such as those caused by arenaviruses and orthohantaviruses used in this study, and recurrent infections would be beneficial for the spread of deltaviruses. It seems plausible that further human or animal disease associations with deltavirus infections will be identified in the future.


title: Global guidance for surgical care during the COVID‐19 pandemic

text: BACKGROUND: Surgeons urgently need guidance on how to deliver surgical services safely and effectively during the COVID‐19 pandemic. The aim was to identify the key domains that should be considered when developing pandemic preparedness plans for surgical services. METHODS: A scoping search was conducted to identify published articles relating to management of surgical patients during pandemics. Key informant interviews were conducted with surgeons and anaesthetists with direct experience of working during infectious disease outbreaks, in order to identify key challenges and solutions to delivering effective surgical services during the COVID‐19 pandemic. RESULTS: Thirteen articles were identified from the scoping search, and surgeons and anaesthetists representing 11 territories were interviewed. To mount an effective response to COVID‐19, a pandemic response plan for surgical services should be developed in advance. Key domains that should be included are: provision of staff training (such as patient transfers, donning and doffing personal protection equipment, recognizing and managing COVID‐19 infection); support for the overall hospital response to COVID‐19 (reduction in non‐urgent activities such as clinics, endoscopy, non‐urgent elective surgery); establishment of a team‐based approach for running emergency services; and recognition and management of COVID‐19 infection in patients treated as an emergency and those who have had surgery. A backlog of procedures after the end of the COVID‐19 pandemic is inevitable, and hospitals should plan how to address this effectively to ensure that patients having elective treatment have the best possible outcomes. CONCLUSION: Hospitals should prepare detailed context‐specific pandemic preparedness plans addressing the identified domains. Specific guidance should be updated continuously to reflect emerging evidence during the COVID‐19 pandemic.


title: Inhibition of hepatitis C virus replication by semi-synthetic derivatives of glycopeptide antibiotics

text: OBJECTIVES: Some semi-synthetic derivatives of glycopeptide antibiotics have been shown to exert in vitro antiviral activity against HIV and coronaviruses. Here we report and characterize the in vitro anti-hepatitis C virus (HCV) activity of several semi-synthetic derivatives of teicoplanin aglycone. METHODS: Anti-HCV activity was analysed in: (i) three different subgenomic HCV replicon systems using a luciferase or quantitative RT–PCR (qRT–PCR) assay; and (ii) an infectious HCV cell culture system by means of qRT–PCR and immunofluorescence assays. RESULTS: Several teicoplanin aglycone derivatives elicited selective anti-HCV activity in replicons as well as infectious cell culture systems, with LCTA-949 being the most potent derivative. LCTA-949 proved, in contrast to several directly acting antivirals for HCV, efficient in clearing cells of their replicons. When LCTA-949 was combined with HCV protease or polymerase inhibitors an overall additive effect was observed. Likewise, LCTA-949 was equipotent against wild-type replicons as well as against replicons resistant to polymerase and protease inhibitors. Following up to 4 months of selective pressure, no drug-resistant replicons were selected. When combined with the HCV NS3 protease inhibitor VX-950, LCTA-949 prevented the development of VX-950-resistant variants. CONCLUSIONS: Semi-synthetic derivatives of teicoplanin aglycone constitute a novel class of HCV replication inhibitors that are not cross-resistant with various HCV protease and polymerase inhibitors and in particular are potent in clearing hepatoma cells of their replicons. This class of molecules also provides a good tool to obtain novel insights into the replication cycle of HCV and into cellular factors/processes that are crucial for viral replication.


title: Use of Tracheostomy During the COVID-19 Pandemic: CHEST/AABIP/AIPPD: Expert Panel Report

text: Abstract Background The role of tracheostomy during the COVID-19 pandemic remains unknown. The goal of this consensus statement is to examine the current evidence for performing tracheostomy in patients with respiratory failure from COVID-19 and offer guidance to physicians on the preparation, timing and technique while minimizing the risk of infection to health care workers (HCW). Methods A panel comprised of intensivists and interventional pulmonologists from three professional societies representing 13 institutions with experience in managing COVID-19 patients across a spectrum of healthcare environments developed key clinical questions addressing specific topics on tracheostomy in COVID-19. A systematic review of the literature and an established modified Delphi consensus methodology were applied to provide a reliable evidenced based consensus statement and expert panel report. Results Eight key questions, corresponding to 14 decision points, were rated by the panel. The results were aggregated, resulting in eight main recommendations and five additional remarks intended to guide health care providers in the decision-making process pertinent to tracheostomy in patients with COVID-19 related respiratory failure. Conclusion This panel suggests performing tracheostomy in patients expected to require prolonged mechanical ventilation. A specific timing of tracheostomy cannot be recommended. There is no evidence for routine repeat RT- PCR testing in patients with confirmed Covid-19 evaluated for tracheostomy. To reduce the risk of infection in HCW, we recommend performing the procedure using techniques that minimize aerosolization while wearing enhanced personal protective equipment (PPE). The recommendations presented in this statement may change as more experience is gained during this pandemic.


title: Living With In-Mask Micro-Climate

text: The in-mask micro-climate is heat and moisture buildup under facemasks but facemask doffing can immediately neutralize in-mask elevations in temperature and relative humidity. Therefore, home/workplace/facility living with in-mask micro-climate during COVID-19 pandemic warrants safe provisions for intermittent facemask “vacation”.


title: Mutations within the nuclear localization signal of the porcine reproductive and respiratory syndrome virus nucleocapsid protein attenuate virus replication

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is an RNA virus replicating in the cytoplasm, but the nucleocapsid (N) protein is specifically localized to the nucleus and nucleolus in virus-infected cells. A ‘pat7’ motif of 41-PGKK(N/S)KK has previously been identified in the N protein as the functional nuclear localization signal (NLS); however, the biological consequences of N protein nuclear localization are unknown. In the present study, the role of N protein nuclear localization during infection was investigated in pigs using an NLS-null mutant virus. When two lysines at 43 and 44 at the NLS locus were substituted to glycines, the modified NLS with 41-PGGGNKK restricted the N protein to the cytoplasm. This NLS-null mutation was introduced into a full-length infectious cDNA clone of PRRSV. Upon transfection of cells, the NLS-null full-length clone induced cytopathic effects and produced infectious progeny. The NLS-null virus grew to a titer 100-fold lower than that of wild-type virus. To examine the response to NLS-null PRRSV in the natural host, three groups of pigs, consisting of seven animals per group, were intranasally inoculated with wild-type, placebo, or NLS-null virus, and the animals were maintained for 4 weeks. The NLS-null-infected pigs had a significantly shorter mean duration of viremia than wild-type-infected pigs but developed significantly higher titers of neutralizing antibodies. Mutations occurred at the NLS locus in one pig during viremia, and four types of mutations were identified: 41-PGRGNKK, 41-PGGRNKK, and 41-PGRRNKK, and 41-PGKKSKK. Both wild-type and NLS-null viruses persisted in the tonsils for at least 4 weeks, and the NLS-null virus persisting in the tonsils was found to be mutated to either 41-PGRGNKK or 41-PGGRNKK in all pigs. No other mutation was found in the N gene. All types of reversions which occurred during viremia and persistence were able to translocate the mutated N proteins to the nucleus, indicating a strong selection pressure for reversion at the NLS locus of the N protein in vivo. Reversions from NLS-null to functional NLS in the tonsils suggest a possible correlation of viral persistence with N protein nuclear localization. These results show that N protein nuclear localization is non-essential for PRRSV multiplication but may play an important role in viral attenuation and in pathogenesis in vivo.


title: Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS

text: Human coronavirus (HCoV) is one of the most common causes of respiratory tract infections throughout the world. Two phenomena observed so far in the development of the SARS-CoV-2 pandemic deserve further attention. First, the relative absence of clinical signs of infections in children, second, the early appearance of IgG in certain patients. From the point of view of immune system physiology, such an early rise of specific IgG is expected in secondary immune responses when memory to a cross-reactive antigen is present, usually from an earlier infection with a coronavirus. It is actually typical for the immune system to respond, to what it already knows, a phenomenon that has been observed in many infections with closely related viruses and has been termed “original antigenic sin.” The question then arises whether such cross-reactive antibodies are protective or not against the new virus. The worst scenario would be when such cross-reactive memory antibodies to related coronaviruses would not only be non-protective but even enhance infection and the clinical course. Such a phenomenon of antibody dependent enhancement (ADE) has already been described in several viral infections. Thus, the development of IgG against SARS-CoV-2 in the course of COVID-19 might not be a simple sign of viral clearance and developing protection against the virus. On the contrary, due to cross-reaction to related coronavirus strains from earlier infections, in certain patients IgG might enhance clinical progression due to ADE. The patient's viral history of coronavirus infection might be crucial to the development of the current infection with SARS-CoV-2. Furthermore, it poses a note of caution when treating COVID-19 patients with convalescent sera.


Toning down the 2019-nCoV media hype—and restoring hope


title: Prospective evaluation of diagnostic tools for respiratory viruses in children and adults

text: Abstract Aim To compare the performances of molecular and non-molecular tests to diagnose respiratory viral infections and to evaluate the pros and contras of each technique. Methods Two hundred ninety-nine respiratory samples were prospectively explored using multiplex molecular techniques (FilmArray Respiratory Panel, Clart Pneumovir), immunological techniques (direct fluorescent assay, lateral flow chromatography) and cell cultures. Findings Molecular techniques permitted the recovery of up to 50% more respiratory pathogens in comparison to non-molecular methods. FilmArray detected at least 30% more pathogens than Clart Pneumovir which could be explained by the differences in their technical designs. The turnaround time under 2 hours for the FilmArray permitted delivery of results when patients were still in the emergency room.


title: The Nature and Treatment of Pandemic-Related Psychological Distress

text: The COVID-19 crisis has created a “mental health pandemic” throughout the world. Scientific data are not available to fully understand the nature of the resulting mental health impact given the very recent onset of the pandemic, nevertheless, there is a need to act immediately to develop psychotherapeutic strategies that may alleviate pandemic-related distress. The psychological distress, in particular fear and sadness, is a function of the pandemic’s negative impact upon people’s ability to meet their most basic needs (e.g., physical safety, financial security, social connection, participation in meaningful activities). This paper presents evidence-based cognitive behavioral strategies that should prove useful in reducing the emotional suffering associated with the COVID crisis.


title: Intracellular complement − the complosome − in immune cell regulation

text: Abstract The complement system was defined over a century ago based on its ability to “complement” the antibody-mediated and cell-mediated immune responses against pathogens. Today our understanding of this ancient part of innate immunity has changed substantially and we know now that complement plays an undisputed pivotal role in the regulation of both innate and adaptive immunity. The complement system consists of over 50 blood-circulating, cell-surface expressed and intracellular proteins. It is key in the recognition and elimination of invading pathogens, also in the removal of self-derived danger such as apoptotic cells, and it supports innate immune responses and the initiation of the general inflammatory reactions. The long prevailing classic view of complement was that of a serum-operative danger sensor and first line of defence system, however, recent experimental and clinical evidences have demonstrated that “local” tissue and surprisingly intracellular complement (the complosome) activation impacts on normal cell physiology. This review will focus on novel aspects of intracellular complement activation and its unexpected roles in basic cell processes such as metabolism. We also discuss what the existence of the complosome potentially means for how the host handles intracellular pathogens such as viruses.


title: Recent applications of affinity interactions in capillary electrophoresis

text: Systems biology depends on a comprehensive assignment and characterization of the interactions of proteins and polypeptides (functional proteomics) and of other classes of biomolecules in a given organism. High‐capacity screening methods are in place for ligand capture and interaction screening, but a detailed dynamic characterization of molecular interactions under physiological conditions in efficiently separated mixtures with minimal sample consumption is presently provided only by electrophoretic interaction analysis in capillaries, affinity CE (ACE). This has been realized in different fields of biology and analytical chemistry, and the resulting advances and uses of ACE during the last 2.5 years are covered in this review. Dealing with anything from small divalent metal ions to large supramolecular assemblies, the applications of ACE span from low‐affinity binding of broad specificity being exploited in optimizing selectivity, e.g., in enantiomer analysis to miniaturized affinity technologies, e.g., for fast processing immunoassay. Also, approaches that provide detailed quantitative characterization of analyte–ligand interaction for drug, immunoassay, and aptamer development are increasingly important, but various approaches to ACE are more and more generally applied in biological research. In addition, the present overview emphasizes that distinct challenges regarding sensitivity, parallel processing, information‐rich detection, interfacing with MS, analyte recovery, and preparative capabilities remain. This will be addressed by future technological improvements that will ensure continuing new applications of ACE in the years to come.


title: Managing Knowledge Integration in a National Health-Care Crisis: Lessons Learned From Combating Sars in Singapore

text: The outbreak of Severe Acute Respiratory Syndrome is the first severe and readily transmissible disease to emerge in the 21st century. Often one new infection meant tracing of several people to monitor their health conditions as well. In Singapore, several agencies coordinated their efforts to quickly bring the outbreak under control. The current breed of health-care information systems (HCIS) was not sufficient to handle new information-sharing needs during the crisis. In this paper, we take a look at the measures taken during the crisis in Singapore through a knowledge integration perspective. This perspective reveals interesting implications for HCIS.


In Regard to Kabarriti et al


title: (18)F-FDG PET/CT in Hodgkin Lymphoma With Unsuspected COVID-19

text: We present an asymptomatic 70-year-old man referred for an (18)F-FDG PET/CT for initial staging of a Hodgkin lymphoma. (18)F-FDG PET/CT showed bilateral cervical lymphadenopathy (stage II). Incidentally, the CT demonstrated bilateral ground-glass opacities with low-grade (18)F-FDG activity. CT findings were suspicious for COVID-19 pneumonitis. The COVID-19 reverse transcriptase polymerase chain reaction (RT-PCR) examination result was negative. Given the high clinical suspicion for COVID-19, the patient was isolated and repeat RT-PCR was positive at 72 hours. RT-PCR may be falsely negative in early COVID-19 disease, even with positive CT findings.


title: Identification of the strain-specifically truncated nonstructural protein 10 of porcine reproductive and respiratory syndrome virus in infected cells

text: Abstract The nonstructural protein 10 (nsp10) of porcine reproductive and respiratory syndrome virus (PRRSV) encodes for helicase which plays a vital role in viral replication. In the present study, a truncated form of nsp10, termed nsp10a, was found in PRRSV-infected cells and the production of nsp10a was strain-specific. Mass spectrometric analysis and deletion mutagenesis indicated that nsp10a may be short of about 70 amino acids in the N terminus of nsp10. Further studies by rescuing recombinant viruses showed that the Glu-69 in nsp10 was the key amino acid for nsp10a production. Finally, we demonstrated that nsp10a exerted little influence on the growth kinetics of PRRSV in vitro.


title: Chapter 477 Otubains

text: The third edition of the Handbook of Proteolytic Enzymes aims to be a comprehensive reference work for the enzymes that cleave proteins and peptides, and contains over 800 chapters. Each chapter is organized into sections describing the name and history, activity and specificity, structural chemistry, preparation, biological aspects, and distinguishing features for a specific peptidase. The subject of Chapter 476 is Otubains. Keywords: Otubains, deubiquitylating enzymes, Ubiquitin, Ubiquitin-like proteins, interferon-stimulated genes, Ubiquitin processing enzymes, crystal structure, interferon stimulated genes, ISG15, DUB, OTU, poly-Ubiquitin chains, signal transduction, protein degradation, protein targeting.


title: Antimicrobial Stewardship at the Core of COVID-19 Response Efforts: Implications for Sustaining and Building Programs

text: We describe traditional antimicrobial stewardship program (ASP) activities with a discussion of how these activities can be refocused in the setting of the COVID-19 pandemic. Additionally, we discuss possible adverse consequences of ASP attention diversion on COVID-19 response efforts and overall implications for future pandemic planning. We also discuss ASP in collaboration with other groups within health systems and how COVID-19 may affect these relationships long term. Despite the paucity of literature on Antimicrobial Stewardship and COVID-19, the potential contributions of ASPs during a pandemic are numerous. ASPs can develop strategies to identify patients with COVID-19-like-illness; this is particularly useful when these patients are missed at the time of health system entry. ASPs can also play a critical role in the management of potential drug shortages, developing local treatment guidelines, optimizing the use of antibiotics, and in the diagnostic stewardship of COVID-19 testing, among other roles. Importantly, it is often difficult to ascertain whether critically ill patients who are hospitalized with COVID-19 have concurrent or secondary bacterial infections—ASPs are ideally situated to help optimize antimicrobial use for these patients via a variety of mechanisms. ASPs are uniquely positioned to aid in pandemic response planning and relief efforts. ASPs are already integrated into health systems and play a key role in optimizing antimicrobial prescribing. As ASPs assist in COVID-19 response, understanding the role of ASPs in pandemic relief efforts may mitigate damage from future outbreaks.


title: Immunologic characterization of a immunosuppressed multiple sclerosis patient that recovered from SARS-CoV-2 infection

text: A multiple sclerosis patient infected by SARS-CoV-2 during fingolimod therapy was hospitalized with moderate clinical features, and recovered in 15 days. High levels of CCL5 and CCL10 chemokines and of antibody-secreting B cells were detected, while the levels other B- and T-cell subsets were comparable to that of appropriate controls. However, CD4+ and CD8+ cells were oligoclonally expanded and prone to apoptosis when stimulated in vitro. This study suggests that fingolimod-immunosuppressed patients, despite the low circulating lymphocytes, may rapidly expand antibody-secreting cells and mount an effective immune response that favors COVID-19 recovery after discontinuation.


title: Can developing countries face novel coronavirus outbreak alone? The Iraqi situation

text: Abstract Iraq is one of seven Arabic countries (Lebanon, Bahrain, Kuwait, Oman, Qatar and Saudi Arabia) that acquired novel coronavirus-19 disease (COVID-19) via people who have visited Iran recently. Iraqi outdated public healthcare settings are already overwhelmed with many acute injuries from ongoing unrest. Iraq faces six challenges in controlling COVID-19 [1]: A shortage in number of quarantine facilities [2], the availability of the testing which is limited to one governmental lab only in Baghdad [3], a shortage in personal protective equipment (PPE) and ambulances [4], a low level of public awareness [5], a shortage in hygiene preparations and [6] a high rate of antibiotic resistance in case of secondary bacterial infection. Thus, Iraq alone cannot control such a rapidly emerging outbreak and needs help from the international community and the World Health Organization (WHO) to prepare additional medical labs, establish high standard quarantine facilities and provide medical equipment for healthcare professionals. On its side, Iraq needs to impose more restrictions on travel from countries with a COVID-19 outbreak as other countries have done.


title: Structure, function and evolution of the hemagglutinin-esterase proteins of corona- and toroviruses

text: Virus attachment to host cells is mediated by dedicated virion proteins, which specifically recognize one or, at most, a limited number of cell surface molecules. Receptor binding often involves protein-protein interactions, but carbohydrates may serve as receptor determinants as well. In fact, many different viruses use members of the sialic acid family either as their main receptor or as an initial attachment factor. Sialic acids (Sias) are 9-carbon negatively-charged monosaccharides commonly occurring as terminal residues of glycoconjugates. They come in a large variety and are differentially expressed in cells and tissues. By targeting specific Sia subtypes, viruses achieve host cell selectivity, but only to a certain extent. The Sia of choice might still be abundantly present on non-cell associated molecules, on non-target cells (including cells already infected) and even on virus particles themselves. This poses a hazard, as high-affinity virion binding to any of such “false'' receptors would result in loss of infectivity. Some enveloped RNA viruses deal with this problem by encoding virion-associated receptor-destroying enzymes (RDEs). These enzymes make the attachment to Sia reversible, thus providing the virus with an escape ticket. RDEs occur in two types: neuraminidases and sialate-O-acetylesterases. The latter, originally discovered in influenza C virus, are also found in certain nidoviruses, namely in group 2 coronaviruses and in toroviruses, as well as in infectious salmon anemia virus, an orthomyxovirus of teleosts. Here, the structure, function and evolution of viral sialate-O-acetylesterases is reviewed with main focus on the hemagglutinin-esterases of nidoviruses.


title: Timely Lessons from a Pandemic on the Benefits of Person Centric Care in Long Term Care Facilities

text: Since the outbreak of Coronavirus Disease 2019 (COVID-19), there have been few deadlier places than in nursing homes. As such, several useful guidelines on coping with COVID-19 in nursing homes have emerged. The critical immediate term measures mentioned in the guidelines have longer term implications especially on quality of care. We discuss how these measures instituted for infection control can be synergistic with person-centered care which has been synonymous with quality of care in nursing homes.


title: Mouse (Mus musculus) stocks derived from tropical islands: new models for genetic analysis of life‐history traits

text: Founder effects, together with access to unoccupied ecological niches, may allow rodent populations on isolated islands to evolve constellations of life‐history traits that distinguish them from their mainland relatives, for example in body size, litter size, and longevity. In particular, low intrinsic mortality risks on islands with reduced predator numbers and not subject to harsh winter climates may in principle support the development of stocks with extended longevity. Conversely, the conditions under which laboratory rodents are typically bred are thought to select for genotypes that produce large, rapidly maturing races with high early reproductive rates but diminished longevity. To test these ideas, and to generate new mouse stocks suitable for genetic and molecular analysis of the processes that time life‐history events, we have developed specific pathogen‐free stocks from mice trapped from three distinct populations: the U.S. mainland (Idaho) and the tropical Pacific islands Majuro and Pohnpei. Mice from all three locations were found to be shorter and lighter, to have smaller litters, and to have higher faecal corticosterone levels than mice of a genetically heterogeneous stock derived from four common laboratory inbred strains. Among the wild‐derived stocks, mice from Pohnpei and Majuro were significantly lighter and shorter than Idaho‐derived animals, even in populations kept from birth under identical housing conditions. Litter size and reproductive success rates did not differ significantly among the three wild‐derived stocks. Although further work will be needed to see if, as predicted, the wild‐derived stocks differ from one another and from laboratory mice in longevity, these stocks provide useful tools for genetic dissection of factors that regulate body size and reproductive success.


title: 4 Cases: HIV and SARS‐CoV‐2 Co‐infection in patients from Long Island, New York

text: Originating from Wuhan, China, the novel coronavirus 2019 (SARS‐CoV‐2) has been spreading worldwide since the end of 2019. The most common features of these patients include fever, cough, myalgia or fatigue [1]. As of April 16, 2020 the CDC has reported 605,390 cases and 24,582 deaths in the United States. The illness continues to spread through the world infecting people with various different comorbid conditions. Presented here are four cases which represent some of the first cases of HIV and SARS‐CoV‐2 coinfection in Long Island, New York. These HIV infected patients were compliant with their HIV medication regimen and had robust CD4 T cell counts. The clinical severity ranged from mild to requiring hospitalization. Three of the four patients had fever and two had cough. One patient presented with diarrhea, the incidence rate of diarrhea in SARS‐CoV‐2 infection range from 2% to 50% of cases [4]. One patient had anosmia and aguesia, in a study by Moein et al, the 98% of SARS‐CoV‐2 infected patient experienced some smell dysfunction [5]. One patient required hospitalization however this patient was also infected with influenza A. These cases suggest that uncomplicated cases of SARS‐CoV‐2 in an HIV infected patient can be managed with self‐isolation at home. This article is protected by copyright. All rights reserved.


title: Characterisation of nosocomial and community-acquired influenza in a large university hospital during two consecutive influenza seasons

text: Abstract Background Nosocomial influenza is increasingly recognized as an important public health threat causing considerable morbidity and mortality each year. However, data on nosocomial influenza is usually collected during outbreaks only and clinical information of nosocomial influenza is sparsely available. Objectives To systematically analyse the distribution of nosocomial and community-acquired influenza and epidemiological characteristics in a tertiary care unit in two consecutive seasons. Study design A retrospective observational study was conducted to identify and characterise cases of nosocomial and community-acquired influenza at Freiburg University hospital from 1 January 2013 to 30 April 2014. A validated multiplex RT-PCR to detect influenza virus and other respiratory pathogens was used throughout. Clinical information was retrieved from the hospital-based information system. Results Overall, 218 patients with laboratory-confirmed influenza were included (179 in the first, 39 patients in the second season). A rate of 20% of nosocomial influenza was observed throughout. A fatal outcome was recorded for 9% of nosocomial cases, which were mainly associated with influenza virus A(H1N1)pdm09. Nosocomial influenza occurred in all age groups, but fatalities were only observed in patients ≥18 years. Patients with nosocomial influenza were significantly older, underwent therapy for blood malignancies and immunosuppressive regimens more frequently, and received solid organ transplantation more often compared to community-acquired patients. Conclusions Despite the different distribution of virus subtypes and epidemiological properties between both influenza seasons, the rate of nosocomial cases remained similar. Systematic detection and targeted prevention measures seem mandatory to minimize nosocomial influenza.


title: Infectious diseases epidemic threats and mass gatherings: refocusing global attention on the continuing spread of the Middle East Respiratory syndrome coronavirus (MERS-CoV)

text: Media and World Health Organization (WHO) attention on Zika virus transmission at the 2016 Rio Olympic Games and the 2015 Ebola virus outbreak in West Africa diverted the attention of global public health authorities from other lethal infectious diseases with epidemic potential. Mass gatherings such as the annual Hajj pilgrimage hosted by Kingdom of Saudi Arabia attract huge crowds from all continents, creating high-risk conditions for the rapid global spread of infectious diseases. The highly lethal Middle Eastern respiratory syndrome coronavirus (MERS-CoV) remains in the WHO list of top emerging diseases likely to cause major epidemics. The 2015 MERS-CoV outbreak in South Korea, in which 184 MERS cases including 33 deaths occurred in 2 months, that was imported from the Middle East by a South Korean businessman was a wake-up call for the global community to refocus attention on MERS-CoV and other emerging and re-emerging infectious diseases with epidemic potential. The international donor community and Middle Eastern countries should make available resources for, and make a serious commitment to, taking forward a “One Health” global network for proactive surveillance, rapid detection, and prevention of MERS-CoV and other epidemic infectious diseases threats.


title: Identification of the active site residues in the nsP2 proteinase of sindbis virus

text: Abstract The nonstructural polyproteins of Sindbis virus are processed by a virus-encoded proteinase which is located in the C-terminal domain of nsP2. Here we have performed a mutagenic analysis to identify the active site residues of this proteinase. Substitution of other amino acids for either Cys-481 or His-558 completely abolished proteolytic processing of Sindbis virus polyproteins in vitro. Substitutions within this domain for a second cysteine conserved among alphaviruses, for four other conserved histidines, or for a conserved serine did not affect the activity of the enzyme. These results suggest that nsP2 is a papain-like proteinase whose catalytic dyad is composed of Cys-481 and His-558. Since an asparagine residue has been implicated in the active site of papain, we changed the four conserved asparagine residues in the C-terminal half of nsP2 and found that all could be substituted without total loss of activity. Among papain-like proteinases, the residue following the catalytic histidine is alanine or glycine in the plant and animal enzymes, and the presence of Trp-559 in alphaviruses is unusual. A mutant enzyme containing Ala-559 was completely inactive, implying that Trp-559 is essential for a functional proteinase. All of these mutations were introduced into a full-length clone of Sindbis virus from which infectious RNA could be transcribed in vitro, and the effects of these changes on viability were tested. In all cases it was found that mutations which abolished proteolytic activity were lethal, whether or not these mutations were in the catalytic residues, indicating that proteolysis of the nonstructural polyprotein is essential for Sindbis replication.


title: The Role of Non-animal Origin Feed Ingredients in Transmission of Viral Pathogens of Swine: A Review of Scientific Literature

text: The emergence of porcine epidemic diarrhea (PED) in commercial swine in North America and growing concerns about the potential for the introduction of African swine fever (ASF) from China, the European Union, or other affected regions has put a spotlight on the possible role of contaminated feed and feed ingredients in the introduction and transmission of viral swine pathogens. This paper systematically reviews the scientific literature regarding whether non-animal origin ingredients of commercial swine feed could introduce or transmit viral pathogens of swine into or within the United States. The purpose of this review is to identify, evaluate, and summarize the relevant scientific knowledge, published through March 2018, and to identify information gaps and research needs, thereby making the available evidence more accessible to policy makers, the swine industry, and the scientific community. A total of 26 documents were selected for the final review process, which included experimental studies, case reports, epidemiological investigations, and scientific opinion, among others. The review found that the scientific literature has addressed some critical experimental questions pertaining to transmission of swine viruses via feed and feed ingredients, but the current body of scientific knowledge lacks conclusive evidence of virus contamination of non-animal origin feed ingredients of commercial swine feed, particularly for imported commodities, and further investigation into the epidemiology of virus transmission via feed to swine under field conditions through natural feeding behavior is warranted. Additional studies of how imported ingredients of commercial swine feed are sourced, processed, transported and, thus, contaminated prior to importation into the United States are needed. Moving forward, studies designed to examine the likely source(s) of contamination and subsequent virus mitigation steps in processing and post-processing may be the most fruitful focus of research.


title: Identification of a novel protein 3a from severe acute respiratory syndrome coronavirus

text: The open reading frame 3 of the severe acute respiratory syndrome coronavirus (SARS-CoV) genome encodes a predicted protein 3a, consisting of 274 amino acids, that lacks any significant similarities to any known protein. We generated specific antibodies against SARS protein 3a by using a synthetic peptide (P2) corresponding to amino acids 261–274 of the putative protein. Anti-P2 antibodies and the sera from SARS patients could specifically detect the recombinant SARS protein 3a expressed in Escherichia coli and in Vero E6 cells. Expression of SARS protein 3a was detected at 8–12 h after infection and reached a higher level after ∼24 h in SARS-CoV-infected Vero E6 cells. Protein 3a was also detected in the alveolar lining pneumocytes and some intra-alveolar cells of a SARS-CoV-infected patient's lung specimen. Recombinant protein 3a expressed in Vero E6 cells and protein 3a in the SARS-CoV-infected cells was distributed over the cytoplasm in a fine punctate pattern with partly concentrated staining in the Golgi apparatus. Our study demonstrates that SARS-CoV indeed expresses a novel protein 3a, which is present only in SARS-CoV and not in other known CoVs.


title: 2-Imino-(3,4-dimethoxybenzyl) ethanesulfonic acid Schiff base anchored silver nanocomplex mediated by sugarcane juice and their antibacterial activities

text: Abstract In this present investigation, 2-imino-(3,4-dimethoxybenzyl)ethane sulphonic acid was anchored on a silver nanoparticle mediated by sugarcane sap. The Schiff base was synthesized from 2-aminoethanesulphonic acid and 3,4-dimethoxybenzaldehyde under lemon juice catalyzed conditions while the nanoparticles were obtained by careful stirring of sugarcane sap and 1mM AgNO3 in the ratio of 1:10 respectively at room temperature. The resulting nanocomplex was formed by gentle heating and stirring of the silver nanoparticles solution and the ligand at a temperature of about 80°C for 3h. The ligand, nanoparticles and nanocomplex were characterized using UV–vis spectrophotometer, scanning electron microscope, FT-IR and XRD machines. From the UV–vis results, surface plasmon bands (SPBs) were observed at 475nm for the nanoparticle within 1h of the reaction and 450nm for the nanocomplex. The ligand exhibited absorption bands at 310nm, 280nm and 230nm which are due to π-electron transitions within the chromophores. The strikingly broad nature of the SPBs especially in the nanoparticles revealed that the particles are kinetically favored, nucleate easily and are polydispersed and the blue shift observed in the nanocomplex suggested further reduction in the particle size therefore giving us a clue on how to tailor the products by tuning the raw materials. From the scanning electron micrographs, the morphologies and growth mechanisms revealed oriented attachment for the nanoparticles onwards digestive ripening for the nanocomplex. All the synthesized materials proved to be potential antibacterial agents as they showed great inhibition to the growth of some bacterial strains with the activity enhanced in the nanocomplex.


title: Distinct Lineage of Vesiculovirus from Big Brown Bats, United States

text: We identified a novel rhabdovirus, American bat vesiculovirus, from postmortem tissue samples from 120 rabies-negative big brown bats with a history of human contact. Five percent of the tested bats were infected with this virus. The extent of zoonotic exposure and possible health effects in humans from this virus are unknown.


title: Mass extinctions, biodiversity and mitochondrial function: are bats ‘special’ as reservoirs for emerging viruses?

text: For the past 10–15 years, bats have attracted growing attention as reservoirs of emerging zoonotic viruses. This has been due to a combination of factors including the emergence of highly virulent zoonotic pathogens, such as Hendra, Nipah, SARS and Ebola viruses, and the high rate of detection of a large number of previously unknown viral sequences in bat specimens. As bats have ancient evolutionary origins and are the only flying mammals, it has been hypothesized that some of their unique biological features may have made them especially suitable hosts for different viruses. So the question ‘Are bats different, special or exceptional?’ has become a focal point in the field of virology, bat biology and virus-host co-evolution. In this brief review, we examine the topic in a relatively unconventional way, that is, our discussion will be based on both scientific discoveries and theoretical predictions. This approach was chosen partially because the data in this field are so limited that it is impossible to conduct a useful review based on published results only and also because we believe it is important to provoke original, speculative or even controversial ideas or theories in this important field of research.


title: Public perceptions of quarantine: community-based telephone survey following an infectious disease outbreak

text: BACKGROUND: The use of restrictive measures such as quarantine draws into sharp relief the dynamic interplay between the individual rights of the citizen on the one hand and the collective rights of the community on the other. Concerns regarding infectious disease outbreaks (SARS, pandemic influenza) have intensified the need to understand public perceptions of quarantine and other social distancing measures. METHODS: We conducted a telephone survey of the general population in the Greater Toronto Area in Ontario, Canada. Computer-assisted telephone interviewing (CATI) technology was used. A final sample of 500 individuals was achieved through standard random-digit dialing. RESULTS: Our data indicate strong public support for the use of quarantine when required and for serious legal sanctions against those who fail to comply. This support is contingent both on the implementation of legal safeguards to protect against inappropriate use and on the provision of psychosocial supports for those affected. CONCLUSION: To engender strong public support for quarantine and other restrictive measures, government officials and public health policy-makers would do well to implement a comprehensive system of supports and safeguards, to educate and inform frontline public health workers, and to engage the public at large in an open dialogue on the ethical use of restrictive measures during infectious disease outbreaks.


title: Umbilical cord blood therapy to prevent progression of COVID-19 related pneumonia: a structured summary of a study protocol for a pilot randomised controlled trial

text: OBJECTIVES: Objective: To undertake a pilot, feasibility RCT of umbilical cord blood derived cell therapy for treatment of adult patients infected with SARS-CoV-2 virus related moderate-to-severe pneumonia to prevent progression to severe ARDS. Hypothesis: Expanded cord blood derived cell therapy will be feasible, well tolerated and show potential efficacy in the treatment of acute COVID-19 related moderate to severe pneumonia in adult patients because of their powerful anti-inflammatory and immunomodulatory properties. TRIAL DESIGN: Pilot, parallel design randomised controlled trial. PARTICIPANTS: The trial will recruit 24 hospitalised patients with confirmed SARS-CoV-2 infection and pneumonia from July to December 2020 at Monash Medical Centre in Melbourne, Australia. INTERVENTION AND COMPARATOR: Intervention: Intravenous injection of expanded umbilical cord blood cells at a dose of 5 million cells/kg (maximum dose - 500 million cells). Cell infusion will occur over 30-60 minutes through a peripheral intravenous cannula. Standard supportive care will continue as needed. Comparator: Standard supportive care. MAIN OUTCOMES: Safety and tolerability of cell administration within first 24 hours of administration; clinical improvement on a seven-category clinical improvement ordinal scale. RANDOMISATION: Randomisation will be done using computer generated allocation to intervention/ control groups in a 1:1 ratio (in blocks of 6) using sealed opaque envelopes. BLINDING (MASKING): This will be an unblinded study, given that it is the first study using expanded cord blood cells in COVID-19 patients. There will be no placebo infusion. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Twelve participants in each group. Total n=24. TRIAL STATUS: CBC-19 protocol v2, dated 23(rd) April 2020. Recruitment has not started yet. Estimated recruitment timeline is between 1st July – 31st December 2020. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12620000478910, registered 16th April 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


title: Population-level COVID-19 mortality risk for non-elderly individuals overall and for non-elderly individuals without underlying diseases in pandemic epicenters

text: OBJECTIVE: To provide estimates of the relative rate of COVID-19 death in people <65 years old versus older individuals in the general population, the absolute risk of COVID-19 death at the population level during the first epidemic wave, and the proportion of COVID-19 deaths in non-elderly people without underlying diseases in epicenters of the pandemic. ELIGIBLE DATA: Cross-sectional survey of countries and US states with at least 800 COVID-19 deaths as of April 24, 2020 and with information on the number of deaths in people with age <65. Data were available for 14 countries (Belgium, Canada, France, Germany, India, Ireland, Italy, Mexico, Netherlands, Portugal, Spain, Sweden, Switzerland, UK) and 13 US states (California, Connecticut, Florida, Georgia, Illinois, Indiana, Louisiana, Maryland, Massachusetts, Michigan, New Jersey, New York, Pennsylvania). We also examined available data on COVID-19 deaths in people with age <65 and no underlying diseases. MAIN OUTCOME MEASURES: Proportion of COVID-19 deaths in people <65 years old; relative mortality rate of COVID-19 death in people <65 versus ≥65 years old; absolute risk of COVID-19 death in people <65 and in those ≥80 years old in the general population as of June 17, 2020; absolute COVID-19 mortality rate expressed as equivalent of mortality rate from driving a motor vehicle. RESULTS: Individuals with age <65 account for 4.5–11.2% of all COVID-19 deaths in European countries and Canada, 8.3–22.7% in the US locations, and were the majority in India and Mexico. People <65 years old had 30- to 100-fold lower risk of COVID-19 death than those ≥65 years old in 11 European countries and Canada, 16- to 52-fold lower risk in US locations, and less than 10-fold in India and Mexico. The absolute risk of COVID-19 death as of June 17, 2020 for people <65 years old in high-income countries ranged from 10 (Germany) to 349 per million (New Jersey) and it was 5 per million in India and 96 per million in Mexico. The absolute risk of COVID-19 death for people ≥80 years old ranged from 0.6 (Florida) to 17.5 per thousand (Connecticut). The COVID-19 mortality rate in people <65 years old during the period of fatalities from the epidemic was equivalent to the mortality rate from driving between 4 and 82 miles per day for 13 countries and 5 states, and was higher (equivalent to the mortality rate from driving 106–483 miles per day) for 8 other states and the UK. People <65 years old without underlying predisposing conditions accounted for only 0.7–3.6% of all COVID-19 deaths in France, Italy, Netherlands, Sweden, Georgia, and New York City and 17.7% in Mexico. CONCLUSIONS: People <65 years old have very small risks of COVID-19 death even in pandemic epicenters and deaths for people <65 years without underlying predisposing conditions are remarkably uncommon. Strategies focusing specifically on protecting high-risk elderly individuals should be considered in managing the pandemic.