title: Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products

text: ABSTRACT: Most recently, an outbreak of severe pneumonia caused by the infection of SARS-CoV-2, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Therefore, the role and inhibition of nsp12 are indispensable. A cryo-EM structure of RdRp from SARs-CoV-2 was used to identify novel drugs from Northern South African medicinal compounds database (NANPDB) by using computational virtual screening and molecular docking approaches. Considering Remdesivir as the control, 42 compounds were shortlisted to have docking score better than Remdesivir. The top 5 hits were validated by using molecular dynamics simulation approach and free energy calculations possess strong inhibitory properties than the Remdesivir. Thus, this study paved a way for designing novel drugs by decoding the architecture of an important enzyme and its inhibition with compounds from natural resources. This disclosing of necessary knowledge regarding the screening and the identification of top hits could help to design effective therapeutic candidates against the coronaviruses and design robust preventive measurements. GRAPHIC ABSTRACT: [Image: see text]


title: The impact of alternative donor types on viral infections in pediatric hematopoietic stem cell transplantation

text: Viral infections remain one of the most important complications following allogeneic HSCT. Few reports compare virus infection between different donor types in pediatric patients. We retrospectively analyzed viral infections and the outcome of one hundred and seventy‐one pediatric patients (median 7.38 years) who underwent allogeneic HSCT from matched related donor (MRD, n = 71), 10 of 10 HLA allele‐matched unrelated donors (MUD1; n = 29), 9 of 10 HLA allele‐matched unrelated donors (MUD2; n = 40), and haploidentical donors (n = 31). PCR screening for BK virus, adenovirus, Epstein‐Barr virus, parvovirus B19, human herpesvirus 6, and CMV were performed routinely weekly. Infections between 0‐30, 31‐100, and 101 days‐2 years were identified separately. BK virus and CMV reactivations were significantly low in MRD transplant patients (P = .046 and P < .0001, respectively), but incidences of all virus infections between MUD1, MUD2, and haplo‐HSCT were found statistically not different. The OS was found to be affected by having one or multiple virus infection (P = .04 and P = .0008). Despite antiviral prophylaxis and treatments, post‐transplant viral infections are associated with reduced overall survival. Haplo‐HSCT is comparable with MUD transplantation in the setting of viral infections. A larger study group and prospective studies are needed to confirm this observation.


title: Surveillance operation for the 141st confirmed case of Middle East Respiratory Syndrome coronavirus in response to the patient’s prior travel to Jeju Island

text: The provincial government of Jeju, South Korea, was notified that a 42-year-old man infected with the Middle East Respiratory Syndrome (MERS) coronavirus had gone sightseeing in Jeju Island. Although the visiting period might be interpreted as the incubation period of MERS, the province decided to conduct active surveillance to prevent a worst-case scenario. Based on the channel of movement of the patient, healthy isolation and active monitoring were conducted for persons who came in contact with the patient. During the active surveillance, none of the 56 persons in self-isolation and 123 persons under active monitoring became infected. This fact supports that MERS is not contagious during the incubation period.


title: Genetic characterization of human bocavirus among children with severe acute respiratory infection in China

text: Summary Objectives To investigate the genetic character of Human bocavirus (HBoV) among children with severe acute respiratory infection (SARI) in China. Methods We screened 993 respiratory samples for HBoV by PCR among hospitalized children with SARI between September 2007 and March 2014. Four of HBoV1 samples were selected for complete genomes analysis by next-generation sequencing. Results The results show that 200 (20.1%) out of 993 samples were HBoV-positive, most of these HBoV belong to HBoV1 subtype (n = 197), HBoV2 (n = 1) and HBoV3 (n = 2) were also detected. Fifty (5.04%) of 993 SARI patient were detected as HBoV-positive only. Four HBoV1 genomes in this study were conserved and showed no significant difference among the nucleotide diversity from different regions. Analyses of evolutionary rates showed that NS1 exhibited the highest degree of conservation while the VP1 gene exhibited the fastest rate of evolution at 4.20 × 10−4 substitutions/site/year. The nucleotide deletions and substitutions occurred in NP1 and VP1 represented novel molecular signatures enabling subtype differentiation between HBoVs. Conclusions We described some new characteristics in the epidemiology of HBoV among children with SARI, these data will significantly expand the current knowledge of HBoV epidemic and genomic characterization among children with SARI.


title: The Rational Design of Therapeutic Peptides for Aminopeptidase N using a Substrate-Based Approach

text: The M1 family of metalloproteases represents a large number of exopeptidases that cleave single amino acid residues from the N-terminus of peptide substrates. One member of this family that has been well studied is aminopeptidase N (APN), a multifunctional protease known to cleave biologically active peptides and aide in coronavirus entry. The proteolytic activity of APN promotes cancer angiogenesis and metastasis making it an important target for cancer therapy. To understand the substrate specificity of APN for the development of targeted inhibitors, we used a global substrate profiling method to determine the P1–P4′ amino acid preferences. The key structural features of the APN pharmacophore required for substrate recognition were elucidated by x-ray crystallography. By combining these substrate profiling and structural data, we were able to design a selective peptide inhibitor of APN that was an effective therapeutic both in vitro and in vivo against APN-expressing prostate cancer models.


title: Trypsin Isoinhibitors with Antiproliferative Activity toward Leukemia Cells from Phaseolus vulgaris cv “White Cloud Bean”

text: A purification protocol that comprised ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-Sepharose, and gel filtration by FPLC on Superdex 75 was complied to isolate two trypsin inhibitors from Phaseolus vulgaris cv “White Cloud Bean”. Both trypsin inhibitors exhibited a molecular mass of 16 kDa and reduced the activity of trypsin with an IC(50) value of about 0.6 μM. Dithiothreitol attenuated the trypsin inhibitory activity, signifying that an intact disulfide bond is indispensable to the activity. [Methyl-(3)H] thymidine incorporation by leukemia L1210 cells was inhibited with an IC(50) value of 28.8 μM and 21.5 μM, respectively. They were lacking in activity toward lymphoma MBL2 cells and inhibitory effect on HIV-1 reverse transcriptase and fungal growth when tested up to 100 μM.


title: Immunotherapy of Bacillus Calmette-Guérin by targeting macrophages against bladder cancer in a NOD/scid (IL2Rg-/−) mouse model

text: Bacillus Calmette-Guérin (BCG) is considered to be a successful biotherapy for treating bladder cancer (BCa). However, the underlying mechanisms of BCG have not been completely clarified, to date. The role of macrophages in BCG therapy for BCa has still not been determined in vivo. In the present study, the role and potential mechanism of BCG (0.25, 1.25 and 6.25 µg/mouse; intravenous) immunotherapy for BCa was investigated in a NOD/scid (IL2Rg−/−) (NSI) mouse model by targeting macrophages in vivo. Notably, it was observed that NSI mice with T24 BCa cells displayed high levels of the macrophage marker CD11b(+) F4/80(+) after injection via the tail vein of live BCG, as well as a significant reduction in tumor volume. The levels of the inflammatory and macrophage maturation cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-12P70, TNF superfamily member 11 and monocyte chemotactic protein 1, were significantly increased in the serum and the tumor supernatant compared to that in normal control subjects. Furthermore, BCG promoted the expression of the pro-differential genes Spi-1 proto-oncogene, early growth response protein 1, nuclear factor (NF)-κB and proto-oncogene c-Fos in bone marrow. In conclusion, these observations indicate that the injection of live BCG can target macrophages against bladder tumor growth in vivo. The mechanism is likely related to the promotion of macrophage maturation, immune activation and increased numbers of macrophages infiltrating the bladder tumor.


Return to sports after COVID-19 infection: Do we have to worry about myocarditis?


title: Optical Fiber Sensors for Rapid Screening of COVID-19

text: Rapid diagnosis of coronavirus disease COVID-19 is challenging in developing countries due to diverse clinical presentations and limited healthcare infrastructure. Biosensors hold immense prospects for diagnosis of the disease. Two approaches are proposed: the first involves measurement of host immune response and second, the detection of viruses or viral cell surface proteins using suitable bioreceptors. The article provides an overview of evanescent wave absorbance and localized surface plasmon resonance-based optic fiber platform for potential screening of COVID-19.


title: At-home self-collection of saliva, oropharyngeal swabs and dried blood spots for SARS-CoV-2 diagnosis and serology: post-collection acceptability of specimen collection process and patient confidence in specimens

text: BACKGROUND: Options to increase the ease of testing for SARS-CoV-2 infection and immune response are needed. Self-collection of diagnostic specimens at home offers an avenue to allow people to test for SARS-CoV-2 infection or immune response without traveling to a clinic or laboratory. Before this study, survey respondents indicated willingness to self-collect specimens for COVID-related tests, but hypothetical willingness can differ from post-collection acceptability after participants collect specimens. METHODS: 153 US adults were enrolled in a study of the willingness and feasibility of patients to self-collect three diagnostic specimens (saliva, oropharyngeal swab (OPS) and dried blood spot (DBS) card) while observed by a clinician through a telehealth session. After the specimens were collected, 148 participants participated in a survey about the acceptability of the collection, packing and shipping process, and their confidence in the samples collected for COVID-related laboratory testing. RESULTS: A large majority of participants (>84%) reported that collecting, packing and shipping of saliva, OPS, and DBS specimens were acceptable. Nearly nine in 10 (87%) reported being confident or very confident that the specimens they collected were sufficient for laboratory analysis. There were no differences in acceptability for any specimen type, packing and shipping, or confidence in samples by gender, age, race/ethnicity, or educational level. CONCLUSIONS: Self-collection of specimens for SARS-CoV-2 testing and preparing and shipping specimens for analysis were acceptable in a diverse group of US adults. Further refinement of materials and instructions to support self-collection of saliva, OPS and DBS specimens for COVID-related testing is needed. TRIAL REGISTRATION: No intervention was tested in this study


title: Spatial epidemiology of networked metapopulation: an overview

text: An emerging disease is one infectious epidemic caused by a newly transmissible pathogen, which has either appeared for the first time or already existed in human populations, having the capacity to increase rapidly in incidence as well as geographic range. Adapting to human immune system, emerging diseases may trigger large-scale pandemic spreading, such as the transnational spreading of SARS, the global outbreak of A(H1N1), and the recent potential invasion of avian influenza A(H7N9). To study the dynamics mediating the transmission of emerging diseases, spatial epidemiology of networked metapopulation provides a valuable modeling framework, which takes spatially distributed factors into consideration. This review elaborates the latest progresses on the spatial metapopulation dynamics, discusses empirical and theoretical findings that verify the validity of networked metapopulations, and the sketches application in evaluating the effectiveness of disease intervention strategies as well.


title: Bilan kinésithérapique de Mr P., patient âgé fragile de 93 ans présentant un Syndrome de Détresse Respiratoire Aiguë suite à une infection au COVID-19

text: Résumé Mr P. est un patient âgé de 93 ans hospitalisé suite à une infection à Covid 19. La démarche évaluative de ce patient a été réalisée grâce à un bilan multisystémique spécifique Covid et à une évaluation systémique des fonctions motrices. Celle-ci a permis de conclure à un tableau clinique mixte associant une dysfonction respiratoire majeure en lien avec le syndrome de détresse respiratoire aiguë et une fragilité motrice associée. Ce diagnostic soulève donc l’importance d’une évaluation à visée holistique pour cibler le profil des patients Covid et les dysfonctions associées afin d’orienter et déterminer les axes de la prise en soin rééducative pluridisciplinaire. Abstract Mr. P. is a 93-year-old patient hospitalized with a Covid 19 infection. The evaluation of this patient was carried out by means of a specific multisystemic Covid assessment and a systemic evaluation of motor functions. This led to the conclusion of a mixed clinical picture associating major respiratory dysfunction in connection with acute respiratory distress syndrome and associated motor fragility. This diagnosis therefore raises the importance of a holistic assessment to target the profile of Covid patients and associated dysfunctions in order to orient and determine the axes of multidisciplinary rehabilitative care.


Public space during COVID‐19


title: Integrating one health in national health policies of developing countries: India’s lost opportunities

text: BACKGROUND: Globally, the threat of infectious diseases, particularly emerging infectious diseases, originating at the human-animal-environment interface, has caught health systems off guard. With forecasts that future pathogen emergence will be centred in hotspots in Asia, Africa, and Latin America, the need to prepare policy frameworks that can combat this threat is urgent. DISCUSSION: Emergence of diseases such as avian influenza and Ebola virus disease, which threatened social disruption, have established the need for intersectoral coordination/collaboration. These events led to the initiation of establishing institutionalised collaborative frameworks in India to adopt a One Health approach to disease prevention and control. However, the gains made in influenza control could not be adapted to other infectious diseases. Intersectoral coordination was briefly carried out, more as a reactive response to threats. The systemic failure to sustain such efforts have therefore, only undermined a coordinated response. The recent draft National Health Policy, 2015, has also failed to establish the need for intersectoral coordination in disease control approaches. Neglecting the need to endorse linkages between human health, animal health and husbandry, agriculture, and environmental sectors, has led to duplicative and weak response systems. The absence of health impact assessment with respect to the development agenda in policies, has cast negative effects on the health and wellbeing of man, animal, and the environment. Lack of attention to building core capacity in these critical sectors has further raised challenges in designing and deploying mitigation strategies. With developing countries like India being home to a major portion of the world’s poorest livestock farmers, the absence of a policy discourse that endorses the One Health approach in development and health policies is a major hurdle in eliminating poverty and poverty-related diseases. CONCLUSIONS: The adoption of One Health approaches in health and related sectoral policies is a critical policy requirement for India and other developing countries. The goal should be to not just establish preparedness plans, but also to encourage a policy environment where assessment and mitigation of downstream impacts of different agenda are incorporated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0181-2) contains supplementary material, which is available to authorized users.


Covid‐19 Impacts


title: Respiratory Testing and Hospital Outcomes in Asymptomatic Infants Undergoing Heart Surgery

text: Respiratory viral infections in infants undergoing congenital heart surgery lead to prolonged intubation time, hospital (HLOS) and cardiac intensive care unit length of stay (CICU LOS). The objective of this study was to evaluate the prevalence of respiratory viruses using molecular testing in otherwise healthy infants presenting for low complexity heart surgery, and to evaluate the impact of a positive viral screen and study questionnaire on post-surgical HLOS, CICU LOS, intubation time, respiratory complications, and oxygen therapy at home discharge. Sixty-nine infants (1 month to 1 year) undergoing cardiac surgery from November to May of the years 2012 to 2014 were prospectively enrolled, surveyed and tested. We compared the outcomes of positive molecular testing and positive study questionnaire to test negative subjects. We also evaluated the predictive value of study questionnaire in identification of viruses by molecular testing. Of the 69 enrolled infants, 58 had complete information available for analysis. 17 (30%) infants tested positive by molecular testing for respiratory pathogens. 38 (65%) had a “positive” questionnaire. Among the 20 viruses detected, Human Rhinovirus was the most common 12 (60%). Seven (12%) of the 58 patients developed respiratory symptoms following surgery prompting molecular testing. Four of these tested positive for a respiratory virus post-surgically. Neither positive molecular testing nor a positive questionnaire prior to surgery was associated with greater post-operative HLOS, CICU LOS, intubation time, respiratory complications, or use of oxygen at discharge compared to negative testing. The questionnaire poorly predicted positive molecular testing. Routine screening for respiratory viruses in asymptomatic infants may not be an effective strategy to predict infants at risk of post-operative complications.


title: A Guide to the Short, Long and Circular RNAs in Hypertension and Cardiovascular Disease

text: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in adults in developed countries. CVD encompasses many diseased states, including hypertension, coronary artery disease and atherosclerosis. Studies in animal models and human studies have elucidated the contribution of many genetic factors, including non-coding RNAs. Non-coding RNAs are RNAs not translated into protein, involved in gene expression regulation post-transcriptionally and implicated in CVD. Of these, circular RNAs (circRNAs) and microRNAs are relevant. CircRNAs are created by the back-splicing of pre-messenger RNA and have been underexplored as contributors to CVD. These circRNAs may also act as biomarkers of human disease, as they can be extracted from whole blood, plasma, saliva and seminal fluid. CircRNAs have recently been implicated in various disease processes, including hypertension and other cardiovascular disease. This review article will explore the promising and emerging roles of circRNAs as potential biomarkers and therapeutic targets in CVD, in particular hypertension.


title: The most common pediatric and adult dermatology patient complaints in a month of the COVID‐19 Pandemic in turkey

text: Severe acute respiratory syndrome coronavirus 2 is the coronavirus strain that causes coronavirus disease 2019 (COVID‐19). The World Health Organization has designated the ongoing COVID‐19 outbreak a Public Health Emergency of International Concern. WHO declared COVID‐19 as a pandemic on March 11, 2020. During the pandemic and lockdown period, many dermatological clinics were temporarily closed in Turkey as well as all over the world. Taking the necessary precautions, the hospital continued to examine all emergent and elective patients who applied to our dermatology clinic. We investigated the most common reasons for admission of pediatric and adult patients who were admitted to our outpatient clinic between 30 March and 30 April 2020, the period with the highest number of COVID‐19 patients in Turkey. In children and adult age groups, the most common reason for admission was acne ([N: 10, 16.4%] and [N: 89, 20.9%], respectively). Of the 99 acne patients, 70 (70.7%) were using systemic isotretinoin and applied to our clinic to repeat the prescription or continue the agent. The number of pediatric patients admitted to the dermatology department drastically reduced during the lockdown period, which was attributed to the curfew for children in the country. This article is protected by copyright. All rights reserved.


title: A Comparison of Two Methods for Retrieving ICD-9-CM data: The Effect of Using an Ontology-based Method for Handling Terminology Changes

text: OBJECTIVE: Most existing controlled terminologies can be characterized as collections of terms, wherein the terms are arranged in a simple list or organized in a hierarchy. These kinds of terminologies are considered useful for standardizing terms and encoding data and are currently used in many existing information systems. However, they suffer from a number of limitations that make data reuse difficult. Relatively recently, it has been proposed that formal ontological methods can be applied to some of the problems of terminological design. Biomedical ontologies organize concepts (embodiments of knowledge about biomedical reality) whereas terminologies organize terms (what is used to code patient data at a certain point in time, based on the particular terminology version). However, the application of these methods to existing terminologies is not straightforward. The use of these terminologies is firmly entrenched in many systems, and what might seem to be a simple option of replacing these terminologies is not possible. Moreover, these terminologies evolve over time in order to suit the needs of users. Any methodology must therefore take these constraints into consideration, hence the need for formal methods of managing changes. Along these lines, we have developed a formal representation of the concept-term relation, around which we have also developed a methodology for management of terminology changes. The objective of this study was to determine whether our methodology would result in improved retrieval of data. DESIGN: Comparison of two methods for retrieving data encoded with terms from the International Classification of Diseases (ICD-9-CM), based on their recall when retrieving data for ICD-9-CM terms whose codes had changed but which had retained their original meaning (code change). MEASUREMENTS: Recall and interclass correlation coefficient. RESULTS: Statistically significant differences were detected (p<0.05) with the McNemar test for two terms whose codes had changed. Furthermore, when all the cases are combined in an overall category, our method also performs statistically significantly better (p < 0.05). CONCLUSION: Our study shows that an ontology-based ICD-9-CM data retrieval method that takes into account the effects of terminology changes performs better on recall than one that does not in the retrieval of data for terms whose codes had changed but which retained their original meaning.


title: Proposed Changes to the 2021 Residency Application Process in the Wake of COVID-19

text: The COVID-19 pandemic has brought unique challenges to the delivery of undergraduate medical education, particularly for current third-year medical students who are preparing to apply to residency. In mid-March, medical schools suspended all clinical rotations for the remainder of the 2019–2020 academic year. As such, third-year medical students may not be able to complete sufficient clinical experiences to make important career choices before they have to submit their residency applications. While the decision to suspend clinical rotations was necessary to protect students, specialty organizations and residency programs must mitigate the deficits in students’ clinical education caused by the COVID-19 pandemic. In this Perspective, the authors identify potential challenges for third-year medical students and advocate for solutions to improve the residency application process for students and programs. First, they propose delaying the date that programs can access applicant data through the Electronic Residency Application Service, thereby affording students more time to complete clinical experiences, solidify their specialty decision, and strengthen their residency application. Second, the authors recommend a restriction on the number of visiting rotations that students are expected to complete to allow for a more equitable distribution of these important experiences. Third, they suggest that program directors from each specialty agree on a maximum number of applications per applicant (based on historical data) to curb an upsurge in applications that may stem from the unique circumstances created by COVID-19 without causing applicants undue stress. Lastly, the authors advocate that residency programs develop infrastructure to conduct video-based interviews and engage students through virtual networking events. Amidst the unique environment created by COVID-19, the authors urge governing bodies, specialty organizations, and residency programs to consider these recommendations to improve the efficiency and reduce the stress surrounding the 2021 Match.


title: Lack of compliance with basic infection control measures during cardiopulmonary resuscitation—Are we ready for another epidemic?

text: Summary Objective Healthcare workers in the emergency department are particularly vulnerable to communicable disease. This study aimed to evaluate compliance with standard precautions by analysis of the incidence and systems sources of such contaminations and by quantifying the use of personal protective equipment. Method A prospective observational study from 1 November 2005 to 30 April 2006, using analysis of video segments. Videotapes were recorded in two rooms designed for cardiopulmonary resuscitation of out-of-hospital cardiac arrests, and compliance with basic infection control measures by all emergency department crews was monitored. Results A total of 44 consecutive performances of cardiopulmonary resuscitation were recorded for time-motion analysis. The percentages of staff wearing personal protective equipment were 90%, 50%, 20% and 75% for masks, eye protection, gowns and gloves, respectively. Compliance ranking scored doctors as high, trainees as moderate and nursing staff as low. Overall contamination rate was 16.9×10−2 events/person-min. The two leading systems sources for contamination were lack of specific task assignments among rescuers (44%) and inadequate preparation for procedures (42%). Conclusions Among healthcare workers in the emergency setting, the study disclosed suboptimal compliance with basic infection control measures, including use of personal protective equipment and avoiding contamination. By further time-motion analysis of resuscitation sessions, major systems sources and strategies for improvement could be identified.


title: RNAi and Cellular miRNAs in Infections by Mammalian Viruses

text: MicroRNAs (miRNAs) play an essential role in the regulation of eukaryotic gene expression. Recent studies demonstrate that miRNAs can also strongly affect the replication of pathogenic viruses. For example, cellular miRNAs can target and repress the expression of viral mRNAs, but there is also at least one example of a cellular miRNA that stimulates virus replication. Furthermore, viruses can encode their own miRNAs, trigger changes in cellular miRNA expression or encode RNA silencing suppressor factors that inhibit cellular miRNAs. These interactions together form a complex regulatory network that controls both viral and host gene expression, which ultimately determines the outcome of viral infection at the cellular level and disease progression in the host. Here, we summarize the literature data on such virus–cell interactions in mammals and discuss how miRNAs can be used as research tools or targets in the development of novel antiviral therapeutics.


title: Earth Day at 50

text: Coronavirus will overshadow Earth Day's golden anniversary, but the movement's successes are worth celebrating, says Gary Paul Nabhan


title: Fruit bats as a natural reservoir of zoonotic viruses

text: As a natural reservoir of manifold zoonotic viruses, fruit bats have been involved in at least three emerging zoonoses in recent years. This paper aims to introduce the epidemiological characteristics of these diseases emerged in the Australasian region between 1994 and 1999, transmission pathways of the newly discovered viruses and the relationship between the changed entironment of fruit bats and occurrences of these emerging diseases and provide a clue for the epidemiological investigations of SARS.


title: Regional Association of Disability and SARS-CoV-2 Infection in 369 Counties of the United States

text: BACKGROUND: There have been outbreaks of SARS-CoV-2 in long term care facilities and recent reports of disproportionate death rates among the vulnerable population. The goal of this study was to better understand the impact of SARS-CoV-2 infection on the non-institutionalized disabled population in the United States using data from the most affected states as of April 9th, 2020. METHODS: This was an ecological study of county-level factors associated with the infection and mortality rate of SARS-CoV-2 in the non-institutionalized disabled population. We analyzed data from 369 counties from the most affected states (Michigan, New York, New Jersey, Pennsylvania, California, Louisiana, Massachusetts) in the United States using data available by April 9th, 2020. The variables include changes in mobility reported by Google, race/ethnicity, median income, education level, health insurance, and disability information from the United States Census Bureau. Bivariate regression analysis adjusted for state and median income was used to analyze the association between death rate and infection rate. RESULTS: The independent sample t-test of two groups (group 1: Death rate≥ 3.4% [median] and group 2: Death rate < 3.4%) indicates that counties with a higher total population, a lower percentage of Black males and females, higher median income, higher education, and lower percentage of disabled population have a lower rate (< 3.4%) of SARS-CoV-2 related mortality (all p-values<4.3E-02). The results of the bivariate regression when controlled for median income and state show counties with a higher White disabled population (est: 0.19, 95% CI: 0.01–0.37; p-value:3.7E-02), and higher population with independent living difficulty (est: 0.15, 95% CI: −0.01–0.30; p-value: 6.0E-02) have a higher rate of SARS-CoV-2 related mortality. Also, the regression analysis indicates that counties with higher White disabled population (est: −0.22, 95% CI: −0.43−(−0.02); p-value: 3.3E-02), higher population with hearing disability (est: −0.26, 95% CI: −0.42–(−0.11); p-value:1.2E-03), and higher population with disability in the 18–34 years age group (est: −0.25, 95% CI: −0.41–(−0.09); p-value:2.4E-03) show a lower rate of SARS-CoV-2 infection. CONCLUSION: Our results indicate that while counties with a higher percentage of non-institutionalized disabled population, especially White disabled population, show a lower infection rate, they have a higher rate of SARS-CoV-2 related mortality.


title: Emerging and Reemerging Diseases in the World Health Organization (WHO) Eastern Mediterranean Region—Progress, Challenges, and WHO Initiatives

text: The Eastern Mediterranean Region (EMR) of the World Health Organization (WHO) continues to be a hotspot for emerging and reemerging infectious diseases and the need to prevent, detect, and respond to any infectious diseases that pose a threat to global health security remains a priority. Many risk factors contribute in the emergence and rapid spread of epidemic diseases in the Region including acute and protracted humanitarian emergencies, resulting in fragile health systems, increased population mobility, rapid urbanization, climate change, weak surveillance and limited laboratory diagnostic capacity, and increased human–animal interaction. In EMR, several infectious disease outbreaks were detected, investigated, and rapidly contained over the past 5 years including: yellow fever in Sudan, Middle East respiratory syndrome in Bahrain, Oman, Qatar, Saudi Arabia, United Arab Emirates, and Yemen, cholera in Iraq, avian influenza A (H5N1) infection in Egypt, and dengue fever in Yemen, Sudan, and Pakistan. Dengue fever remains an important public health concern, with at least eight countries in the region being endemic for the disease. The emergence of MERS-CoV in the region in 2012 and its continued transmission currently poses one of the greatest threats. In response to the growing frequency, duration, and scale of disease outbreaks, WHO has worked closely with member states in the areas of improving public health preparedness, surveillance systems, outbreak response, and addressing critical knowledge gaps. A Regional network for experts and technical institutions has been established to facilitate support for international outbreak response. Major challenges are faced as a result of protracted humanitarian crises in the region. Funding gaps, lack of integrated approaches, weak surveillance systems, and absence of comprehensive response plans are other areas of concern. Accelerated efforts are needed by Regional countries, with the continuous support of WHO, to build and maintain a resilient public health system for detection and response to all acute public health events.


title: Strategies for prevention of coronavirus disease 2019 in the dental field

text: The coronavirus disease 2019 (COVID-19) pandemic, which began in Wuhan, China in December 2019, has become a huge public health issue in China and worldwide, spanning across Asia, including South Korea, Europe, North America, South America, and Oceania (Phelan, Katz, & Gostin, 2020). The fatality rate is 0.2 deaths per 100,000 persons per week globally. On March 11, 2020, the World Health Organization declared COVID-19 outbreak a pandemic of international concern.


title: NTPase and 5′-RNA Triphosphatase Activities of Chikungunya Virus nsP2 Protein

text: Chikungunya virus (CHIKV) is an insect borne virus (genus: Alphavirus) which causes acute febrile illness in humans followed by a prolonged arthralgic disease that affects the joints of the extremities. Re-emergence of the virus in the form of outbreaks in last 6–7 years has posed a serious public health problem. CHIKV has a positive sense single stranded RNA genome of about 12,000 nt. Open reading frame 1 of the viral genome encodes a polyprotein precursor, nsP1234, which is processed further into different non structural proteins (nsP1, nsP2, nsP3 and nsP4). Sequence based analyses have shown helicase domain at the N-terminus and protease domain at C-terminus of nsP2. A detailed biochemical analysis of NTPase/RNA helicase and 5′-RNA phosphatase activities of recombinant CHIKV-nsP2T protein (containing conserved NTPase/helicase motifs in the N-terminus and partial papain like protease domain at the C-terminus) was carried out. The protein could hydrolyze all NTPs except dTTP and showed better efficiency for ATP, dATP, GTP and dGTP hydrolysis. ATP was the most preferred substrate by the enzyme. CHIKV-nsP2T also showed 5′-triphosphatase (RTPase) activity that specifically removes the γ-phosphate from the 5′ end of RNA. Both NTPase and RTPase activities of the protein were completely dependent on Mg(2+) ions. RTPase activity was inhibited by ATP showing sharing of the binding motif by NTP and RNA. Both enzymatic activities were drastically reduced by mutations in the NTP binding motif (GKT) and co-factor, Mg(2+) ion binding motif (DEXX) suggesting that they have a common catalytic site.


Episcleritis as an ocular manifestation in a patient with COVID‐19


title: Chapter 12 A Prescription for the Next Health Care Crisis

text: Abstract This chapter begins by examining the steps that have been taken since the epidemic to safeguard the blood supply. Although these have diminished the risk of disease transmission, there are additional steps that could be taken to prevent another blood-borne viral epidemic. A new Office of Blood Product Safety (OBPS) might be established within the Food and Drug Administration (FDA) to communicate information on the safety and availability of blood and blood products to the public and health care professionals. Furthermore, the costs of collection, processing, and distribution of blood for transfusion should be borne by the public, not individual patients. Another recommendation is to establish an Office for the Control of Pharmaceutical Prices (COPP) within the Department of Health and Human Services to set caps on the prices of blood products, essential drugs, and medical devices. If a pharmaceutical required for human health becomes unavailable, then this Office could authorize subsidies for its production. The chapter concludes by urging greater investment in basic and applied research to identify the causes of disease, develop diagnostic tests and therapeutic materials, and produce vaccines that might prevent future outbreaks of blood-borne diseases.


title: Neural precursor cells derived from induced pluripotent stem cells exhibit reduced susceptibility to infection with a neurotropic coronavirus

text: Abstract The present study examines the susceptibility of mouse induced pluripotent stem cell-derived neural precursor cells (iPSC-NPCs) to infection with the neurotropic JHM strain of mouse hepatitis virus (JHMV). Similar to NPCs derived from striatum of day 1 postnatal GFP-transgenic mice (GFP-NPCs), iPSC-derived NPCs (iPSC-NPCs) are able to differentiate into terminal neural cell types and express MHC class I and II in response to IFN-γ treatment. However, in contrast to postnatally-derived NPCs, iPSC-NPCs express low levels of carcinoembryonic antigen-cell adhesion molecule 1a (CEACAM1a), the surface receptor for JHMV, and are less susceptible to infection and virus-induced cytopathic effects. The relevance of this in terms of therapeutic application of NPCs resistant to viral infection is discussed.


title: COVID‐19 crossing paths with AIDS in the homeless

text: The coronavirus disease of 2019 (COVID-19) pandemic has created new challenges and magnified existing ones for immunocompromised individuals who may be at risk for worse clinical outcomes. Severe COVID-19 has been associated with a hyperimmune response characterized by a surge in cytokine release defined as a cytokine release syndrome (CRS) (1). Among immunocompromised patients, the inability to mount an immune response may be protective against a poor outcome. This article is protected by copyright. All rights reserved.


title: Highlighting the Role of Veterinary Pharmacists in Zoonotic Diseases Including COVID-19

text: SUMMARY Veterinary pharmacy is an often unknown and therefore, underrepresented career path for pharmacists. Uniquely, pharmacists—even untrained in veterinary medicine—are the only healthcare professional legally allowed to provide care for human and non-human patients 1. The 2019 coronavirus (COVID-19) pandemic is a peculiar situation that, not only highlights veterinary pharmacy as a career path, but stresses the role veterinary pharmacists, trained in both human and veterinary medicine, can play in zoonotic diseases. Specialized training in veterinary medicine allows the pharmacist to serve as a resource for both physicians as well as veterinarians during zoonotic events by helping to ascertain feasibility of therapeutic options given the species. Additionally, veterinary pharmacists involved in translational research would be vital for the drug development process as they would be aware of biologic nuances between the species and how they may affect the ultimate therapeutic outcome 2.


title: xMAP Technology: Applications in Detection of Pathogens

text: xMAP technology is applicable for high-throughput, multiplex and simultaneous detection of different analytes within a single complex sample. xMAP multiplex assays are currently available in various nucleic acid and immunoassay formats, enabling simultaneous detection and typing of pathogenic viruses, bacteria, parasites and fungi and also antigen or antibody interception. As an open architecture platform, the xMAP technology is beneficial to end users and therefore it is used in various pharmaceutical, clinical and research laboratories. The main aim of this review is to summarize the latest findings and applications in the field of pathogen detection using microsphere-based multiplex assays.


title: In silico pharmacology for drug discovery: applications to targets and beyond

text: Computational (in silico) methods have been developed and widely applied to pharmacology hypothesis development and testing. These in silico methods include databases, quantitative structure-activity relationships, similarity searching, pharmacophores, homology models and other molecular modeling, machine learning, data mining, network analysis tools and data analysis tools that use a computer. Such methods have seen frequent use in the discovery and optimization of novel molecules with affinity to a target, the clarification of absorption, distribution, metabolism, excretion and toxicity properties as well as physicochemical characterization. The first part of this review discussed the methods that have been used for virtual ligand and target-based screening and profiling to predict biological activity. The aim of this second part of the review is to illustrate some of the varied applications of in silico methods for pharmacology in terms of the targets addressed. We will also discuss some of the advantages and disadvantages of in silico methods with respect to in vitro and in vivo methods for pharmacology research. Our conclusion is that the in silico pharmacology paradigm is ongoing and presents a rich array of opportunities that will assist in expediating the discovery of new targets, and ultimately lead to compounds with predicted biological activity for these novel targets.


title: Assistance of DFT calculations on the design and rationalization of active pharmaceutical ingredients synthesis – Michael addition-isomerization steps in Oseltamivir synthesis

text: The Michael addition step and the following C5 isomerization in Hayashi's synthesis of Oseltamivir was studied by means of a DFT mechanistic study. These steps are crucial for the viability of the process where the formation of a single stereoisomer is required. The results indicate that the addition reaction is under thermodynamic and not kinetic control and that the key factor determining the reaction stereoselectivity are the stereochemical constraints imposed by all substituents in the cyclohexane ring. The DFT results indicate that cyclohexylthiol should behave similarly to p-toluylthiol, the one actually employed, and tert-butylthiol should increase the ratio between isomers favoring the desired S configuration of the C5 atom. This work shows that DFT studies can be useful in the selection of a reactant to improve stereoselectivity of a chemical step.


title: Chapter 24 Clinical Management of Captive Cheetahs

text: Abstract Clinical management of captive cheetahs (Acinonyx jubatus) plays a key role in maintaining a healthy ex situ breeding population, and aids in the conservation of cheetahs in the wild. Cheetahs are prone to noninfectious disorders, as well as multiple infectious diseases that can lead to increased morbidity and decreased reproductive success. Proper management in a captive setting consists of a well-designed cheetah facilities adapted for the institution’s housing and animal movement needs. Breeding facilities should be designed to hold a large number of cheetahs and to provide the best care possible for both the adults and cubs. A thorough cheetah preventative health program should be in place. Breeding facilities should also be prepared for the potential of hand-rearing cubs.


title: Performance of a rapid multi-analyte 2-photon excitation assay in children with acute respiratory infection

text: Abstract The purpose of this study is to evaluate the diagnostic performance of the novel 2-photon excitation-based mariPOC© Assay (ArcDia Laboratories, Turku, Finland) for antigen detection of respiratory viruses versus real-time polymerase chain reaction (PCR). The mariPOC Assay and 2 multiplex real-time PCR techniques were performed on nasopharyngeal samples from pediatric patients with suspicion of acute respiratory infection admitted to a children's hospital in Spain during October 2011 to January 2013. A total of 233 samples were studied. Sensitivities and specificities (95% confidence interval) of the mariPOC Assay were for respiratory syncytial virus (RSV), 78.4% (69.7–85.6) and 99.2% (96.3–100.0); influenza virus (IFV) A, 66.7% (26.2–94.0) and 99.6% (97.9–100.0); IFV-B, 63.6% (33.6–87.2) and 100.0% (98.7–100.0); human metapneumovirus (hMPV), 60.0% (34.5–81.9) and 100.0% (98.6–100.0); adenovirus (ADV), 12.5% (0.6–48.0) and 100.0% (98.7–100.0), respectively. The mariPOC Assay is a highly specific method for simultaneous detection of 8 respiratory viruses but has sensitivities that range from moderately high for RSV to moderate for IFV and hMPV and low for ADV.


title: Activated macrophages are the main inflammatory cell in COVID-19 interstitial pneumonia infiltrates. Is it possible to show their metabolic activity and thus the grade of inflammatory burden with (18)F-Fluorocholine PET/CT?

text: The recent outbreak of Covid-19 has represented a major challenge for the countries affected by the disease, not only in terms of loss of human life, economic downturn, and constraint on individual freedom, but also for the great pressure on the national health systems and hospitals. The 380 kDa virus has been a perfect storm, especially for those national health systems used to working with limited resources and high intensity rhythms, such as Italy. For the first time in the new century, a virtually unknown fast-spreading disease has caused a public health emergency thus forcing most countries to deal with an insurmountable logistic gap. Hence, every branch of Medicine, even though not directly involved in the treatment, has been called upon to provide its contribution to resolve the crisis. It is now becoming more apparent that Covid-19 is not solely a lung disease, but a complex systemic disease involving several organs and systems. This is due to an abnormal inflammatory response which eventually leads to multisystemic coagulopathy which mainly, but not uniquely, targets the lungs. Although the pathophysiology of this syndrome is still not fully understood, macrophages and their immune complex system seem to play a key role. It is not yet clear why some patients develop the violent immune response which results in pneumonitis while others do not. There are clues indicating that the systemic hyper-inflammation defined as macrophage activation syndrome (MAS), or cytokine storm, requires an increase in choline consumption to synthesize phosphatidylcholine and stimulate phagocytosis, organelle biogenesis, secretory functions, and endocytosis. (18)F-Fluorocholine is a synthetic analog of the naturally occurring choline normally used for PET/CT imaging of prostate cancer patients. (18)F-Fluorocholine could image and quantify the macrophage activity in pulmonary interstitial infiltrates of Covid-19 pneumonia. If the hypothesis is confirmed experimentally, (18)F-Fluorocholine PET/CT could be used to in vivo image and quantify the degree of lung inflammation and potentially stratify the gravity of this disease.


title: Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26

text: The newly emergent Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe pulmonary disease in humans(1,2), representing the second example of a highly pathogenic coronavirus, the first being SARS-CoV(3). CD26 (also known as dipeptidyl peptidase 4, DPP4) was recently identified as the cellular receptor for MERS-CoV(4). The engagement of the MERS-CoV spike protein with CD26 mediates viral attachment to host cells and virus–cell fusion, thereby initiating infection. Here we delineate the molecular basis of this specific interaction by presenting the first crystal structures of both the free receptor binding domain (RBD) of the MERS-CoV spike protein and its complex with CD26. Furthermore, binding between the RBD and CD26 is measured using real-time surface plasmon resonance with a dissociation constant of 16.7 nM. The viral RBD is composed of a core subdomain homologous to that of the SARS-CoV spike protein, and a unique strand-dominated external receptor binding motif that recognizes blades IV and V of the CD26 β-propeller. The atomic details at the interface between the two binding entities reveal a surprising protein–protein contact mediated mainly by hydrophilic residues. Sequence alignment indicates, among betacoronaviruses, a possible structural conservation for the region homologous to the MERS-CoV RBD core, but a high variation in the external receptor binding motif region for virus-specific pathogenesis such as receptor recognition. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature12328) contains supplementary material, which is available to authorized users.


title: Employee norm-violations in the service encounter during the corona pandemic and their impact on customer satisfaction

text: Abstract In this study, an experiment was used to examine the effects of employee norm-violations in the service encounter with respect to what was considered appropriate behavior (e.g., social distancing) during the 2020 corona pandemic. The participants were exposed to a grocery store employee whose behavior was manipulated (norm-violating vs. norm-confirming). Norm-violating behavior resulted in lower perceived employee warmth, lower perceived employee competence, higher disgust, and more dehumanization of the employee. These responses mediated the impact of employee behavior on customer satisfaction, so that satisfaction was attenuated when norms were violated. The mediators, however, typically also instill a hostile, avoidance-seeking mindset for those who are subject to norm-violations, which is likely to result in problems when transgressors are to be persuaded to change their behaviors.


Decisiones de final de vida en tiempos de pandemia


title: The PDZ-Binding Motif of Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Is a Determinant of Viral Pathogenesis

text: A recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) lacking the envelope (E) protein is attenuated in vivo. Here we report that E protein PDZ-binding motif (PBM), a domain involved in protein-protein interactions, is a major determinant of virulence. Elimination of SARS-CoV E protein PBM by using reverse genetics caused a reduction in the deleterious exacerbation of the immune response triggered during infection with the parental virus and virus attenuation. Cellular protein syntenin was identified to bind the E protein PBM during SARS-CoV infection by using three complementary strategies, yeast two-hybrid, reciprocal coimmunoprecipitation and confocal microscopy assays. Syntenin redistributed from the nucleus to the cell cytoplasm during infection with viruses containing the E protein PBM, activating p38 MAPK and leading to the overexpression of inflammatory cytokines. Silencing of syntenin using siRNAs led to a decrease in p38 MAPK activation in SARS-CoV infected cells, further reinforcing their functional relationship. Active p38 MAPK was reduced in lungs of mice infected with SARS-CoVs lacking E protein PBM as compared with the parental virus, leading to a decreased expression of inflammatory cytokines and to virus attenuation. Interestingly, administration of a p38 MAPK inhibitor led to an increase in mice survival after infection with SARS-CoV, confirming the relevance of this pathway in SARS-CoV virulence. Therefore, the E protein PBM is a virulence domain that activates immunopathology most likely by using syntenin as a mediator of p38 MAPK induced inflammation.


title: How to Quantify and Interpret Treatment Effects in Comparative Clinical Studies of COVID-19

text: Clinical trials of treatments for coronavirus disease 2019 (COVID-19) draw intense public attention. More than ever, valid, transparent, and intuitive summaries of the treatment effects, including efficacy and harm, are needed. In recently published and ongoing randomized comparative trials evaluating treatments for COVID-19, time to a positive outcome, such as recovery or improvement, has repeatedly been used as either the primary or key secondary end point. Because patients may die before recovery or improvement, data analysis of this end point faces a competing risk problem. Commonly used survival analysis techniques, such as the Kaplan–Meier method, often are not appropriate for such situations. Moreover, almost all trials have quantified treatment effects by using the hazard ratio, which is difficult to interpret for a positive event, especially in the presence of competing risks. Using 2 recent trials evaluating treatments (remdesivir and convalescent plasma) for COVID-19 as examples, a valid, well-established yet underused procedure is presented for estimating the cumulative recovery or improvement rate curve across the study period. Furthermore, an intuitive and clinically interpretable summary of treatment efficacy based on this curve is also proposed. Clinical investigators are encouraged to consider applying these methods for quantifying treatment effects in future studies of COVID-19.


Letter to the Editor: Extracorporeal cardiopulmonary resuscitation should not be performed on confirmed or suspected COVID-19 patients


title: Healthcare workers' willingness to work during an influenza pandemic: a systematic review and meta-analysis

text: To estimate the proportion of healthcare workers (HCWs) willing to work during an influenza pandemic and identify associated risk factors, we undertook a systematic review and meta-analysis compliant with PRISMA guidance. Databases and grey literature were searched to April 2013, and records were screened against protocol eligibility criteria. Data extraction and risk of bias assessments were undertaken using a piloted form. Random-effects meta-analyses estimated (i) pooled proportion of HCWs willing to work and (ii) pooled odds ratios of risk factors associated with willingness to work. Heterogeneity was quantified using the I(2) statistic, and publication bias was assessed using funnel plots and Egger's test. Data were synthesized narratively where meta-analyses were not possible. Forty-three studies met our inclusion criteria. Meta-analysis of the proportion of HCWs willing to work was abandoned due to excessive heterogeneity (I(2) = 99·2%). Narrative synthesis showed study estimates ranged from 23·1% to 95·8% willingness to work, depending on context. Meta-analyses of specific factors showed that male HCWs, physicians and nurses, full-time employment, perceived personal safety, awareness of pandemic risk and clinical knowledge of influenza pandemics, role-specific knowledge, pandemic response training, and confidence in personal skills were statistically significantly associated with increased willingness. Childcare obligations were significantly associated with decreased willingness. HCWs' willingness to work during an influenza pandemic was moderately high, albeit highly variable. Numerous risk factors showed a statistically significant association with willingness to work despite significant heterogeneity between studies. None of the included studies were based on appropriate theoretical constructs of population behaviour.


title: Androgen Regulates SARS-CoV-2 Receptor Levels and Is Associated with Severe COVID-19 Symptoms in Men

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to a global health crisis, and yet our understanding of the disease pathophysiology and potential treatment options remains limited. SARS-CoV-2 infection occurs through binding and internalization of the viral spike protein to angiotensin converting enzyme 2 (ACE2) on the host cell membrane. Lethal complications are caused by damage and failure of vital organs that express high levels of ACE2, including the lungs, the heart and the kidneys. Here, we established a high-throughput drug screening strategy to identify therapeutic candidates that reduce ACE2 levels in human embryonic stem cell (hESC) derived cardiac cells. Drug target analysis of validated hit compounds, including 5 alpha reductase inhibitors, revealed androgen signaling as a key modulator of ACE2 levels. Treatment with the 5 alpha reductase inhibitor dutasteride reduced ACE2 levels and internalization of recombinant spike receptor binding domain (Spike-RBD) in hESC-derived cardiac cells and human alveolar epithelial cells. Finally, clinical data on coronavirus disease 2019 (COVID-19) patients demonstrated that abnormal androgen states are significantly associated with severe disease complications and cardiac injury as measured by blood troponin T levels. These findings provide important insights on the mechanism of increased disease susceptibility in male COVID-19 patients and identify androgen receptor inhibition as a potential therapeutic strategy.


title: Scientific Collaborations: How Do We Measure the Return on Relationships?

text: Emerging infectious diseases (EIDs), the majority of which are zoonotic, represent a tremendous challenge for public health and biosurveillance infrastructure across the globe. Due to the complexity of zoonotic pathogens, it is essential that research and response to EIDs be a transdisciplinary effort. And while crisis and circumstance may be the initial catalyst for responding to an outbreak, we provide examples of how transdisciplinary scientific collectives, which are organized and solidified in advance of crises, can transform the way the world responds to outbreaks and in some cases could even prevent one from occurring (1). Current methods for assessing whether a cooperative engagement between countries is producing measurable and sustainable value is based on the ideas of return on investment and do not consider the inherent importance of relationships. In this article, we apply the idea of return on relationships (ROR) and propose a method for measuring ROR, using a system dynamics modeling framework commonly used in epidemiology. Tracking the numerous and diverse scientific collaborations that emerged from a training workshop for biosurveillance of bats held in Singapore in 2014, we apply a methodology for visualizing and measuring the relationship networks and outcomes that result. Additionally, the collaborative, multidisciplinary network that coalesced in response to the Hantavirus outbreak in New Mexico is 1993 is discussed as an example of the long-term benefits of ROR.


title: Neurological manifestations and implications of COVID-19 pandemic

text: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China and rapidly spread worldwide, with a vast majority of confirmed cases presenting with respiratory symptoms. Potential neurological manifestations and their pathophysiological mechanisms have not been thoroughly established. In this narrative review, we sought to present the neurological manifestations associated with coronavirus disease 2019 (COVID-19). Case reports, case series, editorials, reviews, case-control and cohort studies were evaluated, and relevant information was abstracted. Various reports of neurological manifestations of previous coronavirus epidemics provide a roadmap regarding potential neurological complications of COVID-19, due to many shared characteristics between these viruses and SARS-CoV-2. Studies from the current pandemic are accumulating and report COVID-19 patients presenting with dizziness, headache, myalgias, hypogeusia and hyposmia, but also with more serious manifestations including polyneuropathy, myositis, cerebrovascular diseases, encephalitis and encephalopathy. However, discrimination between causal relationship and incidental comorbidity is often difficult. Severe COVID-19 shares common risk factors with cerebrovascular diseases, and it is currently unclear whether the infection per se represents an independent stroke risk factor. Regardless of any direct or indirect neurological manifestations, the COVID-19 pandemic has a huge impact on the management of neurological patients, whether infected or not. In particular, the majority of stroke services worldwide have been negatively influenced in terms of care delivery and fear to access healthcare services. The effect on healthcare quality in the field of other neurological diseases is additionally evaluated.


Italy and COVID‐19: Winning the war, losing the peace?


title: WU Polyomavirus in Children with Acute Lower Respiratory Tract Infections, South Korea

text: In South Korea, WU polyomavirus (WUPyV) was detected in 34 (7%) of 486 children with acute lower respiratory tract infections, 3 (4.2%) of 72 asymptomatic children, and as coinfection with other respiratory viruses in 23 (67.6%) children. Although WUPyV was frequently detected, its clinical role has not been distinguished from that of coinfecting viruses.


COVID-19 or Lung Cancer: A differential diagnostic experience and management model from Wuhan


Initial data from the COVID-19 Global Rheumatology Alliance provider registries – Authors' reply


title: Annexin A2 as a target endothelial cell membrane autoantigen in Behçet's disease

text: Cell membrane proteins are believed to play a critical role in the pathogenesis of autoimmune diseases. However, few membrane autoantigens have been linked with Behçet's disease. Here, a cell-chip was performed to identify autoantibody target cells, and the suspected autoantigens were detected using immunoblotting. The amino acid sequences of the detected proteins were determined using LC-MALDI-TOF/TOF. Putative proteins were recombinantly expressed and purified, and a corresponding ELISA was developed and clinically validated using real clinical samples. It was found that a 36-kDa membrane protein - annexin A2 - was detected in approximately one-third of the patients' blood circulation. The immunohistochemistry results showed that annexin A2 was highly expressed in vascular endothelial cells. Moreover, vascular involvement was significantly higher in the anti-annexin A2 antibody-positive group versus the anti-annexin A2 antibody-negative group among all the clinical samples analyzed, indicating that annexin A2 is a novel endothelial cell membrane antigen involved in Behçet's disease.


An open market valuation of the effects of COVID-19 on the travel and tourism industry


title: Early institutional head and neck oncologic and microvascular surgery practice patterns across the United States during the SARS‐CoV‐2 (COVID19) pandemic

text: BACKGROUND: The SARS‐CoV‐2 (COVID‐19) pandemic has caused rapid changes in head and neck cancer (HNC) care. “Real‐time” methods to monitor practice patterns can optimize provider safety and patient care. METHODS: Head and neck surgeons from 14 institutions in the United States regularly contributed their practice patterns to a shared spreadsheet. Data from 27 March 2020 to 5 April 2020 was analyzed. RESULTS: All institutions had significantly restricted HNC clinic evaluations. Two institutions stopped free‐flap surgery with the remaining scheduling surgery by committee review. Factors contributing to reduced clinical volume included lack of personal protective equipment (PPE) (35%) and lack of rapid COVID‐19 testing (86%). CONCLUSIONS: The COVID‐19 pandemic has caused a reduction in HNC care. Rapid COVID‐19 testing and correlation with infectious potential remain paramount to resuming the care of patients with head and neck cancer. Cloud‐based platforms to share practice patterns will be essential as the pandemic evolves.


title: A Guide to COVID‐19: a global pandemic caused by the novel coronavirus SARS‐CoV‐2

text: The emergence of the SARS‐CoV‐2 strain of the human coronavirus has thrown the world into the midst of a new pandemic. In the human body, the virus causes COVID‐19, a disease characterized by shortness of breath, fever, and pneumonia, which can be fatal in vulnerable individuals. SARS‐CoV‐2 has characteristics of past human coronaviruses, with close genomic similarities to SARS‐CoV, the virus that causes the disease SARS. Like these related coronaviruses, SARS‐CoV‐2 is transmitted through the inhalation of droplets and interaction with contaminated surfaces. Across the world, laboratories are developing candidate vaccines for the virus – with vaccine trials underway in the US and the United Kingdom ‐ and considering various drugs for possible treatments and prophylaxis. Here, we provide an overview of SARS‐CoV‐2 by analyzing its virology, epidemiology, and modes of transmission while examining the current progress of testing procedures and possible treatments through drugs and vaccines.


title: Two Randomized Controlled Trials of Bacillus Calmette-Guérin Vaccination to reduce absenteeism among health care workers and hospital admission by elderly persons during the COVID-19 pandemic: A structured summary of the study protocols for two randomised controlled trials

text: OBJECTIVES: The objectives of these two separate trials are: (1) to reduce health care workers (HCWs) absenteeism; and (2) to reduce hospital admission among the elderly during the COVID-19 pandemic through BCG vaccination. TRIAL DESIGN: Two separate multi-centre placebo-controlled parallel group randomized trials PARTICIPANTS: (1) Health care personnel working in the hospital or ambulance service where they will take care of patients with the COVID-19 infection and (2) elderly ≥60 years. The HCW trial is being undertaken in 9 hospitals. The elderly trial is being undertaken in locations in the community in Nijmegen, Utrecht, and Veghel, in the Netherlands, using senior citizen organisations to facilitate recruitment. INTERVENTION AND COMPARATOR: For both trials the intervention group will be randomized to vaccination with 0.1 ml of the licensed BCG vaccine (Danish strain 1331, SSI, Denmark, equivalent to 0.075 mg attenuated M. bovis). The placebo group consists of 0.1 ml 0.9% NaCl, which is the same amount, and has the same colour and appearance as the suspended BCG vaccine. MAIN OUTCOMES: (1) Number of days of unplanned work absenteeism in HCWs for any reason which can be continuously measured on a bi-weekly basis, and (2) the cumulative incidence of hospital admission due to documented COVID-19. RANDOMISATION: Participants will be randomized to BCG vaccine or placebo (1;1) centrally using a computer- based system, stratified by study centre. BLINDING (MASKING): Subjects, investigators, physicians and outcome assessors are blinded for the intervention. Only the pharmacist assistant that prepares- and research personnel that administers- study medicines are unblinded. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): (1) The sample size for the first trial is N=1500 HCWs randomised 1:1 to either BCG vaccine (n=750) and placebo (n=750) and (2) The sample size for the second trial is N=1600 elderly persons randomised to BCG vaccine (n=800) and the placebo group (n=800). TRIAL STATUS: HCW: version 4.0, 24-04-2020. Recruitment began 25-03-2020 and was completed on the 23-04-2020. Elderly: version 3.0, 04-04-2020. Recruitment began 16-04- 2020 and is ongoing. TRIAL REGISTRATION: The HCWs trial was registered 31-03-2020 at clinicaltrials.gov (identifier: NCT04328441) and registered 20-03-2020 at the Dutch Trial Registry (trialregister.nl, identifier Trial NL8477). The elderly trial was registered 22-04-2020 at the Dutch trial registry with number NL8547. FULL PROTOCOL: The full protocols will be attached as additional files, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


title: What incentives increase data sharing in health and medical research? A systematic review

text: BACKGROUND: The foundation of health and medical research is data. Data sharing facilitates the progress of research and strengthens science. Data sharing in research is widely discussed in the literature; however, there are seemingly no evidence-based incentives that promote data sharing. METHODS: A systematic review (registration: 10.17605/OSF.IO/6PZ5E) of the health and medical research literature was used to uncover any evidence-based incentives, with pre- and post-empirical data that examined data sharing rates. We were also interested in quantifying and classifying the number of opinion pieces on the importance of incentives, the number observational studies that analysed data sharing rates and practices, and strategies aimed at increasing data sharing rates. RESULTS: Only one incentive (using open data badges) has been tested in health and medical research that examined data sharing rates. The number of opinion pieces (n = 85) out-weighed the number of article-testing strategies (n = 76), and the number of observational studies exceeded them both (n = 106). CONCLUSIONS: Given that data is the foundation of evidence-based health and medical research, it is paradoxical that there is only one evidence-based incentive to promote data sharing. More well-designed studies are needed in order to increase the currently low rates of data sharing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s41073-017-0028-9) contains supplementary material, which is available to authorized users.


title: Ceramide Accumulation Uncovers a Cycling Pathway for the cis-Golgi Network Marker, Infectious Bronchitis Virus M Protein

text: The M glycoprotein from the avian coronavirus, infectious bronchitis virus (IBV), contains information for localization to the cis-Golgi network in its first transmembrane domain. We hypothesize that localization to the Golgi complex may depend in part on specific interactions between protein transmembrane domains and membrane lipids. Because the site of sphingolipid synthesis overlaps the localization of IBV M, we asked whether perturbation of sphingolipids affected localization of IBV M. Short-term treatment with two inhibitors of sphingolipid synthesis had no effect on localization of IBV M or other Golgi markers. Thus, ongoing synthesis of these lipids was not required for proper localization. Surprisingly, a third inhibitor, d,l-threo-1-phenyl-2-decanoylamino-3-morpholino- 1-propanol (PDMP), shifted the steady-state distribution of IBV M from the Golgi complex to the ER. This effect was rapid and reversible and was also observed for ERGIC-53 but not for Golgi stack proteins. At the concentration of PDMP used, conversion of ceramide into both glucosylceramide and sphingomyelin was inhibited. Pretreatment with upstream inhibitors partially reversed the effects of PDMP, suggesting that ceramide accumulation mediates the PDMP-induced alterations. Indeed, an increase in cellular ceramide was measured in PDMP-treated cells. We propose that IBV M is at least in part localized by retrieval mechanisms. Further, ceramide accumulation reveals this cycle by upsetting the balance of anterograde and retrograde traffic and/ or disrupting retention by altering bilayer dynamics.


Anormal pulmonary function and residual CT abnormalities in rehabilitating COVID-19 patients after discharge: a prospective cohort study


title: A Fusion-Inhibiting Peptide against Rift Valley Fever Virus Inhibits Multiple, Diverse Viruses

text: For enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. This fusion process is mediated by at least three classes of fusion proteins (Class I, II, and III) based on the protein sequence and structure. For Rift Valley fever virus (RVFV), the glycoprotein Gc (Class II fusion protein) mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. Here, we show that peptides analogous to the RVFV Gc stem region inhibited RVFV infectivity in cell culture by inhibiting the fusion process. Further, we show that infectivity can be inhibited for diverse, unrelated RNA viruses that have Class I (Ebola virus), Class II (Andes virus), or Class III (vesicular stomatitis virus) fusion proteins using this single peptide. Our findings are consistent with an inhibition mechanism similar to that proposed for stem peptide fusion inhibitors of dengue virus in which the RVFV inhibitory peptide first binds to both the virion and cell membranes, allowing it to traffic with the virus into the endocytic pathway. Upon acidification and rearrangement of Gc, the peptide is then able to specifically bind to Gc and prevent fusion of the viral and endocytic membranes, thus inhibiting viral infection. These results could provide novel insights into conserved features among the three classes of viral fusion proteins and offer direction for the future development of broadly active fusion inhibitors.


title: Viral Respiratory Tract Infections in Transplant Patients: Epidemiology, Recognition and Management

text: Viral respiratory tract infections (RTIs) are common causes of mild illness in immunocompetent children and adults, with occasional significant morbidity or mortality in the very young, very old or infirm. However, recipients of solid organ transplants (SOT) or haematopoietic stem cell transplants (HSCT) are at markedly increased risk for significant morbidity or mortality from these infections. The infections are generally acquired by transmission of large respiratory droplets and can be nosocomial in origin with many documented outbreaks on specialised transplant units. Typically, the infections begin as upper RTIs, with cough or rhinorrhoea predominating. Many will resolve at this stage, but more immunocompromised patients, typically closer in time to their SOT or HSCT, may develop progressive infection to lower RTI or pneumonia. The most common RTI pathogens are influenza viruses, parainfluenza viruses and respiratory syncytial viruses. Newer polymerase chain reaction-based diagnostic strategies are more sensitive than previous assays, and allow rapid and accurate diagnoses of these infections. These newer assays may also detect emerging pathogens of significance, one of which is human metapneumovirus. While diagnostic techniques have advanced significantly in the past decade, well established and effective specific treatments for these infections remain elusive. The epidemiology, clinical presentation, diagnosis and treatment of the common viral RTIs in SOT or HSCT recipients are reviewed, and recommendations presented based on a thorough review of recent literature.


title: Antiviral Activity of Glycyrrhizin against Hepatitis C Virus In Vitro

text: Glycyrrhizin (GL) has been used in Japan to treat patients with chronic viral hepatitis, as an anti-inflammatory drug to reduce serum alanine aminotransferase levels. GL is also known to exhibit various biological activities, including anti-viral effects, but the anti-hepatitis C virus (HCV) effect of GL remains to be clarified. In this study, we demonstrated that GL treatment of HCV-infected Huh7 cells caused a reduction of infectious HCV production using cell culture-produced HCV (HCVcc). To determine the target step in the HCV lifecycle of GL, we used HCV pseudoparticles (HCVpp), replicon, and HCVcc systems. Significant suppressions of viral entry and replication steps were not observed. Interestingly, extracellular infectivity was decreased, and intracellular infectivity was increased. By immunofluorescence and electron microscopic analysis of GL treated cells, HCV core antigens and electron-dense particles had accumulated on endoplasmic reticulum attached to lipid droplet (LD), respectively, which is thought to act as platforms for HCV assembly. Furthermore, the amount of HCV core antigen in LD fraction increased. Taken together, these results suggest that GL inhibits release of infectious HCV particles. GL is known to have an inhibitory effect on phospholipase A2 (PLA2). We found that group 1B PLA2 (PLA2G1B) inhibitor also decreased HCV release, suggesting that suppression of virus release by GL treatment may be due to its inhibitory effect on PLA2G1B. Finally, we demonstrated that combination treatment with GL augmented IFN-induced reduction of virus in the HCVcc system. GL is identified as a novel anti-HCV agent that targets infectious virus particle release.


title: Evaluation on the efficacy and immunogenicity of recombinant DNA plasmids expressing S gene from porcine epidemic diarrhea virus and VP7 gene from porcine rotavirus

text: Porcine rotavirus (PoRV) and porcine epidemic diarrhea virus (PEDV) usually co-infect pigs in modern large-scale piggery, which both can cause severe diarrhea in newborn piglets and lead to significant economic losses to the pig industry. The VP7 protein is the main coat protein of PoRV, and the S protein is the main structural protein of PEDV, which are capable of inducing neutralizing antibodies in vivo. In this study, a DNA vaccine pPI-2.EGFP.VP7.S co-expressing VP7 protein of PoRV and S protein of PEDV was constructed. Six 8-week-old mice were immunized with the recombinant plasmid pPI-2.EGFP.VP7.S. The high humoral immune responses (virus specific antibody) and cellular immune responses (IFN-γ, IL-4, and spleen lymphocyte proliferation) were evaluated. The immune effect through intramuscular injection increased with plasmid dose when compared with subcutaneous injection. The immune-enhancing effect of IFN-α adjuvant was excellent compared with pig spleen transfer factor and IL-12 adjuvant. These results demonstrated that pPI-2.EGFP.VP7.S possess the immunological functions of the VP7 proteins of PoRV and S proteins of PEDV, indicating that pPI-2.EGFP.VP7.S is a candidate vaccine for porcine rotaviral infection (PoR) and porcine epidemic diarrhea (PED).


title: Sorafenib induces autophagy and suppresses activation of human macrophage

text: Abstract Background Sorafenib, a multi-kinase inhibitor approved for treatment of advanced renal cell carcinoma and other malignancies, has been shown as a modulator for dendritic cells. This study was designed to examine the effects of sorafenib on macrophages, the major ontogeny of innate immunity. Materials and methods Macrophages were derived from sorted CD14+ monocytes of human peripheral blood mononuclear cells. Cell viability and surface antigens were examined by trypan blue analysis. Autophagy was characterized by light microscopy and transmission electron microscopy for morphology, Western blotting for microtubule associated light chain protein 3B (LC-3B) I lipidation, and acridine orange staining for acidic component vacuoles. Soluble factors contained in culture medium and serum were measured by ELISA. Results We found that sorafenib inhibited the viability of macrophages accompanied by morphological changes characteristic of autophagy. This autophagy-inducing effect was validated by LC3B-I lipidation and autophagosome accumulation. The surface antigen expression and the function of activated macrophages were inhibited by sorafenib, including the expression of co-stimulatory molecule CD80, phagocytosis, and the production of reactive oxygen species. The secretion of IL-10, but not IL-6, TNF-α nor TGF-β, was reduced by sorafenib. Conclusion Sorafenib, in addition to being a cancer targeted therapeutic agent, can induce autophagy and modulate the function of human macrophages.


title: Molecular Diagnosis of Pneumonia Using Multiplex Real-Time PCR Assay RespiFinder® SMART 22 FAST in a Group of Moroccan Infants

text: BACKGROUND: In Morocco, pediatric pneumonia remains a serious public health problem, as it constitutes the first cause of mortality due to infectious diseases. The etiological diagnosis of acute respiratory tract infections is difficult. Therefore, it is necessary to use Multiplex real-time polymerase chain reaction assay tests in a routine setting for exact and fast identification. OBJECTIVES: In this paper, we present the clinical results of pediatric pneumonia and describe their etiology by using molecular diagnosis. Study design: Tracheal secretion was collected from infants presenting respiratory distress isolated or associated with systemic signs, attending the unit of Neonatology between December 1, 2016, and Mai 31, 2018. Samples were tested with the multiplex RespiFinder® SMART 22 FAST which potentially detects 18 viruses and 4 bacteria. RESULTS: Of the 86 infants considered in this study (mean age 31 ± 19 days) suspected of acute respiratory tract infections, 71 (83%) were positive for one or multiple viruses or/and bacteria. The majority of acute respiratory tract infections had a viral origin (95%): respiratory syncytial viruses (A and B) (49%), rhinovirus (21%), coronaviruses 229E (11%), humain metapneumovirus (5%), influenza A (3%), influenza H1N1 (1%), adenovirus (2%), and parainfluenza virus type 4 (2%). Among our patients, 6% had Mycoplasma pneumoniae. Coinfections were not associated with severe respiratory symptoms. CONCLUSION: The clinical spectrum of respiratory infections is complex and often nonspecific. Thus, the early and fast detection of related causative agents is crucial. The use of multiplex real time polymerase chain reaction may help choose an accurate treatment, reduce the overall use of unnecessary antibiotics, preserve intestinal flora, and decrease nosocomial infection by reducing the length of hospitalization.


title: Murine AKAP7 Has a 2′,5′-Phosphodiesterase Domain That Can Complement an Inactive Murine Coronavirus ns2 Gene

text: Viral 2′,5′-phosphodiesterases (2′,5′-PDEs) help disparate RNA viruses evade the antiviral activity of interferon (IFN) by degrading 2′,5′-oligoadenylate (2-5A) activators of RNase L. A kinase anchoring proteins (AKAPs) bind the regulatory subunits of protein kinase A (PKA) to localize and organize cyclic AMP (cAMP) signaling during diverse physiological processes. Among more than 43 AKAP isoforms, AKAP7 appears to be unique in its homology to viral 2′,5′-PDEs. Here we show that mouse AKAP7 rapidly degrades 2-5A with kinetics similar to that of murine coronavirus (mouse hepatitis virus [MHV]) strain A59 ns2 and human rotavirus strain WA VP3 proteins. To determine whether AKAP7 could substitute for a viral 2′,5′-PDE, we inserted AKAP7 cDNA into an MHV genome with an inactivated ns2 gene. The AKAP7 PDE domain or N-terminally truncated AKAP7 (both lacking a nuclear localization motif), but not full-length AKAP7 or a mutant, AKAP7(H185R), PDE domain restored the infectivity of ns2 mutant MHV in bone marrow macrophages and in livers of infected mice. Interestingly, the AKAP7 PDE domain and N-terminally deleted AKAP7 were present in the cytoplasm (the site of MHV replication), whereas full-length AKAP7 was observed only in nuclei. We suggest the possibility that viral acquisition of the host AKAP7 PDE domain might have occurred during evolution, allowing diverse RNA viruses to antagonize the RNase L pathway.


title: Appropriate Models for the Management of Infectious Diseases

text: BACKGROUND: Mathematical models have become invaluable management tools for epidemiologists, both shedding light on the mechanisms underlying observed dynamics as well as making quantitative predictions on the effectiveness of different control measures. Here, we explain how substantial biases are introduced by two important, yet largely ignored, assumptions at the core of the vast majority of such models. METHODS AND FINDINGS: First, we use analytical methods to show that (i) ignoring the latent period or (ii) making the common assumption of exponentially distributed latent and infectious periods (when including the latent period) always results in underestimating the basic reproductive ratio of an infection from outbreak data. We then proceed to illustrate these points by fitting epidemic models to data from an influenza outbreak. Finally, we document how such unrealistic a priori assumptions concerning model structure give rise to systematically overoptimistic predictions on the outcome of potential management options. CONCLUSION: This work aims to highlight that, when developing models for public health use, we need to pay careful attention to the intrinsic assumptions embedded within classical frameworks.


Are Nonhuman Primates Good Models for SARS?


title: Considerations for Setting up a Small-Animal Imaging Facility

text: Imaging techniques allow for the conduct of noninvasive, in vivo longitudinal small-animal studies, but also require access to expensive and complex equipment, and personnel who are properly trained in their use. The authors describe their planning and staffing of the NIH Mouse Imaging Facility, and highlight important issues to consider when designing a similar facility.


Crossing the species barrier


title: Is the effect of COVID‐19 on children underestimated in low‐ and middle‐ income countries?

text: The COVID‐19 pandemic has had a huge impact on health and society, worldwide. While most high income countries are felt to be reaching their COVID‐19 peak, most low‐ and middle‐income countries (LMICs), particularly sub‐Saharan countries, are anticipating an exponential growth of cases.(1) Overall it has been documented that children are less affected.(2) However, in this commentary we describe how in Kenya, a LMIC in sub‐Saharan Africa, COVID‐19 is likely to have far‐reaching direct and indirect implications on children.


title: The Serum Profile of Hypercytokinemia Factors Identified in H7N9-Infected Patients can Predict Fatal Outcomes

text: The novel avian origin influenza A (H7N9) virus has caused severe diseases in humans in eastern China since the spring of 2013. Fatal outcomes of H7N9 infections are often attributed to the severe pneumonia and acute respiratory distress syndrome (ARDS). There is urgent need to discover biomarkers predicting the progression of disease and fatal outcome of potentially lethal flu infections, based on sound statistical analysis. We discovered that 34 of the 48 cytokines and chemokines examined in this study were significantly elevated in the plasma samples from patients infected with H7N9. We report for the first time that the levels of MIF, SCF, MCP-1, HGF, and SCGF-β are highly positively linked to disease severity and the profile of mediators MIF, SCF, MCP-1, HGF, SCGF-β, IP-10, IL-18, and IFN-γ is an independent outcome predictor.


title: Proactive social distancing mitigates COVID-19 outbreaks within a month across 58 mainland China cities

text: In early 2020, cities across China enacted strict social distancing measures to contain emerging coronavirus (COVID-19) outbreaks. We estimated the speed with which these measures contained community transmission in each of 58 Chinese cities. On average, containment was achieved 7.83 days (SD 6.79 days) after the implementation of social distancing interventions, with an average reduction in the reproduction number (R(t)) of 54.3% (SD 17.6%) over that time period. A single day delay in the implementation of social distancing led to a 2.41 (95% CI: 0.97, 3.86) day delay in containment. Swift social distancing interventions may thus achieve rapid containment of newly emerging COVID-19 outbreaks.


title: Experiences of Patients With Rheumatic Diseases in the United States During Early Days of the COVID‐19 Pandemic

text: OBJECTIVE: Patients with rheumatic diseases such as rheumatoid arthritis (RA) and lupus have increased risk of infection and are treated with medications that may increase this risk yet are also hypothesized to help treat COVID‐19. We set out to understand how the COVID‐19 pandemic has impacted the lives of these patients in the United States. METHODS: Participants in a US‐wide longitudinal observational registry responded to a supplemental COVID‐19 questionnaire by e‐mail on March 25, 2020, about their symptoms, COVID‐19 testing, health care changes, and related experiences during the prior 2 weeks. Analysis compared responses by diagnosis, disease activity, and new onset of symptoms. Qualitative analysis was conducted on optional free‐text comment fields. RESULTS: Of the 7061 participants invited to participate, 530 responded, with RA as the most frequent diagnosis (61%). Eleven participants met COVID‐19 screening criteria, of whom two sought testing unsuccessfully. Six others sought testing, three of whom were successful, and all test results were negative. Not quite half of participants (42%) reported a change to their care in the prior 2 weeks. Qualitative analysis revealed four key themes: emotions in response to the pandemic, perceptions of risks from immunosuppressive medications, protective measures to reduce risk of COVID‐19 infection, and disruptions in accessing rheumatic disease medications, including hydroxychloroquine. CONCLUSION: After 2 weeks, many participants with rheumatic diseases already had important changes to their health care, with many altering medications without professional consultation or because of hydroxychloroquine shortage. As evidence accumulates on the effectiveness of potential COVID‐19 treatments, effort is needed to safeguard access to established treatments for rheumatic diseases.


title: Shifting Geographies of Knowledge Production: The Coronavirus Effect

text: This research note analyses the evolving geographies of coronavirus disease research before and during the first three months of the 2020 epidemic outbreak. An examination of global networks of scientific co‐production highlights the increasing centrality and knowledge intermediation profile of Chinese organisations. It is argued that it is important to understand these global geographies and networks, as they may signal varying (and cumulative) abilities to generate, intermediate, and access relevant knowledge in the face of epidemic outbreaks.


title: In vitro inhibition of CSFV replication by multiple siRNA expression

text: Abstract Classical swine fever (CSF) is a highly contagious viral disease of pigs which causes major economic losses worldwide. No specific drug is currently available for the effective treatment of CSFV infection; however, RNA interference (RNAi) has been applied successfully to inhibit the replication of human and other animal viruses. In this study, three effective siRNAs targeting NS3 of CSFV were selected. siNS3-2 targeting NS3 gene was chosen for further experimentation, while siN1 and siN2 targeting Npro gene, and siNS5B targeting NS5B gene describe previously. Single, double and quadruple anti-CSFV siRNA expression plasmids, with loxp sites at each end of the selectable marker genes, were constructed and analyzed using the same promoters or four different promoters, targeting Npro , NS3 and NS5B genes of CSFV. Results indicate that single or multiple siRNA expression plasmids can efficiently inhibit CSFV replication and that inhibition was markedly stronger when multiple siRNAs were expressed targeting different genes of CSFV. Since RNAi applied to anti-CSFV research, this study provides anti-CSFV methods by single and multiple siRNA expression which can target most viral isolates of different subtypes and prevent viral escape. It also provides a basis for development of CSFV-resistant transgenic pigs.


title: Facing the COVID-19 epidemic in NYC: a stochastic agent-based model of various intervention strategies

text: Global spread of coronavirus disease 2019 (COVID-19) has created an unprecedented infectious disease crisis worldwide. Despite uncertainties about COVID-19, model-based forecasting of competing mitigation measures on its course is urgently needed to inform mitigation policy. We used a stochastic agent-based microsimulation model of the COVID-19 epidemic in New York City and evaluated the potential impact of quarantine duration (from 4 to 16 weeks), quarantine lifting type (1-step lifting for all individuals versus a 2-step lifting according to age), post-quarantine screening, and use of a hypothetical effective treatment against COVID-19 on the disease's cumulative incidence and mortality, and on ICU-bed occupancy. The source code of the model has been deposited in a public source code repository. The model calibrated well and variation of model parameter values had little impact on outcome estimates. While quarantine is efficient to contain the viral spread, it is unlikely to prevent a rebound of the epidemic once lifted. We projected that lifting quarantine in a single step for the full population would be unlikely to substantially lower the cumulative mortality, regardless of quarantine duration. By contrast, a two-step quarantine lifting according to age was associated with a substantially lower cumulative mortality and incidence, up to 71% and 23%, respectively, as well as lower ICU-bed occupancy. Although post-quarantine screening was associated with diminished epidemic rebound, this strategy may not prevent ICUs from being overcrowded. It may even become deleterious after a 2-step quarantine lifting according to age if the herd immunity effect does not had sufficient time to become established in the younger population when the quarantine is lifted for the older population. An effective treatment against COVID-19 would considerably reduce the consequences of the epidemic, even more so if ICU capacity is not exceeded.


title: Dissemination of intestinal pathogens between lambs and puppies in sheep farms

text: Abstract Objectives of the present work were (i) to confirm pathogens implicated in cases of diarrhoea in newborn and young lambs in sheep farms in Greece and (ii) to investigate a possible relation in dissemination of pathogens between lambs and dogs present in the farm. Work was carried out in 22 sheep farms, with (i) flock size over 150 animals, (ii) presence of clinical signs of diarrhoea in lambs in the flock and (iii) close and continuous contact and movement of shepherd dogs within the animal shed of each farm. Faecal sample collection from lambs was performed within 48h of onset of clinical signs and prior to administration of any antimicrobial or antiparasitic medication to lambs. Faecal samples were also collected from puppies in the farm. In total, samples were collected from 126 lambs and 58 puppies. Samples were processed by using established techniques for isolation of bacteria, detection of viruses and observation of protozoan oocycts. Escherichia coli isolates obtained during the study, were tested for antimicrobial resistance against a variety of antimicrobial agents. In total, 236 bacterial isolates were recovered from faecal samples of lambs and 165 isolates from faecal samples of puppies. E. coli was the most frequently isolated microorganism: 104 isolates from lambs and 109 isolates from puppies were recovered. Other bacteria isolated were Enterobacter spp., Proteus spp., Klebsiella spp., (lambs and puppies), Clostridium perfringens, Citrobacter freundi, Salmonella enterica subsp. diarizonae (only lambs) and Streptococcus spp. (only puppies). Group A Rotavirus was detected in samples from lambs (2.5%) and Parvovirus in samples from puppies (5%). Cryptosporidium spp. oocysts were observed in samples from lambs and puppies. This is the first report of isolation of S. enterica subsp. diarizonae and of detection of Rotavirus from lambs in Greece. Rates of E. coli isolates from puppies resistant to antimicrobial agents were, in general, smaller than respective rates in isolates from lambs. Two pairs of isolates from the same farm (one from a lamb and one from a puppy) with identical patterns of resistance to antimicrobial agents were detected, which provides some evidence in support of a hypothesis that members of each pair might possibly have been spread from one animal species to the other.


title: Framing consumer food demand responses in a viral pandemic

text: In this paper, I explore several issues related to how the COVID‐19 pandemic might impact consumer demand for food. These impacts relate to the structure of preferences in the context of a pandemic, income and time constraints, and price effects. Discussion includes accounting for differential impacts of COVID‐19 on demand for food across sociodemographic characteristics, and several high‐level issues and observations related to where and how consumers shop and what they buy. My own thinking leads me to conclude that demand‐side factors will account for most of the changes we see in retail food market. These demand‐side effects will be dominated by income effects, the opportunity cost of time, and longer planning horizons on the part of consumers.