docid: imusyaot

title: Worrying decrease in hospital admissions for myocardial infarction during the COVID-19 pandemic

text: Summary Background: How coronavirus 2019 (COVID-19) is affecting management of myocardial infarction is a matter of concern, as medical resources have been massively reorientated and the population has been in lockdown since 17 March 2020 in France. Aims: To describe how lockdown has affected the evolution of the weekly rate of myocardial infarctions (non–ST-segment and ST-segment elevation) hospital admissions in Lyon, the second largest city in France. To verify the trend observed, the same analysis was conducted for an identical time window during 2018–2019 and for an unavoidable emergency, i.e. birth. Methods: Based on the national hospitalization database (Programme de médicalisation des systèmes d'information [PMSI]), all patients admitted to the main public hospitals for a principal diagnosis of myocardial infarction or birth during the 2nd to the 14th week of 2020 were included. These were compared with the average number of patients admitted for the same diagnosis during the same time window in 2018 and 2019. Results: Before lockdown, the number of admissions for myocardial infarction in 2020 differed from that in 2018–2019 by less than 10%; after the start of lockdown, it decreased by 31% compared with the corresponding time window in 2018–2019. Conversely, the numbers of births remained stable across years and before and after the start of lockdown. Conclusion: This study strongly suggests a decrease in the number of admissions for myocardial infarction during lockdown. Although we do not have a long follow-up to determine whether this trend will endure, this is an important warning for the medical community and health authorities.


Balancing infection control and frailty prevention during and after the COVID‐19 pandemic: Introduction of the NCGG Home Exercise Program for Older People 2020


docid: bxapqnmh

title: Guiding airway management and PPE for COVID-19 intubating teams


title: A Multiscale and Comparative Model for Receptor Binding of 2019 Novel Coronavirus and the Implication of its Life Cycle in Host Cells

text: The respiratory syndrome caused by a new type of coronavirus has been emerging from China and caused more than 1000 death globally since December 2019. This new virus, called 2019 novel coronavirus (2019-nCoV) uses the same receptor called Angiotensinconverting enzyme 2 (ACE2) to attack humans as the coronavirus that caused the severe acute respiratory syndrome (SARS) seventeen years ago. Both viruses recognize ACE2 through the spike proteins (S-protein) on their surfaces. It was found that the S-protein from the SARS coronavirus (SARS-CoV) bind stronger to ACE2 than 2019-nCoV. However, function of a bio-system is often under kinetic, rather than thermodynamic, control. To address this issue, we constructed a structural model for complex formed between ACE2 and the S-protein from 2019-nCoV, so that the rate of their association can be estimated and compared with the binding of S-protein from SARS-CoV by a multiscale simulation method. Our simulation results suggest that the association of new virus to the receptor is slower than SARS, which is consistent with the experimental data obtained very recently. We further integrated this difference of association rate between virus and receptor into a mathematical model which describes the life cycle of virus in host cells and its interplay with the innate immune system. Interestingly, we found that the slower association between virus and receptor can result in longer incubation period, while still maintaining a relatively higher level of viral concentration in human body. Our computational study therefore provides, from the molecular level, one possible explanation that the new disease by far spread much faster than SARS.


title: The COVID-19 Pandemic: A Month of Bioethics in Finland

text: Finland’s first COVID-19 infection was recorded in late January 2020. The person infected was a tourist from China in Lapland. Authorities recommended regular handwashing, coughing in one’s sleeve, not touching your face, physical distancing, and home lockdown for those at risk. The pandemic spread at different paces in different regions, and the first Finnish fatality was recorded on March 20 in Uusimaa province, where the number of documented infections was considerably higher than elsewhere. In late March, the parliament granted the government emergency powers for swift regulations and restrictions. Uusimaa province was isolated from the rest of the country for a fortnight, restaurants were closed, meetings of more than 10 people were forbidden, and schools and universities assumed distant-working modes, as did businesses and civil services where this was feasible.


title: A Mouse Model for MERS Coronavirus Induced Acute Respiratory Distress Syndrome

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that emerged in 2012, causing acute respiratory distress syndrome (ARDS), severe pneumonia-like symptoms, and multi-organ failure, with a case fatality rate of ~36%. Limited clinical studies indicate that humans infected with MERS-CoV exhibited pathology consistent with late stages of ARDS, which is reminiscent of disease observed in patients infected with SARS coronavirus. Models of MERS-CoV-induced severe respiratory disease have been difficult to achieve, and small animal models traditionally used to investigate viral pathogenesis (mouse, hamster, guinea pig, and ferret) are naturally resistant to MERS-CoV. Therefore, we used CRISPR/Cas9 to modify the mouse genome to encode two human amino acids (288 and 330) in the dipeptidyl peptidase 4 receptor, making mice susceptible to MERS-CoV replication. Serial MERS-CoV passage in these engineered mice was then used to generate a mouse-adapted virus that replicated efficiently within the lungs, and evoked symptoms indicative of severe acute respiratory distress syndrome (ARDS), including decreased survival, extreme weight loss, decreased pulmonary function, pulmonary hemorrhage, and pathological signs indicative of end stage lung disease. Importantly, therapeutic countermeasures comprising MERS-CoV neutralizing antibody treatment or a MERS-CoV spike protein vaccine protected engineered mice against MERS-CoV-induced ARDS.


Gulf War Servicemen and Servicewomen: The Long Road Home and the Role of Health Care Professionals to Enhance the Troops' Health and Healing


title: 21 New developments in safety testing of soft fruits

text: Abstract: The chapter begins by establishing the definition of soft fruit, then discusses microbial and chemical hazards that might be found in soft fruit. Methods developed for virus detection in soft fruit are reviewed and, finally, the factors that mainly affect virus detection are detailed as these pathogens are currently linked to outbreaks caused by soft fruit consumption.


title: In Silico Analysis of ORF1ab in Coronavirus HKU1 Genome Reveals a Unique Putative Cleavage Site of Coronavirus HKU1 3C‐Like Protease

text: Recently we have described the discovery and complete genome sequence of a novel coronavirus associated with pneumonia, coronavirus HKU1 (CoV‐HKU1). In this study, a detailed in silico analysis of the ORF1ab, encoding the 7,182‐amino acid replicase polyprotein in the CoV‐HKU1 genome showed that the replicase polyprotein of CoV‐HKU1 is cleaved by its papain‐like proteases and 3C‐like protease (3CL(pro)) into 16 polypeptides homologous to the corresponding polypeptides in other coronaviruses. Surprisingly, analysis of the putative cleavage sites of the 3CL(pro) revealed a unique putative cleavage site. In all known coronaviruses, the P1 positions at the cleavage sites of the 3CL(pro) are occupied by glutamine. This is also observed in CoV‐HKU1, except for one site at the junction between nsp10 (helicase) and nsp11 (member of exonuclease family), where the P1 position is occupied by histidine. This amino acid substitution is due to a single nucleotide mutation in the CoV‐HKU1 genome, CAG/A to CAT. This probably represents a novel cleavage site because the same mutation was consistently observed in CoV‐HKU1 sequences from multiple specimens of different patients; the P2 and P1′‐P12′ positions of this cleavage site are consistent between CoV‐HKU1 and other coronaviruses; and as the helicase is one of the most conserved proteins in coronaviruses, cleavage between nsp10 and nsp11 should be an essential step for the generation of the mature functional helicase. Experiments, including purification and C‐terminal amino acid sequencing of the CoV‐HKU1 helicase and trans‐cleavage assays of the CoV‐HKU1 3CL(pro) will confirm the presence of this novel cleavage site.


title: A guideline for homology modeling of the proteins from newly discovered betacoronavirus, 2019 novel coronavirus (2019‐nCoV)

text: During an outbreak of respiratory diseases including atypical pneumonia in Wuhan, a previously unknown β‐coronavirus was detected in patients. The newly discovered coronavirus is similar to some β‐coronaviruses found in bats but different from previously known SARS‐CoV and MERS‐CoV. High sequence identities and similarities between 2019‐nCoV and SARS‐CoV were found. In this study, we searched the homologous templates of all nonstructural and structural proteins of 2019‐nCoV. Among the nonstructural proteins, the leader protein (nsp1), the papain‐like protease (nsp3), the nsp4, the 3C‐like protease (nsp5), the nsp7, the nsp8, the nsp9, the nsp10, the RNA‐directed RNA polymerase (nsp12), the helicase (nsp13), the guanine‐N7 methyltransferase (nsp14), the uridylate‐specific endoribonuclease (nsp15), the 2'‐O‐methyltransferase (nsp16), and the ORF7a protein could be built on the basis of homology templates. Among the structural proteins, the spike protein (S‐protein), the envelope protein (E‐protein), and the nucleocapsid protein (N‐protein) can be constructed based on the crystal structures of the proteins from SARS‐CoV. It is known that PL‐Pro, 3CL‐Pro, and RdRp are important targets for design antiviral drugs against 2019‐nCoV. And S protein is a critical target candidate for inhibitor screening or vaccine design against 2019‐nCoV because coronavirus replication is initiated by the binding of S protein to cell surface receptors. It is believed that these proteins should be useful for further structure‐based virtual screening and related computer‐aided drug development and vaccine design.


title: Microbiological control in stem cell banks: approaches to standardisation

text: The transplant of cells of human origin is an increasingly complex sector of medicine which entails great opportunities for the treatment of a range of diseases. Stem cell banks should assure the quality, traceability and safety of cultures for transplantation and must implement an effective programme to prevent contamination of the final product. In donors, the presence of infectious micro-organisms, like human immunodeficiency virus, hepatitis B virus, hepatitis C virus and human T cell lymphotrophic virus, should be evaluated in addition to the possibility of other new infectious agents (e.g. transmissible spongiform encephalopathies and severe acute respiratory syndrome). The introduction of the nucleic acid amplification can avoid the window period of these viral infections. Contamination from the laboratory environment can be achieved by routine screening for bacteria, fungi, yeast and mycoplasma by European pharmacopoeia tests. Fastidious micro-organisms, and an adventitious or endogenous virus, is a well-known fact that will also have to be considered for processes involving in vitro culture of stem cells. It is also a standard part of current good practice in stem cell banks to carry out routine environmental microbiological monitoring of the cleanrooms where the cell cultures and their products are prepared. The risk of viral contamination from products of animal origin, like bovine serum and mouse fibroblasts as a “feeder layer” for the development of embryonic cell lines, should also be considered. Stem cell lines should be tested for prion particles and a virus of animal origin that assure an acceptable quality.


title: Lessons learnt from implementation of the International Health Regulations: a systematic review

text: OBJECTIVE: To respond to the World Health Assembly call for dissemination of lessons learnt from countries that have begun implementing the International Health Regulations, 2005 revision; IHR (2005). METHODS: In November 2015, we conducted a systematic search of the following online databases and sources: PubMed®, Embase®, Global Health, Scopus, World Health Organization (WHO) Global Index Medicus, WHO Bulletin on IHR Implementation and the International Society for Disease Surveillance. We included identified studies and reports summarizing national experience in implementing any of the IHR (2005) core capacities or their components. We excluded studies that were theoretical or referred to IHR (1969). Qualitative systematic review methodology, including meta-ethnography, was used for qualitative synthesis. FINDINGS: We analysed 51 articles from 77 countries representing all WHO Regions. The meta-syntheses identified a total of 44 lessons learnt across the eight core capacities of IHR (2005). Major themes included the need to mobilize and sustain political commitment; to adapt global requirements based on local sociocultural, epidemiological, health system and economic contexts; and to conduct baseline and follow-up assessments to monitor the status of IHR (2005) implementation. CONCLUSION: Although experiences of IHR (2005) implementation covered a wide global range, more documentation from Africa and Eastern Europe is needed. We did not find specific areas of weakness in monitoring IHR (2005); sustained monitoring of all core capacities is required to ensure effective systems. These lessons learnt could be adapted by countries in the process of meeting IHR (2005) requirements.


title: Development of Lectin-Linked Immunomagnetic Separation for the Detection of Hepatitis A Virus

text: The accuracy and sensitivity of PCR-based methods for detection of hepatitis A virus (HAV) are dependent on the methods used to separate and concentrate the HAV from the infected cells. The pH and ionic strength affect the binding affinity of the virus to cells. In this study, we initially investigated the effects of pH (4.0–10.0) and metal ions (Fe(2+), Co(2+), Cu(2+), Mg(2+), K(+), and Ca(2+)) on the binding of HAV to oyster digestive cells. The lowest relative binding (RB) of HAV to the cells was found at pH 4.0 and in FeSO(4) solution (64.6% and 68.1%, respectively). To develop an alternative to antibody-dependent immunomagnetic separation prior to detection of HAV using RT-PCR, the binding of HAV to five lectins, peanut agglutinin (PNA), Dolichos biflorus agglutinin (DBA), Helix pomatia agglutinin (HPA), Ulex europaeus agglutinin (UEA-1) and soybean agglutinin (SBA), was evaluated using ELISAs. SBA showed significantly higher RB to HAV than the other lectins tested. In addition, HAV could be concentrated within 30 min using SBA-linked magnetic bead separation (SMS) prior to the RT-PCR assay. Our findings demonstrate the feasibility of using SMS combined with RT-PCR to detect HAV at dilutions ranging from 10(−1)–10(−4) of a HAV stock (titer: 10(4) TCID(50)/mL).


title: Disease features of equine coronavirus and enteric salmonellosis are similar in horses

text: BACKGROUND: Equine coronavirus (ECoV) is an emerging pathogen associated with fever and enteric disease in adult horses. Clinical features of ECoV infection have been described, but no study has compared these features to those of Salmonella infections. OBJECTIVES: Compare the clinical features of ECoV infection with enteric salmonellosis and establish a disease signature to increase clinical suspicion of ECoV infection in adult horses. ANIMALS: Forty‐three horses >1 year of age with results of CBC, serum biochemistry, and fecal diagnostic testing for ECoV and Salmonella spp. METHODS: Medical records of horses presented to the North Carolina State University Equine and Farm Animal Veterinary Center (2003‐016) were retrospectively reviewed. Horses were divided into 3 groups based on fecal diagnostic test results: ECoV‐positive, Salmonella‐positive, or unknown diagnosis (UNK). Time of year presented, clinical signs, CBC, and serum biochemistry test results were recorded. Data were analyzed by 1‐way analysis of variance, Kruskal‐Wallis test, or Fisher's exact test with significance set at P < .05. RESULTS: Most common presenting complaints were fever and colic and were similar across groups. Horses with ECoV had significantly decreased neutrophil counts when compared to those with no diagnosis but were not different from horses with Salmonella. Horses with Salmonella had significantly lower mean leukocyte counts compared to those with UNK. No significant differences were found among groups for any other examined variable. CONCLUSIONS AND CLINICAL IMPORTANCE: Equine coronavirus and Salmonella infections share clinical features, suggesting both diseases should be differential diagnoses for horses with fever and enteric clinical signs.


title: Generating and evaluating type I interferon receptor-deficient and feline TMPRSS2-expressing cells for propagating serotype I feline infectious peritonitis virus

text: Abstract Feline coronavirus infection can progress to a fatal infectious peritonitis, which is a widespread feline disease without an effective vaccine. Generating feline cells with reduced ability to respond to interferon (IFN) is an essential step facilitating isolation of new candidate vaccine strains. Here, we describe the use of Crispr/Cas technology to disrupt type I IFN signaling in two feline cell lines, AK-D and Fcwf-4 CU, and evaluate the replication kinetics of a serotype I feline infectious peritonitis virus (FIPV) within these cells. We report that polyclonal cell populations and a clonal isolate, termed Fcwf-4 IRN, exhibited significantly diminished IFN-responsiveness and allowed FIPV replication kinetics comparable to parental cells. Furthermore, we demonstrate that replication of FIPV is enhanced by ectopic expression of a host serine protease, TMPRSS2, in these cells. We discuss the potential of these cells for isolating new clinical strains and for propagating candidate vaccine strains of FIPV.


title: The RNA shapes studio

text: Motivation: Abstract shape analysis, first proposed in 2004, allows one to extract several relevant structures from the folding space of an RNA sequence, preferable to focusing in a single structure of minimal free energy. We report recent extensions to this approach. Results: We have rebuilt the original RNAshapes as a repository of components that allows us to integrate several established tools for RNA structure analysis: RNAshapes, RNAalishapes and pknotsRG, including its recent extension pKiss. As a spin-off, we obtain heretofore unavailable functionality: e. g. with pKiss, we can now perform abstract shape analysis for structures holding pseudoknots up to the complexity of kissing hairpin motifs. The new tool pAliKiss can predict kissing hairpin motifs from aligned sequences. Along with the integration, the functionality of the tools was also extended in manifold ways. Availability and implementation: As before, the tool is available on the Bielefeld Bioinformatics server at http://bibiserv.cebitec.uni-bielefeld.de/rnashapesstudio. Contact: bibi-help@cebitec.uni-bielefeld.de


docid: bumlarqa

title: From SARS to pandemic influenza: the framing of high-risk populations

text: The 2003 global outbreak of severe acute respiratory syndrome (SARS) was a wake-up call for health systems in Canada, with realization of occupational health risks faced by health care workers and first responders in public health emergency response. The need for investment in critical social infrastructure—including explicitly articulated plans—became a priority for managing future pandemics. Over the past 15 years, pandemic planning has evolved with the adoption of a whole-of-society approach to disaster risk reduction. There is recognition of the social gradient of risk, which emerges from the interaction between social determinants of health, risk of exposure, and adverse impacts from a pandemic. Additionally, there is better understanding of the benefits of planning according to functional needs, rather than deficit-oriented labelling. In this paper, we reflect on how the framing of vulnerable or high-risk populations has evolved since SARS. Looking to the future, we present the imperative for the creation of institutional space for engagement of high-risk populations in pandemic planning processes, including participatory governance. Innovative consultation strategies are needed to enhance collective asset literacy and ensure planning is adaptive to the changing social fabric. Progressive pandemic planning in the next decade must be inclusive and sensitive to modern definitions of family, varied abilities, cultural practices and gender and sexual diversity, thereby reflecting a whole-of-society approach to disaster risk reduction.


title: Discovery of a missing disease spreader

text: This study presents a method to discover an outbreak of an infectious disease in a region for which data are missing, but which is at work as a disease spreader. Node discovery for the spread of an infectious disease is defined as discriminating between the nodes which are neighboring to a missing disease spreader node, and the rest, given a dataset on the number of cases. The spread is described by stochastic differential equations. A perturbation theory quantifies the impact of the missing spreader on the moments of the number of cases. Statistical discriminators examine the mid-body or tail-ends of the probability density function, and search for the disturbance from the missing spreader. They are tested with computationally synthesized datasets, and applied to the SARS outbreak and flu pandemic.


Cytochemical identification of callose deposits around plasmodesmaia of virus-infected phloem cells


Covid-19 health crisis management in Europe: decisive assessment is needed now


title: Awake Prone Positioning for Non-intubated Oxygen Dependent COVID-19 Pneumonia Patients

text: Oxygenation failure recalcitrant to increasing positive end-expiratory pressure is a feature of severe coronavirus disease 2019 (COVID-19) pneumonia [1]. A Chinese group [2] used prone positioning to improve oxygenation for intubated patients with severe COVID-19 pneumonia. However, prone positioning in unconscious patients is labour-intensive and is associated with various complications [3, 4]. As the incidence of severe COVID-19 pneumonia worldwide increases rapidly, many countries are also facing the problem of diminishing intensive care resources.


title: Structural proteins of bovine coronavirus strain L9: effects of the host cell and trypsin treatment

text: The polypeptide profile of the cell-adapted strain of bovine coronavirus (Mebus BCV-L9) is remarkably affected by the host cell and trypsin. We compared the structural proteins of virus purified from different cell lines and found cell-dependent differences in the virus structure. BCV was purified from four clones of human rectal tumour cells (HRT-18): 3 F3, D 2, 3 E 3, and 4 B 3. The structural profiles of BCV propagated in clones 3 E 3 and 3 F 3 were identical, consisting of proteins with molecular weights of 185, 160, 140, 125, 110, 100, 52, 46, 37, 31–34, and 26–28 kilodaltons (kd). BCV purified from clone D2 lacked the 100 kd species, and clone 4 B 3 yielded virus lacking the 46 kd protein. We compared the structures of BCV propagated in HRT-18 cells [BCV(HRT-18)] and virus raised in bovine fetal spleen cells [BCV(D 2 BFS)]. The concentration of the 185 kd protein was higher in BCV (D 2BFS), and it also contained a 200 kd species. Protein profiles of in vitro trypsin treated and untreated BCV(HRT-18) differed only under reducing conditions, suggesting that trypsin cleavage sites are located within disulfide-linked regions of affected proteins. Propagation of BCV in D 2 BFS cells in the presence of trypsin resulted in cleavage of the 185 kd protein and a concommitant increase of the 100 kd protein. Activation of the fusion function probably depends on this cleavage process because fusion of BCV-infected D 2 BFS cells is trypsin dependent.


title: COVID-19: implications for immunosuppression in kidney disease and transplantation

text: The coronavirus disease 2019 (COVID-19) pandemic poses important challenges to the care of patients with immune-mediated kidney diseases and to kidney transplant recipients. Here, we discuss the management of immunosuppression for these patients during the pandemic and suggest potential approaches that could be considered in the absence of validated strategies.


title: Chinese Public's Attention to the COVID-19 Epidemic on Social Media: Observational Descriptive Study

text: BACKGROUND: Since the coronavirus disease (COVID-19) epidemic in China in December 2019, information and discussions about COVID-19 have spread rapidly on the internet and have quickly become the focus of worldwide attention, especially on social media. OBJECTIVE: This study aims to investigate and analyze the public’s attention to events related to COVID-19 in China at the beginning of the COVID-19 epidemic (December 31, 2019, to February 20, 2020) through the Sina Microblog hot search list. METHODS: We collected topics related to the COVID-19 epidemic on the Sina Microblog hot search list from December 31, 2019, to February 20, 2020, and described the trend of public attention on COVID-19 epidemic-related topics. ROST Content Mining System version 6.0 was used to analyze the collected text for word segmentation, word frequency, and sentiment analysis. We further described the hot topic keywords and sentiment trends of public attention. We used VOSviewer to implement a visual cluster analysis of hot keywords and build a social network of public opinion content. RESULTS: The study has four main findings. First, we analyzed the changing trend of the public’s attention to the COVID-19 epidemic, which can be divided into three stages. Second, the hot topic keywords of public attention at each stage were slightly different. Third, the emotional tendency of the public toward the COVID-19 epidemic-related hot topics changed from negative to neutral, with negative emotions weakening and positive emotions increasing as a whole. Fourth, we divided the COVID-19 topics with the most public concern into five categories: the situation of the new cases of COVID-19 and its impact, frontline reporting of the epidemic and the measures of prevention and control, expert interpretation and discussion on the source of infection, medical services on the frontline of the epidemic, and focus on the worldwide epidemic and the search for suspected cases. CONCLUSIONS: Our study found that social media (eg, Sina Microblog) can be used to measure public attention toward public health emergencies. During the epidemic of the novel coronavirus, a large amount of information about the COVID-19 epidemic was disseminated on Sina Microblog and received widespread public attention. We have learned about the hotspots of public concern regarding the COVID-19 epidemic. These findings can help the government and health departments better communicate with the public on health and translate public health needs into practice to create targeted measures to prevent and control the spread of COVID-19.


The Era of Human-Induced Diseases


docid: evbsdfhp

title: Rapid diagnostic test for respiratory infections

text: Abstract Acute respiratory infections are the second cause of morbidity and mortality in children and adults worldwide, being viruses, bacteria and fungi involved in their aetiology. The rapid diagnosis allows for a better clinical management of the patient, for adopting public health measures and for controlling possible outbreaks. The main etiologic agents can be diagnosed within the first hours after the onset of symptoms with antigen detection techniques, primarily immunochromatography. Results are obtained in 15–30min, with 70–90% sensitivity and >95% specificity for the diagnosis of Streptococcus pneumoniae and Legionella pneumophila serogroup O1 infections from urine, Streptococcus pyogenes from throat swabs and respiratory syncytial virus from nasopharyngeal aspirates. Worse results are obtained for influenza viruses and Pneumocystis jirovecii with these techniques; however, other easy-to-perform molecular techniques are available for the rapid diagnosis of these microorganisms. In general, these techniques should not be used for monitoring the outcome or response to treatment.


title: Severe Acute Respiratory Syndrome – a New Coronavirus from the Chinese Dragon's Lair

text: The recent identification of a novel clinical entity, the severe acute respiratory syndrome (SARS), the rapid subsequent spread and case fatality rates of 14–15% have prompted a massive international collaborative investigation facilitated by a network of laboratories established by the World Health Organization (WHO). As SARS has the potential of becoming the first pandemic of the new millennium, a global warning by the WHO was issued on 12 March 2003. The disease, which is believed to have its origin in the Chinese Guangdong province, spread from Hong Kong via international airports to its current worldwide distribution. The concerted efforts of a globally united scientific community have led to the independent isolation and identification of a novel coronavirus from SARS patients by several groups. The extraordinarily rapid isolation of a causative agent of this newly emerged infectious disease constitutes an unprecedented scientific achievement. The main scope of the article is to provide the clinician with an overview of the natural history, epidemiology and clinical characteristics of SARS. On the basis of the recently published viral genome and structural features common to the members of the coronavirus family, a model for host cell–virus interaction and possible targets for antiviral drugs are presented. The epidemiological consequences of introducing a novel pathogen in a previously unexposed population and the origin and evolution of a new and more pathogenic strain of coronavirus are discussed.


title: Low-tech solutions for the COVID-19 supply chain crisis

text: A global effort is ongoing in the scientific community and in the maker movement, which focuses on creating devices and tinkering with them, to reverse-engineer commercial medical equipment and get it to healthcare workers. For these ‘low-tech’ solutions to have a real impact, it is important for them to coalesce around approved designs.


title: ERK signaling is triggered by hepatitis C virus E2 protein through DC-SIGN

text: Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is a binding receptor for hepatitis C virus (HCV). Binding of HCV envelope protein E2 to target cells is a prerequisite to DC-SIGN-mediated signaling. Using cell lines with stable or transient expression of DC-SIGN, we investigated effects of soluble HCV E2 protein on ERK pathway. MEK and ERK are activated by the E2 in NIH3T3 cells stably expressing DC-SIGN. Treatment of the cells with antibody to DC-SIGN results in inhibition of the E2 binding as well as the E2-induced MEK and ERK activation. In HEK293T cells transiently expressing DC-SIGN, activation of MEK and ERK is also induced by the E2. Activation of ERK pathway by HCV E2 through DC-SIGN provides useful information for understanding cellular receptor-mediated signaling.


title: Big-game hunting in the history of epidemics Frank Snowden

text: Unknown


title: Systematic Review and Meta-Analysis of the Persistence and Disinfection of Human Coronaviruses and Their Viral Surrogates in Water and Wastewater

text: [Image: see text] A systematic review and meta-analysis was conducted to identify decay rate constants (k) of human coronaviruses and their viral surrogates (i.e., animal coronaviruses and the enveloped bacteriophage Phi6) in water and wastewater and disinfection rates with exposure to free chlorine and germicidal ultraviolet light (UV(254)). Here, 73 k were identified, with only 12 for human coronaviruses, as opposed to animal coronaviruses or Phi6. In the absence of disinfectants, k increased with temperature. Between 22 and 25 °C, mean k for coronaviruses ranged from 0.19 ± 0.06 d(–1) in laboratory buffer (n = 4) to 2.9 ± 0.03 d(–1) in sterilized wastewater (n = 3), which are within the ranges observed for Phi6 and nonenveloped viruses. No free chlorine or UV(254) disinfection studies for coronaviruses were identified that met the systematic review inclusion criteria, although evidence from the literature suggests that coronaviruses would be inactivated if disinfectant doses recommended for nonenveloped viruses were applied. Three disinfection experiments were identified for Phi6. However, given different genome compositions and virion structures between coronaviruses and Phi6, it is not clear whether Phi6 should be used as a surrogate for evaluating free chlorine or UV(254)k. Therefore, there is a critical need for additional studies that specifically evaluate disinfection kinetics of coronaviruses in the aqueous environment.


DRESS syndrome in a patient with SARS-CoV-2 disease


title: Atypical SARS in Geriatric Patient

text: We describe an atypical presentation of severe acute respiratory syndrome (SARS) in a geriatric patient with multiple coexisting conditions. Interpretation of radiographic changes was confounded by cardiac failure, with resolution of fever causing delayed diagnosis and a cluster of cases. SARS should be considered even if a contact history is unavailable, during an ongoing outbreak.


docid: jomutdxf

title: Synthetic viruses: a new opportunity to understand and prevent viral disease

text: Rapid progress in DNA synthesis and sequencing is spearheading the deliberate, large-scale genetic alteration of organisms. These new advances in DNA manipulation have been extended to the level of whole-genome synthesis, as evident from the synthesis of poliovirus, from the resurrection of the extinct 1918 strain of influenza virus and of human endogenous retroviruses and from the restructuring of the phage T7 genome. The largest DNA synthesized so far is the 582,970 base pair genome of Mycoplasma genitalium, although, as yet, this synthetic DNA has not been ‘booted’ to life. As genome synthesis is independent of a natural template, it allows modification of the structure and function of a virus’s genetic information to an extent that was hitherto impossible. The common goal of this new strategy is to further our understanding of an organism’s properties, particularly its pathogenic armory if it causes disease in humans, and to make use of this new information to protect from, or treat, human viral disease. Although only a few applications of virus synthesis have been described as yet, key recent findings have been the resurrection of the 1918 influenza virus and the generation of codon- and codon pair–deoptimized polioviruses.


title: Rich at risk: socio-economic drivers of COVID-19 pandemic spread

text: COVID-19, the novel coronavirus affecting the most part of worldwide countries since early 2020, is fast increasing its prevalence around the world, representing a significant emergency for the population and the health systems at large. While proper treatments are being developed, in-depth studies concerning its way of diffusion are necessary, in order to understand how the virus is actually spreading, through the investigation on some socio-economic indicators for the various countries in the world, retrieved through open-access data publicly available. The correlation analysis displayed significant relationships between COVID-19 incidence with several of such indicators, including the Gross Domestic Product per capita and the number of flights per capita, whereas mortality is mainly related to the main age of the population. All such data displayed an interesting mean to understand the way the virus has diffused worldwide, possibly representing the basis for future preventive measures to effectively challenge a new COVID-19 pandemic wave, but also other, similar pandemics.


title: A novel hierarchical clustering algorithm for gene sequences

text: BACKGROUND: Clustering DNA sequences into functional groups is an important problem in bioinformatics. We propose a new alignment-free algorithm, mBKM, based on a new distance measure, DMk, for clustering gene sequences. This method transforms DNA sequences into the feature vectors which contain the occurrence, location and order relation of k-tuples in DNA sequence. Afterwards, a hierarchical procedure is applied to clustering DNA sequences based on the feature vectors. RESULTS: The proposed distance measure and clustering method are evaluated by clustering functionally related genes and by phylogenetic analysis. This method is also compared with BlastClust, CD-HIT-EST and some others. The experimental results show our method is effective in classifying DNA sequences with similar biological characteristics and in discovering the underlying relationship among the sequences. CONCLUSIONS: We introduced a novel clustering algorithm which is based on a new sequence similarity measure. It is effective in classifying DNA sequences with similar biological characteristics and in discovering the relationship among the sequences.


title: Features of enteric disease from human coronaviruses: Implications for COVID‐19

text: Coronaviruses have long been studied in both human and veterinary fields. Whereas the initial detection of endemic human respiratory coronaviruses was problematic, detection of these and newly discovered human coronaviruses has been greatly facilitated with major advances in the laboratory. Nevertheless, technological factors can affect the accuracy and timeliness of virus detection. Many human coronaviruses can be variably found in stool samples. All human coronaviruses have been variably associated with symptoms of gastroenteritis. Coronaviruses can occasionally be cultured from enteric specimens, but most detection is accomplished with genetic amplification technologies. Excretion of viral RNA in stool can extend for a prolonged period. Culture‐positive stool samples have been found to exceed a fourteen day period after onset of infection for some coronaviruses. Virus can also sometimes be cultured from patients' respiratory samples during the late incubation period. Relatively asymptomatic patients may excrete virus. Both viable and nonviable virus can be found in the immediate environment of the patient, the health care worker, and less often the public. These lessons from the past study of animal and human coronaviruses can be extended to presumptions for severe acute respiratory syndrome coronavirus 2. Already, the early reports from the coronavirus disease‐2019 pandemic are confirming some concerns. These data have the cumulative potential to cause us to rethink some current and common public health and infection control strategies.


title: Interplay of global multi-scale human mobility, social distancing, government interventions, and COVID-19 dynamics

text: This work quantifies the impact of interventions to curtail mobility and social interactions in order to control the COVID-19 pandemic. We analyze the change in world-wide mobility at multiple spatio-temporal resolutions -- county, state, country -- using an anonymized aggregate mobility map that captures population flows between geographic cells of size 5 km2. We show that human mobility underwent an abrupt and significant change, partly in response to the interventions, resulting in 87% reduction of international travel and up to 75% reduction of domestic travel. Taking two very different countries sampled from the global spectrum, we observe a maximum reduction of 42% in mobility across different states of the United States (US), and a 68% reduction across the states of India between late March and late April. Since then, there has been an uptick in flows, with the US seeing 53% increase and India up to 38% increase with respect to flows seen during the lockdown. As we overlay this global map with epidemic incidence curves and dates of government interventions, we observe that as case counts rose, mobility fell -- often before stay-at-home orders were issued. Further, in order to understand mixing within a region, we propose a new metric to quantify the effect of social distancing on the basis of mobility. We find that population mixing has decreased considerably as the pandemic has progressed and are able to measure this effect across the world. Finally, we carry out a counterfactual analysis of delaying the lockdown and show that a one week delay would have doubled the reported number of cases in the US and India. To our knowledge, this work is the first to model in near real-time, the interplay of human mobility, epidemic dynamics and public policies across multiple spatial resolutions and at a global scale.


title: Detection of Adeno-Associated Virus Viremia in Hematopoietic Cell Transplant Recipients

text: Adeno-associated virus (AAV) is widely considered to be nonpathogenic, but the clinical epidemiology of this virus is limited. By use of polymerase chain reaction assays, we investigated the incidence and clinical significance of AAV viremia in a population of consecutive recipients of a hematopoietic cell transplant (HCT). Four (2.8%) of 145 patients developed AAV viremia after HCT. Viremia was low level and transient in all patients. Two patients were admitted to the hospital and died in proximity to AAV viremia (<7 weeks between diagnosis and death); however, AAV was not detected in tissue specimens obtained at autopsy. Thus, AAV does not appear to play a pathogenic role in organ-specific illness, even in a highly immunocompromised population.


title: The Discomfort of Death Counts: Mourning through the distorted lens of reported COVID-19 death data

text: Summary In data science, there's long been an acknowledgment of the way data can flatten and dehumanize the people it represents - this limitation becomes most obvious when considering the pure inability of such numbers and figures to truly capture the reality of lives lost.


Movement Disorders in the World of COVID-19.


title: Health and Economy in COVID-19 Era: A Plan for Reconstituting Long-Term Economic Security

text: COVID-19 is a rapidly evolving pandemic, which represents a multifaceted global threat. Given the economic consequences, most researchers agree that social distancing measures are an effective strategy relative to the cost. Previous studies indicate that community size as well as viral population risk groups should be considered in forming an effective targeted social distancing strategy. The resultant delay in the occurrence of infections in order to support vaccine development has been shown to be an effective policy. However, a return to normalcy from the current situation would require policy intervention that transforms the American economy along with continued targeted social distancing and the use of medical science as a tool to facilitate gradual personal interactions of low-risk individuals. We believe that the adoption of rapid IgG testing would be best suitable for widespread population-level screening as part of a comprehensive plan for incrementally rebuilding the in-person workforce. As such, this crisis represents an opportunity for the United States to increase automation of the manufacturing sector, shrink supply chains, and create higher-level jobs in order to reduce the dependency on other countries for critical supplies. This economic transition to better utilize technology along with reconstruction of the workforce could improve the standard of living for many Americans as well as better prepare the US for future pandemics.


title: Impact of SARS on Avian Influenza Preparedness in Healthcare Workers

text: BACKGROUND: SARS was an unprecedented outbreak which brought about 1,755 infections and 302 deaths in Hong Kong. The similarity of SARS and avian influenza prompted us to examine the relationship between SARS experience and preparedness on a potential avian influenza outbreak. METHODS: A self-administered questionnaire was delivered to nurses in Hong Kong to assess their attitude towards avian influenza; risk perception, and their relationships with previous level of exposure to SARS patients. RESULTS: Nine hundred and ninety-nine respondents were included in data analysis. About half of them perceived there would be an avian influenza outbreak in Hong Kong. The majority accepted a personal risk of infection in the course of their work (72.7%), and prepared to take care of patients infected with avian influenza (84.0%). Respondents were classified into two groups: high exposure (44.1%) and low exposure (55.9%) as defined by having worked in SARS ward or hospitals. High exposure nurses were less likely to avoid patients, less inclined to change their job if they were required to take care of infected patients, and had therefore a more positive attitude towards an impending avian influenza epidemic. About half of the nurses had frequent involuntary recalls of incidents relating to SARS, the frequency of which was positively correlated with knowing a person suffering from long-term complications of SARS. CONCLUSION: Healthcare workers who had been actively involved in SARS work were more “positive” in responding to the impending avian influenza epidemic. Whether the level of preparedness can be sustained would need to be further explored.


title: Evaluation of COVID-19 epidemic outbreak caused by temporal contact-increase in South Korea

text: OBJECTIVES: On March 15, 2020, 61.3% of the confirmed cases of COVID-19 infection are associated with the worship service that was organized on February 9 in the Shincheonji Church of Jesus in Daegu, South Korea. In this study, we aim to evaluate the effects of mass infection in South Korea and assess the preventive control intervention. METHOD: Using opened data of daily cumulative confirmed cases and deaths, the basic and effective reproduction numbers was estimated using a modified susceptible–exposed–infected–recovered-type epidemic model. RESULTS: The basic reproduction number was estimated to be [Formula: see text]. The effective reproduction number increased approximately 20 times after the mass infections from the 31 st patient, which was confirmed on February 9 in the Shincheonji Church of Jesus, Daegu. However, the effective reproduction number decreased to less than unity after February 28 owing to the implementation of high-level preventive control interventions in South Korea, coupled with voluntary prevention actions by citizens. CONCLUSION: Preventive action and control intervention were fairly established in South Korea.


title: Molecular model of SARS coronavirus polymerase: implications for biochemical functions and drug design

text: The causative agent of severe acute respiratory syndrome (SARS) is a previously unidentified coronavirus, SARS-CoV. The RNA-dependent RNA polymerase (RdRp) of SARS-CoV plays a pivotal role in viral replication and is a potential target for anti-SARS therapy. There is a lack of structural or biochemical data on any coronavirus polymerase. To provide insights into the structure and function of SARS-CoV RdRp, we have located its conserved motifs that are shared by all RdRps, and built a three-dimensional model of the catalytic domain. The structural model permits us to discuss the potential functional roles of the conserved motifs and residues in replication and their potential interactions with inhibitors of related enzymes. We predict important structural attributes of potential anti-SARS-CoV RdRp nucleotide analog inhibitors: hydrogen-bonding capability for the 2′ and 3′ groups of the sugar ring and C3′ endo sugar puckering, and the absence of a hydrophobic binding pocket for non-nucleoside analog inhibitors similar to those observed in hepatitis C virus RdRp and human immunodeficiency virus type 1 reverse transcriptase. We propose that the clinically observed resistance of SARS to ribavirin is probably due to perturbation of the conserved motif A that controls rNTP binding and fidelity of polymerization. Our results suggest that designing anti-SARS therapies can benefit from successful experiences in design of other antiviral drugs. This work should also provide guidance for future biochemical experiments.


title: Reduced likelihood of bovine coronavirus and bovine respiratory syncytial virus infection on organic compared to conventional dairy farms

text: Abstract The prevalence of antibodies to bovine coronavirus (BCV) and bovine respiratory syncytial virus (BRSV) infections was studied in 20 conventional and 20 organic dairy herds. The organic farms had produced ‘certified’ milk for at least 2 years. On two occasions, with a 1-year interval, 699 serum samples from 624 peri-parturient cows were tested by ELISA for antibodies to BCV and BRSV. Accompanying data relating to the sampled animals were collected in order to identify potential factors associated with increased antibody prevalence. The antibody prevalence was high at both sampling times with approximately 85% and 80% of animals positive for antibodies to BCV and to BRSV, respectively. Conventional herds had a significantly higher mean antibody prevalence to BCV and BRSV than the organically managed herds (P <0.01). Animal age was significantly associated with increased antibody prevalence (P <0.001). The findings of this study suggest that organic farm management may be effective in reducing the seroprevalence of these viruses relative to conventional farming methods.


Cohort Profile: The Flu Watch Study


title: Time-calibrated phylogenomics of the porcine epidemic diarrhea virus: genome-wide insights into the spatio-temporal dynamics

text: Porcine epidemic diarrhea virus (PEDV), the causative agent of porcine epidemic diarrhea (PED), has led to tremendous economic losses in the global swine industry. Although the phylogeny of PEDV has been investigated extensively at the molecular level, there was no time-calibrated phylogenomic study on the virus. To improve insight into this topic, we analyzed 138 published genome sequences using the Bayesian coalescent analyses as well as Bayesian inferences and maximum likelihood methods. All of the global PEDV isolates were divided into six groups, except for one unclassified isolate. Of the six groups, Groups 1–5 comprised pandemic viruses while the remaining Group 6 contained classical isolates. Interestingly, the two clades, both pandemic and classical, consisted of clade-specific amino acid sequences in five genes: ORF1a, ORF1b, S, ORF3, and N. Within the pandemic clade, Group 1 and Group 2 originated from North America, whereas Group 3–Group 5 were derived from Asia. In Group 2, there was a common origin of S INDEL isolates. Within each group, there was no apparent association between temporal or geographic origin and heterogeneity of PEDVs. Our findings also showed that the PEDV virus evolved at a rate of 3.38 × 10(−4) substitutions/site/year, and the most recent common ancestor of the virus emerged 75.9 years ago. Our Bayesian skyline plot analysis indicated that the PEDV had maintained constant effective population size excluding only a short period, around 2012, when a valley shaped decline in the effective number of infections occurred. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13258-018-0686-0) contains supplementary material, which is available to authorized users.


title: Sublingual Delivery of Vaccines for the Induction of Mucosal Immunity

text: The mucosal surfaces are constantly exposed to incoming pathogens which can cause infections that result in severe morbidity and/or mortality. Studies have reported that mucosal immunity is important for providing protection against these pathogens and that mucosal vaccination is effective in preventing local infections. For many years, the sublingual mucosa has been targeted to deliver immunotherapy to treat allergic hypersensitivities. However, the potential of vaccine delivery via sublingual mucosal has received little attention until recently. Recent studies exploring such potential have documented the safety and effectiveness of sublingual immunization, demonstrating the ability of sublingual immunization to induce both systemic and mucosal immune responses against a variety of antigens, including soluble proteins, inter particulate antigens, and live-attenuated viruses. This review will summarize the recent findings that address the promising potential of sublingual immunization in proving protection against various mucosal pathogens.


title: Critical Role of Perforin-dependent CD8+ T Cell Immunity for Rapid Protective Vaccination in a Murine Model for Human Smallpox

text: Vaccination is highly effective in preventing various infectious diseases, whereas the constant threat of new emerging pathogens necessitates the development of innovative vaccination principles that also confer rapid protection in a case of emergency. Although increasing evidence points to T cell immunity playing a critical role in vaccination against viral diseases, vaccine efficacy is mostly associated with the induction of antibody responses. Here we analyze the immunological mechanism(s) of rapidly protective vaccinia virus immunization using mousepox as surrogate model for human smallpox. We found that fast protection against lethal systemic poxvirus disease solely depended on CD4 and CD8 T cell responses induced by vaccination with highly attenuated modified vaccinia virus Ankara (MVA) or conventional vaccinia virus. Of note, CD4 T cells were critically required to allow for MVA induced CD8 T cell expansion and perforin-mediated cytotoxicity was a key mechanism of MVA induced protection. In contrast, selected components of the innate immune system and B cell-mediated responses were fully dispensable for prevention of fatal disease by immunization given two days before challenge. In conclusion, our data clearly demonstrate that perforin-dependent CD8 T cell immunity plays a key role in MVA conferred short term protection against lethal mousepox. Rapid induction of T cell immunity might serve as a new paradigm for treatments that need to fit into a scenario of protective emergency vaccination.


title: Epidemiological Profile and Clinical Associations of Human Bocavirus and Other Human Parvoviruses

text: BackgroundHuman bocavirus (HBoV) and PARV4 are newly discovered human parvoviruses. HBoV, which was first detected in respiratory samples, has a potential role in the development of human respiratory disease. The present study compared the frequencies, epidemiological profiles, and clinical backgrounds of HBoV and PARV4 infections with those of other respiratory virus infections, by evaluating diagnostic samples referred to the Specialist Virology Laboratory (SVL) at the Royal Infirmary of Edinburgh (Edinburgh, United Kingdom) MethodsAnonymized samples and study subject information were obtained from the respiratory sample archive of the SVL. Samples were screened for HBoV, PARV4, B19, respiratory syncytial virus (RSV), adenoviruses, influenza viruses, and parainfluenza viruses by use of nested polymerase chain reaction ResultsHBoV infection was detected in 47 (8.2%) of 574 study subjects,&ranking third in prevalence behind RSV infection (15.7%) and adenovirus infection (10.3%). Peak incidences of HBoV were noted among infants and young children (age, 6–24 months) during the midwinter months (December and January) and were specifically associated with lower respiratory tract infections. HBoV infections were frequently accompanied by other respiratory viruses (frequency, 43%), and they were more prevalent among individuals infected with other respiratory viruses (17%), frequently adenovirus or RSV. All respiratory samples were negative for PARV4 ConclusionsIn the present study, HBoV was a frequently detected, potential respiratory pathogen, with a prevalence and an epidemiological profile comparable to those of RSV. Identification of HBoV infections may be clinically important in the future


title: Preventing airborne infection with an intranasal cellulose powder formulation (Nasaleze Travel®)

text: A total of 52 volunteers were recruited to take part in a dual-centered, randomized, blinded study so investigators could determine whether the level of airborne infection could be significantly reduced in patients randomly assigned to treatment with either Nasaleze® cellulose extract alone or a combination of Nasaleze cellulose and powdered garlic extract (PGE). One puff into each nostril was recommended, and volunteers who developed an infection while traveling were told to use at least 3 puffs per nostril until symptoms were reduced. This study took place over an 8-wk period across Finland and the United Kingdom between November 2006 and March 2007. Volunteers were instructed to use a 5-point scale to assess their health and to record infectious episodes and symptoms in a daily diary. The activetreatment group (Nasaleze cellulose with PCE) experienced significantly fewer infections than the control group (20 vs 57; P<.001) and far fewer days on which an infection was obviously present (126 d in the active group vs 240 d in the control group; P<.05). Consequently, volunteers in the active group were less likely to pick up an airborne infection when PCE was added to this novel cellulose extract. Volunteers in the control group were much more likely to report more than 1 infectious episode over the treatment period or to endure longer periods of infection. The investigators concluded that the combination Nasaleze Travel formulation significantly reduced the number of airborne infections to which volunteers were exposed while traveling.


title: Preparation of a radiology department in an Italian hospital dedicated to COVID-19 patients

text: Preparedness for the ongoing coronavirus disease 2019 (COVID-19) and its spread in Italy called for setting up of adequately equipped and dedicated health facilities to manage sick patients while protecting healthcare workers, uninfected patients, and the community. In our country, in a short time span, the demand for critical care beds exceeded supply. A new sequestered hospital completely dedicated to intensive care (IC) for isolated COVID-19 patients needed to be designed, constructed, and deployed. Along with this new initiative, the new concept of “Pandemic Radiology Unit” was implemented as a practical solution to the emerging crisis, born out of a critical and urgent acute need. The present article describes logistics, planning, and practical design issues for such a pandemic radiology and critical care unit (e.g., space, infection control, safety of healthcare workers, etc.) adopted in the IC Hospital Unit for the care and management of COVID-19 patients.


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title: Stimulation with a class A CpG oligonucleotide enhances resistance to infection with feline viruses from five different families

text: Domestic cats are commonly affected by viral pathogens that induce lengthy infections with fatal outcomes. Prevention of viral propagation is of primordial importance in shelters and catteries, where cats from different backgrounds have narrow contacts. Oligonucleotides (ODN) containing cytosine-phosphate-guanosine motifs of class A (CpG-A) are highly potent synthetic inducers of innate antiviral mechanisms. The aim of this study was to test their ability to modulate innate immune responses and prevent viral replication as stand-alone agents in the domestic cat. CpG-A stimulation of feline peripheral blood mononuclear cells (PBMCs) enhanced their proliferation, increased the presence of co-stimulatory molecules on their surface and influenced their gene expression profiles in an antiviral orientation. Incubation of the supernatants of CpG-A stimulated PBMCs with feline cell lines of epithelial and fibroblastic origin induced expression of the antiviral myxovirus resistance (Mx) gene in these target cells, which also showed enhanced resistance to feline viruses from five distinct families, namely Coronaviridae, Herpesviridae, Caliciviridae, Parvoviridae, and Retroviridae. Most importantly, subcutaneous administration of CpG-A in domestic cats systemically increased the expression of Mx, reaching maximal levels within 24 h. Plasma from treated cats could furthermore inhibit viral replication in vitro. Altogether, our data highlight the promising potential of CpG-A to induce a preventive antiviral state in the cat and to protect feline populations against a broad range of virus infections.


title: Cell attachment protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen

text: As with many other viruses, the initial cell attachment of rotaviruses, major causative agent of infantile gastroenteritis, is mediated by interactions with specific cellular glycans(1–4). The distally located VP8* domain of the rotavirus spike protein VP4(5) mediates such interactions. The existing paradigm is that ‘sialidase-sensitive’ animal rotavirus strains bind to glycans with terminal sialic acid (Sia), whereas ‘sialidase-insensitive’ human rotavirus (HR) strains bind to glycans with internal Sia such as GM1(3). Although the involvement of Sia in the animal strains is firmly supported by crystallographic studies(1,3,6,7), it is not yet known how VP8* of HRs interacts with Sia and whether their cell attachment necessarily involves sialoglycans. We found that VP8* of a HR strain specifically recognizes A-type histo-blood group antigen (HBGA) using a glycan array screen comprised of 511 glycans, and that virus infectivity in HT-29 cells is abrogated by anti-Atype antibodies as well as significantly enhanced in CHO cells genetically modified to express the A-type HBGA, providing a novel paradigm for initial cell attachment of HR. HBGAs are genetically determined glycoconjugates present in mucosal secretions, epithelial and on red blood cells(8), and are recognized as susceptibility and cell attachment factors for gastric pathogens like H. pylori(9) and noroviruses(10). Our crystallographic studies show that the A-type HBGA binds to the HR VP8* at the same location as the Sia in the VP8* of animal rotavirus, and suggest how subtle changes within the same structural framework allow for such receptor switching. These results raise the possibility that host susceptibility to specific HR strains and pathogenesis are influenced by genetically controlled expression of different HBGAs among the world’s population.


title: Analysis of Spatiotemporal Characteristics of Pandemic SARS Spread in Mainland China

text: Severe acute respiratory syndrome (SARS) is one of the most severe emerging infectious diseases of the 21st century so far. SARS caused a pandemic that spread throughout mainland China for 7 months, infecting 5318 persons in 194 administrative regions. Using detailed mainland China epidemiological data, we study spatiotemporal aspects of this person-to-person contagious disease and simulate its spatiotemporal transmission dynamics via the Bayesian Maximum Entropy (BME) method. The BME reveals that SARS outbreaks show autocorrelation within certain spatial and temporal distances. We use BME to fit a theoretical covariance model that has a sine hole spatial component and exponential temporal component and obtain the weights of geographical and temporal autocorrelation factors. Using the covariance model, SARS dynamics were estimated and simulated under the most probable conditions. Our study suggests that SARS transmission varies in its epidemiological characteristics and SARS outbreak distributions exhibit palpable clusters on both spatial and temporal scales. In addition, the BME modelling demonstrates that SARS transmission features are affected by spatial heterogeneity, so we analyze potential causes. This may benefit epidemiological control of pandemic infectious diseases.


title: High prevalence of obesity in severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) requiring invasive mechanical ventilation

text: OBJECTIVE: The Covid‐19 pandemic is rapidly spreading worldwide, notably in Europe and North America, where obesity is highly prevalent. The relation between obesity and severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) has not been fully documented. METHODS: In this retrospective cohort study we analyzed the relationship between clinical characteristics, including body mass index (BMI), and the requirement for invasive mechanical ventilation (IMV) in 124 consecutive patients admitted in intensive care for SARS‐CoV‐2, in a single French center. RESULTS: Obesity (BMI >30 kg/m2) and severe obesity (BMI >35 kg/m2) were present in 47.6% and 28.2% of cases, respectively. Overall, 85 patients (68.6%) required IMV. The proportion of patients who required IMV increased with BMI categories (p<0.01, Chi square test for trend), and it was greatest in patients with BMI >35 kg/m2 (85.7%). In multivariate logistic regression, the need for IMV was significantly associated with male sex (p<0.05) and BMI (p<0.05), independent of age, diabetes, and hypertension. The odds ratio for IMV in patients with BMI >35 kg/m2 vs patients with BMI <25 kg/m2 was 7.36 (1.63‐33.14; p=0.02) CONCLUSION: The present study showed a high frequency of obesity among patients admitted in intensive care for SARS‐CoV‐2. Disease severity increased with BMI. Obesity is a risk factor for SARS‐CoV‐2 severity requiring increased attention to preventive measures in susceptible individuals.


title: Infectious Disease Outbreak Response: Mind the Rights Gap

text: The international organization responsible for international coordinated response to disease outbreaks—the World Health Organization (WHO)—was given permission to receive reports from sources other than the state in revisions to the International Health Regulations (IHR) in 2005. However, the organization struggles to protect its corresponding right to receive reports from non-state actors on outbreak events. This article examines the consequences of this implementation gap between what is stated in the IHR—the right of WHO to receive reports from non-state actors on outbreak events—and the reality that states remain able and willing to act to ensure that this right is not exercised. The article examines two recent cases: the first detection of Middle East Respiratory Syndrome (MERS) outbreak in Saudi Arabia, and the first months of the Ebola outbreak in Guinea. Both cases demonstrate how the WHO has struggled to balance states’ concern with managing risk communication against WHO’s right to receive reports from non-state actors. The article argues that to realize the full potential of a transparent disease outbreak reporting process, there is a need for a human rights framework that expressly articulates its right to receive reports and outlines appropriate behaviour for the WHO, states, and non-state actors.


title: Hendra virus infection in a veterinarian

text: A veterinarian became infected with Hendra virus (HeV) after managing a terminally ill horse and performing a limited autopsy with inadequate precautions. Although she was initially only mildly ill, serological tests suggested latent HeV infection. Nevertheless, she remains well 2 years after her initial illness. Recently emerged zoonotic viruses, such as HeV, necessitate appropriate working procedures and personal protective equipment in veterinary practice.


title: Epidemiological and Virological Characteristics of Influenza Viruses Circulating in Cambodia from 2009 to 2011

text: BACKGROUND: The Cambodian National Influenza Center (NIC) monitored and characterized circulating influenza strains from 2009 to 2011. METHODOLOGY/PRINCIPAL FINDINGS: Sentinel and study sites collected nasopharyngeal specimens for diagnostic detection, virus isolation, antigenic characterization, sequencing and antiviral susceptibility analysis from patients who fulfilled case definitions for influenza-like illness, acute lower respiratory infections and event-based surveillance. Each year in Cambodia, influenza viruses were detected mainly from June to November, during the rainy season. Antigenic analysis show that A/H1N1pdm09 isolates belonged to the A/California/7/2009-like group. Circulating A/H3N2 strains were A/Brisbane/10/2007-like in 2009 before drifting to A/Perth/16/2009-like in 2010 and 2011. The Cambodian influenza B isolates from 2009 to 2011 all belonged to the B/Victoria lineage represented by the vaccine strains B/Brisbane/60/2008 and B/Malaysia/2506/2004. Sequences of the M2 gene obtained from representative 2009–2011 A/H3N2 and A/H1N1pdm09 strains all contained the S31N mutation associated with adamantanes resistance except for one A/H1N1pdm09 strain isolated in 2011 that lacked this mutation. No reduction in the susceptibility to neuraminidase inhibitors was observed among the influenza viruses circulating from 2009 to 2011. Phylogenetic analysis revealed that A/H3N2 strains clustered each year to a distinct group while most A/H1N1pdm09 isolates belonged to the S203T clade. CONCLUSIONS/SIGNIFICANCE: In Cambodia, from 2009 to 2011, influenza activity occurred throughout the year with peak seasonality during the rainy season from June to November. Seasonal influenza epidemics were due to multiple genetically distinct viruses, even though all of the isolates were antigenically similar to the reference vaccine strains. The drug susceptibility profile of Cambodian influenza strains revealed that neuraminidase inhibitors would be the drug of choice for influenza treatment and chemoprophylaxis in Cambodia, as adamantanes are no longer expected to be effective.


title: Design, Synthesis, and Antiviral Activity of Novel Ribonucleosides of 1,2,3‐Triazolylbenzyl‐aminophosphonates

text: A novel series of ribonucleosides of 1,2,3‐triazolylbenzyl‐aminophosphonates was synthesized through the Kabachnik–Fields reaction using I(2) as catalyst followed by copper‐catalyzed cycloaddition of the azide–alkyne reaction (CuAAC). All structures of the newly prepared compounds were characterized by (1)H NMR, (13)C NMR, and HRMS spectra. The structures of 2e, 2f, 3d, and 3g were further confirmed by X‐ray diffraction analysis. These compounds were tested against various strains of DNA and RNA viruses; compounds 4b and 4c showed a modest inhibitory activity against respiratory syncytial virus (RSV) and compound 4h displayed modest inhibitory activity against Coxsackie virus B4.


title: An approach to and web-based tool for infectious disease outbreak intervention analysis

text: Infectious diseases are a leading cause of death globally. Decisions surrounding how to control an infectious disease outbreak currently rely on a subjective process involving surveillance and expert opinion. However, there are many situations where neither may be available. Modeling can fill gaps in the decision making process by using available data to provide quantitative estimates of outbreak trajectories. Effective reduction of the spread of infectious diseases can be achieved through collaboration between the modeling community and public health policy community. However, such collaboration is rare, resulting in a lack of models that meet the needs of the public health community. Here we show a Susceptible-Infectious-Recovered (SIR) model modified to include control measures that allows parameter ranges, rather than parameter point estimates, and includes a web user interface for broad adoption. We apply the model to three diseases, measles, norovirus and influenza, to show the feasibility of its use and describe a research agenda to further promote interactions between decision makers and the modeling community.


Acral edema during the COVID‐19 pandemic


title: Ultrasensitive label-free electrochemiluminescence immunosensor based on N-(4-aminobutyl)-N-ethylisoluminol-functionalized graphene composite

text: The electrochemiluminescence (ECL) behavior of N-(4-aminobutyl)-N-ethylisoluminol (ABEI)-functionalized graphene composite (ABEI-GC) modified on an indium tin oxide (ITO) electrode was studied. ABEI-GC exhibited excellent ECL activity. On this basis, a label-free ECL immunosensor was developed for the sensitive detection of human immunoglobulin G (hIgG) by using ABEI-GC as the ECL nano-interface via a layer-by-layer assembly technique. ABEI-GC was first assembled onto an ITO electrode. Positively charged chitosan was then electrostatically adsorbed to the modified electrode. Finally, negatively charged antibody-coated gold nanoparticles were attached to the surface to form the ECL immunosensor. In the presence of hIgG, hIgG was captured by its antibody. In addition, an ECL signal was detected in the presence of H(2)O(2) when a double potential was applied. The ECL immunosensor for the determination of hIgG showed a linear range of 1.0×10(−13)–1.0×10(−8) g/mL with a detection limit of 5.0×10(−14) g/mL. This immunosensor has high sensitivity, wide linearity and good reproducibility. The superior sensitivity of the proposed ECL immunoassay mainly derives from the incorporation of ABEI-GC, which not only improves the ECL intensity, response speed, and stability, but also provides a large specific surface for high levels of protein loading. This work reveals that ABEI-GC is good nano-interface for the construction of ECL biosensors. Our strategy is promising for protein detection and may open up a new avenue for ultrasensitive label-free immunoassays.


title: Chapter 15 Application of Microbial Cleaning Technology for Removal of Surface Contamination

text: Abstract Microbial cleaning takes advantage of naturally-occurring microbes to remove a wide variety of contaminants from various surfaces. The method is based on the affinity of microbes for hydrocarbons that are digested, producing harmless carbon dioxide, water, and soluble fatty acids. The microbes are nonpathogenic and are safe to handle and dispose. The process is environmentally-friendly and is less expensive than solvent cleaning, but it is not applicable to high precision cleaning applications. Typical applications include parts washing; oil and grease removal from concrete and other floor surfaces, and from drains and grease traps; cleaning and disinfection in healthcare facilities; cleaning of historical artworks and structures; and household and institutional cleaning applications.


title: Vigorous inflammatory responses in noninfectious pulmonary complication induced by donor lymphocyte infusion

text: BACKGROUND: Donor lymphocyte infusion (DLI) is used for treatment of hematologic malignancy relapse or mixed chimerism after allogeneic hematopoietic stem cell transplantation. Although graft‐versus‐host disease is well recognized as one of the adverse effects of DLI, there are limited reports on noninfectious pulmonary complications (NIPCs) after DLI. CASE REPORT: A 55‐year‐old woman with acute myeloid leukemia received DLI for conversion from recipient predominant to complete donor chimerism on Day +193 after allogeneic HSCT. Eight weeks later, she complained of dyspnea with fever; chest computed tomography revealed diffuse, bilateral, ground glass opacity and reticular appearance. She was diagnosed as having NIPC based on serum and bronchoalveolar lavage fluid (BALF) findings. She was successfully treated with prednisolone (PSL) and completely recovered. DISCUSSION: We analyzed the cell profile from the BALF and 27 cytokines and chemokines in the serum using the Bio‐Plex platform. The cells consisted of recipient predominant macrophages and T cells. The serum cytokine and chemokine profile showed significant elevation of interleukin (IL)−1β, IL‐6, IL‐8, tumor necrosis factor‐α, macrophage inflammatory protein (MIP)−1α, and MIP‐1β, which declined with the improvement of symptoms after initiation of PSL treatment. CONCLUSION: Inflammatory effectors by recipient cells, rather than allogeneic responses by donor cells, played an important role in the pathogenesis of NIPCs after DLI in the present case.


title: Sensitive and Specific Detection of Low-Level Antibody Responses in Mild Middle East Respiratory Syndrome Coronavirus Infections

text: Middle East respiratory syndrome coronavirus (MERS-CoV) infections in humans can cause asymptomatic to fatal lower respiratory lung disease. Despite posing a probable risk for virus transmission, asymptomatic to mild infections can go unnoticed; a lack of seroconversion among some PCR-confirmed cases has been reported. We found that a MERS-CoV spike S1 protein–based ELISA, routinely used in surveillance studies, showed low sensitivity in detecting infections among PCR-confirmed patients with mild clinical symptoms and cross-reactivity of human coronavirus OC43–positive serum samples. Using in-house S1 ELISA and protein microarray, we demonstrate that most PCR-confirmed MERS-CoV case-patients with mild infections seroconverted; nonetheless, some of these samples did not have detectable levels of virus-neutralizing antibodies. The use of a sensitive and specific serologic S1-based assay can be instrumental in the accurate estimation of MERS-CoV prevalence.


title: Why lockdown of the elderly is not ageist and why levelling down equality is wrong

text: In order to prevent the rapid spread of COVID-19, governments have placed significant restrictions on liberty, including preventing all non-essential travel. These restrictions were justified on the basis the health system may be overwhelmed by COVID-19 cases and in order to prevent deaths. Governments are now considering how they may de-escalate these restrictions. This article argues that an appropriate approach may be to lift the general lockdown but implement selective isolation of the elderly. While this discriminates against the elderly, there is a morally relevant difference—the elderly are far more likely to require hospitalisation and die than the rest of the population. If the aim is to ensure the health system is not overwhelmed and to reduce the death rate, preventing the elderly from contracting the virus may be an effective means of achieving this. The alternative is to continue to keep everyone in lockdown. It is argued that this is levelling down equality and is unethical. It suggests that in order for the elderly to avoid contracting the virus, the whole population should have their liberty deprived, even though the same result could be achieved by only restricting the liberty of the elderly. Similar arguments may also be applied to all groups at increased risk of COVID-19, such as men and those with comorbidities, the obese and people from ethnic minorities or socially deprived groups. This utilitarian concern must be balanced against other considerations, such as equality and justice, and the benefits gained from discriminating in these ways must be proportionately greater than the negative consequences of doing so. Such selective discrimination will be most justified when the liberty restriction to a group promotes the well-being of that group (apart from its wider social benefits).


Genetic Characterization of Cryptosporidium parvum Isolates from Cattle in Portugal: Animal and Human Implications


title: Switching to teleconsultation for rheumatology in the wake of the COVID-19 pandemic: feasibility and patient response in India

text: The emergent COVID-19 pandemic dictates an urgent switch to teleconsultation. India has high patient to rheumatologist ratio, and patients have limited concepts about telemedicine. Thus, we attempted to find the feasibility and acceptance of patients in switching to teleconsultation. The CARE rheumatology clinic at Kerala, India, caters to average 170 (range: 140–240) patients per day. Patients with prefixed appointments had two-level screening for eligibility for teleconsultation. Those eligible were given the option for teleconsultation on the widely available WhatsApp app. Of those who completed teleconsultations, 100 were chosen at random to provide feedback. In the first 7 days, out of 1469 appointments, 975 were found eligible for teleconsultation. Of these, 723 (74%) opted for it. The average footfall in the clinic was reduced to 67 (range 29–117). The proportion of patients accepting teleconsultations increased with time. Amongst the 100 respondents, median satisfaction was 9 (IQR 8–10) and recommendation for continuing was 9.5 (IQR 8–10) on a 0–10 scale. Multivariate analysis showed the recommendation score was dependent on beliefs about social distancing, perceptions about clinical examination, and the satisfaction score of the first teleconsultation. Age, sex, availability of personal video conferencing app or of vehicles did not independently influence this score. Without teleconsultation facilities, three-fourths of the respondents would have stopped drugs or self-medicated. The switch was feasible and accepted by patients. It enabled quick reduction in the number of persons travelling to the centre. Not making the switch could have deprived approximately three-quarters of these patients of proper medical care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10067-020-05200-6) contains supplementary material, which is available to authorized users.


title: First detection, clinical presentation and phylogenetic characterization of Porcine epidemic diarrhea virus in Austria

text: BACKGROUND: Porcine epidemic diarrhea (PED) is a syndrome that is characterized by rapidly spreading watery diarrhea affecting pigs of all ages, but with major effects on suckling piglets. The disease, as well as the causative Alphacoronavirus, the Porcine epidemic diarrhea virus (PEDV), was first described in Europe in the 1970s and since then has spread over many Asian and American countries, where it recently led to devastating effects on swine health and pork industry. While the disease was seldom reported in Europe within the last few decades, a few recent reports re-emergence of PED in German pig farms. The hitherto isolated German strain seems to be closely related to a low pathogenic PEDV variant from the USA. This case report describes the first detection of PEDV in Austria. CASE PRESENTATION: Reduced feed uptake and occasional diarrhea were observed in December 2014 in a group of fattening pigs, kept on an Austrian swine farm. The concerned pigs had been recently purchased from Germany. Within a few weeks, diarrhea became apparent also in pigs of Austrian origin, which were kept in a different stable on the same farm. Gastrointestinal symptoms among fattening pigs were generally mild, quickly resolving and did not lead to death. PEDV RNA was identified by RT-qPCR in pooled feces and serum and PEDV antibodies were detectable in serum in both groups of pigs. Phylogenetic analysis of the nearly complete PEDV spike gene shows that the Austrian PEDV strain is highly similar to other strains involved in recent outbreaks in Western and Central Europe. CONCLUSION: This is the first report demonstrating the presence of PEDV in Austria. The virus was probably introduced by purchasing piglets from a German source, which underlines the significance of trans-boundary animal trade for the distribution of highly contagious diseases, such as PED. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0624-1) contains supplementary material, which is available to authorized users.


title: Challenges and Responses: A Tertiary Hospital in 2019-nCoV Epidemic

text: The recent outbreak of coronavirus in Wuhan, China, has imposed challenges on the Chinese medical system. Not only the dramatically increasing number of infected cases and insufficient medical resources, but also the peoples’ panic throughout the whole country have made medical services extremely difficult. To respond to these challenges effectively, our hospital implemented an urgent response strategy, including human resources and medical resources preparation and re-allocation, immediate fever screening, strict patient-visiting flow management, and reasonable information communication. Our experience and response measures could provide a reference for other hospitals in the current situation.


title: Early diagnosis of dengue disease severity in a resource-limited Asian country

text: BACKGROUND: Dengue is endemic throughout Cambodia, a country faced with significant health and economic challenges. We undertook a clinical study at the National Paediatric Hospital in Phnom Penh to evaluate clinical diagnostic parameters for dengue and predictors of disease outcome. METHODS: Between September 2011 and January 2013, all consecutive inpatients aged between 1 and 15 years and presenting with suspected dengue were enrolled. They were clinically assessed using both the 1997 and 2009 WHO dengue classifications. Specimens were collected upon admission and discharge and tested for dengue at Institut Pasteur in Cambodia. RESULTS: A total of 701 patients were screened. Of these, 79 % were dengue-confirmed by laboratory testing, and 21 % tested dengue-negative. A positive tourniquet test, absence of upper respiratory symptoms, leukopenia, thrombocytopenia, and elevated liver transaminases were independent predictors for laboratory-confirmed dengue among the children. The presence of several warning signs on hospital admission was associated with a concurrent laboratory-confirmed diagnosis of severe disease outcome. CONCLUSIONS: The presence of two or more warning signs was associated with a concurrent laboratory-confirmed diagnosis of severe dengue at hospital admission. Thus, a cumulative score combining simple clinical parameters and first-line laboratory findings could be used to accurately predict dengue virus infection in pediatric populations, optimizing triage in settings with limited laboratory resources. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1849-8) contains supplementary material, which is available to authorized users.


Power and politics: the case for linking resilience to health system governance


title: Acute Hemorrhagic Edema of Infancy after Coronavirus Infection with Recurrent Rash

text: Purpura, particularly when accompanied by fever, is a worrisome finding in children. Acute hemorrhagic edema of infancy (AHEI) is a benign type of small-vessel leukocytoclastic vasculitis that presents with progressive purpura and has an excellent prognosis. Patients with AHEI present with large, target-like purpuric plaques affecting the face, ear lobes, and extremities. While the rapid onset of these skin findings can be dramatic, the child with AHEI is usually well appearing with reassuring laboratory testing. We describe a case of a previously healthy 8-month-old female who presented with progressive purpura in a nondependent distribution, low-grade fevers, and extremity swelling. An extensive workup was performed prior to making the diagnosis of AHEI. Coronavirus was implicated as the likely triggering pathogen, and the patient suffered a recurrence of purpuric rash and swelling several weeks after her initial presentation.


docid: dixoqyrs

title: Infectious cDNA clones of porcine reproductive and respiratory syndrome virus and their potential as vaccine vectors

text: Abstract Full-length infectious cDNA clones have recently become available for both European and North American genotypes of porcine reproductive and respiratory syndrome virus (PRRSV), and it is now possible to alter the PRRSV genome and create genetically defined mutant viruses. Among many possible applications of the PRRSV infectious cDNA clones, development of genetically modified vaccines is of particular interest. Using infectious clones, the PRRSV genome has been manipulated by changing individual amino acids, deleting coding regions, inserting foreign sequences, and generating arterivirus chimeras. The limited available data suggest that all structural proteins of PRRSV are essential for replication of the virus, and that PRRSV infectivity is relatively intolerant of subtle changes within the structural proteins. The major tasks in PRRSV research are to identify virulence factors and pathogenic mechanisms, and to understand the structure–function relationships of individual viral proteins. Utilizing these infectious clones as tools, a new generation of safe and efficacious PRRS vaccines may be constructed.


title: Bocavirus Viremia and Hepatitis in an Immunocompetent Child

text: BACKGROUND: So far, many studies have shown that Human Bocavirus ( HBoV) is the main pathogen of the respiratory tract. Until now, there is no study that proves the association between HBoV and hepatitis. HBoV viremia/DNAemia has been associated closely with acute primary infection and moderate-to-severe illness but, more detailed clinical data about HBoV dissemination are still unavailable. CASE REPORT: Here we report a 2-years-5-months-old girl suffering from respiratory distress and heptitis followed in our intensive care unit. HBoV was detected in our patients nose and throat swabs concurrent with whole blood sample by positive polymerase chain reactions. After a through investigation no causative agent other than HBoV viremia was found. CONCLUSION: Human Bocavirus viremia with high viral loads may be associated with hepatitis.


title: Disease X ver1.0: COVID-19

text: The SARS-Cov2 has presented the world with a novel pandemic challenge requiring a rapid response. This article provides a May 2020 snapshot from Professor Paul Young, who is part of a group working with urgency on Australia’s leading COVID-19 candidate vaccine.


title: Genetic Loci That Influence Cause of Death in a Heterogeneous Mouse Stock

text: A genome scan was conducted to seek evidence for polymorphic genes that influence cause of death in mice produced by a cross between CB6F1 females and C3D2F1 males. Loci on chromosomes 1 and 4 were found to modulate risk of lymphoma. A locus on chromosome 4 influenced risk of mammary adenocarcinoma among multiparous female mice, but had no significant effect in virgin females. A chromosome 4 locus was found to modulate risk of death from either hemangiosarcoma or fibrosarcoma. A suggestive linkage was noted (at p =.09) between a marker on chromosome 11 and hepatocellular carcinoma. Lastly, a locus on chromosome 6 was noted to influence the likelihood that pulmonary adenocarcinoma would be present at death. The collection of normal and neoplastic tissues from 1004 terminal necropsies, together with genetic information, provides a valuable resource for further studies of the genetic influences on late-life diseases in mice.


title: Syndrome respiratoire aigu sévère

text: Résumé Le syndrome respiratoire aigu sévère (severe acute respiratory syndrome, SARS) est apparu à l’automne 2002 dans la province de Guangdong en Chine. L’épidémie s’est rapidement propagée à travers le monde pour toucher, courant avril, plus de 26 pays avec un total de cas à cette même date proche de 3500 cas. La symptomatologie associe des formes modérées se manifestant par une fièvre, une hypoxie, avec des formes de gravité majeure responsables de syndrome de détresse aigue nécessitant l’hospitalisation en unité de réanimation. Des formes digestives ont aussi récemment été décrites. Cette épidémie a suscité une réponse extrêmement rapide de la communauté internationale qui en quelques semaines a permis d’isoler l’agent responsable, un nouveau Coronavirus, de proposer une prise en charge thérapeutique et des mesures spécifiques pour limiter la diffusion de l’épidémie. Cette revue rassemble l’ensemble des données actuellement disponibles sur le SARS, de l’histoire de l’épidémie aux propositions thérapeutiques disponibles en date d’avril 2003. Abstract In the Fall of 2002 a report from Guangdong Province in China showed the occurrence of an outbreak of atypical pneumonia. This outbreak rapidly progressed from China to Hong Kong, Singapore, Toronto, and the USA, to more than 25 countries worldwide and almost 3500 cases to date in april 2003. The clinical features associate a fever with mild respiratory symptoms which can progress to a typical acute respiratory distress syndrome requiring intensive care unit admission. Enteric forms with diarrhea were recently described in Hong Kong. The medical community responded very rapidly and united in front of this major health crisis. In a couple weeks, the agent, a new Coronavirus was isolated, therapeutic guidelines were proposed and measures to limit the outbreak diffusion were started worldwide. We summarize here the history of the outbreak, the clinical, laboratory and radiological features of SARS. April 2003 therapeutic guidelines are also reported.


Keynote Lectures (KL)


title: The expanding field of poly(ADP-ribosyl)ation reactions. ‘Protein Modifications: Beyond the Usual Suspects' Review Series

text: Poly(ADP-ribosyl)ation is a post-translational modification of proteins that is mediated by poly(ADP-ribose) polymerases (PARPs). Although the existence and nature of the nucleic acid-like molecule poly(ADP-ribose) (PAR) has been known for 40 years, understanding its biological functions—originally thought to be only the regulation of chromatin superstructure when DNA is broken—is still the subject of intense research. Here, we review the mechanisms controlling the biosynthesis of this complex macromolecule and some of its main biological functions, with an emphasis on the most recent advances and hypotheses that have developed in this rapidly growing field.


title: Improving Preparedness for and Response to Coronavirus Disease 19 (COVID-19) in Long-Term Care Hospitals in Korea

text: Clusters of coronavirus disease 2019 (COVID-19) in long-term care facilities (LTCFs) have been widely reported in Korea and around the world. COVID-19 has a high mortality rate, and older patients and those with underlying diseases are at particularly high risk of being infected. Outbreaks in LTCFs, where many high-risk patients reside, result in the occupation of beds meant for severely ill patients and even death in many patients. Long-term care hospitals (LTCH) are major LTCFs in Korea. Therefore, it is very important to protect patients in LTCHs from COVID-19. The reality is that preparedness for COVID-19 in LTCHs is inadequate, and there are barriers to improvements in preparedness. Through institutional improvement and policy support, the government should help healthcare personnel and LTCHs improve installation and raise the level of knowledge of infection prevention and control. With these improvement, prevention, surveillance, and screening for COVID-19 should be done and a response system to the COVID-19 outbreak should be established. There are many challenges that must be overcome to meet the goals proposed in this article. This may be possible only with a spirit of solidarity and cooperation of government, public and private healthcare facilities.


title: Combined Antiviral-Antimediator Treatment for the Common Cold

text: A randomized, controlled, double-masked clinical trial was conducted with a combination antiviral-antimediator treatment for experimental rhinovirus colds. In all, 150 healthy men and women (aged 18–51 years) were randomly assigned to 1 of 3 groups: intranasal interferon (IFN)–α2b (6×10(6) U every 12 h × 3) plus oral chlorpheniramine (12 mg extended release) and ibuprofen (400 mg) every 12 h for 4.5 days (n=59 subjects); intranasal placebo plus oral chlorpheniramine and ibuprofen (n=61 subjects); or intranasal and oral placebos (n=30 subjects). Treatment was started 24 h after intranasal viral challenge. During the 4.5 days of treatment with IFN-α2b, chlorpheniramine, and ibuprofen, the daily mean total symptom score was reduced by 33%–73%, compared with placebo. Treatment reduced the severity of rhinorrhea, sneezing, nasal obstruction, sore throat, cough, and headache and reduced nasal mucus production, nasal tissue use, and virus concentrations in nasal secretions. IFN-α2b added to the effectiveness of chlorpheniramine and ibuprofen and was well tolerated


Towards Stronger EU Governance of Health Threats after the COVID-19 Pandemic


title: The Role of Extracellular Vesicles as Allies of HIV, HCV and SARS Viruses

text: Extracellular vesicles (EVs) are lipid bilayer-enclosed entities containing proteins and nucleic acids that mediate intercellular communication, in both physiological and pathological conditions. EVs resemble enveloped viruses in both structural and functional aspects. In full analogy with viral biogenesis, some of these vesicles are generated inside cells and, once released into the extracellular milieu, are called “exosomes”. Others bud from the plasma membrane and are generally referred to as “microvesicles”. In this review, we will discuss the state of the art of the current studies on the relationship between EVs and viruses and their involvement in three important viral infections caused by HIV, HCV and Severe Acute Respiratory Syndrome (SARS) viruses. HIV and HCV are two well-known pathogens that hijack EVs content and release to create a suitable environment for viral infection. SARS viruses are a new entry in the world of EVs studies, but are equally important in this historical framework. A thorough knowledge of the involvement of the EVs in viral infections could be helpful for the development of new therapeutic strategies to counteract different pathogens.