title: Socially optimal lockdown and travel restrictions for fighting communicable virus including COVID-19

text: This paper examines the socially optimal lockdown and travel (social activity) restriction policies for communicable virus including COVID-19. In our simple model, we exploit the remarkable similarity in the structure of external costs causing market failure between the socially optimal choices of the COVID-19 pandemic case and the socially optimal urban traffic congestion level. By identifying this similarity, the results obtained from our simple model allow for future pandemic researchers to use the well-established research methodologies for designing socially optimal traffic levels and associated policy tools to find the socially optimal lockdown and travel restrictions. The key results obtained from our COVID-19 model are: (1) individuals do not internalize the external cost of infection risks they impose on others and health care system when making their own travel (social-activity) decisions; In order to induce individual travel decision makers to internalize this external cost, the government actions are necessary; The travel restrictions via lockdown or monetary penalty is one form of such actions; (2) the existence of external cost implies that the socially optimal length of lockdown is always longer than the privately optimal length of the lockdown period; (3) the strictness of the travel restriction and the amount of violation penalty should be higher in the areas with high population density and in larger cities because the external cost of spreading virus by a traveler would be higher. The monetary penalty in this model resembles the classical Pigouvian tax, which should increase with the city's population, people density, and economic prosperity; (4) when a government subsidizes or fully covers medical expenses of COVID-19 patients, stricter travel restrictions with heavier penalties are required. This is to avoid crowding out of the health care system.


20.083 Middle East Respiratory Syndrome Coronavirus (MERS-CoV): A systematic literature review


COVID-19 and remembering Professor Dennis H. Wright


title: Development of a neutralization assay based on the pseudotyped chikungunya virus of a Korean isolate

text: The Chikungunya virus (CHIKV) belongs to the Alphavirus genus of Togaviridae family and contains a positive-sense single stranded RNA genome. Infection by this virus mainly causes sudden high fever, rashes, headache, and severe joint pain that can last for several months or years. CHIKV, a mosquito-borne arbovirus, is considered a re-emerging pathogen that has become one of the most pressing global health concerns due to a rapid increase in epidemics. Because handling of CHIKV is restricted to Biosafety Level 3 (BSL-3) facilities, the evaluation of prophylactic vaccines or antivirals has been substantially hampered. In this study, we first iden-tified the whole structural polyprotein sequence of a CHIKV strain isolated in South Korea (KNIH/2009/77). Phylogenetic analysis showed that this sequence clustered within the East/ Central/South African CHIKV genotype. Using this sequence information, we constructed a CHIKV-pseudotyped lenti-virus expressing the structural polyprotein of the Korean CHIKV isolate (CHIKVpseudo) and dual reporter genes of green fluorescence protein and luciferase. We then developed a pseudovirus-based neutralization assay (PBNA) using CHIKVpseudo. Results from this assay compared to those from the conventional plaque reduction neutralization test showed that our PBNA was a reliable and rapid method to evaluate the efficacy of neutralizing antibodies. More importantly, the neutralizing activities of human sera from CHIKV-infected individuals were quantitated by PBNA using CHIKVpseudo. Taken together, these results suggest that our PBNA for CHIKV may serve as a useful and safe method for testing the neutralizing activity of antibodies against CHIKV in BSL-2 facilities.


title: How Efficacious Must a COVID-19 Coronavirus Vaccine be to Prevent or Stop an Epidemic by Itself

text: Background: Given the continuing coronavirus disease 2019 (COVID-19) pandemic and much of the U.S. implementing social distancing due to the lack of alternatives, there has been a push to develop a vaccine to eliminate the need for social distancing. Methods: In 2020, we developed a computational model of the U.S. simulating the spread of COVID-19 coronavirus and vaccination. Results: Simulation experiments revealed that when vaccine efficacy exceeded 70%, coverage exceeded 60%, and vaccination occurred on day 1, the attack rate dropped to 22% with daily cases not exceeding 3.2 million (reproductive rate, R0, 2.5). When R0 was 3.5, the attack rate dropped to 41% with daily cases not exceeding 14.4 million. Increasing coverage to 75% when vaccination occurred by day 90 resulted in 5% attack rate and daily cases not exceeding 258,029when R0 was 2.5 and a 26% attack rate and maximum daily cases of 22.6 million when R0 was 3.5. When vaccination did not occur until day 180, coverage (i.e., those vaccinated plus those otherwise immune) had to reach 100%. A vaccine with an efficacy between 40% and 70% could still obviate the need for other measures under certain circumstances such as much higher, and in some cases, potentially unachievable, vaccination coverages. Conclusion: Our study found that to either prevent or largely extinguish an epidemic without any other measures (e.g., social distancing), the vaccine has to have an efficacy of at least 70%.


title: Service industries, globalization, and urban restructuring within the Asia-Pacific: new development trajectories and planning responses

text: Abstract While industralization programmes have been central to the development of Asia-Pacific states and city-regions over the past half-century, service industries are increasingly important as instruments of urban growth and change. The purpose of this paper is to establish service industries as increasingly significant aspects of urban development within the Asia-Pacific, and to propose a conceptual and analytical framework for scholarly investigation within this important research domain. To this end the paper explores a sequence of related themes and issues, concerning the larger developmental implications of urban services growth (or tertiarization), the facets of urban transformation associated with tertiarization, and a preliminary typology of urban service functions which acknowledges the rich diversity of service vocations and stages of development within the Asia-Pacific. The paper concludes that “advanced services”—specialized, intermediate service industries, advanced-technology services, and creative service industries—will be quite crucial to the development of city-regions within the Asia-Pacific, with respect to employment growth and human capital formation, to the urban economic (or export) base, to the operation of flexible production systems, and to competitive advantage. The development of these urban service poles will require innovative policy commitments and regulatory adjustments, as will the multi-centred specialized urban service corridors which function as engines of regional economic growth, and which provide platforms for national modernization and responses to the pressures (and opportunities) of globalization. To date, urban and regional development strategies for service industries within the Asia-Pacific have privileged globalization, industrial restructuring, and modernization aims, but there is also an encouraging record of more progressive planning experimentation in some jurisdictions, incorporating principles of sustainability and co-operative development. There is also increasing interest in policies to support cultural and creative industries among Asia-Pacific city-regions, informed by some recent urban policy experimentation in this domain. These experiences can offer models for further policy and programmatic innovation in the 21st century, as service industries continue to play larger roles in urban and regional development within the Asia-Pacific.


title: Genetic diversity of coronaviruses in bats in Lao PDR and Cambodia

text: Abstract South-East Asia is a hot spot for emerging zoonotic diseases, and bats have been recognized as hosts for a large number of zoonotic viruses such as Severe Acute Respiratory Syndrome (SARS), responsible for acute respiratory syndrome outbreaks. Thus, it is important to expand our knowledge of the presence of viruses in bats which could represent a risk to humans. Coronaviruses (CoVs) have been reported in bat species from Thailand, China, Indonesia, Taiwan and the Philippines. However no such work was conducted in Cambodia or Lao PDR. Between 2010 and 2013, 1965 bats were therefore sampled at interfaces with human populations in these two countries. They were tested for the presence of coronavirus by consensus reverse transcription-PCR assay. A total of 93 samples (4.7%) from 17 genera of bats tested positive. Sequence analysis revealed the presence of potentially 37 and 56 coronavirus belonging to alpha-coronavirus (αCoV) and beta-CoV (βCoV), respectively. The βCoVs group is known to include some coronaviruses highly pathogenic to human, such as SARS-CoV and MERS-CoV. All coronavirus sequences generated from frugivorous bats (family Pteropodidae) (n =55) clustered with other bat βCoVs of lineage D, whereas one coronavirus from Pipistrellus coromandra fell in the lineage C of βCoVs which also includes the MERS-CoV. αCoVs were all detected in various genera of insectivorous bats and clustered with diverse bat αCoV sequences previously published. A closely related strain of PEDV, responsible for severe diarrhea in pigs (PEDV-CoV), was detected in 2 Myotis bats. We highlighted the presence and the high diversity of coronaviruses circulating in bats from Cambodia and Lao PDR. Three new bat genera and species were newly identified as host of coronaviruses, namely Macroglossus sp., Megaerops niphanae and Myotis horsfieldii


title: Growth, detection, quantification, and inactivation of SARS-CoV-2

text: Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is the agent responsible for the coronavirus disease 2019 (COVID-19) global pandemic. SARS-CoV-2 is closely related to SARS-CoV, which caused the 2003 SARS outbreak but disappeared rapidly. Although numerous reagents were developed to study SARS-CoV infections, few have been applicable to evaluating SARS-CoV-2 infection and immunity. Current limitations in studying SARS-CoV-2 include few validated assays with fully replication-competent wild-type virus. We have developed protocols to propagate, quantify, and work with infectious SARS-CoV-2. Here, we describe: (1) virus stock generation, (2) RT-qPCR quantification of SARS-CoV-2 RNA; (3) detection of SARS-CoV-2 antigen by flow cytometry, (4) quantification of infectious SARS-CoV-2 by focus-forming and plaque assays; and 5) validated protocols for virus inactivation. Collectively, these methods can be adapted to a variety of experimental designs, which should accelerate our understanding of SARS-CoV-2 biology and the development of effective countermeasures against COVID-19.


title: Association of Toll-like receptor 2-positive monocytes with coronary artery lesions and treatment nonresponse in Kawasaki disease

text: PURPOSE: Activation of Toll-like receptor 2 (TLR2) present on circulating monocytes in patients with Kawasaki disease (KD) can lead to the production of proinflammatory cytokines and interleukin-10 (IL-10). We aimed to determine the association of the frequency of circulating TLR2+/CD14+ monocytes (FTLR2%) with the outcomes of KD, as well as to compare FTLR2% to the usefulness of sIL-10. METHODS: The FTLR2% in patients with KD was measured by flow cytometry. Serum levels of IL-10 (sIL-10) were determined in 31 patients with KD before the initial treatment with intravenous immunoglobulin (IVIG) and in 21 febrile controls by using enzyme-linked immunosorbent assay. Patients were classified as having coronary artery lesions (CALs) based on the maximal internal diameters of the proximal right coronary artery and proximal left anterior descending coronary artery one month after the initial diagnosis. RESULTS: We found that FTLR2% greater than 92.62% predicted CALs with 80% sensitivity and 68.4% specificity, whereas FTLR2% more than 94.61% predicted IVIG resistance with 66.7% sensitivity and 71.4% specificity. Moreover, sIL-10 more than 15.52 pg/mL predicted CALs and IVIG resistance with 40% and 66.7% sensitivity, respectively, and 73.7% and 76.2% specificity, respectively. CONCLUSION: We showed that measuring FTLR2% before the initial treatment could be useful in predicting CAL development with better sensitivity than sIL-10 and with results comparable to sIL-10 results for the prediction of IVIG resistance in patients with KD. However, further studies are necessary to validate FTLR2% as a marker of prognosis and severity of KD.


Handlungsempfehlungen DGHNO-KHC und BVHNO für die HNO-Elektiv-/nicht notfallmäßige Behandlung zu Corona-Zeiten (29.04.2020)


title: Use of Carbon Dioxide as Raw Material to close the Carbon Cycle for the German Chemical and Polymer Industries

text: This article explores how far the use of CO(2) as raw material could enable the German chemical and polymer industries to contribute to a circular economy. Material Flow Analysis was conducted for all carbon flows for material use in Germany, comprising chemical production, polymer production, domestic use and waste management. For scenario modelling, Carbon Capture and Utilization technologies were included, and key parameters determining carbon flows were altered to show potential corridors for the future development. The results show that current carbon flows are dominated by fossil sources and are highly linear, with a secondary input rate of only 6 %. Additionally, 11 % (2 Mt/a) of the primary carbon input is lost due to dissipation. Currently available Carbon Capture and Utilization technologies would allow reaching a secondary input rate of 65 % for the chemical industry. However, to achieve this rate between 80 % (processes of direct synthesis) and 103 % (methanol-based processes) of the total net supply for renewable electricity in Germany would be required in 2030 and between 41 % and 50 % in 2050. In contrast, the unavoidable substance related CO(2)-point sources in Germany could probably fulfill the carbon requirement for material use of the chemical industry in 2050. The authors conclude that the utilization of CO(2) as a carbon source is necessary to close the carbon cycle where material or chemical recycling is technically not feasible or reasonable. The very high demand for renewable electricity indicates that the required production facilities for CO(2)-based chemicals will probably not be completely based in Germany.


title: Feline coronavirus: Insights into viral pathogenesis based on the spike protein structure and function

text: Abstract Feline coronavirus (FCoV) is an etiological agent that causes a benign enteric illness and the fatal systemic disease feline infectious peritonitis (FIP). The FCoV spike (S) protein is considered the viral regulator for binding and entry to the cell. This protein is also involved in FCoV tropism and virulence, as well as in the switch from enteric disease to FIP. This regulation is carried out by spike's major functions: receptor binding and virus-cell membrane fusion. In this review, we address important aspects in FCoV genetics, replication and pathogenesis, focusing on the role of S. To better understand this, FCoV S protein models were constructed, based on the human coronavirus NL63 (HCoV-NL63) S structure. We describe the specific structural characteristics of the FCoV S, in comparison with other coronavirus spikes. We also revise the biochemical events needed for FCoV S activation and its relation to the structural features of the protein.


title: The impact of the Covid-19 pandemic in the precipitation of intimate partner violence

text: Intimate Partner Violence (IPV) is a global pandemic and many have been victims of it long before Covid-19. International organizations have documented an increase in IPV reports during the current pandemic, raising awareness of the potential causes for such an increase. Reflecting on risk factors associated with IPV, and the underlying need of the perpetrators to exert control over the victims, it becomes increasingly important to understand how the current policies of social distancing, self-isolation, and lockdown can precipitate episodes of IPV. Furthermore, access to specialized services and health care can be compromised, and health care professionals face new challenges and demands imposed by the pandemic while managing IPV cases. This article begins by examining the main risk factors more commonly associated with IPV in the literature. It proceeds by reflecting on how these risk factors may be exacerbated during the Covid-19 pandemic, which can explain the increased number of reports. Finally, it emphasizes the new challenges faced by health care professionals, while assisting IPV victims during the pandemic and provides possible recommendations on actions to implement during and beyond the Covid-19 pandemic to prevent such cases.


docid: uyuajaug

title: Experimental Infection of Young Pigs with an Early European Strain of Porcine Epidemic Diarrhoea Virus and a Recent US Strain

text: Outbreaks of porcine epidemic diarrhoea (PED) were reported across Europe during the 1980s and 1990s, but only sporadic outbreaks occurred in recent years. PED virus (PEDV) spread for the first time into the USA in 2013 and has caused severe economic losses. Retrospectively, it was found that two different strains of PEDV have been introduced into the United States, both are closely related to strains circulating in China where a new wave of the disease occurred from 2010 onwards. Since autumn 2014, new outbreaks of PED have occurred in Europe. In this study, weaned piglets were inoculated with an early European isolate (Br1/87) or faecal/intestinal suspensions derived from pigs infected with a recent European strain of PEDV (from Germany) or a US strain of PEDV. No evidence for infection resulted from inoculation of pigs with the German sample that contained high levels of PEDV RNA; there were no clinical signs, excretion of viral RNA or anti‐PEDV antibody production. In contrast, all the pigs in the other two groups showed evidence of infection. Mild clinical signs of disease, mainly diarrhoea, occurred in piglets inoculated with the Br1/87 and US PEDV strains. PEDV RNA was detected throughout the intestine in euthanized animals at 4 days post‐inoculation. In addition, within these animals, low levels of viral RNA were detected in lungs and livers with higher levels in spleens. Seroconversion against PEDV occurred in all surviving infected animals within 10 days. PEDV RNA excretion occurred for at least 2 weeks. The US PEDV RNA was detected at low levels in serum samples on multiple days. It is apparent that current diagnostic systems can detect infection by the different virus strains.


Letter from Hong Kong


title: RNA chaperones encoded by RNA viruses

text: RNAs are functionally diverse macromolecules whose proper functions rely strictly upon their correct tertiary structures. However, because of their high structural flexibility, correct folding of RNAs is challenging and slow. Therefore, cells and viruses encode a variety of RNA remodeling proteins, including helicases and RNA chaperones. In RNA viruses, these proteins are believed to play pivotal roles in all the processes involving viral RNAs during the life cycle. RNA helicases have been studied extensively for decades, whereas RNA chaperones, particularly virus-encoded RNA chaperones, are often overlooked. This review describes the activities of RNA chaperones encoded by RNA viruses, particularly the ones identified and characterized in recent years, and the functions of these proteins in different steps of viral life cycles, and presents an overview of this unique group of proteins. [Image: see text]


title: Differentiating Rhinitis in the Paediatric Population by Giving Focus on Medical History and Clinical Examination

text: Chronic rhinitis is defined as an inflammation of the nasal epithelium, and is characterized by the presence of two or more specific nasal symptoms including obstruction, rhinorrhea, sneezing, and/or itching for at least 12 weeks. In childhood, this clinical entity is very common and carries a significant socioeconomic burden. The impact on the physical, social, and psychological well-being of family cannot be underestimated. Rhinitis is an umbrella term which includes different phenotypes of rhinitis with distinct underlying pathophysiologic mechanisms. In most cases the diagnosis of rhinitis is rather straightforward; however, sometimes when based on clinical symptomatology, characterization may be challenging. Herein, we provide guidance for getting all the data needed for the differential diagnosis of rhinitis based on medical history and clinical examination.


title: Haemagglutination by mouse hepatitis virus type 3

text: Abstract Partially purified preparations of mouse hepatitis virus type 3 (MHV3) agglutinated fowl, day-old chick, ferret, hamster and human O erythrocytes at 4, 20 and 37°C and mouse erythrocytes at° C.


docid: rtpbltkf

title: Predicting linear B-cell epitopes using string kernels

text: The identification and characterization of B-cell epitopes play an important role in vaccine design, immunodiagnostic tests, and antibody production. Therefore, computational tools for reliably predicting linear B-cell epitopes are highly desirable. We evaluated Support Vector Machine (SVM) classifiers trained utilizing five different kernel methods using fivefold cross-validation on a homology-reduced data set of 701 linear B-cell epitopes, extracted from Bcipep database, and 701 non-epitopes, randomly extracted from SwissProt sequences. Based on the results of our computational experiments, we propose BCPred, a novel method for predicting linear B-cell epitopes using the subsequence kernel. We show that the predictive performance of BCPred (AUC = 0.758) outperforms 11 SVM-based classifiers developed and evaluated in our experiments as well as our implementation of AAP (AUC = 0.7), a recently proposed method for predicting linear B-cell epitopes using amino acid pair antigenicity. Furthermore, we compared BCPred with AAP and ABCPred, a method that uses recurrent neural networks, using two data sets of unique B-cell epitopes that had been previously used to evaluate ABCPred. Analysis of the data sets used and the results of this comparison show that conclusions about the relative performance of different B-cell epitope prediction methods drawn on the basis of experiments using data sets of unique B-cell epitopes are likely to yield overly optimistic estimates of performance of evaluated methods. This argues for the use of carefully homology-reduced data sets in comparing B-cell epitope prediction methods to avoid misleading conclusions about how different methods compare to each other. Our homology-reduced data set and implementations of BCPred as well as the APP method are publicly available through our web-based server, BCPREDS, at: http://ailab.cs.iastate.edu/bcpreds/.


title: Multiplex PCR analysis of clusters of unexplained viral respiratory tract infection in Cambodia

text: BACKGROUND: Fevers of unknown origin constitute a substantial disease burden in Southeast Asia. In majority of the cases, the cause of acute febrile illness is not identified. METHODS: We used MassTag PCR, a multiplex assay platform, to test for the presence of 15 viral respiratory agents from 85 patients with unexplained respiratory illness representing six disease clusters that occurred in Cambodia between 2009 and 2012. RESULTS: We detected a virus in 37 (44%) of the cases. Human rhinovirus, the virus detected most frequently, was found in both children and adults. The viruses most frequently detected in children and adults, respectively, were respiratory syncytial virus and enterovirus 68. Sequence analysis indicated that two distinct clades of enterovirus 68 were circulating during this time period. CONCLUSIONS: This is the first report of enterovirus 68 in Cambodia and contributes to the appreciation of this virus as an important respiratory pathogen.


title: Modeling the hospital safety partnership preferences of patients and their families: a discrete choice conjoint experiment

text: BACKGROUND: Patients and their families play an important role in efforts to improve health service safety. OBJECTIVE: The objective of this study is to understand the safety partnership preferences of patients and their families. METHOD: We used a discrete choice conjoint experiment to model the safety partnership preferences of 1,084 patients or those such as parents acting on their behalf. Participants made choices between hypothetical safety partnerships composed by experimentally varying 15 four-level partnership design attributes. RESULTS: Participants preferred an approach to safety based on partnerships between patients and staff rather than a model delegating responsibility for safety to hospital staff. They valued the opportunity to participate in point of service safety partnerships, such as identity and medication double checks, that might afford an immediate risk reduction. Latent class analysis yielded two segments. Actively engaged participants (73.3%) comprised outpatients with higher education, who anticipated more benefits to safety partnerships, were more confident in their ability to contribute, and were more intent on participating. They were more likely to prefer a personal engagement strategy, valued scientific evidence, preferred a more active approach to safety education, and advocated disclosure of errors. The passively engaged segment (26.7%) anticipated fewer benefits, were less confident in their ability to contribute, and were less intent on participating. They were more likely to prefer an engagement strategy based on signage. They preferred that staff explain why they thought patients should help make care safer and decide whether errors were disclosed. Inpatients, those with immigrant backgrounds, and those with less education were more likely to be in this segment. CONCLUSION: Health services need to communicate information regarding risks, ask about partnership preferences, create opportunities respecting individual differences, and ensure a positive response when patients raise safety concerns.


title: Role of early life immune regulation in asthma development

text: Development of childhood asthma is complex with a strong interaction of genetic, epigenetic, and environmental factors. Ultimately, it is critical how the immune system of a child responds to these influences and whether effective strategies for a balanced and healthy immune maturation can be assured. Pregnancy and early childhood are particularly susceptible for exogenous influences due to the developing nature of a child’s immune system. While endogenous influences such as family history and the genetic background are immutable, epigenetic regulations can be modulated by both heredity and environmental exposures. Prenatal influences such as a mother’s nutrition, smoking, or infections influence the complex interplay of innate and adaptive immune regulation as well as peri- and postnatal influences including mode of delivery. Early in life, induction and continuous training of healthy maturation include balanced innate immunity (e.g., via innate lymphoid cells) and an equilibrium of T-cell subpopulations (e.g., via regulatory T cells) to counter-regulate potential pro-inflammatory or exuberant immune reactions. Later in childhood, rather compensatory immune mechanisms are required to modulate deviant regulation of a child’s already primed immune trajectory. The specific effects of exogenous and endogenous influences on a child’s maturing immune system are summarized in this review, and its importance and potential intervention for early prevention and treatment strategies are delineated.


Risk of COVID‐19 for patients with obesity


title: Chapter 28 Selected Zoonoses

text: Human risks of acquiring a zoonotic disease from animals used in biomedical research have declined over the last decade because higher quality research animals have defined microbiologic profiles. Even with diminished risks, the potential for exposure to infectious agents still exists, especially from larger species such as nonhuman primates, which may be obtained from the wild, and from livestock, dogs, ferrets, and cats, which are generally not raised in barrier facilities and are not subject to the intensive health monitoring performed routinely on laboratory rodents and rabbits. Additionally, when laboratory animals are used as models for infectious disease studies, exposure to microbial pathogens presents a threat to human health. Also, with the recognition of emerging diseases, some of which are zoonotic, constant vigilance and surveillance of laboratory animals for zoonotic diseases are still required.


title: Isolation and Propagation of Coronaviruses inEmbryonated Eggs

text: The embryonated egg is a complex structure comprising an embryo and its supporting membranes (chorioallantoic, amniotic, yolk). The developing embryo and its membranes provide the diversity of cell types that are needed for successful replication of a wide variety of different viruses. Within the family Coronaviridae, the embryonated egg has been used as a host system primarily for two group 3 coronaviruses, infectious bronchitis virus (IBV) and turkey coronavirus (TCoV), but it also has been shown to be suitable for pheasant coronavirus. IBV replicates well in the embryonated chicken egg, regardless of the inoculation route; however, the allantoic route is favored as the virus replicates extensively in chorioallantoic membrane and high titers are found in allantoic fluid. TCoV replicates only in embryo tissues, within epithelium of the intestines and bursa of Fabricius; thus amniotic inoculation is required for isolation and propagation of this virus. Embryonated eggs also provide a potential host system for studies aimed at identifying other, novel coronavirus species.


title: Three months of COVID‐19: A systematic review and meta‐analysis

text: The pandemic of 2019 novel coronavirus (SARS‐CoV‐2019), reminiscent of the 2002‐SARS‐CoV outbreak, has completely isolated countries, disrupted health systems and partially paralyzed international trade and travel. In order to be better equipped to anticipate transmission of this virus to new regions, it is imperative to track the progress of the virus over time. This review analyses information on progression of the pandemic in the past 3 months and systematically discusses the characteristics of SARS‐CoV‐2019 virus including its epidemiologic, pathophysiologic, and clinical manifestations. Furthermore, the review also encompasses some recently proposed conceptual models that estimate the spread of this disease based on the basic reproductive number for better prevention and control procedures. Finally, we shed light on how the virus has endangered the global economy, impacting it both from the supply and demand side.


title: Progress in Global Surveillance and Response Capacity 10 Years after Severe Acute Respiratory Syndrome

text: Ten years have elapsed since the World Health Organization issued its first global alert for an unexplained illness named severe acute respiratory syndrome (SARS). The anniversary provides an opportunity to reflect on the international response to this new global microbial threat. While global surveillance and response capacity for public health threats have been strengthened, critical gaps remain. Of 194 World Health Organization member states that signed on to the International Health Regulations (2005), <20% had achieved compliance with the core capacities required by the deadline in June 2012. Lessons learned from the global SARS outbreak highlight the need to avoid complacency, strengthen efforts to improve global capacity to address the next pandemic using all available 21st century tools, and support research to develop new treatment options, countermeasures, and insights while striving to address the global inequities that are the root cause of many of these challenges.


title: Retroviral and Lentiviral Vectors for the Induction of Immunological Tolerance

text: Retroviral and lentiviral vectors have proven to be particularly efficient systems to deliver genes of interest into target cells, either in vivo or in cell cultures. They have been used for some time for gene therapy and the development of gene vaccines. Recently retroviral and lentiviral vectors have been used to generate tolerogenic dendritic cells, key professional antigen presenting cells that regulate immune responses. Thus, three main approaches have been undertaken to induce immunological tolerance; delivery of potent immunosuppressive cytokines and other molecules, modification of intracellular signalling pathways in dendritic cells, and de-targeting transgene expression from dendritic cells using microRNA technology. In this review we briefly describe retroviral and lentiviral vector biology, and their application to induce immunological tolerance.


title: Structural basis of development of multi-epitope vaccine against Middle East respiratory syndrome using in silico approach

text: BACKGROUND: Middle East respiratory syndrome (MERS) is caused by MERS coronavirus (MERS-CoV). Thus far, MERS outbreaks have been reported from Saudi Arabia (2013 and 2014) and South Korea (2015). No specific vaccine has yet been reported against MERS. PURPOSE: To address the urgent need for an MERS vaccine, in the present study, we have designed two multi-epitope vaccines (MEVs) against MERS utilizing several in silico methods and tools. METHODS: The design of both the multi-epitope vaccines (MEVs) are composed of cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) epitopes, screened form thirteen different proteins of MERS-CoV. Both the MEVs also carry potential B-cell linear epitope regions, B-cell discontinuous epitopes as well as interferon-γ-inducing epitopes. Human β-defensin-2 and β-defensin-3 were used as adjuvants to enhance the immune response of MEVs. To design the MEVs, short peptide molecular linkers were utilized to link screened most potential CTL epitopes, HTL epitopes and the adjuvants. Tertiary models for both the MEVs were generated, refined, and further studied for their molecular interaction with toll-like receptor 3. The cDNAs of both MEVs were generated and analyzed in silico for their expression in a mammalian host cell line (human). RESULTS: Screened CTL and HTL epitopes were found to have high propensity for stable molecular interaction with HLA alleles molecules. CTL epitopes were also found to have favorable molecular interaction within the cavity of transporter associated with antigen processing. The selected CTL and HTL epitopes jointly cover upto 94.0% of worldwide human population. Both the CTL and HTL MEVs molecular models have shown to have stable binding and complex formation propensity with toll-like receptor 3. The cDNA analysis of both the MEVs have shown high expression tendency in mammalian host cell line (human). CONCLUSION: After multistage in silico analysis, both the MEVs are predicted to elicit humoral as well as cell mediated immune response. Epitopes of the designed MEVs are predicted to cover large human population worldwide. Hence both the designed MEVs could be tried in vivo as potential vaccine candidates against MERS.


title: Palivizumab immunoprophylaxis effectiveness in children with cystic fibrosis,

text: BACKGROUND: Evidence on the effectiveness of respiratory syncytial virus (RSV) immunoprophylaxis with palivizumab in children with cystic fibrosis (CF) is lacking. METHODS: We utilized Medicaid Extract files from 27 states from 1999 to 2006 linked to the National Cystic Fibrosis Registry to establish a cohort of children 0–2 years with CF diagnosis. Eligible children entered the cohort after CF diagnosis and after RSV season onset, and were followed until season end, second birthday, death, or hospitalizations for reasons other then the study outcome. Two outcomes were examined: hospitalization for RSV infections (RSV‐ha), or hospitalization for acute respiratory infections (ARI‐ha). Palivizumab exposure was defined based on pharmacy or procedure claims as current (claim date plus 30 days), former (day 31–60 after a claim), and no exposure (days before the first or >60 days after any claim). Both outcomes were examined in a Cox regression model, adjusting for RSV risk factors and CF severity via exposure propensity score. RESULTS: The matched cohort included 1,974 infants (2,875 infant seasons), who experienced 32 RSV‐ha and 212 ARI‐ha (3.9 and 26.2/1,000 season months, respectively). Compared to periods of no use, the adjusted hazard ratio for current use was 0.57 (95% confidence interval [CI]: 0.20–1.60) for RSV‐related hospitalization and 0.85 (95% CI: 0.59–1.21) for ARI‐related hospitalization. Each month of increasing age reduced the ARI‐ha by 5.8%. CONCLUSION: RSV hospitalization incidence was low suggesting either little contribution of the virus to respiratory infections in patients with CF or lack of RSV testing. Unadjusted and adjusted RSV‐hospitalization incidence rates suggested potentially positive effects of palivizumab, but results were inconclusive due to small event rates. Hospitalizations for acute respiratory illness with possible RSV contribution showed no association with palivizumab use, suggesting limited overall effect of palivizumab. Younger age greatly increased infection risk. Pediatr Pulmonol. 2013; 48:874–884. © 2012 Wiley Periodicals, Inc.


title: Sex Differences in COVID-19 Case Fatality Rate: Insights From a Multinational Registry

text: Abstract Objective To confirm whether a relationship exists between male sex and coronavirus disease 2019 (COVID-19) mortality and if this relationship is age-dependent. Methods We queried the COVID-19 Research Network; a multinational database utilizing the TriNetX Network to identify patients with confirmed COVID-19 infection. The main endpoint of the study was all-cause mortality. Results 14,712 patients were included, of whom, 6,387 (43.4%) were males. Males were older (55.0±17.7 vs. 51.1±17.9 years, P<.001), and had higher prevalence of hypertension, diabetes, coronary disease, obstructive pulmonary disease, nicotine dependence and heart failure, but a lower prevalence of obesity. Before propensity score matching (PSM), all-cause mortality was 8.8% in males and 4.3% in females (OR 2.15; 95% CI, 1.87-2.46; P<.001), at median follow-up of 34, and 32 days, respectively. In the Kaplan Meier survival analysis, the cumulative probability of survival was significantly lower in males than in females (73% vs. 86%, P-log rank <.001). After PSM, all-cause mortality remained significantly higher in males than in females (8.13% vs. 4.60%, OR 1.81; 95% CI, 1.55-2.11; P<.001). In the Kaplan Meier survival analysis, the cumulative probability of survival remained significantly lower in males than in females (74% vs. 86%, P-log rank <.001). The cumulative probability of survival remained significantly lower in PSM males than females after excluding patients <50 years of age, and those who were taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blocker (ARB) on admission. Conclusion Among patients with COVID-19 infection, males had significantly higher mortality than females, and this difference was not completely explained by the higher prevalence of co-morbidities in males.


docid: tpqwgxsg

title: Epidemiological and pathological study of feline morbillivirus infection in domestic cats in Japan

text: BACKGROUND: Feline morbillivirus (FmoPV) is a novel paramyxovirus found to infect domestic cats. FmoPV has been isolated in several countries in Asia and Europe and is considered to have genetic diversity. Also, it is suspected to be associated with feline renal diseases including tubulointerstitial nephritis (TIN), which affects domestic cats with a high incidence rate. RESULTS: To clarify the state of FmoPV infection among domestic cats in Japan, an epidemiological survey was conducted. Twenty-one out of 100 cats were found to have serum antibodies (Ab) against FmoPV-N protein by indirect immunofluorescence assay (IF) using FmoPV-N protein-expressing HeLa cells. Twenty-two of the cats were positive for FmoPV RNA in the urine and/or renal tissues. In total, 29 cats were positive for Ab and/or viral RNA. These FmoPV-infected cats were classified into three different phases of infection: RNA+/Ab + (14 cats), RNA+/Ab- (8 cats) and RNA-/Ab + (7 cats). In immunohistochemistry (IHC), 19 out of 29 cats were positive for FmoPV-N protein in kidney tissues; however, the FmoPV-N protein was located in the inflammatory lesions with severe grade in only four out of the 19 cats. Since 15 out of 29 infected cats were positive for viral RNA and Ab, approximately half of the infected cats were persistently infected with FmoPV. CONCLUSIONS: A statistically significant difference was observed between infection of FmoPV and the presence of inflammatory changes in renal lesions, indicating a relationship between FmoPV infection and feline renal diseases. However, we could not obtain histopathological evidence of a relationship between FmoPV infection and TIN.


title: Buccal and sublingual vaccine delivery

text: Abstract Because of their large surface area and immunological competence, mucosal tissues are attractive administration and target sites for vaccination. An important characteristic of mucosal vaccination is its ability to elicit local immune responses, which act against infection at the site of pathogen entry. However, mucosal surfaces are endowed with potent and sophisticated tolerance mechanisms to prevent the immune system from overreacting to the many environmental antigens. Hence, mucosal vaccination may suppress the immune system instead of induce a protective immune response. Therefore, mucosal adjuvants and/or special antigen delivery systems as well as appropriate dosage forms are required in order to develop potent mucosal vaccines. Whereas oral, nasal and pulmonary vaccine delivery strategies have been described extensively, the sublingual and buccal routes have received considerably less attention. In this review, the characteristics of and approaches for sublingual and buccal vaccine delivery are described and compared with other mucosal vaccine delivery sites. We discuss recent progress and highlight promising developments in the search for vaccine formulations, including adjuvants and suitable dosage forms, which are likely critical for designing a successful sublingual or buccal vaccine. Finally, we outline the challenges, hurdles to overcome and formulation issues relevant for sublingual or buccal vaccine delivery.


title: Impact of media coverage on epidemic spreading in complex networks

text: Abstract An SIS network model incorporating the influence of media coverage on transmission rate is formulated and analyzed. We calculate the basic reproduction number R 0 by utilizing the local stability of the disease-free equilibrium. Our results show that the disease-free equilibrium is globally asymptotically stable and that the disease dies out if R 0 is below 1; otherwise, the disease will persist and converge to a unique positive stationary state. This result may suggest effective control strategies to prevent disease through media coverage and education activities in finite-size scale-free networks. Numerical simulations are also performed to illustrate our results and to give more insights into the dynamical process.


title: Genetically Engineering a Susceptible Mouse Model for MERS-CoV-Induced Acute Respiratory Distress Syndrome

text: Since 2012, monthly cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to cause severe respiratory disease that is fatal in ~35% of diagnosed individuals. The ongoing threat to global public health and the need for novel therapeutic countermeasures have driven the development of animal models that can reproducibly replicate the pathology associated with MERS-CoV in human infections. The inability of MERS-CoV to replicate in the respiratory tracts of mice, hamsters, and ferrets stymied initial attempts to generate small animal models. Identification of human dipeptidyl peptidase IV (hDPP4) as the receptor for MERS-CoV infection opened the door for genetic engineering of mice. Precise molecular engineering of mouse DPP4 (mDPP4) with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology maintained inherent expression profiles, and limited MERS-CoV susceptibility to tissues that naturally express mDPP4, notably the lower respiratory tract wherein MERS-CoV elicits severe pulmonary pathology. Here, we describe the generation of the 288–330(+/+) MERS-CoV mouse model in which mice were made susceptible to MERS-CoV by modifying two amino acids on mDPP4 (A288 and T330), and the use of adaptive evolution to generate novel MERS-CoV isolates that cause fatal respiratory disease. The 288–330(+/+) mice are currently being used to evaluate novel drug, antibody, and vaccine therapeutic countermeasures for MERS-CoV. The chapter starts with a historical perspective on the emergence of MERS-CoV and animal models evaluated for MERS-CoV pathogenesis, and then outlines the development of the 288–330(+/+) mouse model, assays for assessing a MERS-CoV pulmonary infection in a mouse model, and describes some of the challenges associated with using genetically engineered mice.


docid: rbsdctnz

title: COVID-19 with Different Severities: A Multicenter Study of Clinical Features

text: Rationale: The coronavirus disease (COVID-19) pandemic is now a global health concern. Objectives: We compared the clinical characteristics, laboratory examinations, computed tomography images, and treatments of patients with COVID-19 from three different cities in China. Methods: A total of 476 patients were recruited from January 1, 2020, to February 15, 2020, at three hospitals in Wuhan, Shanghai, and Anhui. The patients were divided into four groups according to age and into three groups (moderate, severe, and critical) according to the fifth edition of the Guidelines on the Diagnosis and Treatment of COVID-19 issued by the National Health Commission of China. Measurements and Main Results: The incidence of comorbidities was higher in the severe (46.3%) and critical (67.1%) groups than in the moderate group (37.8%). More patients were taking angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in the moderate group than in the severe and critical groups. More patients had multiple lung lobe involvement and pleural effusion in the critical group than in the moderate group. More patients received antiviral agents within the first 4 days in the moderate group than in the severe group, and more patients received antibiotics and corticosteroids in the critical and severe groups. Patients >75 years old had a significantly lower survival rate than younger patients. Conclusions: Multiple organ dysfunction and impaired immune function were the typical characteristics of patients with severe or critical illness. There was a significant difference in the use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers among patients with different severities of disease. Involvement of multiple lung lobes and pleural effusion were associated with the severity of COVID-19. Advanced age (≥75 yr) was a risk factor for mortality.


title: Draft Genome Sequence of the Bordetella bronchiseptica Swine Isolate KM22

text: Bordetella bronchiseptica swine isolate KM22 has been used in experimental infections of swine as a model of clinical B. bronchiseptica infections within swine herds and to study host-to-host transmission. Here we report the draft genome sequence of KM22.


docid: xqcfzngi

title: Serological evaluation of relationship between viral pathogens (BHV-1, BVDV, BRSV, PI-3V, and Adeno3) and dairy calf pneumonia by indirect ELISA

text: In this study, viral pathogens associated with nine outbreaks of naturally occurring dairy calf pneumonia in Mashhad area of Khorasan Razavi province from September 2008 to May 2009 were assessed. Five diseased calves from each farm were chosen for examination. Acute and convalescent serum samples were taken from calves with signs of respiratory disease. Sera were analyzed for antibodies to bovine viral diarrhea virus (BVDV), bovine herpesvirus type 1 (BHV-1), bovine respiratory syncytial virus (BRSV), parainfluenza virus type 3 (PI-3V), and bovine adenovirus-3 (BAV-3) by indirect ELISA kits. Among 42 serum samples collected at sample 1, seroprevalence values for viruses BHV-1, BVDV, BRSV, PI-3V, and BAV-3 were 61.9% (26), 57.1% (24), 64.2% (27), 90% (38), and 61.9% (26), respectively. Seroconversion to BVDV, BRSV, PI-3V, and BAV-3 occurred in 11.9% (5), 16.6% (7), 26.1% (11), and 21.4% (9) of animals, and 52.3% (22) had generated antibodies against one or more viral infections at sample 2. In addition, no significant relationship between seroprevalence of BHV-1, BVDV, BRSV, PI-3V, and BAV-3 and dairy herd size was observed (P > 0.05). According to serological findings, BHV-1, BVDV, BRSV, PI-3V, and BAV-3 are common pathogens of the dairy calf pneumonia in dairy herds in Mashhad area of Khorasan Razavi province, Iran.


title: Detection of novel viruses in porcine fecal samples from China

text: BACKGROUND: Pigs are well known source of human infectious disease. To better understand the spectrum of viruses present in pigs, we utilized the 454 Life Sciences GS-FLX high-throughput sequencing platform to sequence stool samples from healthy pigs. FINDINGS: Total nucleic acid was extracted from stool samples of healthy piglets and randomly amplified. The amplified materials were pooled and processed using a high-throughput pyrosequencing technique. The raw sequences were deconvoluted on the basis of the barcode and then processed through a standardized bioinformatics pipeline. The unique reads (348, 70 and 13) had limited similarity to known astroviruses, bocaviruses and parechoviruses. Specific primers were synthesized to assess the prevalence of the viruses in healthy piglets. Our results indicate extremely high rates of positivity. CONCLUSIONS: Several novel astroviruses, bocaviruses and Ljungan-like viruses were identified in stool samples from healthy pigs. The rates of isolation for the new viruses were high. The high detection rate, diverse sequences and categories indicate that pigs are well-established reservoirs for and likely sources of different enteric viruses.


title: Cellular and molecular mechanisms of viral infection in the human placenta

text: The placenta is a highly specialized organ that is formed during human gestation for conferring protection and generating an optimal microenvironment to maintain the equilibrium between immunological and biochemical factors for fetal development. Diverse pathogens, including viruses, can infect several cellular components of the placenta, such as trophoblasts, syncytiotrophoblasts and other hematopoietic cells. Viral infections during pregnancy have been associated with fetal malformation and pregnancy complications such as preterm labor. In this minireview, we describe the most recent findings regarding virus–host interactions at the placental interface and investigate the mechanisms through which viruses may access trophoblasts and the pathogenic processes involved in viral dissemination at the maternal–fetal interface.


title: Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection

text: Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data.


title: A mobile genetic element with unknown function found in distantly related viruses

text: BACKGROUND: The genetic element s2m seems to represent one of very few examples of mobile genetic elements in viruses. The function remains obscure and a scattered taxonomical distribution has been reported by numerous groups. METHODS: We have searched GenBank in order to identify all viral accessions that have s2m(−like) sequence motifs. Rigorous phylogenetic analyses and constrained tree topology testing were also performed in order to investigate the apparently mobile nature of s2m. RESULTS: The stem-loop s2m structure can be found in four families of + ssRNA viruses; Astroviridae, Caliciviridae, Picornaviridae and Coronaviridae. In all of these virus families, with the possible exception of Caliciviridae, multiple gains and/or losses of s2m would have to be postulated in order to explain the distribution of this character. CONCLUSIONS: s2m appears to be a mobile genetic element with a unique evolutionary history in all of the four virus families where it can be found. Based on our findings and a review of the current literature on s2m, a hypothesis implying an RNAi-like function for the s2m element is also outlined.


title: Preliminary Estimates of the Prevalence of Selected Underlying Health Conditions Among Patients with Coronavirus Disease 2019 — United States, February 12–March 28, 2020

text: On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic (1). As of March 28, 2020, a total of 571,678 confirmed COVID-19 cases and 26,494 deaths have been reported worldwide (2). Reports from China and Italy suggest that risk factors for severe disease include older age and the presence of at least one of several underlying health conditions (3,4). U.S. older adults, including those aged ≥65 years and particularly those aged ≥85 years, also appear to be at higher risk for severe COVID-19-associated outcomes; however, data describing underlying health conditions among U.S. COVID-19 patients have not yet been reported (5). As of March 28, 2020, U.S. states and territories have reported 122,653 U.S. COVID-19 cases to CDC, including 7,162 (5.8%) for whom data on underlying health conditions and other known risk factors for severe outcomes from respiratory infections were reported. Among these 7,162 cases, 2,692 (37.6%) patients had one or more underlying health condition or risk factor, and 4,470 (62.4%) had none of these conditions reported. The percentage of COVID-19 patients with at least one underlying health condition or risk factor was higher among those requiring intensive care unit (ICU) admission (358 of 457, 78%) and those requiring hospitalization without ICU admission (732 of 1,037, 71%) than that among those who were not hospitalized (1,388 of 5,143, 27%). The most commonly reported conditions were diabetes mellitus, chronic lung disease, and cardiovascular disease. These preliminary findings suggest that in the United States, persons with underlying health conditions or other recognized risk factors for severe outcomes from respiratory infections appear to be at a higher risk for severe disease from COVID-19 than are persons without these conditions.


title: Scanning the horizon: emerging hospital-wide technologies and their impact on critical care

text: This commentary represents a selective survey of developments relevant to critical care. Selected themes include advances in point-of-care diagnostic testing, glucose control, novel microbiological diagnostics and infection control measures, and developments in information technology that have implications for intensive care. The latter encompasses an early example of an artificially intelligent clinical decision support mechanism, the introduction of a national health care information technology programme (UK NPfIT) and its implications, and exotic threats to patient safety due to emergent behaviour in complex information systems.


title: Transcriptome profile within the mouse central nervous system and activation of myelin-reactive T cells following murine coronavirus infection

text: Abstract Multiple sclerosis (MS) is an autoimmune disease associated with environmental factors, possibly including several viruses such as the coronaviruses. Indeed, murine coronavirus (MHV) infection provides a well-known experimental model for MS studies. Intracerebral infection of C57BL/6 mice with MHV-A59 revealed that viral replication was efficient and that clearance of infectious virus occurred as soon as 7 days post-infection. Using cDNA arrays, analysis of gene expression profile in the brain revealed a modulation of 80 different genes following infection, with at least 27 of these genes having previously been directly related to innate or acquired immune responses. Concordingly, an important activation of auto-reactive T cells specific to myelin basic protein was demonstrated. Altogether, these results indicate that an MHV infection of the central nervous system (CNS) leads to an important host genomic response implicating immunity-related genes and to the activation of myelin-reactive autoimmune T cells.


title: The Clinical Characteristics and Outcomes of Diabetes Mellitus and Secondary Hyperglycaemia Patients with Coronavirus Disease 2019: a Single‐center, Retrospective, Observational Study in Wuhan

text: AIMS: Since the pandemic outbreak of COVID‐19, limited information is available on diabetic patients with COVID‐19. MATERIALS AND METHODS: We retrospectively analysed 166 COVID‐19 patients at Tongji Hospital (Wuhan) from February 8 to March 21, 2020. Clinical characteristics and outcomes (as of April 4, 2020) were compared among control (group 1), secondary hyperglycaemia (group 2: no diabetes history, FPG levels ≥7.0 mmol/L once and HbA1c values <6.5%) and diabetic (group 3) patients. RESULTS: Compared to group 1, groups 2 and 3 had higher rates of leukocytosis, neutrophilia, lymphocytopenia, eosinopenia, and levels of sCRP, ferritin and d‐dimer (P < 0.05 for all). Group 2 patients have higher levels of LDH, prevalence of liver dysfunction and increased IL‐8 than those in group 1, a higher prevalence of increased IL‐8 was found in group 2 than in group 3 (P < 0.05 for all). The proportions of critical patients in groups 2 and 3 were significantly higher compared to group 1 (38.1%, 32.8% vs. 9.5%, P < 0.05 for both). Groups 2 and 3 had significantly longer hospital stays than group 1, which was nearly one week longer. The composite outcomes risks were 5.47 (1.56–19.82) and 2.61 (0.86–7.88) times greater in group 2 and 3 than in group 1. CONCLUSIONS: Hyperglycemia in both diabetes and secondary hyperglycemia patients with COVID‐19 may indicate poor prognoses. There were differences between secondary hyperglycemia and diabetes patients. We recommend that clinicians pay more attention to the blood glucose status of COVID‐19 patients, even those not diagnosed with diabetes before admission.


The COVID-19 Pandemic Battlefield: Protection of Long Term Care Hospitals


Back to the Basics: Propolis and COVID‐19


title: The interferons and their receptors—distribution and regulation

text: The interferons (IFNs) were originally described over 50 years ago, identified by their ability to confer viral resistance to cells. We now know that they are much more than just anti‐viral cytokines collectively having roles in both innate and adaptive immune responses, in tumor surveillance and defense, and modulation of immune cell function. Three types of IFN have now been described, simply referred to as type I, II and III. Distinguishable by the unique receptors that they rely on for signal transduction, the three types of IFN have specific and varied roles in the maintenance of human health and defense against pathogens. In mounting an IFN‐mediated immune response, the human body has developed the ability to regulate IFN‐mediated signal transduction. Like all cytokines, the ability of a cell to respond to IFN is completely dependent on the presence of its cognate receptor on the surface of the target cell. Thus, one of the major mechanisms used by the human body to regulate the strength and duration of the IFN response is through regulation of receptor levels, thereby altering the cytokine‐specific responsiveness of the target cell. This review will discuss the receptor system utilized by the type I IFNs and compare it with that of the type II and III IFNs, which also regulate immune responses through controlling receptor level on the cell surface.


title: Chapter 116 The Mammary Gland in Mucosal and Regional Immunity

text: Abstract The mammary gland (MG) lacks a mucosa but is part of the mucosal immune system because of its role in passive mucosal immunity. The MG is not an inductive site for mucosal immunity. Rather, synthesis of immunoglobulin (Ig)A by plasma cells stimulated at distal inductive sites dominate in the milk of rodents, humans, and swine whereas IgG1 derived from serum predominates in ruminants. Despite the considerable biodiversity in the role of the MG, IgG passively transfers the maternal systemic immunological experience whereas IgA transfers the mucosal immunological experience. Although passive antibodies are protective, they and other lacteal constituents can be immunoregulatory. Immune protection of the MG largely depends on the innate immune system; the monocytes–macrophages group together with intraepithelial lymphocytes is dominant in the healthy gland. An increase in somatic cells (neutrophils) and various interleukins signal infection (mastitis) and a local immune response in the MG. The major role of the MG to mucosal immunity is the passive immunity supplied to the suckling neonate.


title: Factors influencing preventive behavior against Middle East Respiratory Syndrome-Coronavirus among nursing students in South Korea()

text: BACKGROUND: Middle East Respiratory Syndrome Coronavirus (MERS-CoV), an emerging infectious disease introduced in South Korea in 2015, spreads quickly through hospitals, and Korea became one of the major areas affected by the disease after the Middle East region. To stop the spread of an emerging disease, it is important to practice prevention guidelines correctly. OBJECTIVES: The purpose of this study was to investigate factors influencing preventive behavior against MERS-CoV among Korean nursing students. METHODS: This is a cross-sectional study using a questionnaire survey. Data were collected from 429 nursing students from three colleges of nursing in Korea from June 25 to July 3 in 2015. RESULTS: Preventive behavior against MERS-CoV was affected mostly by attitude (β = .243, p < .001). Such behavior was also high in relation to the variables of perceived risk (β = .232, p < .001), older students (β = .202, p < .001), knowledge level (β = .153, p < .01), and female respondents (β = .115, p < .05). CONCLUSION: Preventive behavior against emerging infectious diseases such as MERS-CoV was found to be affected most significantly by attitude and risk perception. It is crucial to provide nursing students with information or knowledge, but it is also important to help those in nursing education recognize that active preventive behavior can prevent this infectious disease and stop its spread.


title: Rotavirus-mediated alteration of gut microbiota and its correlation with physiological characteristics in neonatal calves

text: Diarrhea is a fatal disease to neonatal calves, and rotavirus is the main pathogen associated with neonatal calf diarrhea. Although previous studies have reported that the gut microbiota is changed in calves during diarrhea, less is known about whether rotavirus infection alters the structure of the gut microbiota. Here, we characterized fecal microbial communities and identified possible relationships between the gut microbiota profiles and physiological parameters. Five fecal specimens of rotavirus-infected calves from 1 to 30 days after birth and five fecal specimens of age-matched healthy calves were used for the microbial community analysis using the Illumina MiSeq sequencer. Rotavirus infection was associated with reduced rotavirus infection significantly reduced the richness and diversity of the bacterial community. Weighted unique fraction metric analysis exhibited significant differences in community membership and structure between healthy and rotavirus-infected calves. Based on relative abundance analysis and linear discriminant analysis effect size, we found that the representative genera from Lactobacillus, Subdoligranulum, Blautia, and Bacteroides were closely related to healthy calves, while the genera Escherichia and Clostridium were closely affiliated to rotavirus-infected calves. Furthermore, canonical correlation analysis and Pearson correlation coefficient results revealed that the increased relative abundances of Lactobacillus, Subdoligranulum, and Bacteroides were correlated with normal levels of physiological characteristics such as white blood cells, blood urea nitrogen, serum amyloid protein A, and glucose concentration in serum. These results suggest that rotavirus infection alters the structure of the gut microbiota, correlating changes in physiological parameters. This study provides new information on the relationship between gut microbiota and the physiological parameters of rotavirus-mediated diarrheic calves.


title: Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID): Study Design and Rationale

text: BACKGROUND: As the COVID-19 pandemic developed, reports of neurological dysfunctions spanning the central and peripheral nervous systems have emerged. The spectrum of acute neurological dysfunctions may implicate direct viral invasion, para-infectious complications, neurological manifestations of systemic diseases, or co-incident neurological dysfunction in the context of high SARS-CoV-2 prevalence. A rapid and pragmatic approach to understanding the prevalence, phenotypes, pathophysiology and prognostic implications of COVID-19 neurological syndromes is urgently needed. METHODS: The Global Consortium to Study Neurological dysfunction in COVID-19 (GCS-NeuroCOVID), endorsed by the Neurocritical Care Society (NCS), was rapidly established to address this need in a tiered approach. Tier-1 consists of focused, pragmatic, low-cost, observational common data element (CDE) collection, which can be launched immediately at many sites in the first phase of this pandemic and is designed for expedited ethical board review with waiver-of-consent. Tier 2 consists of prospective functional and cognitive outcomes assessments with more detailed clinical, laboratory and radiographic data collection that would require informed consent. Tier 3 overlays Tiers 1 and 2 with experimental molecular, electrophysiology, pathology and imaging studies with longitudinal outcomes assessment and would require centers with specific resources. A multicenter pediatrics core has developed and launched a parallel study focusing on patients ages <18 years. Study sites are eligible for participation if they provide clinical care to COVID-19 patients and are able to conduct patient-oriented research under approval of an internal or global ethics committee. Hospitalized pediatric and adult patients with SARS-CoV-2 and with acute neurological signs or symptoms are eligible to participate. The primary study outcome is the overall prevalence of neurological complications among hospitalized COVID-19 patients, which will be calculated by pooled estimates of each neurological finding divided by the average census of COVID-19 positive patients over the study period. Secondary outcomes include: in-hospital, 30 and 90-day morality, discharge modified Rankin score, ventilator-free survival, ventilator days, discharge disposition, and hospital length of stay. RESULTS: In a one-month period (3/27/20–4/27/20) the GCS-NeuroCOVID consortium was able to recruit 71 adult study sites, representing 17 countries and 5 continents and 34 pediatrics study sites. CONCLUSIONS: This is one of the first large-scale global research collaboratives urgently assembled to evaluate acute neurological events in the context of a pandemic. The innovative and pragmatic tiered study approach has allowed for rapid recruitment and activation of numerous sites across the world—an approach essential to capture real-time critical neurological data to inform treatment strategies in this pandemic crisis.


title: Cell-mediated immune responses in the head-associated lymphoid tissues induced to a live attenuated avian coronavirus vaccine

text: Humoral immunity is important for controlling viral diseases of poultry, but recent studies have indicated that cytotoxic T cells also play an important role in the immune response to infectious bronchitis virus (IBV). To better understand the cell mediated immune responses to IBV in the mucosal and systemic immune compartments chickens were ocularly vaccinated with IBV. This induced a lymphocyte expansion in head-associated lymphoid tissues (HALT) and to a lesser extent in the spleen, followed by a rapid decline, probably due to homing of lymphocytes out of these organs and contraction of the lymphocyte population. This interpretation was supported by observations that changes in mononuclear cells were mirrored by that in CD3(+)CD44(+) T cell abundance, which presumably represent T effector cells. Increased interferon gamma (IFN-γ) expression was observed in the mucosal immune compartment, i.e., HALT, after primary vaccination, but shifted to the systemic immune compartment after boosting. In contrast, the expression of cytotoxicity-associated genes, i.e., granzyme A (GZMA) and perforin mRNA, remained associated with the HALT after boosting. Thus, an Ark-type IBV ocular vaccine induces a central memory IFN-γ response in the spleen while the cytotoxic effector memory response, as measured by GZMA and perforin mRNA expression, remains associated with CALT after boosting.


docid: hdmeyomt

title: Morphology of COVID-19–affected cells in peripheral blood film


title: Ethical and legal challenges of artificial intelligence-driven healthcare

text: This chapter will map the ethical and legal challenges posed by artificial intelligence (AI) in healthcare and suggest directions for resolving them. Section 1 will briefly clarify what AI is and Section 2 will give an idea of the trends and strategies in the United States (US) and Europe, thereby tailoring the discussion to the ethical and legal debate of AI-driven healthcare. This will be followed in Section 3 by a discussion of four primary ethical challenges, namely, (1) informed consent to use, (2) safety and transparency, (3) algorithmic fairness and biases, and (4) data privacy. Section 4 will then analyze five legal challenges in the US and Europe: (1) safety and effectiveness, (2) liability, (3) data protection and privacy, (4) cybersecurity, and (5) intellectual property law. Finally, Section 5 will summarize the major conclusions and especially emphasize the importance of building an AI-driven healthcare system that is successful and promotes trust and the motto Health AIs for All of Us.


title: Prevalence of positive COVID-19 among asymptomatic health care workers who care patients infected with the novel coronavirus: A retrospective study

text: BACKGROUND: Limited information is available about COVID-19 infections among health care workers. Sensitive detection of COVID-19 cases in health care workers is crucial for hospital infection prevention policy, particularly for those who work with vulnerable patients. The aim of this study is to describe the prevalence of positive COVID-19 among asymptomatic health care workers who took care of patients with COVID-19 during the pandemic. METHODS: This retrospective study included all health care workers at King Abdullah University Hospital who take care of patients infected with COVID-19 patients from March 18, 2020 to April 29, 2020. They were tested for COVID-19 infection by use of real-time reverse-transcriptase rRT-PCR on samples from nasopharyngeal swabs. RESULTS: A total number of 370 health care workers were screened. The majority were nurses followed by physicians and other personnel. This study showed that all asymptomatic health care workers were tested negative for COVID-19Q. CONCLUSION: Unexpectedly, the prevalence of positive COVID-19 among asymptomatic health care workers who take care of patients infected with the novel coronavirus was 0%. This result must be cautiously interpreted. Further studies are needed in order to find effective strategy of screening health care workers to insure a safe working environment.


“One World: Together At Home” event raises $127 million


docid: qrwxqhws

title: Liver diseases in the Asia-Pacific region: a Lancet Gastroenterology & Hepatology Commission

text: The Asia-Pacific region is home to more than half of the global population and accounted for 62·6% of global deaths due to liver diseases in 2015. 54·3% of global deaths due to cirrhosis, 72·7% of global deaths due to hepatocellular carcinoma, and more than two-thirds of the global burden of acute viral hepatitis occurred in this region in 2015. Chronic hepatitis B virus (HBV) infection caused more than half of the deaths due to cirrhosis in the region, followed by alcohol consumption (20·8%), non-alcoholic fatty liver disease (NAFLD; 12·1%), and chronic infection with hepatitis C virus (HCV; 15·7%). In 2015, HBV accounted for about half the cases of hepatocellular carcinoma in the region. Preventive strategies for viral hepatitis-related liver disease include increasing access to clean drinking water and sanitation. HBV vaccination programmes for neonates have been implemented by all countries, although birth-dose coverage is extremely suboptimal in some. Availability of screening tests for blood and tissue, donor recall policies, and harm reduction strategies are in their initial stages in most countries. Many governments have put HBV and HCV drugs on their essential medicines lists and the availability of generic versions of these drugs has reduced costs. Efforts to eliminate viral hepatitis as a public health threat, together with the rapid increase in per-capita alcohol consumption in countries and the epidemic of obesity, are expected to change the spectrum of liver diseases in the Asia-Pacific region in the near future. The increasing burden of alcohol-related liver diseases can be contained through government policies to limit consumption and promote less harmful patterns of alcohol use, which are in place in some countries but need to be enforced more strictly. Steps are needed to control obesity and NAFLD, including policies to promote healthy lifestyles and regulate the food industry. Inadequate infrastructure and insufficient health-care personnel trained in liver diseases are issues that also need to be addressed in the Asia-Pacific region. The policy response of most governments to liver diseases has thus far been inadequate and poorly funded. There must be a renewed focus on prevention, early detection, timely referral, and research into the best means to introduce and improve health interventions to reduce the burden of liver diseases in the Asia-Pacific region.


title: Nasopharyngeal viral PCR in immunosuppressed patients and its association with virus detection in bronchoalveolar lavage by PCR

text: BACKGROUND AND OBJECTIVE: Pulmonary infiltrates are common in immunosuppressed patients. Bronchoscopy with bronchoalveolar lavage (BAL) is often used to evaluate their aetiology. However, it may not always be easily performed. Thus, alternative diagnostic strategies may be needed. There is limited data on the correlation of nasopharyngeal (NP) respiratory viral panel (RVP)‐PCR testing compared with BAL. We aimed to identify the predictive value of NP RVP‐PCR samples compared with samples obtained from BAL in immunosuppressed patients with pulmonary infiltrates. METHODS: We conducted an observational retrospective study of immunosuppressed adults who underwent bronchoscopy in the Pulmonary Department at the University of Rochester Medical Center between January 2011 and June 2016. We compared the positive and negative predictive values, sensitivity, specificity and false negative rate of NP RVP‐PCR and BAL RVP‐PCR, as well as identified clinical predictors of positive viral BAL RVP‐PCR. RESULTS: Eighty‐nine immunosuppressed patients had both NP and bronchoalveolar RVP‐PCR testing. Twenty‐one patients had NP(+)BAL(+) RVP‐PCR testing. Seven patients had false negative (NP(−)BAL(+)) RVP‐PCR testing. Three patients had NP(+)BAL(−) RVP‐PCR testing. The positive and negative predictive values of NP RVP‐PCR testing were 88% and 89%, respectively. Allogeneic bone marrow transplantation and testing performed in the winter and spring months were significantly associated with positive BAL RVP‐PCR (OR = 3.3 (1.19–9.12); OR = 4.62 (1.64–12.99), respectively). CONCLUSION: NP RVP‐PCR testing has high concordance with testing performed on BAL samples. Repeat testing through BAL is beneficial when there is high concern for viral infection after initial NP RVP‐PCR testing is negative.


title: Immortalization and Characterization of Porcine Macrophages That Had Been Transduced with Lentiviral Vectors Encoding the SV40 Large T Antigen and Porcine Telomerase Reverse Transcriptase

text: The domestic pig is an important agricultural animal, and thus, infectious diseases that affect pigs can cause severe economic losses in the global swine industry. Various porcine pathogens target macrophages, which are classical innate immune cells. Although macrophages basically protect the host from pathogens, they also seem to contribute to infectious processes. Therefore, cultured macrophages can be used to develop in vitro models for studying not only genes associated with porcine innate immunity but also the infectious processes of porcine pathogens. However, the availability of porcine macrophage cell lines is limited. In this study, we describe a novel immortalized porcine kidney-derived macrophage (IPKM) cell line, which was generated by transferring the SV40 large T antigen (SV40LT) and porcine telomerase reverse transcriptase (pTERT) genes into primary porcine kidney-derived macrophages using lentiviral vectors. The IPKM displayed a typical macrophage morphology and was routinely passaged (doubling time: about 4 days). These cells were immunostained for macrophage markers. In addition, they exhibited substantial phagocytosis of polystyrene microbeads and released inflammatory cytokines upon lipopolysaccharide (LPS) stimulation. Furthermore, the maturation and secretion of interleukin-1β were observed after nigericin-induced inflammasome activation in LPS-primed IPKM. These findings suggest that IPKM exhibit the typical inflammatory characteristics of macrophages. By transferring the SV40LT and pTERT genes using lentiviral vectors, we also successfully immortalized macrophages derived from the peripheral blood of a low-density lipoprotein receptor-deficient pig. These results suggest that the co-expression of SV40LT and pTERT is an effective way of immortalizing porcine macrophages.


title: A cross‐sectional community‐based observational study of asymptomatic SARS‐CoV‐2 prevalence in the greater Indianapolis area

text: The Asymptomatic novel CORonavirus iNfection (ACORN) study was designed to investigate the prevalence of SARS‐CoV‐2 infection in the asymptomatic adult population of the Indianapolis metropolitan area, to follow individuals testing positive for the development of symptoms, and to understand duration of positive test results. ACORN is a cross‐sectional community‐based observational study of adult residents presenting asymptomatic for COVID‐like illness, defined as the self‐reported absence of the following 3‐symptoms in the last 7‐days: fever (≥100°F), new onset or worsening cough, and new onset or worsening shortness of breath. SARS‐CoV‐2 infection was determined by RT‐PCR in nasopharyngeal swab samples. SARS‐CoV‐2 infection prevalence was expressed as a point estimate with 95%‐CI. Test results are reported for 2953 participants who enrolled and underwent nasopharyngeal swab testing between April 7, 2020 and May 16, 2020. Among tested participants, 91 (3.1%; 95%‐CI; 2.5%‐3.7%) were positive for SARS‐CoV‐2. Overall, baseline characteristics, medical history, and infection risk factors were comparable between SARS‐CoV‐2 positive and negative participants. Within the ongoing 14‐day follow‐up period for positive participants, 58 (71.6%) of 81‐assessed participants remained asymptomatic while others (n=23, 28.4%) reported one or more symptoms. Indiana had “Stay‐at‐Home” orders in place during nearly the entire test period reported here, yet 3.1% of asymptomatic participants tested positive for SARS‐CoV‐2. These results indicate screening questions had limited predictive utility for testing in an asymptomatic population and suggest broader testing strategies are needed. Importantly, these findings underscore that more research is needed to understand the viral transmission and the role asymptomatic and pre‐symptomatic individuals play in this global pandemic. This article is protected by copyright. All rights reserved.


title: At the Center of Autophagy: Autophagosomes

text: Abstract Autophagosomes are double-membrane sequestering vesicles that are the hallmark of the intracellular catabolic process called macroautophagy. They are formed by the orchestrated interplay of the AuTophaGy-related (ATG) proteins. The cargo molecules targeted by autophagosomes ranges from long-lived proteins and superfluous or excess organelles to invading pathogens. Autophagosomes finally fuse with lysosomes delivering the sequestered material in the interior of these organelles where it is degraded by resident hydrolases. Autophagy represents a key survival mechanism because it clears the cytoplasm from unwanted and potentially toxic structures, and the autophagosomes are the central stage of it.


title: Trafficking motifs in the SARS-coronavirus nucleocapsid protein

text: Abstract The severe acute respiratory syndrome-coronavirus nucleocapsid (N) protein is involved in virus replication and modulation of cell processes. In this latter respect control may in part be achieved through the sub-cellular localisation of the protein. N protein predominately localises in the cytoplasm (the site of virus replication and assembly) but also in the nucleus/nucleolus. Using a combination of live-cell and confocal microscopy coupled to mutagenesis we identified a cryptic nucleolar localisation signal in the central part of the N protein. In addition, based on structural comparison to the avian coronavirus N protein, a nuclear export signal was identified in the C-terminal region of the protein.


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title: Genotyping and pathobiologic characterization of canine parvovirus circulating in Nanjing, China

text: BACKGROUND: Canine parvovirus (CPV) is an important pathogen that causes acute enteric disease in dogs. It has mutated and spread throughout the world in dog populations. We provide an update on the molecular characterization of CPV that circulated in Nanjing, a provincial capital in China between 2009 and 2012. RESULTS: Seventy rectal swab samples were collected from the dogs diagnosed with CPV infection in 8 animal hospitals of Nanjing. Sequence analysis of VP2 genes of 31 samples revealed that 29 viral strains belonged to CPV-2a subtype, while other two strains were classified into CPV-2b. To investigate the pathogenicity of the prevalent virus, we isolated CPV-2a and performed the animal experiment. Nine beagles were inoculated with 10(5.86) of 50% tissue culture infectious doses (TCID(50)) of the virus. All the experimentally infected beagles exhibited mild to moderate mucoid or watery diarrhea on day 4 post-infection (p.i.). On day 9 p.i., characteristic histopathological lesions were clearly observed in multiple organs of infected dogs, including liver, spleen, kidney, brain and all segments of the small and large intestines, while viral DNA and antigen staining could be detected in the sampled tissues. It is notable that canine parvovirus was isolated in one from two brain samples processed. CONCLUSION: Our results indicated that CPV-2a is the predominant subtype in Nanjing of China. And this virus caused extensive lesions in a variety of tissues, including the brain.


title: COVID-19, SARS and MERS: A neurological perspective

text: Abstract Central to COVID-19 pathophysiology is an acute respiratory infection primarily manifesting as pneumonia. Two months into the COVID-19 outbreak, however, a retrospective study in China involving more than 200 participants revealed a neurological component to COVID-19 in a subset of patients. The observed symptoms, the cause of which remains unclear, included impaired consciousness, skeletal muscle injury and acute cerebrovascular disease, and appeared more frequently in severe disease. Since then, findings from several studies have hinted at various possible neurological outcomes in COVID-19 patients. Here, we review the historical association between neurological complications and highly pathological coronaviruses including SARS, MERS and COVID-19. We draw from evidence derived from past coronavirus outbreaks, noting the similarities and differences between SARS and MERS and the current COVID-19 pandemic. We end by briefly discussing possible mechanisms by which the coronavirus impacts on the human nervous system, as well as neurology-specific considerations that arise from the repercussions of COVID-19.


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title: EU-Asia should defend multilateralism


Urgent need for an integrated policy framework for biodiversity loss and climate change


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title: The first case of COVID-19 pneumonia in a hemodialysis patient in Japan

text: On 31 December 2019, cases of pneumonia whose cause was later identified as SARS-CoV-2 were detected in Wuhan City, Hubei Province of China, and now COVID-19 has spread worldwide. On March 1, 2020, a 69-year-old Japanese man who had been on hemodialysis for 3 years was diagnosed as having COVID-19 pneumonia and hospitalized at our Medical Center. Pulmonary CT revealed bilateral multiple consolidation with bilateral pleural effusion. Aggressive weight reduction was needed to improve the patient’s respiratory condition. Hemodialysis therapy was performed in isolation with hydroxychloroquine administration, but the formation of a dialysis membrane clot forced the withdrawal of dialysis therapy. Changing the dialysis membrane material and anticoagulant enabled the resumption of dialysis therapy, allowing the body weight to correct downward. On the 5th hospitalization day, the patient’s fever dropped and he showed improved oxygenation and chest X-ray. He was eventually discharged. The hydroxychloroquine and appropriate fluid management may have contributed to the patient’s recovery. Clinicians should pay close attention to avoid dialysis-related problems when treating a patient with COVID-19.


title: The Economic Cost of COVID Lockdowns: An Out-of-Equilibrium Analysis

text: This paper estimates the cost of the lockdown of some sectors of the world economy in the wake of COVID-19. We develop a multi sector disequilibrium model with buyer-seller relations between agents located in different countries. The production network model allows us to study not only the direct cost of the lockdown but also indirect costs which emerge from the reductions in the availability of intermediate inputs. Agents determine the quantity of output and the proportions in which to combine inputs using prices that emerge from local interactions. The model is calibrated to the world economy using input-output data on 56 industries in 44 countries including all major economies. Within our model, the lockdowns are implemented as partial reductions in the output of some sectors using data on sectoral decomposition of capacity reductions. We use computational experiments to replicate the temporal sequence of the lockdowns implemented in different countries. World output falls by 7% at the early stage of the crisis when only China is under lockdown and by 23% at the peak of the crisis when many countries are under a lockdown. These direct impacts are amplified as the shock propagates through the world economy because of the buyer-seller relations. Supply-chain spillovers are capable of amplifying the direct impact by more than two folds. Naturally, the substitutability between intermediate inputs is a major determinant of the amplification. We also study the process of economic recovery following the end of the lockdowns. Price flexibility and minor technological adaptations help in reducing the time it takes for the economy to recover. The world economy takes about one quarter to move towards the new equilibrium in the optimistic and unlikely scenario of the end of all lockdowns. Recovery time is likely to be significantly greater if partial lockdowns persist.


Cardiovascular Disease


title: Mortality of people with intellectual disabilities during the 2017/2018 influenza epidemic in the Netherlands: potential implications for the COVID‐19 pandemic

text: BACKGROUND: Data on the development of Covid‐19 among people with intellectual disabilities (IDs) are scarce and it is uncertain to what extent general population data applies to people with ID. To give an indication of possible implications, this study investigated excess mortality patterns during a previous influenza epidemic. METHODS: Using Dutch population and mortality registers, a historical cohort study was designed to compare mortality during the 2017–2018 influenza epidemic with mortality in the same period in the three previous years. People with ID were identified by entitlements to residential ID‐care services as retrieved from a national database. RESULTS: Data covered the entire adult Dutch population (12.6 million; GenPop), of which 91 064 individuals were identified with an ID. During the influenza epidemic, mortality among people with ID increased almost three times as much than in the GenPop (15.2% vs. 5.4%), and more among male individuals with ID (+19.5%) than among female individuals with ID (+10.6%), as compared with baseline. In both cohorts, comparable increases in mortality within older age groups and due to respiratory causes were seen. Particularly in the ID‐cohort, excess deaths also occurred in younger age groups, due to endocrine diseases and ID‐specific causes. CONCLUSIONS: During the 2017–2018 influenza epidemic, excess mortality among people with ID was three times higher than in the general Dutch population, appeared more often at young age and with a broader range of underlying causes. These findings suggest that a pandemic may disproportionally affect people with ID while population data may not immediately raise warnings. Early detection of diverging patterns and faster implementation of tailored strategies therefore require collection of good quality data.


title: Echo in Pandemic: Front Line Perspective, Expanding Role of Ultrasound and Ethics of Resource Allocation

text: Abstract The grave clinical context of the pandemic must be understood. Italy is immersed in COVID-19. Most of the world will soon follow. The United States currently has the most documented cases of COVID-19 of any nation. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) associated acute cardiomyopathy is common in critical care patients and is associated with a high mortality. COVID-19 patients frequently require mechanical support for adequate oxygenation. A severe shortfall of ventilators is predicted. Of equal concern is the projected shortage of trained professionals required to care for patients on mechanical ventilation. Ultrasonography is proving to be a valuable tool for identifying the pulmonary manifestations and progression of COVID-19. Lung ultrasound also facilitates successful weaning from mechanical ventilation. Ultrasonography of the lung, pleura and diaphragm are easily mastered by experienced echocardiographers. Echocardiography has an established role for optimal fluid management and recognition of cardiac disease including SARS-CoV-2 associated acute cardiomyopathy. Cardiologists, anesthesiologists, sonographers, and all providers should be prepared to commit their full spectrum of skills to mitigate the consequences of the pandemic. We should also be prepared to collaborate and cross-train to expand professional services as necessary. During a declared health care crisis, providers must be familiar with the ethical principles, organizational structure, practical application, and gravity of limited resource allocation.


title: Detection and Phylogenetic Analysis of Porcine Deltacoronavirus in Korean Swine Farms, 2015

text: This study applied molecular‐based method to investigate the presence of porcine deltacoronavirus (PDCoV) in 59 commercial pig farms in South Korea. The results of RT‐PCR screening on a relatively large collection of faeces samples (n = 681) from January 2013 to March 2015 did not reveal the presence of PDCoV until the end of 2014. However, on March 2015, PDCoV‐positive samples (SL2, SL5) were detected from SL swine farm in Gyeongbuk province. The phylogenetic trees based on the complete spike‐ and nucleocapsid protein‐coding genes showed that SL2 and SL5 closely related to the US PDCoV strains rather than those in China. Thought Korean strains of PDCoV isolated in 2014 (KNU14.04) and in 2015 (SL2 and SL5) grouped within US PDCoV cluster, the reconstruction of ancestral amino acid changes suggested that they are different.


The Third Annual Meeting of the European Virus Bioinformatics Center (EVBC) took place in Glasgow, United Kingdom, 28–29 March 2019. Virus bioinformatics has become central to virology research, and advances in bioinformatics have led to improved approaches to investigate viral infections and outbreaks, being successfully used to detect, control, and treat infections of humans and animals. This active field of research has attracted approximately 110 experts in virology and bioinformatics/computational biology from Europe and other parts of the world to attend the two-day meeting in Glasgow to increase scientific exchange between laboratory- and computer-based researchers. The meeting was held at the McIntyre Building of the University of Glasgow; a perfect location, as it was originally built to be a place for “rubbing your brains with those of other people”, as Rector Stanley Baldwin described it. The goal of the meeting was to provide a meaningful and interactive scientific environment to promote discussion and collaboration and to inspire and suggest new research directions and questions. The meeting featured eight invited and twelve contributed talks, on the four main topics: (1) systems virology, (2) virus-host interactions and the virome, (3) virus classification and evolution and (4) epidemiology, surveillance and evolution. Further, the meeting featured 34 oral poster presentations, all of which focused on specific areas of virus bioinformatics. This report summarizes the main research findings and highlights presented at the meeting.