title: Risk of COVID-19 among frontline healthcare workers and the general community: a prospective cohort study

text: BACKGROUND: Data for frontline healthcare workers (HCWs) and risk of SARS-CoV-2 infection are limited and whether personal protective equipment (PPE) mitigates this risk is unknown. We evaluated risk for COVID-19 among frontline HCWs compared to the general community and the influence of PPE. METHODS: We performed a prospective cohort study of the general community, including frontline HCWs, who reported information through the COVID Symptom Study smartphone application beginning on March 24 (United Kingdom, U.K.) and March 29 (United States, U.S.) through April 23, 2020. We used Cox proportional hazards modeling to estimate multivariate-adjusted hazard ratios (aHRs) of a positive COVID-19 test. FINDINGS: Among 2,035,395 community individuals and 99,795 frontline HCWs, we documented 5,545 incident reports of a positive COVID-19 test over 34,435,272 person-days. Compared with the general community, frontline HCWs had an aHR of 11·6 (95% CI: 10·9 to 12·3) for reporting a positive test. The corresponding aHR was 3·40 (95% CI: 3·37 to 3·43) using an inverse probability weighted Cox model adjusting for the likelihood of receiving a test. A symptom-based classifier of predicted COVID-19 yielded similar risk estimates. Compared with HCWs reporting adequate PPE, the aHRs for reporting a positive test were 1·46 (95% CI: 1·21 to 1·76) for those reporting PPE reuse and 1·31 (95% CI: 1·10 to 1·56) for reporting inadequate PPE. Compared with HCWs reporting adequate PPE who did not care for COVID-19 patients, HCWs caring for patients with documented COVID-19 had aHRs for a positive test of 4·83 (95% CI: 3·99 to 5·85) if they had adequate PPE, 5·06 (95% CI: 3·90 to 6·57) for reused PPE, and 5·91 (95% CI: 4·53 to 7·71) for inadequate PPE. INTERPRETATION: Frontline HCWs had a significantly increased risk of COVID-19 infection, highest among HCWs who reused PPE or had inadequate access to PPE. However, adequate supplies of PPE did not completely mitigate high-risk exposures. FUNDING: Zoe Global Ltd., Wellcome Trust, EPSRC, NIHR, UK Research and Innovation, Alzheimer’s Society, NIH, NIOSH, Massachusetts Consortium on Pathogen Readiness


Letter to the Editor: From Katrina to COVID-19: Still Re-building New Orleans, One Nurse At A Time


title: Patients who challenge

text: Individuals have different values. They seek to express their individuality even when receiving medical care. It is a part of modern medical practice and respect for patient autonomy to show respect for different values. We give an account of what it means to respect different values and challenging patients in medical practice. Challenging choices are often choices which are perceived by many to be either irrational or against a person's interests, such as engaging in harmful or excessively risky activities. When the medical profession is involved in such choices, the basic medical principle of acting in a person's best interests is challenged. Often doctors refuse to respect controversial choices on paternalistic grounds. We should all respect and facilitate the controversial choices of competent individuals, subject to resource limitations, our own and others well-being and autonomy, and the public interest. But more importantly, sometimes such choices make for a better, more autonomous life. Sometimes, such choices reflect considerations of global well-being or altruism, or idiosyncratic attitudes to risk. Sometimes, they reflect unusual values. However, in some other cases, controversial choices are irrational and are not expressions of our autonomy. Doctors should assist patients to make rational if individual choices. The patient also bears the responsibility for bringing his beliefs to the attention of the clinician.


Mental health services in Italy during the Covid‐19 Pandemic


title: Is there really such a thing as “one health”? Thinking about a more than human world from the perspective of cultural anthropology

text: Today's era of globalization is characterized by intensified interspecies encounters, growing ecological concerns and the (re-)emergence of infectious diseases, manifesting themselves in the interplay of medical and biological, but also social, cultural and political processes. One health approaches – which combine multidisciplinary efforts to stimulate collaborations between different health professionals such as veterinarians, medical practitioners, biologists, and public health professionals – can be understood as a response to this complex interconnectedness. Integrating a social science perspective might prove beneficial to this endeavor. This essay locates the one health discussion on disease ecologies in a more than human world within recent developments in cultural and medical anthropology that focus on the entanglements between health and a multitude of animals, plants or microbes, as they are characteristic of a globalized modernity. The paper aims to examine the social dimensions of human–animal-disease-interactions, claiming that disease is a biocultural phenomenon and that social factors generally play a crucial role in the emergence, spread and management of (infectious) disease. Consequently, it will be argued that there is a need to rethink our objects of inquiry and any given assumptions of human health, the human body or the constitution of “the global” as such. Incorporating the social sciences into one health approaches can help address topics such as consumption patterns, human–animal behavior or environmental conflicts in a novel way and on a grander scale than ever before. Yet, a greater sensitivity to context may entail some skepticism about the idea of one health – not in spite of the complex entanglements between humans, environments, animals and pathogens, but precisely because of them.


title: Clinical Hepatozoon canis infection in a dog in Turkey

text: A five‐year‐old female dog was presented with a four‐week history of inappetence, weight loss, and skin and gait abnormalities. Physical examination revealed weakness, depression, incoordination of the posterior limbs, emaciation, skin and hair coat alterations, peripheral lymphadenopathy, pale mucous membranes and fever. Laboratory analysis of samples revealed abnormalities which included anaemia, neutrophilic leucocytosis, thrombocytopenia, low serum glucose and albumin concentrations, and increased serum alkaline phosphatase activity. The diagnosis was confirmed microscopically, by demonstrating the presence of Hepatozoon canis gametocytes within neutrophils in Giemsa‐stained peripheral blood smears. Treatment consisting of toltrazuril and a trimethoprim‐sulfamethoxazole combination was effective in relieving the clinical signs and clearing the blood of H canis gametocytes. To the authors’knowledge, this is the first detailed clinical description of H canis infection in a dog in Turkey.


title: Are infection control measures helpful in reducing paediatric ward infections?

text: As the majority of children on paediatric wards, especially in winter, have infections all paediatricians will be involved in infection control and prevention (ICP) without realising it. ICP measures include decisions on isolation of patients, which can be difficult with small numbers of cubicles. Children, who are highly infectious, have potential severe infections and those who are more at risk of developing severe infections (e.g. immunocompromised) should be isolated. Handwashing/decontamination is the central and most essential part of ICP measures. It should be actively encouraged and regularly monitored to ensure adherence. The ward layout will influence how we manage ICP. This includes placement and number of alcohol dispensers, sinks, bathrooms, equipment storage and the number of cubicles. It is also worth reviewing ward cleaning policies to assess whether these can be streamlined, potentially freeing up beds/cubicles earlier and leading to cost improvement without putting patients and staff at risk. We encourage all our staff to be fully vaccinated (including seasonal influenza vaccines and MMR). Paediatricians need to be closely involved in antibiotic stewardship and act as role models for all aspects of infection control, particularly proper handwashing.


title: Disaster and emergency management systems in urban areas

text: This article focuses on the factors shaping and constituting governance in urban/metropolitan emergency management. The main focus of the article is the multi-faceted inter-organizational relationships producing shared goals that are practiced at the local level, and specifically within the context of county-level metropolitan emergency management. The article presents a conceptual understanding of the governance concept, a brief summary of related research in the context of emergency management, and an example of the Orlando Metropolitan Area in the State of Florida for practical purposes.


title: Why are ethnic minorities worse affected?

text: Inequalities mean a disproportionate number of covid-19 patients are from minority ethnic backgrounds, reports Layal Liverpool


title: RNA delivery by extracellular vesicles in mammalian cells and its applications

text: The term ‘extracellular vesicles’ refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells, both in the direct vicinity of the source cell and at distant sites in the body via biofluids, and elicit a variety of phenotypic responses. Owing to their unique biology and roles in cell–cell communication, extracellular vesicles have attracted strong interest, which is further enhanced by their potential clinical utility. Because extracellular vesicles derive their cargo from the contents of the cells that produce them, they are attractive sources of biomarkers for a variety of diseases. Furthermore, studies demonstrating phenotypic effects of specific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular vesicles as therapeutic vehicles. There is particularly strong evidence that the RNA cargo of extracellular vesicles can alter recipient cell gene expression and function. During the past decade, extracellular vesicles and their RNA cargo have become better defined, but many aspects of extracellular vesicle biology remain to be elucidated. These include selective cargo loading resulting in substantial differences between the composition of extracellular vesicles and source cells; heterogeneity in extracellular vesicle size and composition; and undefined mechanisms for the uptake of extracellular vesicles into recipient cells and the fates of their cargo. Further progress in unravelling the basic mechanisms of extracellular vesicle biogenesis, transport, and cargo delivery and function is needed for successful clinical implementation. This Review focuses on the current state of knowledge pertaining to packaging, transport and function of RNAs in extracellular vesicles and outlines the progress made thus far towards their clinical applications.


COVID 19 Fear, Stress, Anxiety, and Substance Use Among Russian and Belarusian University Students


title: Inhibition of SARS Pseudovirus Cell Entry by Lactoferrin Binding to Heparan Sulfate Proteoglycans

text: It has been reported that lactoferrin (LF) participates in the host immune response against Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) invasion by enhancing NK cell activity and stimulating neutrophil aggregation and adhesion. We further investigated the role of LF in the entry of SARS pseudovirus into HEK293E/ACE2-Myc cells. Our results reveal that LF inhibits SARS pseudovirus infection in a dose-dependent manner. Further analysis suggested that LF was able to block the binding of spike protein to host cells at 4°C, indicating that LF exerted its inhibitory function at the viral attachment stage. However, LF did not disrupt the interaction of spike protein with angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV. Previous studies have shown that LF colocalizes with the widely distributed cell-surface heparan sulfate proteoglycans (HSPGs). Our experiments have also confirmed this conclusion. Treatment of the cells with heparinase or exogenous heparin prevented binding of spike protein to host cells and inhibited SARS pseudovirus infection, demonstrating that HSPGs provide the binding sites for SARS-CoV invasion at the early attachment phase. Taken together, our results suggest that, in addition to ACE2, HSPGs are essential cell-surface molecules involved in SARS-CoV cell entry. LF may play a protective role in host defense against SARS-CoV infection through binding to HSPGs and blocking the preliminary interaction between SARS-CoV and host cells. Our findings may provide further understanding of SARS-CoV pathogenesis and aid in treatment of this deadly disease.


title: Implications for lipids during replication of enveloped viruses

text: Abstract Enveloped viruses, which include many medically important viruses such as human immunodeficiency virus, influenza virus and hepatitis C virus, are intracellular parasites that acquire lipid envelopes from their host cells. Success of replication is intimately linked to their ability to hijack host cell mechanisms, particularly those related to membrane dynamics and lipid metabolism. Despite recent progress, our knowledge of lipid mediated virus–host interactions remains highly incomplete. In addition, diverse experimental systems are used to study different stages of virus replication thus complicating comparisons. This review aims to present a unifying view of the widely diverse strategies used by enveloped viruses at distinct stages of their replication cycles.


Peer-Based Education Regarding the COVID-19 Pandemic


title: Forecasting US recessions: The role of economic uncertainty()

text: This letter highlights the role of macroeconomic and financial uncertainty in predicting US recessions. In-sample forecasts using probit models indicate that the two variables are the best predictors of recessions at short horizons. Macroeconomic uncertainty has the highest predictive power up to 7 months ahead and becomes the second best predictor—after the yield curve slope—at longer horizons. Using data up to end-2018, out-of-sample forecasts show that uncertainty has significantly contributed to lower the probability of a recession in 2019, which indeed did not occur.


A Previously Unrecognized Unr Stem-Loop Structure in the Coronavirus 5’ Untranslated Region Plays a Functional role in Replication


title: Structure of a SARS coronavirus-derived peptide bound to the human major histocompatibility complex class I molecule HLA-B*1501

text: The human leukocyte antigen (HLA) class I system comprises a highly polymorphic set of molecules that specifically bind and present peptides to cytotoxic T cells. HLA-B*1501 is a prototypical member of the HLA-B62 supertype and only two peptide–HLA-B*1501 structures have been determined. Here, the crystal structure of HLA-B*1501 in complex with a SARS coronavirus-derived nonapeptide (VQQESSFVM) has been determined at high resolution (1.87 Å). The peptide is deeply anchored in the B and F pockets, but with the Glu4 residue pointing away from the floor in the peptide-binding groove, making it available for interactions with a potential T-cell receptor.


title: A Descriptive Study of Coronavirus Disease 2019–Related Experiences and Perspectives of a National Sample of College Students in Spring 2020

text: PURPOSE: This is one of the first surveys of a USA-wide sample of full-time college students about their coronavirus disease 2019 (COVID-19)–related experiences in spring 2020. METHODS: We surveyed 725 full-time college students aged 18–22 years recruited via Instagram promotions on April 25–30, 2020. We inquired about their COVID-19–related experiences and perspectives, documented opportunities for transmission, and assessed COVID-19's perceived impacts to date. RESULTS: Thirty-five percent of participants experienced any COVID-19–related symptoms from February to April 2020, but less than 5% of them got tested, and only 46% stayed home exclusively while experiencing symptoms. Almost all (95%) had sheltered in place/stayed primarily at home by late April 2020; 53% started sheltering in place before any state had an official stay-at-home order, and more than one-third started sheltering before any metropolitan area had an order. Participants were more stressed about COVID-19's health implications for their family and for American society than for themselves. Participants were open to continuing the restrictions in place in late April 2020 for an extended period of time to reduce pandemic spread. CONCLUSIONS: There is substantial opportunity for improved public health responses to COVID-19 among college students, including for testing and contact tracing. In addition, because most participants restricted their behaviors before official stay-at-home orders went into effect, they may continue to restrict movement after stay-at-home orders are lifted, including when colleges reopen for in-person activities, if they decide it is not yet prudent to circulate freely. The public health, economic, and educational implications of COVID-19 are continuing to unfold; future studies must continue to monitor college student experiences and perspectives.


title: Pathogenesis and outcome of extrahepatic biliary obstruction in cats

text: Extrahepatic biliary obstruction (EHBO) was confirmed at surgery or necropsy in 22 cats. Biliary or pancreatic adenocarcinoma was diagnosed by histopathology in six cats and one cat had an undiagnosed mass in the common bile duct. The remaining 15 cats had at least one of a complex of inflammatory diseases including pancreatitis, cholangiohepatitis, cholelithiasis and cholecystitis. The most common clinical signs were jaundice, anorexia, lethargy, weight loss and vomiting. Hyperbilirubinaemia was present in all cases. Distension of the common bile duct and gall bladder was the most commonly observed finding on abdominal ultrasound. Nineteen cats underwent exploratory laparotomy for biliary decompression and diversion. Mortality in cats with underlying neoplasia was 100 per cent and, in those with non‐neoplastic lesions, was 40 per cent. Long‐term complications, in those that survived, included recurrence of cholangiohepatitis, chronic weight loss and recurrence of obstruction. Based on these findings, the prognosis for EHBO in cats must be considered guarded.


title: Asymptotic estimates of SARS-CoV-2 infection counts and their sensitivity to stochastic perturbation

text: Despite the importance of having robust estimates of the time-asymptotic total number of infections, early estimates of COVID-19 show enormous fluctuations. Using COVID-19 data from different countries, we show that predictions are extremely sensitive to the reporting protocol and crucially depend on the last available data point before the maximum number of daily infections is reached. We propose a physical explanation for this sensitivity, using a susceptible–exposed–infected–recovered model, where the parameters are stochastically perturbed to simulate the difficulty in detecting patients, different confinement measures taken by different countries, as well as changes in the virus characteristics. Our results suggest that there are physical and statistical reasons to assign low confidence to statistical and dynamical fits, despite their apparently good statistical scores. These considerations are general and can be applied to other epidemics.


title: Filoviruses: Interactions with the host cell

text: The highly pathogenic filoviruses, Marburg and Ebola virus, are difficult to handle and knowledge of the interactions between filoviruses and their host cells remained enigmatic for many years. Two developments were crucial for the presented advances in our understanding of the cell biology of filoviruses, which is still fragmentary. On the one hand, the number of high containment laboratories increased where handling of the highly pathogenic filoviruses is possible. On the other hand, molecular biological tools have been developed that allow investigation of certain aspects of filoviral replication under normal laboratory conditions which considerably accelerated research on filoviruses. This review describes advances in understanding the interactions between host cells and filoviruses during viral attachment, entry, transcription, assembly and budding.


title: Detection of bovine viral diarrhea virus genotype 1 in aerosol by a real time RT-PCR assay

text: BACKGROUND: As a pestivirus of the Flaviviridae family, bovine viral diarrhea virus (BVDV), has imposed a large burden on animal husbandry worldwide, and such virus can be transmitted mainly through direct contact with other infected animals and probably via aerosols. In the present study, we aimed to develop a real-time RT-PCR method for detection of BVDV-1 in aerosol samples. METHODS: A pair of primers specific for highly conserved regions of the BVDV-1 5′-UTR was designed. The standard curve and sensitivity of the developed assay were assessed based on 10-fold serial dilutions of RNA molecular standard. The specificity of the assay was evaluated with other pestiviruses and infectious bovine viruses. The clinical performance was examined by testing 169 aerosol samples. RESULTS: The results showed that a good linear relationship existed between the standard curve and the concentration of template. The lowest detection limit was 5.2 RNA molecules per reaction. This assay was specific for detection of BVDV-1, and no amplification was found for other pestiviruses such as classical swine fever virus (CSFV), border disease virus (BDV), and common infectious bovine viruses, including BVDV-2, infectious bovine rhinotracheitis virus (IBRV), bovine parainfluenza virus type 3 (BPIV-3), bovine respiratory syncytial virus (BRSV), bovine ephemeral fever virus (BEFV) and bovine coronavirus (BcoV). The assay was highly reproducible with low variation coefficient values (CVs) for intra-assay and inter-assay. A total of 169 aerosol samples collected from six dairy herds were tested using this method. The results showed that the positive detection rate of BVDV-1 was 17.2% (29/169), which was significantly higher compared with the conventional RT-PCR. Additionally, the positive samples (n = 29) detected by real-time RT-PCR were verified by BVDV RPA-LFD, and a concordance rate of 100% was obtained between them. CONCLUSIONS: Taken together, we developed a real-time RT-PCR assay for quantitative analysis of BVDV-1 in aerosol samples, and our finding provided valuable insights into the risk on aerosol transmission of BVDV-1.


title: Nasoseptal Flap Necrosis After Endoscopic Skull Base Surgery in the Setting of SARS-CoV-2/COVID-19

text: ABSTRACT Background A novel viral strain known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a worldwide pandemic known as Coronavirus 2019 (COVID-19). Early reports from China highlighted the risks associated with performing endoscopic endonasal skull base surgery in patients with SARS-CoV-2. We present a rare complication of nasoseptal flap (NSF) necrosis associated with COVID-19, further emphasizing the challenges of performing these procedures in this era. Case Description A 78-year-old male underwent an extended endoscopic endonasal transplanum resection of a pituitary macroadenoma for decompression of the optic chiasm. The resulting skull base defect was repaired using a pedicled nasoseptal flap (NSF). The patient developed meningitis and a cerebrospinal fluid (CSF) leak on post-operative day thirteen requiring revision repair of the defect. Twelve days later, he developed persistent fevers and rhinorrhea. The patient was re-explored endoscopically, and the NSF was noted to be necrotic and devitalized with evident CSF leakage. At that time, the patient tested positive for Sars-CoV-2. Post-operatively, he developed acute respiratory distress syndrome complicated by hypoxic respiratory failure and death. Conclusion To our knowledge, this is the first reported case of NSF necrosis in a patient with COVID-19. We postulate that the thrombotic complications of COVID-19 may have contributed to vascular pedicle thrombosis and NSF necrosis. Although the pathophysiology of SARS-CoV-2 and its effect on the nasal tissues is still being elucidated, this case highlights some challenges of performing endoscopic skull base surgery in the era of COVID-19.


title: CRISPR-Cas Targeting of Host Genes as an Antiviral Strategy

text: Currently, a new gene editing tool—the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated (Cas) system—is becoming a promising approach for genetic manipulation at the genomic level. This simple method, originating from the adaptive immune defense system in prokaryotes, has been developed and applied to antiviral research in humans. Based on the characteristics of virus-host interactions and the basic rules of nucleic acid cleavage or gene activation of the CRISPR-Cas system, it can be used to target both the virus genome and host factors to clear viral reservoirs and prohibit virus infection or replication. Here, we summarize recent progress of the CRISPR-Cas technology in editing host genes as an antiviral strategy.


Virtually-supported home peanut introduction during COVID-19 for at-risk infants


title: Too little too late: Waiting for TB to come

text: Abstract There is a new paradigm that preventing tuberculosis (TB) and addressing the reservoir of latent TB infection in combination with curing all TB cases is essential to accelerate the decline of TB rates and ending TB by 2050. However, complacency and incremental change eludes radical policy transformation needed to meet global targets. This essay explores current attitudes, policy disparities between high and lower burden settings, and what changes are needed to remove the obstacles to progress.


title: Food Markets with Live Birds as Source of Avian Influenza

text: A patient may have been infected with highly pathogenic avian influenza virus H5N1 in Guangzhou, People's Republic of China, at a food market that had live birds. Virus genes were detected in 1 of 79 wire cages for birds at 9 markets. One of 110 persons in the poultry business at markets had neutralizing antibody against H5N1.


title: COVID-19 Related Loneliness and Psychiatric Symptoms among Older Adults: The Buffering Role of Subjective Age

text: OBJECTIVES: The study examined whether subjective age moderated the relationship between loneliness due to the COVID-19 pandemic and psychiatric symptoms. METHODS: A convenience sample of older adult Israelis (N=277, mean age=69.58±6.72) completed web-based questionnaires comprising loneliness, anxiety, depressive and peritraumatic distress symptoms. They also reported how old they felt. RESULTS: The positive relationship between loneliness due to the COVID-19 pandemic and psychiatric symptoms was weak among those who felt younger than their age while this very same relationship was robust among those feeling older. CONCLUSIONS: Young subjective age may weaken the loneliness-symptom association among older adults during the COVID-19 pandemic. Older adults holding an older age identity are more susceptible to the adverse effects of loneliness. Although preliminary, the findings may inform screening and interventions. Subjective age may help identify those at high risk in suffering from loneliness, and suggest interventions aimed at ameliorating both loneliness and older subjective ages.


COVID-19: Now is the time to come together


title: Chapter 31 Coronaviruses

text: Abstract Coronaviruses possess a distinctive morphology, the name being derived from the outer fringe, or “corona” of embedded envelope protein. Members of the family Coronaviridae cause a broad spectrum of animal and human diseases. Uniquely, replication of the RNA genome proceeds through the generation of a nested set of viral mRNA molecules. Until 2003, coronaviruses attracted little interest beyond causing mild upper respiratory tract infections. This changed dramatically in 2003 with the zoonotic SARS-CoV and the more recent emergence of MERS-CoV has confirmed the coronaviruses as significant causes of severe respiratory disease.


Use of a protective shield successfully prevents exposure to aerosols and droplets during transesophageal echocardiography


title: Agile Requirements Engineering and Software Planning for a Digital Health Platform to Engage the Effects of Isolation Caused by Social Distancing: Case Study

text: BACKGROUND: Social distancing and shielding measures have been put in place to reduce social interaction and slow the transmission of the coronavirus disease (COVID-19). For older people, self-isolation presents particular challenges for mental health and social relationships. As time progresses, continued social distancing could have a compounding impact on these concerns. OBJECTIVE: This project aims to provide a tool for older people and their families and peers to improve their well-being and health during and after regulated social distancing. First, we will evaluate the tool’s feasibility, acceptability, and usability to encourage positive nutrition, enhance physical activity, and enable virtual interaction while social distancing. Second, we will be implementing the app to provide an online community to assist families and peer groups in maintaining contact with older people using goal setting. Anonymized data from the app will be aggregated with other real-world data sources to develop a machine learning algorithm to improve the identification of patients with COVID-19 and track for real time use by health systems. METHODS: Development of this project is occurring at the time of publication, and therefore, a case study design was selected to provide a systematic means of capturing software engineering in progress. The app development framework for software design was based on agile methods. The evaluation of the app’s feasibility, acceptability and usability shall be conducted using Public Health England's guidance on evaluating digital health products, Bandura’s model of health promotion, the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework and the Nonadoption, Abandonment and Challenges to the Scale-up, Spread and Suitability (NASSS) framework. RESULTS: Making use of a pre-existing software framework for health behavior change, a proof of concept was developed, and a multistage app development and deployment for the solution was created. Grant submissions to fund the project and study execution have been sought at the time of publication, and prediscovery iteration of the solution has begun. Ethical approval for a feasibility study design is being sought. CONCLUSIONS: This case study lays the foundations for future app development to combat mental and societal issues arising from social distancing measures. The app will be tested and evaluated in future studies to allow continuous improvement of the app. This novel contribution will provide an evidence-based exemplar for future app development in the space of social isolation and loneliness.


Ventilatory Ratio in Hypercapnic Mechanically Ventilated Patients with COVID-19–associated Acute Respiratory Distress Syndrome


title: Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody

text: The henipaviruses, represented by Hendra (HeV) and Nipah (NiV) viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The high morbidity and mortality rates associated with infection and lack of licensed antiviral therapies make the henipaviruses a potential biological threat to humans and livestock. Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors. Previously, henipavirus-neutralizing human monoclonal antibodies (hmAb) have been isolated using the HeV-G glycoprotein and a human naïve antibody library. One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. Here, we report the crystal structure of the complex of HeV-G with m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This structure provides detailed insight into the mechanism of HeV and NiV neutralization by m102.4, and serves as a blueprint for further optimization of m102.4 as a therapeutic agent and for the development of entry inhibitors and vaccines.


title: Rapid detection and monitoring of human coronavirus infections

text: Human coronaviruses (CoVs) are increasingly recognized as important respiratory pathogens associated with a broad range of clinical diseases. We sought to increase the insight into clinically relevant CoV infections by monitoring antigen concentrations in six confirmed CoV-positive patients using a newly developed assay for rapid detection of CoV OC43 infections. Antigen positivity lasted 3 to 6 days in secondary infections and 13 days in primary infection. CoV infections are clinically diverse, are common, and cannot be diagnosed from clinical symptoms alone.


title: Bird flu: lessons from SARS

text: Summary Severe acute respiratory syndrome (SARS) and avian influenza are two important newly emerged infections with pandemic potential. Both infections have crossed the species barrier to infect humans. SARS originated from southern China and spread to many countries in early 2003. The close collaboration of scientists around the world resulted in a rapid identification of the causative agent, and the early isolation of infected cases and meticulous infection control measures were the key to successfully controlling the outbreak of SARS. The first outbreak of human cases of avian influenza was reported in 1997 in Hong Kong. Since 2003, there have been many small outbreaks of human cases around the world, and the reported mortality is greater than 50%. Current evidence suggests that the human-to-human transmission of avian influenza is rather inefficient, but mutation might occur in the future resulting in improved transmission and possibly a pandemic in humans. As with the outbreak of SARS, the development of sensitive and accurate early diagnostic tests is extremely important for successful control of the outbreak at source. The availability of isolation facilities, the stockpiling of antiviral agents and effective and safe vaccination will be extremely important in minimising the damage of a new influenza pandemic.


title: Two patients with acute meningoencephalitis concomitant with SARS‐CoV‐2 infection

text: In December 2019, a cluster of patients with pneumonia of unknown cause led to the identification of a new strain of pandemic coronavirus called Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first SARS-CoV outbreak, human coronaviruses are known for their neurological tropism. If respiratory complications are at the forefront of clinical presentation of SARS-CoV-2, neurological involvement remains poorly described and understood. We report here two patients infected with SARS-CoV-2 who presented with neurological symptoms and signs.


title: Comparison of the photosynthetic characteristics of four Lycoris species with leaf appearing in autumn under field conditions

text: The diurnal trends of gas exchange and chlorophyll fluorescence parameters in four Lycoris species (L. houdyshelii, L. aurea, L. radiata var. pumila and L. albiflora) were determined and compared with a portable photosynthesis analysis system. Our study revealed that L. houdyshelii had the lowest light compensation point (LCP), while the other three species had higher LCP (12.37–14.99 μmol m(−2) s(−1)); L. aurea had the highest light saturation point (LSP) (1,189 μmol m(−2) s(−1)), and L. houdyshelii and L. albiflora had lower LSP with the values being 322 and 345 μmol m(−2) s(−1), respectively, and L. radiata var. pumila showed the intermediate LSP. Both the species L. houdyshelii and L. albiflora exhibited a typical and obvious decline in net photosynthetic rate (P (N)) during midday, which was not observed in L. aurea. This indicated a possible photoinhibition in L. houdyshelii and L. albiflora as the ratio of variable to maximum fluorescence (Fv/Fm) values were higher in these two species. The minimal fluorescence (F(0)) values were lower in L. aurea and L. radiata var. pumila. The diurnal changes of transpiration rate (E) in all four species presented only one peak, appearing between 11:00 h or 13:00 h. By using simple correlation analyses, it was observed that the environmental factors affecting P (N) were different among four species and the main factors were photosynthetic photon flux density (PPFD) and relative humidity especially for L. aurea and L. radiata. The results of studying indicated that the four species could be divided into two groups. The species L. radiata var. pumila and L. aurea were more adapted to a relatively high irradiance, and L. houdyshelii and L. albiflora could be grown in moderate-shade environment in order to scale up their growth and productivity.


title: Performance of VIDISCA-454 in Feces-Suspensions and Serum

text: Virus discovery combining sequence unbiased amplification with next generation sequencing is now state-of-the-art. We have previously determined that the performance of the unbiased amplification technique which is operational at our institute, VIDISCA-454, is efficient when respiratory samples are used as input. The performance of the assay is, however, not known for other clinical materials like blood or stool samples. Here, we investigated the sensitivity of VIDISCA-454 with feces-suspensions and serum samples that are positive and that have been quantified for norovirus and human immunodeficiency virus type 1, respectively. The performance of VIDISCA-454 in serum samples was equal to its performance in respiratory material, with an estimated lower threshold of 1,000 viral genome copies. The estimated threshold in feces-suspension is around 200,000 viral genome copies. The decreased sensitivity in feces suspension is mainly due to sequences that share no recognizable identity with known sequences. Most likely these sequences originate from bacteria and phages which are not completely sequenced.


title: The cirrhosis care Alberta (CCAB) protocol: implementing an evidence-based best practice order set for the management of liver cirrhosis - a hybrid type I effectiveness-implementation trial

text: BACKGROUND: Liver cirrhosis is a leading cause of morbidity, premature mortality and acute care utilization in patients with digestive disease. In the province of Alberta, hospital readmission rates for patients with cirrhosis are estimated at 44% at 90 days. For hospitalized patients, multiple care gaps exist, the most notable stemming from i) the lack of a structured approach to best practice care for cirrhosis complications, ii) the lack of a structured approach to broader health needs and iii) suboptimal preparation for transition of care into the community. Cirrhosis Care Alberta (CCAB) is a 4-year multi-component pragmatic trial which aims to address these gaps. The proposed intervention is initiated at the time of hospitalization through implementation of a clinical information system embedded electronic order set for delivering evidence-based best practices under real-world conditions. The overarching objective of the CCAB trial is to demonstrate effectiveness and implementation feasibility for use of the order set in routine patient care within eight hospital sites in Alberta. METHODS: A mixed methods hybrid type I effectiveness-implementation design will be used to evaluate the effectiveness of the order set intervention. The primary outcome is a reduction in 90-day cumulative length of stay. Implementation outcomes such as reach, adoption, fidelity and maintenance will also be evaluated alongside other patient and service outcomes such as readmission rates, quality of care and cost-effectiveness. This theory-based trial will be guided by Normalization Process Theory, Consolidated Framework on Implementation Research (CFIR) and the Reach-Effectiveness-Adoption-Implementation-Maintenance (RE-AIM) Framework. DISCUSSION: The CCAB project is unique in its breadth, both in the comprehensiveness of the multi-component order set and also for the breadth of its roll-out. Lessons learned will ultimately inform the feasibility and effectiveness of this approach in “real-world” conditions as well as adoption and adaptation of these best practices within the rest of Alberta, other provinces in Canada, and beyond. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04149223, November 4, 2019.


title: Cutaneous manifestations and considerations in COVID‐19 pandemic: A systematic review

text: BACKGROUND: COVID‐19 had a great impact on medical approaches among dermatologist OBJECTIVE: This systematic review focuses on all skin problems related to COVID‐19, including primary and secondary COVID‐related cutaneous presentations and the experts recommendations about dermatological managements especially immunomodulators usage issues METHOD: Search was performed on PubMed, Scopus, Embase and ScienceDirect. Other additional resources were searched included Cochrane, WHO, Medscape and coronavirus dermatology resource of Nottingham university. The search completed on May/03/2020. 377 articles assigned to the inclusion and exclusion groups RESULT: Eighty‐nine articles entered the review. Primary mucocutaneous and appendageal presentations could be the initial or evolving signs of COVID‐19. It could be manifest most commonly as a maculopapular exanthamatous or morbiliform eruption, generalized urticaria or pseudo chilblains recognized as “COVID toes” (pernio‐like acral lesions or vasculopathic rashes). Conclusion: During pandemic, Non‐infected non‐at risk patients with immune‐medicated dermatologic disorders under treatment with immunosuppressive immunomodulators are not needed to alter their regimen or discontinue the therapies. At‐risk and infection‐suspected patients needed to dose reduction, interval increase or temporary drug discontinuation (at least 2 weeks). Patients with an active COVID‐19 infection should hold the biologic or non‐biologic immunosuppressives until the complete recovery occur (at least 4 weeks). This article is protected by copyright. All rights reserved.


title: Changes in cold-related mortalities between 1995 and 2016 in South East England

text: Abstract Objective The aim of the study was to examine trends in cold-related mortalities between 1995 and 2016. Study design This is a longitudinal mortality study. Methods For men and women aged 65–74 years or those older than 85 years in South East England, the relationship between daily mortality (deaths per million population) and outdoor temperatures below 18 °C, with allowance for influenza epidemics, was assessed by linear regression on an annual basis. The regression coefficients were expressed as a percentage of the mortality at 18 °C to adjust for changes in mortality through health care. Trends in ‘specific’ cold-related mortalities were then examined over two periods, 1977–1994 and 1995–2016. Results In contrast to the early period, annual trends in cold-related specific mortalities showed no decline between 1995 and 2016. ‘Specific’ cold-related mortality of women, but not men, in the age group older than 85 years showed a significant increase over the 1995–2016 period, which was different from the trend over the earlier period (P < 0.01). Conclusion Despite state-funded benefits to help alleviate fuel poverty and public health advice, very elderly women appear to be at increasing risk of cold-related mortality—greater help may be necessary.


title: Patients with diabetes are at higher risk for severe illness from COVID-19

text: • It is currently uncertain whether people with diabetes are at higher risk of severe illness from coronavirus disease 2019 (COVID-19). • We found that diabetes was associated with an approximately 4-fold increased risk of having severe/critical COVID-19 illness. • This association was independent of age, sex, obesity, hypertension and smoking. • These findings highlight the urgent need for a multidisciplinary team-based approach to management of this patient population.


title: Use of camel single-domain antibodies for the diagnosis and treatment of zoonotic diseases

text: Abstract Camelids produce both conventional heterotetrameric antibodies and homodimeric heavy-chain only antibodies. The antigen-binding region of such homodimeric heavy-chain only antibodies consists of one single domain, called VHH. VHHs provide many advantages over conventional full-sized antibodies and currently used antibody-based fragments (Fab, scFv), including high specificity, stability and solubility, and small size, allowing them to recognize unusual antigenic sites and deeply penetrate tissues. Since their discovery, VHHs have been used extensively in diagnostics and therapy. In recent decades, the number of outbreaks of diseases transmissible from animals to humans has been on the rise. In this review, we evaluate the status of VHHs as diagnostic and therapeutic biomolecular agents for the detection and treatment of zoonotic diseases, such as bacterial, parasitic, and viral zoonosis. VHHs show great adaptability to inhibit or neutralize pathogenic agents for the creation of multifunctional VHH-based diagnostic and therapeutic molecules against zoonotic diseases.


title: Association between management practices and within-herd prevalence of Cryptosporidium parvum shedding on dairy farms in southern Ontario

text: Abstract To identify management practices associated with an increased within-herd prevalence of Cryptosporidium parvum shedding on dairy farms in southern Ontario, fecal samples were taken from 1089 calves aged 7–28 days, from 119 herds. Information on management practices was obtained by administering a questionnaire compiled using a modified Delphi technique. Data were analyzed using univariable and multivariable negative binomial regression. Overall, 30% of the calves in the study were shedding C. parvum oocysts, with at least one positive calf detected in 77% of herds. Within-herd prevalence ranged from 0 to 80%. Predictors significantly associated with an increased prevalence of shedding in multivariable modelling were the use of calf scour prophylaxis in cows (risk ratio [RR] 1.70, P <0.01) and calves (RR 1.38, P =0.02) and the feeding of milk replacer in the first week of life (RR 1.40, P =0.02). In contrast, the presence of concrete flooring in calf housing areas (RR 0.59, P <0.01) and the use of soap or detergent when washing calf feeding utensils (RR 0.61, P <0.01) appeared to be protective.


COVID-19 and Trauma Care: Improvise, Adapt, and Overcome!


COVID-19 and balance in access to health care in Ethiopia


title: Advancements in Nucleic Acid Based Therapeutics against Respiratory Viral Infections

text: Several viruses cause pulmonary infections due to their shared tropism with cells of the respiratory tract. These respiratory problems due to viral infection become a public health concern due to rapid transmission through air/aerosols or via direct-indirect contact with infected persons. In addition, the cross-species transmission causes alterations to viral genetic makeup thereby increasing the risk of emergence of pathogens with new and more potent infectivity. With the introduction of effective nucleic acid-based technologies, post translational gene silencing (PTGS) is being increasingly used to silence viral gene targets and has shown promising approach towards management of many viral infections. Since several host factors are also utilized by these viruses during various stages of infection, silencing these host factors can also serve as promising therapeutic tool. Several nucleic acid-based technologies such as short interfering RNAs (siRNA), antisense oligonucleotides, aptamers, deoxyribozymes (DNAzymes), and ribozymes have been studied and used against management of respiratory viruses. These therapeutic nucleic acids can be efficiently delivered through the airways. Studies have also shown efficacy of gene therapy in clinical trials against respiratory syncytial virus (RSV) as well as models of respiratory diseases including severe acute respiratory syndrome (SARS), measles and influenza. In this review, we have summarized some of the recent advancements made in the area of nucleic acid based therapeutics and highlighted the emerging roles of nucleic acids in the management of some of the severe respiratory viral infections. We have also focused on the methods of their delivery and associated challenges.


title: Central ions and lateral asparagine/glutamine zippers stabilize the post-fusion hairpin conformation of the SARS coronavirus spike glycoprotein

text: Abstract The coronavirus spike glycoprotein is a class I membrane fusion protein with two characteristic heptad repeat regions (HR1 and HR2) in its ectodomain. Here, we report the X-ray structure of a previously characterized HR1/HR2 complex of the severe acute respiratory syndrome coronavirus spike protein. As expected, the HR1 and HR2 segments are organized in antiparallel orientations within a rod-like molecule. The HR1 helices form an exceptionally long (120 Å) internal coiled coil stabilized by hydrophobic and polar interactions. A striking arrangement of conserved asparagine and glutamine residues of HR1 propagates from two central chloride ions, providing hydrogen-bonding “zippers” that strongly constrain the path of the HR2 main chain, forcing it to adopt an extended conformation at either end of a short HR2 α-helix.


title: Respiratory protection against bioaerosols: Literature review and research needs

text: Research on respiratory protection against biologic agents is important to address major concerns such as occupational safety and terrorist attack. This review describes the literature on respiratory protection against bioaerosols and identifies research gaps. Respiratory protection is a complex field involving a number of factors, such as the efficiency of respirator filter material; face-piece fitting; and maintenance, storage, and reuse of respirators. Several studies used nonpathogenic microorganisms having physical characteristics similar to that of Mycobacterium tuberculosis to analyze microbial penetration through respirators. Some studies showed that high-efficiency particulate air (HEPA) and N95 filters provided a higher level of protection than dust/mist (DM) and dust/mist/fume (DMF) filters. Flow rate and relative humidity appear to alter the level of penetration of microorganisms through respirator filters. The relationship between microbial penetration through respirator filters and the aerodynamic diameter, length, or other physical characteristics of microorganisms remains controversial. Whether reaerosolization of bioaerosol particles should be a concern is unclear, given the fact that one study has demonstrated significant reaerosolization of 1- to 5-μm particles loaded onto respirator filters. Respirator maintenance, storage, and decontamination are important factors to be considered when reusing respirators. The respiratory protection against biologic warfare agents such as anthrax in military and civilian situations is described.


title: NS5A Domain 1 and Polyprotein Cleavage Kinetics Are Critical for Induction of Double-Membrane Vesicles Associated with Hepatitis C Virus Replication

text: Induction of membrane rearrangements in the cytoplasm of infected cells is a hallmark of positive-strand RNA viruses. These altered membranes serve as scaffolds for the assembly of viral replication factories (RFs). We have recently shown that hepatitis C virus (HCV) infection induces endoplasmic reticulum-derived double-membrane vesicles (DMVs) representing the major constituent of the RF within the infected cell. RF formation requires the concerted action of nonstructural action of nonstructural protein (NS)3, -4A, protein (NS)3 -4A, -4B, -5A, and -5B. Although the sole expression of NS5A is sufficient to induce DMV formation, its efficiency is very low. In this study, we dissected the determinants within NS5A responsible for DMV formation and found that RNA-binding domain 1 (D1) and the amino-terminal membrane anchor are indispensable for this process. In contrast, deletion of NS5A D2 or D3 did not affect DMV formation but disrupted RNA replication and virus assembly, respectively. To identify cis- and trans-acting factors of DMV formation, we established a trans cleavage assay. We found that induction of DMVs requires full-length NS3, whereas a helicase-lacking mutant was unable to trigger DMV formation in spite of efficient polyprotein cleavage. Importantly, a mutation accelerating cleavage kinetics at the NS4B-5A site diminished DMV formation, while the insertion of an internal ribosome entry site mimicking constitutive cleavage at this boundary completely abolished this process. These results identify key determinants governing the biogenesis of the HCV RF with possible implications for our understanding of how RFs are formed in other positive-strand RNA viruses.


Threats and challenges of emerging viral diseases and scope of Ayurveda in its prevention


title: Optimization of phosphorus localization by EFTEM of nucleic acid containing structures

text: Abstract Energy Filtered Transmission Electron Microscopy (EFTEM) has been used to study nucleic acids localization in unstained thin sections of virus-infected cells. For this purpose, phosphorus maps (P-maps) have been obtained by applying the N-windows Egerton model for background subtraction from data acquired by a non-dedicated TEM Jeol 1200EXII equipped with a post-column PEELS Gatan 666–9000 and a Gatan Image Filter (GIF-100). To prevent possible errors in the evaluation of elemental maps and thus incorrect nucleic acid localization, we have studied different regions of swine testis (ST) cells with similar local density containing either high concentration of nucleic acids (condensed chromatin and ribosomes) or a very low concentration (mitochondria). Special care was taken to optimize the sample preparation conditions to avoid as much as possible the traditional artifacts derived from this source. Selection of the best set of pre-edge images for background fitting was also considered in order to produce “true P-maps”. A new software for interactive processing of images series has been applied to estimate this set. Multivariate Statistical Analysis was used as a filtering tool to separate the “useful information” present in the inelastic image series (characteristic signal) from the “non-useful information” (noise and acquisition artifacts). The reconstitution of the original image series preserving mainly the useful information allowed the computation of P-maps with improved signal-to-noise ratio (SNR). This methodology has been applied to study the RNA content of maturation intermediate coronavirus particles found inside infected cells.


title: Conduite à tenir devant un enfant fébrile au retour de voyage

text: Résumé Les pathologies le plus fréquentes au retour de voyage à l’étranger sont les infections gastro-intestinales, les maladies fébriles et les problèmes dermatologiques. L’évaluation d’un enfant fébrile de retour de voyage est clinique : vérification des antécédents et des vaccinations, recherche d’autres cas au contact, signes fonctionnels et physiques, caractéristiques du voyage. Un bilan paraclinique de débrouillage complète souvent l’évaluation pour une orientation syndromique. Si les causes de fièvre sont surtout cosmopolites, la gravité des pathologies exotiques doit les faire rechercher en priorité. Le paludisme doit être évoqué devant toute fièvre en provenance d’Afrique subsaharienne. Le diagnostic repose sur l’association d’un frottis sanguin et d’un test sensible (goutte épaisse, polymerase chain reaction [PCR]) ou d’un test de diagnostic rapide (pour Plasmodium [P]. falciparum). Les critères clinicobiologiques de gravité sont essentiels pour orienter et traiter le patient. En cas d’accès non compliqué à P. falciparum, le traitement repose sur une thérapie combinée à base d’artémisinine (ACT), artéméther-luméfantrine ou arténimol-pipéraquine. Les accès graves sont traités par l’artésunate intraveineux, puis un ACT oral. Dengue, chikungunya et infection à virus Zika ont des caractéristiques cliniques communes (association fièvre-éruption-arthralgies, traitement symptomatique). En cas de dengue, il faut surveiller l’apparition de signes d’alerte qui pourraient faire craindre une évolution péjorative. Le chikungunya est grave en cas de transmission per partum, avec un risque d’encéphalite néonatale. Chez l’enfant, le Zika est a- ou peu symptomatique. Mais en cas d’infection pendant une grossesse, le risque est celui d’une embryofœtopathie. Le diagnostic de ces arboviroses repose sur la PCR à la phase aiguë et la sérologie secondairement. La symptomatologie de la typhoïde est peu spécifique, justifiant la pratique d’hémocultures systématiques devant une fièvre du retour. Son traitement repose sur les céphalosporines de troisième génération ou la ciprofloxacine, mais les résistances augmentent. Au total, la diversité des étiologies d’une fièvre de retour et la gravité potentielle des infections importées imposent une réflexion sur le parcours de soins de ces patients, en particulier vis-à-vis du risque de fièvre hémorragique.


title: Are Animals a Neglected Transmission Route of SARS-CoV-2?

text: Little information on the SARS-CoV-2 virus in animals is available to date. Whereas no one husbandry animal case has been reported to date, which would have significant implications in food safety, companion animals play a role in COVID-19 epidemiology that opens up new questions. There is evidence that SARS-CoV-2 can infect felines, dogs and minks, and there is evidence of human-to-animal infection. Likewise, the S protein nucleotide sequence of the SARS-CoV-2 virus isolated in domestic animals and humans is identical, and the replication of the SARS-CoV-2 in cats is efficient. Besides, the epidemiological evidence for this current pandemic indicates that the spillover to humans was associated with close contact between man and exotic animals, very probably in Chinese wet markets, thus there is a growing general consensus that the exotic animal markets, should be strictly regulated. The examination of these findings and the particular role of animals in COVID-19 should be carefully analyzed in order to establish preparation and containment measures. Animal management and epidemiological surveillance must be also considered for COVID-19 control, and it can open up new questions regarding COVID-19 epidemiology and the role that animals play in it.


Severe acute respiratory syndrome coronavirus and viral mimicry


title: C-reactive protein levels in the early stage of COVID-19

text: Abstract Background COVID-19 is a new infectious disease, for which there is currently no treatment. It is therefore necessary to explore biomarkers to determine the extent of lung lesions and disease severity. Objective We aimed to assess the usefulness of CRP levels in the early stage of COVID-19 and to correlate them with lung lesions and severe presentation. Methods Confirmed cases of COVID-19 were selected at the Fever Unit in two regions of Guizhou, China. On admission CRP levels were collected, and the diameter of the largest lung lesion was measured in the most severe lung lesion by lung CT scan. Differences in the diameter and CRP levels were compared in the following groups of patients: mild group, moderate group, severe group, and critical group. Result CRP levels and the diameter of the largest lung lesion in the moderate group were higher than those in the mild group (Mann-Whitney test=−2.647, −2.171, P ˂0.05), those in the severe group were higher than those in the moderate group (Mann-Whitney test=0.693, −2.177, P ˂0.05), and those in the critical group were higher than those in the severe group (Mann-Whitney test=−0.068, −1.549, P ˂0.05). The difference was statistically significant. CRP levels were positively correlated with the diameter of lung lesion and severe presentation (correlation coefficient=0.873, 0.734, P ˂0.001). Conclusion In the early stage of COVID-19 CRP levels were positively correlated with lung lesions and could reflect disease severity.


title: SARS‐CoV‐2 surveillance for a non‐human primate breeding research facility

text: BACKGROUND: The emergence of SARS‐CoV‐2 and the ensuing COVID‐19 pandemic prompted the need for a surveillance program to determine the viral status of the California National Primate Research Center non‐human primate breeding colony, both for reasons of maintaining colony health and minimizing the risk of interference in COVID‐19 and other research studies. METHODS: We collected biological samples from 10% of the rhesus macaque population for systematic testing to detect SARS‐CoV‐2 virus by RT‐PCR and host antibody response by ELISA. Testing required the development and validation of new assays and an algorithm using in laboratory‐developed and commercially available reagents and protocols. RESULTS AND CONCLUSIONS: No SARS‐CoV‐2 RNA or antibody was detected in this study; therefore, we have proposed a modified testing algorithm for sentinel surveillance to monitor for any future transmissions. As additional reagents and controls become available, assay development and validation will continue, leading to the enhanced sensitivity, specificity, accuracy, and efficiency of testing.


title: From the “Madding Crowd” to mass gatherings-religion, sport, culture and public health

text: Abstract Human behavior has long engaged in collective behavior assembling in crowds. The Christian pilgrimage to the Holy Land has been recorded since the 4th century, while the Hajj, Islam's great pilgrimage, has existed for fourteen centuries, of which a body of literature devoted to the travelogues of the Hajj has been recorded for over ten centuries. Football is a sport played worldwide by more than 1.5 million teams and in 300,000 clubs. Most however play outside of the officially organized sphere: more than 4 percent of the global population plays football, including 270 million amateur players. Assembling for specific events is a uniquely human behavior, though the formal study of crowds did not begin until the mid-Twentieth Century. Today Mass Gathering Medicine focuses on the public health challenges to hosting events attended by a large enough number of people, at a specific site, for a defined period of time, likely to strain both the planning and response to the mass gathering of a community, state, or nation. All of us can recall attending a mass gathering, whether it be watching one's favorite rock group in performance or assembling for religious pilgrimage. Certainly, the event itself is transporting and transforming and the unison of behaviors and activities can be enormously enriching, uplifting and overwhelming, just as much as they may be at times dangerous and high risk. This review seeks to draw contrasts and comparisons between sporting gatherings and religious gatherings with a chief focus on Hajj, among the largest of all mass gatherings today. We will find there are some powerful similarities as well as stark differences. Each bequeaths a legacy which can inform the other and, as we make our observations, we join with you and the legions of other investigators who continue to remain fascinated and enthralled by mass gatherings which are among the most beloved and beholden events of modern humanity.


title: Chapter 6 Cubic Membranes The Missing Dimension of Cell Membrane Organization

text: Abstract Biological membranes are among the most fascinating assemblies of biomolecules: a bilayer less than 10 nm thick, composed of rather small lipid molecules that are held together simply by noncovalent forces, defines the cell and discriminates between “inside” and “outside”, survival, and death. Intracellular compartmentalization—governed by biomembranes as well—is a characteristic feature of eukaryotic cells, which allows them to fulfill multiple and highly specialized anabolic and catabolic functions in strictly controlled environments. Although cellular membranes are generally visualized as flat sheets or closely folded isolated objects, multiple observations also demonstrate that membranes may fold into “unusual”, highly organized structures with 2D or 3D periodicity. The obvious correlation of highly convoluted membrane organizations with pathological cellular states, for example, as a consequence of viral infection, deserves close consideration. However, knowledge about formation and function of these highly organized 3D periodic membrane structures is scarce, primarily due to the lack of appropriate techniques for their analysis in vivo. Currently, the only direct way to characterize cellular membrane architecture is by transmission electron microscopy (TEM). However, deciphering the spatial architecture solely based on two-dimensionally projected TEM images is a challenging task and prone to artifacts. In this review, we will provide an update on the current progress in identifying and analyzing 3D membrane architectures in biological systems, with a special focus on membranes with cubic symmetry, and their potential role in physiological and pathophysiological conditions. Proteomics and lipidomics approaches in defined experimental cell systems may prove instrumental to understand formation and function of 3D membrane morphologies.


title: Immune Biomarkers Predictive of Respiratory Viral Infection in Elderly Nursing Home Residents

text: OBJECTIVE: To determine if immune phenotypes associated with immunosenescence predict risk of respiratory viral infection in elderly nursing home residents. METHODS: Residents ≥65 years from 32 nursing homes in 4 Canadian cities were enrolled in Fall 2009, 2010 and 2011, and followed for one influenza season. Following influenza vaccination, peripheral blood mononuclear cells (PBMCs) were obtained and analysed by flow cytometry for T-regs, CD4+ and CD8+ T-cell subsets (CCR7+CD45RA+, CCR7-CD45RA+ and CD28-CD57+) and CMV-reactive CD4+ and CD8+ T-cells. Nasopharyngeal swabs were obtained and tested for viruses in symptomatic residents. A Cox proportional hazards model adjusted for age, sex and frailty, determined the relationship between immune phenotypes and time to viral infection. RESULTS: 1072 residents were enrolled; median age 86 years and 72% female. 269 swabs were obtained, 87 were positive for virus: influenza (24%), RSV (14%), coronavirus (32%), rhinovirus (17%), human metapneumovirus (9%) and parainfluenza (5%). In multivariable analysis, high T-reg% (HR 0.41, 95% CI 0.20–0.81) and high CMV-reactive CD4+ T-cell% (HR 1.69, 95% CI 1.03–2.78) were predictive of respiratory viral infection. CONCLUSIONS: In elderly nursing home residents, high CMV-reactive CD4+ T-cells were associated with an increased risk and high T-regs were associated with a reduced risk of respiratory viral infection.


title: Association of Seropositivity for Influenza and Coronaviruses with History of Mood Disorders and Suicide Attempts

text: BACKGROUND: Anecdotal reports of mood disorder following infection with common respiratory viruses with neurotropic potential have been in existence since the last century. Nevertheless, systematic studies on the association between these viruses and mood disorders are lacking. METHODS: Influenza A, B and coronavirus antibody titers were measured in 257 subjects with recurrent unipolar and bipolar disorder and healthy controls, by SCID. Pearson’s χ(2) tests and logistic regression models were used to analyze associations between seropositivity for coronaviruses, influenza A and B viruses and the following: a) history of recurrent mood disorders b) having attempted suicide in the past c) uni- vs. bi-polarity and d) presence of psychotic features during mood episodes. RESULTS: Seropositivity for influenza A (p=0.004), B (p<0.0001) and coronaviruses (p<0.0001) were associated with history of mood disorders but not with the specific diagnosis of unipolar or bipolar depression. Seropositivity for influenza B was significantly associated with a history of suicide attempt (p =0.001) and history of psychotic features (p =0.005). LIMITATIONS: The design was cross-sectional Socioeconomic factors, inflammatory markers, and axis II psychopathology were not assessed. CONCLUSIONS: The association of seropositivity for influenza and coronaviruses with a history of mood disorders, and influenza B with suicidal behavior require replication in larger longitudinal samples. The need for these studies is additionally supported by the high incidence of these viral infections, the high prevalence of mood disorders, and resilience of suicide epidemics.


title: Reservoirs and vectors of emerging viruses

text: Wildlife, especially mammals and birds, are hosts to an enormous number of viruses, most of which we have absolutely no knowledge about even though we know these viruses circulate readily in their specific niches. More often than not, these viruses are silent or asymptomatic in their natural hosts. In some instances, they can infect other species, and in rare cases, this cross-species transmission might lead to human infection. There are also instances where we know the reservoir hosts of zoonotic viruses that can and do infect humans. Studies of these animal hosts, the reservoirs of the viruses, provide us with the knowledge of the types of virus circulating in wildlife species, their incidence, pathogenicity for their host, and in some instances, the potential for transmission to other hosts. This paper describes examples of some of the viruses that have been detected in wildlife, and the reservoir hosts from which they have been detected. It also briefly explores the spread of arthropod-borne viruses and their diseases through the movement and establishment of vectors in new habitats.


title: Optimism-pessimism, conspiracy theories and general trust as factors contributing to COVID-19 related behavior – A cross-cultural study

text: The main aim of this research was to examine the role of optimism-pessimism, general trust and belief in conspiracy theories, in COVID-19 related fears, preventive and hoarding behaviors. We also examined the role of different sources of information in these relations. The convenience sample was used (N = 412) and it consisted of individuals from Serbia (N = 292) and Latin-America (N = 120). Following instruments were used: The Life Orientation Test (Scheier, Carver, & Bridges, 1994), Trust in people scale (Arbor, 1964), questions regarding fear, source of information, preventive behaviors and conspiracy constructed for the purposes of this research. The results suggest that fear of food shortage was the most pronounces one in both samples, followed by fear for oneself and finally by the fear for beloved others. Results suggest that optimists, those with high level of general trust and those who do not believe in conspiracy theories show lower level of fear and higher level of preventive behaviors. Pessimists on the other hand, show higher level of fear. Fear was related to all information sources suggesting that more information leads to higher intensity of fear – except information from the president which did not show any effect.


title: Pandemic Surge Models in the Time of Severe Acute Respiratory Syndrome Coronavirus-2: Wrong or Useful?

text: Public health decision making during the COVID-19 pandemic involves tradeoffs, uncertainty, and values, and models have been developed to inform administrative and policy decision makers to forecast demand for hospital resources, to understand hospital capacity constraints, and to determine when peak demand occurs. This editorial discusses fundamental differences among 3 models in current use.


title: The annual Hajj pilgrimage—minimizing the risk of ill health in pilgrims from Europe and opportunity for driving the best prevention and health promotion guidelines

text: Summary Mass gatherings at religious events can pose major public health challenges, particularly the transmission of infectious diseases. Every year the Kingdom of Saudi Arabia (KSA) hosts the Hajj pilgrimage, the largest gathering held on an annual basis where over 2 million people come to KSA from over 180 countries. Living together in crowded conditions exposes the pilgrims and the local population to a range infectious diseases. Respiratory and gastrointestinal tract bacterial and viral infections can spread rapidly and affect attendees of mass gatherings. Lethal infectious disease outbreaks were common during Hajj in the 19th and 20th centuries although they have now been controlled to a great extent by the huge investments made by the KSA into public health prevention and surveillance programs. The KSA provides regular updated Hajj travel advice and health regulations through international public health agencies such as the WHO, Public Health England, the Centers for Disease Control and Prevention, and Hajj travel agencies. During the Hajj, an additional 25 000 health workers are deployed; there are eight hospitals in Makkah and Mina complete with state-of-the-art surgical wards and intensive care units made specifically available for pilgrims. All medical facilities offer high quality of care, and services are offered free to Hajj pilgrims to ensure the risks of ill health to all pilgrims and KSA residents are minimal. A summary of the key health issues that arise in pilgrims from Europe during Hajj and of the KSA Hajj guidelines, together with other factors that may play a role in reducing the risks to pilgrims and to wider global health security, is provided herein.


title: Swine enteric coronavirus disease: A review of 4 years with porcine epidemic diarrhoea virus and porcine deltacoronavirus in the United States and Canada

text: Swine enteric coronaviruses, including porcine epidemic diarrhoea virus (PEDV) and porcine deltacoronavirus (PDCoV), have emerged and spread throughout the North American swine industry over the last four years. These diseases cause significant losses within the pork industry and within the first year after PEDV introduction, approximately 10% of the US herd died due to the disease. Similar to other enteric coronaviruses, such as transmissible gastroenteritis virus (TGEV), these emerging swine enteric coronavirus diseases (SECD) are age‐dependent, with high morbidity and mortality in neonatal pigs. Since the introduction of SECD, research has focused on investigating viral pathogenesis through experimental inoculation, increasing maternal antibody for neonatal protection, understanding transmission risks through feed and transportation, and outlining the importance of biosecurity in preventing SECD introduction and spread. A survey of swine professionals conducted for this review revealed that the majority of respondents (75%) believe SECD can be eradicated and that most herds have been successful at long‐term elimination of SECD after exposure (80%). However, unique properties of SECD, such as ineffective immunity through parenteral vaccination and a low oral infectious dose, play a major role in management of SECD. This review serves to describe the current knowledge of SECD and the characteristics of these viruses which provide both opportunities and challenges for long‐term disease control and potential eradication from the US swine population.


title: Disease Diffusion

text: Geographically, disease distribution or occurrence can be perceived either as the locations where cases are found or as the places where the necessary circumstances for causing illness are prevalent. Spatial diffusion theory distinguishes between two dimensions of a diffusion process. On the one hand, the routes may be determined by proximity – spreading to nearby places – or by hierarchical levels – spreading between places in a stepwise manner. On the other hand, the structure of diffusion appears as either expansion or relocation. The geographical context of health and disease can be conceived as epidemiological landscapes or landscapes of exposure. These are dynamic, i.e., their contents and extensions will change over time. The epidemiological transition might appear as a spatial diffusion of diseases, but is rather the outcome of changing ecological preconditions for disease and disease determinants. Increasing spatial connectivity has radically altered the routes and speed of diffusion. Global and local environmental changes alter the prospects for health. In the future, climatic change might affect the living conditions for agents and vectors involved in disease ecology. Understanding the geographical diffusion of diseases is important for predicting and containing diseases. GIS can be very useful tools for public health surveillance, simulation, analysis, and early warning.


title: Reassessing the risk from rabies: A continuing threat to the UK?

text: Abstract The threat of re-introduction of rabies virus into the United Kingdom exists on several levels. Firstly, importation of live animals into the UK continues to challenge the regulations in place to ensure that the virus does not enter the country. Secondly, the indigenous bat population is known to carry a virus genetically related to rabies virus, the European bat lyssavirus (EBLV). Molecular characterization of this virus has further characterized it as being EBLV type 2, genetically distinct from a similar virus that has caused several human deaths across Europe. Finally, a lack of awareness of the threat of rabies and related viruses to travelers visiting endemic areas also constitutes a re-introduction threat to the UK population. This review will address the most recent cases of lyssavirus infection, in both humans and animals, either contracted within the UK or from abroad. We highlight the current diagnostic necessity for testing indigenous and foreign cases and comment on current UK government policy in light of a European call to harmonise rabies legislation across Europe.


title: Chapter 3.2 Viral Infections of Laboratory Mice

text: Viral infections of laboratory mice have considerable impact on research results, and prevention of such infections is therefore of crucial importance. This chapter covers infections of mice with the following viruses: herpesviruses, mousepox virus, murine adenoviruses, polyomaviruses, parvoviruses, lactate dehydrogenase-elevating virus, lymphocytic choriomeningitis virus, mammalian orthoreovirus serotype 3, murine hepatitis virus, murine norovirus, murine pneumonia virus, murine rotavirus, Sendai virus, and Theiler’s murine encephalomyelitis virus. For each virus, there is a description of the agent, epizootiology, clinical symptoms, pathology, methods of diagnosis and control, and its impact on research.


title: Screening of a composite library of clinically used drugs and well-characterized pharmacological compounds for cystathionine β-synthase inhibition identifies benserazide as a drug potentially suitable for repurposing for the experimental therapy of colon cancer

text: Cystathionine-β-synthase (CBS) has been recently identified as a drug target for several forms of cancer. Currently no potent and selective CBS inhibitors are available. Using a composite collection of 8871 clinically used drugs and well-annotated pharmacological compounds (including the LOPAC library, the FDA Approved Drug Library, the NIH Clinical Collection, the New Prestwick Chemical Library, the US Drug Collection, the International Drug Collection, the `Killer Plates' collection and a small custom collection of PLP-dependent enzyme inhibitors), we conducted an in vitro screen in order to identify inhibitors for CBS using a primary 7-azido-4-methylcoumarin (AzMc) screen to detect CBS-derived hydrogen sulfide (H(2)S) production. Initial hits were subjected to counterscreens using the methylene blue assay (a secondary assay to measure H(2)S production) and were assessed for their ability to quench the H(2)S signal produced by the H(2)S donor compound GYY4137. Four compounds, hexachlorophene, tannic acid, aurintricarboxylic acid and benserazide showed concentration-dependent CBS inhibitory actions without scavenging H(2)S released from GYY4137, identifying them as direct CBS inhibitors. Hexachlorophene (IC(50): ~60 μM), tannic acid (IC(50): ~40 μM) and benserazide (IC(50): ~30 μM) were less potent CBS inhibitors than the two reference compounds AOAA (IC(50): ~3 μM) and NSC67078 (IC(50): ~1 μM), while aurintricarboxylic acid (IC(50): ~3 μM) was equipotent with AOAA. The second reference compound NSC67078 not only inhibited the CBS-induced AzMC fluorescence signal (IC(50): ~1 μM), but also inhibited with the GYY4137-induced AzMC fluorescence signal with (IC(50) of ~6 μM) indicative of scavenging/non-specific effects. Hexachlorophene (IC(50): ~6 μM), tannic acid (IC(50): ~20 μM), benserazide (IC(50): ~20 μM), and NSC67078 (IC(50): ~0.3 μM) inhibited HCT116 colon cancer cells proliferation with greater potency than AOAA (IC(50): ~300 μM). In contrast, although a CBS inhibitor in the cell-free assay, aurintricarboxylic acid failed to inhibit HCT116 proliferation at lower concentrations, and stimulated cell proliferation at 300 μM. Copper-containing compounds present in the libraries, were also found to be potent inhibitors of recombinant CBS; however this activity was due to the CBS inhibitory effect of copper ions themselves. However, copper ions, up to 300 μM, did not inhibit HCT116 cell proliferation. Benserazide was only a weak inhibitor of the activity of the other H(2)S-generating enzymes CSE and 3-MST activity (16% and 35% inhibition at 100 μM, respectively) in vitro. Benserazide suppressed HCT116 mitochondrial function and inhibited proliferation of the high CBS-expressing colon cancer cell line HT29, but not the low CBS-expressing line, LoVo. The major benserazide metabolite 2,3,4-trihydroxybenzylhydrazine also inhibited CBS activity and suppressed HCT116 cell proliferation in vitro. In an in vivo study of nude mice bearing human colon cancer cell xenografts, benserazide (50 mg/kg/day s.q.) prevented tumor growth. In silico docking simulations showed that benserazide binds in the active site of the enzyme and reacts with the PLP cofactor by forming reversible but kinetically stable Schiff base-like adducts with the formyl moiety of pyridoxal. We conclude that benserazide inhibits CBS activity and suppresses colon cancer cell proliferation and bioenergetics in vitro, and tumor growth in vivo. Further pharmacokinetic, pharmacodynamic and preclinical animal studies are necessary to evaluate the potential of repurposing benserazide for the treatment of colorectal cancers.


title: First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020

text: In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters’ index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases.


title: SmartBac, a new baculovirus system for large protein complex production

text: Abstract Recent revolution of cryo-electron microscopy has opened a new door to solve high-resolution structures of macromolecule complexes without crystallization while how to efficiently obtain homogenous macromolecule complex sample is therefore becoming a bottleneck. Here we report SmartBac, an easy and versatile system for constructing large-sized transfer plasmids used to generate recombinant baculoviruses that express large multiprotein complexes in insect cells. The SmartBac system integrates the univector plasmid-fusion system, Gibson assembly method and polyprotein strategy to construct the final transfer plasmid. The fluorescent proteins are designed co-expressed with the target to monitor transfection and expression efficiencies. A scheme of screening an optimal tagged subunit for efficient purification is provided. Six large multiprotein complexes including the human exocyst complex and dynactin complex were successfully expressed and purified, suggesting a great potential of SmartBac system for its wide application in the future.


title: Influence of BioChrome on the response of metabolic hormones in PEMS-infected poults 1

text: Abstract Poult enteritis and mortality syndrome (PEMS), a disease that affects turkeys between 7 and 28 d of age, causes a severe inflammation of the intestinal tract and is characterized in poults by severe diarrhea, high morbidity, mortality, and stunting. The PEMS-associated mortality and growth depression is related to malabsorption and decreased metabolic activity caused, in part, by a possible insulin deficiency or insensitivity. Insulin receptors are stimulated by the glucose tolerance factor (GTF) that incorporates Cr. Body Cr deficiency can be exacerbated by dietary deficiency and by increased excretion due to stress associated with a diarrheal disease such as PEMS. BioChrome® (BC) contains natural, preformed GTF, the bioactive form of Cr. Experiments were conducted in which BC was blended into poult starter feed at 400 ppb during the first 21 d posthatch. Body weights were determined at 1, 7, 14, and 21 d of age, and weekly feed conversions were calculated for each treatment group (control, BC, PEMS, and BC+PEMS). At 6 d post-hatch, each PEMS-designated poult was given a 0.1-mL oral gavage of a 10% suspension of feces from PEMS-infected poults. Blood samples were taken via cardiac puncture from four birds per treatment group at 7, 10, 14, 17, and 21 d of age. Radioimmunoassays were conducted for plasma insulin, glucagon, thyroxine (T4), and triiodothyronine (T3). Plasma insulin levels were depressed in PEMS-infected poults from Days 10 through 17, but plasma glucagon levels in the PEMS-infected poults were significantly elevated at 14 and 17 d, after which they returned to control levels in both of the PEMS-infected groups. The T3 and T4 levels were depressed through Day 21 in PEMS-infected poults, but with BC treatment these blood hormone levels rebounded by Day 21. Body weights of PEMS-infected poults were increased significantly by the BC treatment but not to the level of noninfected controls.


title: Monomeric catechin and dimeric procyanidin B2 against human norovirus surrogates and their physicochemical interactions

text: Abstract Plant polyphenols have shown antiviral activity against several human pathogens, but their physicochemical interactions are not well-understood. The objectives of this study were to compare the antiviral activity between monomeric catechin and dimeric procyanidin B2 (PB2) using cultivable human norovirus surrogates (feline calicivirus (FCV-F9) and murine norovirus (MNV-1)) and to understand their potential antiviral mechanism using virus-like particles (VLPs) and the P domain of human norovirus GII (HNoV GII.4). Surrogate viruses at 5 log PFU/mL were treated with 0.5–5 mg/mL monomeric catechin monohydrate, PB2 or phosphate buffered saline (PBS, pH 7.2; control) at 37 °C over 24 h. Infectivity was determined using plaque assays and data from triplicate experiments were statistically analyzed. PB2 at 0.5 mg/mL and 1 mg/mL reduced FCV-F9 to undetectable levels after 3 h and MNV-1 by 0.21 and 1.23 log PFU after 24 h, respectively. Monomeric catechins at 1 mg/mL reduced FCV-F9 to undetectable levels after 6 h and MNV-1 titers to undetectable levels after 24 h. In addition, PB2 was shown to directly bind the P domain, the main capsid structure of HNoVs in the ratio of 1:1 through spontaneous interactions. Electrostatic interactions played a dominant role between PB2 and the P domain. PB2 significantly altered tertiary but not secondary structures of VLPs. Transmission electron microscopy demonstrated that PB2 aggregated VLPs, further indicating interactions between them. These findings indicate that PB2 causes structural changes of the P domain of VLPs, mainly through direct interaction leading to HNoV inactivation.


title: Daily Surveillance of COVID-19 using the Prospective Space-Time Scan Statistic in the United States

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first discovered in late 2019 in Wuhan City, China. The virus may cause novel coronavirus disease 2019 (COVID-19) in symptomatic individuals. Since December of 2019, there have been over 7,000,000 confirmed cases and over 400,000 confirmed deaths worldwide. In the United States (U.S.), there have been over 2,000,000 confirmed cases and over 110,000 confirmed deaths. COVID-19 case data in the United States has been updated daily at the county level since the first case was reported in January of 2020. There currently lacks a study that showcases the novelty of daily COVID-19 surveillance using space-time cluster detection techniques. In this paper, we utilize a prospective Poisson space-time scan statistic to detect daily clusters of COVID-19 at the county level in the contiguous 48 U.S. and Washington D.C. As the pandemic progresses, we generally find an increase of smaller clusters of remarkably steady relative risk. Daily tracking of significant space-time clusters can facilitate decision-making and public health resource allocation by evaluating and visualizing the size, relative risk, and locations that are identified as COVID-19 hotspots.


title: Clinical Characteristics and Outcome for Four SARS-CoV-2-infected Cancer Patients Treated with Immune Checkpoint Inhibitors

text: Preliminary data suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with higher mortality among cancer patients, particularly in those on systemic therapy. It is unclear whether this applies to patients receiving immune checkpoint inhibitors (ICIs). In this case series, 74 patients from a single institution with genitourinary (GU) cancer on ICI were followed up during a 12-wk period. During this period, 11 patients (15%) developed symptoms consistent with coronavirus disease 2019 (COVID-19) and four (5%) tested positive. Two patients had metastatic urothelial cancer (treated with atezolizumab) and two had metastatic renal cancer (treated with ipilimumab and nivolumab). All had additional risk factors associated with COVID-19 mortality and two received steroids within 1 mo of infection. Two patients developed symptoms requiring hospitalisation. All four are alive 32–45 d after their first symptoms and 28–38 d after testing positive. These patients all had multiple risk factors associated with severe COVID-19. These data suggest that the higher risk of COVID-19 death associated with systemic therapy in cancer may not apply to patients on ICIs. Assessment of COVID-19 severity in these patients can be complicated by the underlying cancer and its treatment.


title: Acute Type A Aortic Dissection during COVID-19 Outbreak

text: Abstract As of April 7, 2020, approximately 1,300,000 cases and 80,000 deaths related to coronavirus disease 2019 (COVID-19) have been reported in > 180 countries/territories. Healthcare infrastructures and resources, particularly as it relates to the care of the most critically ill patients, are currently being strained globally. In this context, however, there has been little clinical guidance or information regarding life-threatening conditions requiring emergency surgery that cannot be delayed. We herein present a case of acute type A aortic dissection with COVID-19 in order to highlight the clinical implications of a true emergent procedure during the COVID-19 outbreak.


Abstract Background Despite the mainly reassuring outcomes for pregnant women with COVID-19 infection reported by previous case series with small sample sizes, some recent reports of severe maternal morbidity requiring intubation and of maternal deaths show the need for additional data about the impact of COVID-19 on pregnancy outcomes. This study aimed to report the maternal characteristics and clinical outcomes of pregnant women with COVID-19 disease. Study design This retrospective single-center study includes all consecutive pregnant women with confirmed (laboratory-confirmed) or suspected (according to version 7.0 of the Chinese management guideline) COVID-19 infection, regardless of gestational age at diagnosis, admitted to the Strasbourg University Hospital (France) from March 1 to April 3, 2020. Maternal characteristics, laboratory and imaging findings, and maternal and neonatal outcomes were extracted from medical records. Results The study includes 54 pregnant women with confirmed (n=38) and suspected (n=16) COVID-19 infection. Of these, 32 had an ongoing pregnancy, one a miscarriage, and 21 live births: 12 vaginal and 9 cesarean deliveries. Among the women who gave birth, preterm deliveries were medically indicated for their COVID-19-related condition for 23.8% (5/21): 14.3% (3/21) before 32 weeks' gestation and 9.5% (2/21) before 28 weeks. Oxygen support was required for 24.1% (13/54), including high flow oxygen (n=2), noninvasive (n=1) and invasive (n=3) mechanical ventilation, and extracorporeal membrane oxygenation (n=1). Of these, three, aged 35 years or older with positive COVID-19 RT-PCR, had respiratory failure requiring indicated delivery before 29 weeks' gestation. All three women were overweight or obese, and two had an additional comorbidity. Conclusion COVID-19 in pregnancy was associated with maternal morbidity and preterm birth. Its association with other well-known risk factors for severe maternal morbidity in noninfected pregnant women, including maternal age above 35 years, overweight, and obesity, suggests further studies are required to determine whether these risk factors are also associated with poorer maternal outcome in these women.


title: Influence of coronavirus (transmissible gastroenteritis) infection on jejunal myoelectrical activity of the neonatal pig

text: Abstract Four silver—silver chloride electrodes were surgically implanted at 5-cm intervals on the jejunal serosa of 7 neonatal pigs. Daily recordings, 7 h in duration, were made from each piglet beginning 3 days after surgery. Characteristic migrating motility complexes and short, distinct (2.5–5.0 s), rapidly aboral migrating bursts of intense spike activity (“migrating action potential complexes”) were seen in all preinfection recordings. Piglets were inoculated with a 1-ml oral dose of a 0.1% gut suspension from coronavirus (transmissible gastroenteritis) infected pigs. This resulted in inappetence, vomiting, and diarrhea, most marked on the second day postinfection, but which had abated by the third day. When compared to recordings from both fed and fasted noninfected (control) animals, infection significantly altered jejunal myoelectrical activity by (a) shortening the duration of the migrating motility complex on day 1 postinfection and prolonging it on day 2, (b) increasing the number of abnormal activity fronts, and (c) decreasing the number of migrating action potential complexes. Slow wave frequency and the duration of phase 3 of the migrating motility complex were unaffected. When compared to fed control animals, infected piglets also showed a slight shortening of phase 1 of the migrating motility complex on day 1 postinfection and a prolongation on days 2 and 3, as well as a shortening of phase 2 on the second and third days postinfection. Changes in myoelectrical activity were not solely due to decreases in food intake, as abnormalities persisted when food intake returned to normal on postinfection day 3, and disruption of the activity front and migrating motility complex duration were purely transmissible-gastroenteritis-virus-induced phenomena. These findings suggest that infection with transmissible gastroenteritis virus disrupts organized propulsive activity in the jejunum of the neonatal pig.


title: Insertion of the CXC chemokine ligand 9 (CXCL9) into the mouse hepatitis virus genome results in protection from viral-induced encephalitis and hepatitis

text: The role of the CXC chemokine ligand 9 (CXCL9) in host defense following infection with mouse hepatitis virus (MHV) was determined. Inoculation of the central nervous system (CNS) of CXCL9−/− mice with MHV resulted in accelerated and increased mortality compared to wildtype mice supporting an important role for CXCL9 in antiviral defense. In addition, infection of RAG1−/− or CXCL9−/− mice with a recombinant MHV expressing CXCL9 (MHV-CXCL9) resulted in protection from disease that correlated with reduced viral titers within the brain and NK cell-mediated protection in the liver. Survival in MHV-CXCL9-infected CXCL9−/− mice was associated with reduced viral burden within the brain that coincided with increased T cell infiltration. Similarly, viral clearance from the livers of MHV-CXCL9-infected mice was accelerated but independent of increased T cell or NK cell infiltration. These observations indicate that CXCL9 promotes protection from coronavirus-induced neurological and liver disease.


title: Former Minister Zhang's discourse on SARS: Government's image restoration or destruction?

text: Abstract This study analyzes the image repair discourse by Chinese Health Minister Zhang Wenkang's discourse on SARS. The minister faced several accusations: the SARS outbreak was growing, the Chinese government had covered up the severity of this problem, the Chinese government ignored Taiwanese who suffered from SARS, and the Health Ministry provided information that was neither timely nor accurate. He employed several image repair strategies (denial, defeasibility, bolstering, minimization, differentiation, attack accuser, and corrective action). However, his messages were contradictory and apparently related on false information, so his efforts were unsuccessful and he was stripped of his office.