title: Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence

text: Importance: Vitamin D treatment has been found to decrease incidence of viral respiratory tract infection, especially in vitamin D deficiency. It is unknown whether COVID-19 incidence is associated with vitamin D deficiency and treatment. Objective: To examine whether vitamin D deficiency and treatment are associated with testing positive for COVID-19. Design: Retrospective cohort study Setting: University of Chicago Medicine Participants: Patients tested for COVID-19 from 3/3/2020-4/10/2020. Vitamin D deficiency was defined by the most recent 25-hydroxycholecalciferol <20ng/ml or 1,25-dihydroxycholecalciferol <18pg/ml within 1 year before COVID-19 testing. Treatment was defined by the most recent vitamin D type and dose, and treatment changes between the time of the most recent vitamin D level and time of COVID-19 testing. Vitamin D deficiency and treatment changes were combined to categorize vitamin D status at the time of COVID-19 testing as likely deficient(last-level-deficient/treatment-not-increased), likely sufficient(last-level-not-deficient/treatment-not-decreased), or uncertain deficiency(last-level-deficient/treatment-increased or last-level-not-deficient/treatment-decreased). Main Outcomes and Measures: The main outcome was testing positive for COVID-19. Multivariable analysis tested whether the most recent vitamin D level and treatment changes after that level were associated with testing positive for COVID-19 controlling for demographic and comorbidity indicators. Bivariate analyses of associations of treatment with vitamin D deficiency and COVID-19 were performed. Results: Among 4,314 patients tested for COVID-19, 499 had a vitamin D level in the year before testing. Vitamin D status at the time of COVID-19 testing was categorized as likely deficient for 127(25%) patients, likely sufficient for 291(58%) patients, and uncertain for 81(16%) patients. In multivariate analysis, testing positive for COVID-19 was associated with increasing age(RR(age<50)=1.05,p<0.021;RR(age[≥]50)=1.02,p<0.064)), non-white race(RR=2.54,p<0.01) and being likely vitamin D deficient (deficient/treatment-not-increased:RR=1.77,p<0.02) as compared to likely vitamin D sufficient(not-deficient/treatment-not-decreased), with predicted COVID-19 rates in the vitamin D deficient group of 21.6%(95%CI[14.0%-29.2%] ) versus 12.2%(95%CI[8.9%-15.4%]) in the vitamin D sufficient group. Vitamin D deficiency declined with increasing vitamin D dose, especially of vitamin D3. Vitamin D dose was not significantly associated with testing positive for COVID-19. Conclusions and Relevance: Vitamin D deficiency that is not sufficiently treated is associated with COVID-19 risk. Testing and treatment for vitamin D deficiency to address COVID-19 warrant aggressive pursuit and study.


title: Chapter 14 Kampo Medicines for Infectious Diseases

text: Abstract Numerous Kampo medicines and Oriental herbs have been used for the treatment of infectious diseases for several reasons, such as genetic background, economical reasons, fewer adverse effects, and so on. This chapter describes Kampo medicines and related Oriental herbs that are effective or promising in the treatment of infectious diseases at the clinical level and/or in animal models. In addition, effective Kampo medicines tested in vitro in cultured-cell studies are also included in this chapter. Each section is categorized by infectious disease and according to the popularity of the Kampo medicine.


title: Assessment of intestinal damage in rotavirus infected neonatal mice by a d-xylose absorption test

text: Abstract A d-xylose absorption test has been standardized for use in newborn mice. It was used to measure small intestine dysfunction in neonate mice following infection with various isolates of rotaviruses. A xylose dose of 1 mg/g body weight was required to produce a maximum level of 100 μg/100 μl of plasma 2 h after administration of d-xylose. The mice inoculated with rotavirus absorbed significantly less d-xylose compared with uninoculated control mice. A micromethod is described which proved to be suitable to quantitate d-xylose for determination of absorptive function of the small intestine in small animals such as newborn mice.


title: Activation and Role of NACHT, LRR, and PYD Domains-Containing Protein 3 Inflammasome in RNA Viral Infection

text: NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome activation and effects during ribonucleic acid (RNA) viral infection are the focus of a wide range of research currently. Both the pathogen-associated molecule pattern derived from virions and intracellular stress molecules involved in the process of viral infection lead to activation of the NLRP3 inflammasome, which in turn triggers inflammatory responses for antiviral defense and tissue healing. However, aberrant activation of the NLRP3 inflammasome can instead support viral pathogenesis and promote disease progression. Here, we summarize and expound upon the recent literature describing the molecular mechanisms underlying the activation and effects of the NLRP3 inflammasome in RNA viral infection to highlight how it provides protection against RNA viral infection.


title: Vaccines in a hurry

text: Abstract Preparing populations for health threats, including threats from new or re-emerging infectious diseases is recognised as an important public health priority. The development, production and application of emergency vaccinations are the important measures against such threats. Vaccines are cost-effective tools to prevent disease, and emergency vaccines may be the only means to prevent a true disaster for global society in the event of a new pandemic with potential to cause morbidity and mortality comparable to the Spanish flu, the polio epidemics in the 1950s, or the SARS outbreak in 2003 if its spread had not been contained in time. Given the early recognition of a new threat, and given the advances of biotechnology, vaccinology and information systems, it is not an unrealistic goal to have promising prototype vaccine candidates available in a short time span following the identification of a new infectious agent; this is based on the assumption that the emerging infection is followed by natural immunity. However, major bottlenecks for the deployment of emergency vaccine are lack of established systems for fast-track regulatory approval of such candidates and limited international vaccine production capacity. In the present discussion paper, we propose mechanisms to facilitate development of emergency vaccines in Europe by focusing on public–private scientific partnerships, fast-track approval of emergency vaccine by regulatory agencies and proposing incentives for emergency vaccine production in private vaccine companies.


title: Some Cell Culture Procedures in Diagnostic Medical Virology

text: This chapter discusses the cell culture procedures as an invaluable tool in diagnostic medical virology. Culture of cells in monolayers is the most common method used in diagnostic virology laboratories. Primary or secondary cultures cells retain their diploid chromosome number, a factor which makes them particularly susceptible to certain viruses. The ideal cell system for a diagnostic virology laboratory would be a continuous line which retained its diploid chromosome number. It would be impossible in a routine laboratory to inoculate each specimen into every type of cell culture. A routine procedure is therefore employed and the specimen is inoculated into three types of cells which will support the growth of as many viruses as possible. Mixed culture technique (cocultivation) has proved of value when a viral agent is difficult to isolate from the original tissue, for example, isolation of measles from a brain biopsy. Cultures of chopped tissues have been used for many years to support the growth of viruses but the techniques were not readily applicable to diagnostic virology. A simple method of cultivating fragments of ciliated epithelium was described, which resulted in the isolation of new rhinoviruses and a new member of the corona virus group.


COVID-19 and the Challenges of Frailty Screening in Older Adults


title: Clinical course and treatment efficacy of COVID‐19 near Hubei Province, China: a multicentre, retrospective study

text: Currently, COVID‐19 has been reported in nearly all countries globally. To date, little is known about the viral shedding duration, clinical course, and treatment efficacy of COVID‐19 near Hubei Province, China. This multicentre, retrospective study was performed in 12 hospitals in Henan and Shaanxi Provinces from January 20 to February 8, 2020. Clinical outcomes were followed up until March 26, 2020. The viral shedding duration, full clinical course, and treatment efficacy were analysed in different subgroups of patients. A total of 149 COVID‐19 patients were enrolled. The median age was 42 years, and 61.1% (91) were males. Of them, 133 (89.3%) had fever, 131 of 144 (91%) had pneumonia, 27 (18.1%) required intensive care unit (ICU) management, 3 (2%) were pregnant, and 3 (2%) died. Two premature newborns were negative for SARS‐CoV‐2. In total, the median SARS‐CoV‐2 shedding period and clinical course were 12 (IQR: 9‐17; mean: 13.4, 95% CI: 12.5, 14.2) and 20 (IQR: 16‐24; mean: 21.2, 95% CI: 20.1, 22.3) days, respectively; and ICU patients had longer median viral shedding periods (21 [17‐24] vs 11 [9‐15]) and clinical courses (30 [22‐33] vs 19 [15.8‐22]) than non‐ICU patients (both p<0.0001). SARS‐CoV‐2 clearances occurred at least 2 days before fatality in 3 non‐survivors. Current treatment with any antiviral agent or combination did not present the benefit of shortening viral shedding period and clinical course (all p>0.05) in real‐life settings. In conclusion, the viral shedding duration and clinical course in Henan and Shaanxi Provinces were shorter than those in Hubei Province, and current antiviral therapies were ineffective for shortening viral shedding duration and clinical course in real‐world settings. These findings expand our knowledge of the SARS‐CoV‐2 infection and may be helpful for management of the epidemic outbreak of COVID‐19 worldwide. Further studies concerning effective antiviral agents and vaccines are urgently needed.


title: Characterisation of bubaline coronavirus strains associated with gastroenteritis in water buffalo (Bubalus bubalis) calves

text: Abstract Recently, a coronavirus strain (179/07-11) was isolated from water buffalo (Bubalus bubalis) and the virus which displayed a strict genetic and biological relatedness with bovine coronavirus (BCoV) was referred to as bubaline coronavirus (BuCoV). Here, we report the characterisation of four BuCoVs strains identified in the faeces or intestinal contents of water buffalo calves with acute gastroenteritis. Single BuCoV infections were detected in all but one cases from which two clostridia species were also isolated. Sequence and phylogenetic analyses of the 5′ end of the spike-protein gene showed that three BuCoVs were closely related to the prototype strain 179/07-11, whereas the fourth isolate (339/08-C) displayed a higher genetic identity to recent BCoV reference strains. Three strains adapted to the in vitro grow on human rectal tumour cells were also evaluated for their ability to replicate in a bovine cell line (Madin Darby bovine kidney) and to cause haemagglutination of chicken erythrocytes and all displayed biological properties similar to those already described for the prototype BuCoV. The present report shows that albeit genetically heterogeneous, the different BuCoV strains possess a common biological pattern which is different from most BCoV and BCoV-like isolates.


title: Chemotactic Ligands that Activate G-Protein-Coupled Formylpeptide Receptors

text: Leukocyte infiltration is a hallmark of inflammatory responses. This process depends on the bacterial and host tissue-derived chemotactic factors interacting with G-protein-coupled seven-transmembrane receptors (GPCRs) expressed on the cell surface. Formylpeptide receptors (FPRs in human and Fprs in mice) belong to the family of chemoattractant GPCRs that are critical mediators of myeloid cell trafficking in microbial infection, inflammation, immune responses and cancer progression. Both murine Fprs and human FPRs participate in many patho-physiological processes due to their expression on a variety of cell types in addition to myeloid cells. FPR contribution to numerous pathologies is in part due to its capacity to interact with a plethora of structurally diverse chemotactic ligands. One of the murine Fpr members, Fpr2, and its endogenous agonist peptide, Cathelicidin-related antimicrobial peptide (CRAMP), control normal mouse colon epithelial growth, repair and protection against inflammation-associated tumorigenesis. Recent developments in FPR (Fpr) and ligand studies have greatly expanded the scope of these receptors and ligands in host homeostasis and disease conditions, therefore helping to establish these molecules as potential targets for therapeutic intervention.


COVID-19 - Computed tomography findings in two patients in Petrópolis, Rio de Janeiro, Brazil


title: Estimation of incubation period distribution of COVID-19 using disease onset forward time: a novel cross-sectional and forward follow-up study

text: BACKGROUND: The current outbreak of coronavirus disease 2019 (COVID-19) has quickly spread across countries and become a global crisis. However, one of the most important clinical characteristics in epidemiology, the distribution of the incubation period, remains unclear. Different estimates of the incubation period of COVID-19 were reported in recent published studies, but all have their own limitations. In this study, we propose a novel low-cost and accurate method to estimate the incubation distribution. METHODS: We have conducted a cross-sectional and forward follow-up study by identifying those asymptomatic individuals at their time of departure from Wuhan and then following them until their symptoms developed. The renewal process is hence adopted by considering the incubation period as a renewal and the duration between departure and symptom onset as a forward recurrence time. Under mild assumptions, the observations of selected forward times can be used to consistently estimate the parameters in the distribution of the incubation period. Such a method enhances the accuracy of estimation by reducing recall bias and utilizing the abundant and readily available forward time data. FINDINGS: The estimated distribution of forward time fits the observations in the collected data well. The estimated median of incubation period is 8·13 days (95% confidence interval [CI]: 7·37–8·91), the mean is 8·62 days (95% CI: 8·02–9·28), the 90th percentile is 14·65 days (95% CI: 14·00–15·26), and the 99th percentile is 20·59 days (95% CI: 19·47, 21·62). Compared with results in other studies, the incubation period estimated in this study is longer. INTERPRETATION: Based on the estimated incubation distribution in this study, about 10% of patients with COVID-19 would not develop symptoms until 14 days after infection. Further study of the incubation distribution is warranted to directly estimate the proportion with long incubation periods.


title: Current status of Crimean-Congo haemorrhagic fever in the World Health Organization Eastern Mediterranean Region: issues, challenges, and future directions

text: Summary Crimean-Congo haemorrhagic fever (CCHF) is the most widespread, tick-borne viral disease affecting humans. The disease is endemic in many regions, such as Africa, Asia, Eastern and Southern Europe, and Central Asia. Recently, the incidence of CCHF has increased rapidly in the countries of the World Health Organization Eastern Mediterranean Region (WHO EMR), with sporadic human cases and outbreaks of CCHF being reported from a number of countries in the region. Despite the rapidly growing incidence of the disease, there are currently no accurate data on the burden of the disease in the region due to the different surveillance systems used for CCHF in these countries. In an effort to increase our understanding of the epidemiology and risk factors for the transmission of the CCHF virus (CCHFV; a Nairovirus of the family Bunyaviridae) in the WHO EMR, and to identify the current knowledge gaps that are hindering effective control interventions, a sub-regional meeting was organized in Muscat, Oman, from December 7 to 9, 2015. This article summarizes the current knowledge of the disease in the region, identifies the knowledge gaps that present challenges for the prevention and control of CCHFV, and details a strategic framework for research and development activities that would be necessary to curb the ongoing and new threats posed by CCHFV.


title: Host and Viral Factors in Respiratory Syncytial Virus Infection

text: Respiratory syncytial virus (RSV) is a major worldwide pathogen for which there is still no effective vaccine or antiviral treatment available, and immunoprophylaxis with RSV-specific antibodies (e.g., palivizumab) is used in limited clinical settings. In this review, we discuss virus–host interactions relevant to RSV pathobiology and how advances in cell and systems biology have accelerated knowledge in this area. We also highlight recent advances in understanding the relationship between RSV bronchiolitis and sequelae of recurrent wheezing and asthma, new findings into an intriguing interaction between RSV and air pollution, and exciting developments toward the goal of realizing a safe and effective RSV vaccine.


title: Chapter 16 A Pandemic Flu Outbreak in New Jersey

text: Publisher Summary In recent years, a number of books have been written about the worldwide influenza epidemic of 1918. Although medical care is much better now, mobility is also much greater, and thus there is the potential for infectious disease to spread much faster. This chapter is designed to test the knowledge of the legal concepts examined so far. Engaging with the exercise will give one a sense of strengths and weaknesses in understanding the material and will be good preparation for a final examination. The facts in the briefings and the scenario are grounded in science, but they are not intended to substitute for the most authoritative research. Obviously, the narrative and many of the details are invented. The exercise encompasses only a small number of the many issues that would arise when a real outbreak occur. While reading the scenario, it should be noted that some of the most important additional issues would be if the event actually occurred.


title: Peptidoglycan associated cyclic lipopeptide disrupts viral infectivity

text: Enteric viruses exploit bacterial components including lipopolysaccharides (LPS) and peptidoglycan (PG) to facilitate infection in humans. With origins in the bat enteric system, we wondered if severe acute respiratory syndrome-coronavirus (SARS-CoV) or Middle East respiratory syndrome-CoV (MERS-CoV) also use bacterial components to modulate infectivity. To test this question, we incubated CoVs with LPS and PG and evaluated infectivity finding no change following LPS treatment. However, PG from B. subtilis reduced infection >10,000-fold while PG from other bacterial species failed to recapitulate this. Treatment with an alcohol solvent transferred inhibitory activity to the wash and mass spectrometry revealed surfactin, a cyclic lipopeptide antibiotic, as the inhibitory compound. This antibiotic had robust dose- and temperature-dependent inhibition of CoV infectivity. Mechanistic studies indicated that surfactin disrupts CoV virion integrity and surfactin treatment of the virus inoculum ablated infection in vivo. Finally, similar cyclic lipopeptides had no effect on CoV infectivity and the inhibitory effect of surfactin extended broadly to enveloped viruses including influenza, Ebola, Zika, Nipah, Chikungunya, Una, Mayaro, Dugbe, and Crimean-Congo hemorrhagic fever viruses. Overall, our results indicate that peptidoglycan-associated surfactin has broad virucidal activity and suggest bacteria byproducts may negatively modulate virus infection. In this manuscript, we considered a role for bacteria in shaping coronavirus infection. Taking cues from studies of enteric viruses, we initially investigated how bacterial surface components might improve CoV infection. Instead, we found that peptidoglycan-associated surfactin is a potent viricidal compound that disrupts virion integrity with broad activity against enveloped viruses. Our results indicate that interactions with commensal bacterial may improve or disrupt viral infections highlighting the importance of understanding these microbial interactions and their implications for viral pathogenesis and treatment.


title: Chapter 5 Role of Chemokines in Rabies Pathogenesis and Protection

text: Abstract Chemokines are a family of structurally related proteins that are expressed by almost all types of nucleated cells and mediate leukocyte activation and/or chemotactic activities. The role of chemokines in rabies pathogenesis and protection has only recently been investigated. Expression of chemokines is induced by infection with laboratory-adapted, but not street, rabies viruses (RABVs), and it has been hypothesized that expression of chemokines is one of the mechanisms by which RABV is attenuated. To further define the role of chemokines in rabies pathogenesis and protection, chemokine genes such as MIP-1α, RANTES, IP-10, and macrophage-derived chemokine (MDC) have been cloned into RABV genome. It has been found that recombinant RABVs expressing RANTES or IP-10 induce high and persistent expression of these chemokines, resulting in massive infiltration of inflammatory cells into the central nervous system (CNS) and development of diseases and death in the mouse model. However, recombinant RABVs expressing MIP-1α, MDC, as well as GM-CSF further attenuate RABV by inducing a transient expression of chemokines, infiltration of inflammatory cells, enhancement of blood–brain barrier (BBB) permeability. Yet, these recombinant RABVs show increased adaptive immune responses by recruiting/activating dendritic cells, T and B cells in the periphery as well as in the CNS. Further, direct administration of these recombinant RABVs into the CNS can prevent mice from developing rabies days after infection with street RABV. All these studies together suggest that chemokines are both protective and pathogenic in RABV infections. Those with protective roles could be exploited for development of future RABV vaccines or therapeutic agents.


title: Preparedness of Hospitals in the Republic of Ireland for an Influenza Pandemic, an Infection Control Perspective

text: BACKGROUND: When an influenza pandemic occurs most of the population is susceptible and attack rates can range as high as 40–50 %. The most important failure in pandemic planning is the lack of standards or guidelines regarding what it means to be ‘prepared’. The aim of this study was to assess the preparedness of acute hospitals in the Republic of Ireland for an influenza pandemic from an infection control perspective. METHODS: This was a cross sectional study involving a questionnaire completed by infection control nurses, time period from June – July 2013, (3 weeks) from acute public and private hospitals in the Republic of Ireland. A total of 46 out of 56 hospitals responded to the questionnaire. RESULTS: From a sample of 46 Irish hospitals, it was found that Irish hospitals are not fully prepared for an influenza pandemic despite the 2009 Influenza A (H1N1) pandemic. In 2013, thirty five per cent of Irish hospitals have participated in an emergency plan or infectious disease exercise and have plans or been involved in local planning efforts to care for patients at non-health care facilities. Sixty per cent of Irish hospitals did not compile or did not know if the hospital had compiled a “lessons learned” from any exercise that were then used to revise emergency response plans. Fifty two per cent of hospitals have sufficient airborne isolation capacity to address routine needs and have an interim emergency plan to address needs during an outbreak. Fifty one percent of hospitals have taken specific measures to stockpile or have reserve medical supplies e.g. masks, ventilators and linen. CONCLUSIONS: This is the first study carried out in the Republic of Ireland investigating the current preparedness for an influenza pandemic from an infection control perspective. Deficits exist in the provision of emergency planning committees, testing of emergency plans, airborne isolation facilities, stockpiling of personal protective equipment (PPE) and medical supplies and organisational schemes/incentives for healthcare workers to continue to work in a pandemic. While Irish standards are comparable to findings from international studies, the health care service needs to continue to enhance preparedness for an influenza pandemic and implement standard preparedness guidance for all Irish hospitals.


title: (+)RNA viruses rewire cellular pathways to build replication organelles

text: Positive-strand RNA [(+)RNA] viruses show a significant degree of conservation of their mechanisms of replication. The universal requirement of (+)RNA viruses for cellular membranes for genome replication, and the formation of membranous replication organelles with similar architecture, suggest that they target essential control mechanisms of membrane metabolism conserved among eukaryotes. Recently, significant progress has been made in understanding the role of key host factors and pathways that are hijacked for the development of replication organelles. In addition, electron tomography studies have shed new light on their ultrastructure. Collectively, these studies reveal an unexpected complexity of the spatial organization of the replication membranes and suggest that (+)RNA viruses actively change cellular membrane composition to build their replication organelles.


title: Recommender Systems in Antiviral Drug Discovery

text: [Image: see text] Recommender systems (RSs), which underwent rapid development and had an enormous impact on e-commerce, have the potential to become useful tools for drug discovery. In this paper, we applied RS methods for the prediction of the antiviral activity class (active/inactive) for compounds extracted from ChEMBL. Two main RS approaches were applied: collaborative filtering (Surprise implementation) and content-based filtering (sparse-group inductive matrix completion (SGIMC) method). The effectiveness of RS approaches was investigated for prediction of antiviral activity classes (“interactions”) for compounds and viruses, for which some of their interactions with other viruses or compounds are known, and for prediction of interaction profiles for new compounds. Both approaches achieved relatively good prediction quality for binary classification of individual interactions and compound profiles, as quantified by cross-validation and external validation receiver operating characteristic (ROC) score >0.9. Thus, even simple recommender systems may serve as an effective tool in antiviral drug discovery.


title: Antimicrobial activity of novel synthesized coumarin based transitional metal complexes

text: OBJECTIVES: To synthesize new transitional metal complexes derived from 3-aryl-azo-4-hydroxy coumarin analogues and to evaluate their antimicrobial activities. METHODS: The syntheses of complexes of coumarin analogues were accomplished by mixing a hydro-alcoholic solution of 3-aryl-azo-4-hydroxy coumarin analogues with transition metal chlorides. The structural environment of the synthesized molecules was characterized using different instrumental methods. The antimicrobial activity of the compounds was determined by the agar well diffusion method. RESULTS: The cobalt complexes of (E)-3-((4-chlorophenyl) diazenyl)-4-hydroxy-2H-chromen-2-one (HL(1)): (4a) and (E)-3-((4-methoxyphenyl) diazenyl)-4-hydroxy-2H-chromen-2-one (HL(2)): (4e) showed excellent antimicrobial activities compared with their ligands. CONCLUSION: The reports of the antimicrobial investigation showed that the cobalt complexes of 3-aryl-azo-4-hydroxy coumarin analogues exhibited potential antimicrobial activity that was stronger than that of their ligands.


title: The Changing Face of Orthopedic Education: Searching for the New Reality After COVID-19

text: Abstract The COVID-19 pandemic has had immediate impact on the practice of medicine and orthopaedic education. As the practice of social distancing has been put into place to help slow the spread of disease as well as to conserve medical supplies and equipment, elective surgery has come to a grinding halt. This dramatic change has forced our leaders to critically evaluate the delivery of education and skills training for our residents, fellows as well as all orthopaedic surgeons. We must continue to develop technologies such as virtual meeting platforms, distance learning, simulation-based training, virtual reality andaugmented reality to augment the new world of orthopaedic education.


title: Clinical Outcomes of Coronavirus Disease 2019 With Evidence-based Supportive Care

text: Calls for adherence to evidence-based medicine have emerged during the initial wave of the COVID-19 pandemic but reports of outcomes are lacking. This retrospective study of an institutional cohort including 135 patients with confirmed COVID-19 demonstrates positive outcomes when organizational standards of care consist of evidence-based supportive therapies.


title: Inflammatory monocytes damage the hippocampus during acute picornavirus infection of the brain

text: BACKGROUND: Neuropathology caused by acute viral infection of the brain is associated with the development of persistent neurological deficits. Identification of the immune effectors responsible for injuring the brain during acute infection is necessary for the development of therapeutic strategies that reduce neuropathology but maintain immune control of the virus. METHODS: The identity of brain-infiltrating leukocytes was determined using microscopy and flow cytometry at several acute time points following intracranial infection of mice with the Theiler's murine encephalomyelitis virus. Behavioral consequences of immune cell depletion were assessed by Morris water maze. RESULTS: Inflammatory monocytes, defined as CD45(hi)CD11b(++)F4/80(+)Gr1(+)1A8(-), and neutrophils, defined as CD45(hi)CD11b(+++)F4/80(-)Gr1(+)1A8(+), were found in the brain at 12 h after infection. Flow cytometry of brain-infiltrating leukocytes collected from LysM: GFP reporter mice confirmed the identification of neutrophils and inflammatory monocytes in the brain. Microscopy of sections from infected LysM:GFP mice showed that infiltrating cells were concentrated in the hippocampal formation. Immunostaining confirmed that neutrophils and inflammatory monocytes were localized to the hippocampal formation at 12 h after infection. Immunodepletion of inflammatory monocytes and neutrophils but not of neutrophils only resulted in preservation of hippocampal neurons. Immunodepletion of inflammatory monocytes also preserved cognitive function as assessed by the Morris water maze. CONCLUSIONS: Neutrophils and inflammatory monocytes rapidly and robustly responded to Theiler's virus infection by infiltrating the brain. Inflammatory monocytes preceded neutrophils, but both cell types were present in the hippocampal formation at a timepoint that is consistent with a role in triggering hippocampal pathology. Depletion of inflammatory monocytes and neutrophils with the Gr1 antibody resulted in hippocampal neuroprotection and preservation of cognitive function. Specific depletion of neutrophils with the 1A8 antibody failed to preserve neurons, suggesting that inflammatory monocytes are the key effectors of brain injury during acute picornavirus infection of the brain. These effector cells may be important therapeutic targets for immunomodulatory or immunosuppressive therapies aimed at reducing or preventing central nervous system pathology associated with acute viral infection.


Headaches Due to Personal Protective Equipment During COVID‐19 Pandemic: A Comment


title: Severe Acute Respiratory Syndrome epidemic and change of people's health behavior in China

text: Severe Acute Respiratory Syndrome (SARS) has become a new worldwide epidemic whose origin was until recently unknown. It is the unpredictable nature of this epidemic that makes people want answers to some important questions about what they can do to protect themselves. This study presents an inquiry into people's knowledge and self-reported changes in behavior in response to the epidemic. Respondents were drawn from seven major occupational groups in the large central city of Wuhan. Although most respondents knew of SARS, there was still 8.4% who did not know about it. Knowledge was lowest among farmers who had come to the city for temporary work. Most respondents took action to avoid being infected by SARS, including, most commonly, efforts to improve indoor ventilation, to disinfect the indoor environment and to increase hand-washing frequency. Self-reported increases in hand-washing frequency were significant; however, among the seven occupational groups, reports of increased hand-washing were consistently greater among commercial service workers, students and farmers. While it seems that possible fears induced by the epidemic led to these changes, there are still about one-third of respondents who do not wash their hands as frequently as desired. There is also the challenge of devising strategies for maintaining the desired frequency of hand-washing among those who did change.


title: Panleucopénie féline aiguë : à propos d’un cas traité avec succès par l’interféron-ω

text: Résumé La panleucopénie féline est une infection virale (due à un petit parvovirus FPV). Ce virus est très stable et capable de survivre une année à température ambiante dans les matières organiques sur un support solide. Quasiment tous les chats sensibles sont exposés et infectés au cours de leur première année de vie. La forme aiguë de la maladie est fréquente, avec hyperthermie, anorexie et léthargie, précédant de trois ou quatre jours les premiers signes cliniques. Dans la plupart des cas, la mortalité peut être évitée par un traitement symptomatique et des soins appropriés. Cependant, la maladie, dans sa forme aiguë, est souvent associée à une bactériémie chez les jeunes chats non vaccinés, pouvant se révéler mortelle. Lorsqu’un traitement symptomatique n’est pas suffisamment efficace, le recours à une thérapie antivirale pourrait être une alternative. L’interféron recombinant félin oméga a été utilisé avec succès selon un protocole d’administration décrit, le statut médical du chat étant suivi avant, pendant et après le traitement mis en place. Summary Feline panleukopenia is caused by a small parvovirus (FPV) which is very stable and able to survive for one year at room temperature in organic material on solid fomites. Virtually all susceptible cats are exposed and infected within the first year of life. The acute form is common, with hyperthermia, depression and anorexia occurring within three to four days before presentation. In most cases, mortality caused by FPV infection can be avoided with appropriate symptomatic therapy and nursing care. However, severe clinical illness associated with bacteraemia is often the rule in young unvaccinated cats and frequently fatal. If a symptomatic therapy is not enough efficient, then it must be quickly associated with antiviral treatment. The feline recombinant interferon omega was used successfully, according to a published protocol design, the status of the cat being monitored before, during and after treatment.


title: Effects of acute and chronic dimethylamine exposure on the nasal mucociliary apparatus of F-344 rats

text: Abstract Dimethylamine (DMA) is a highly water soluble gas with many industrial applications. Male F-344 rats were exposed to 175 ppm DMA 6 hr per day for 1, 2, 4, or 9 days or 2 years. Gross changes in nasal structure were recorded, effects of DMA on the mucociliary apparatus were assessed using video analysis, and tissues were evaluated for histopathology. In vitro nasal mucociliary flow patterns, mucus flow rates, and ciliary activity were studied and recorded for video motion analysis. There were distinct and generally consistent differences in the shape of the naso-, maxillo-, and ethmoid turbinates between young and old animals. Acute and chronic DMA exposures resulted in erosion of the anterior margins of the naso- and maxillo-turbinates and fenestration of the adjacent septum. Ciliastasis and mucostasis were observed only on the anteromedial aspect of the maxilloturbinate. In the chronically exposed rats, mucociliary activity was present in areas adjacent to erosions of the turbinates and septum. Abnormal mucus flow patterns, including altered or reversed direction of flow and “whirlpool-like” formation, were observed in all treated rats, but were more severe following chronic exposure. There was a good correlation between the distribution of responses as assessed by histopathology and abnormal mucociliary function at all time points. In conclusion, the mucociliary apparatus continues to function in the nasal passages of rats having localized destruction of nasal epithelium, induced by DMA exposure, and this clearance system responds to alterations of nasal structure by modification of mucus flow patterns.


title: Epidemiological and clinical characteristics of respiratory viral infections in children in Shanghai, China

text: Acute respiratory tract infections (ARTIs) due to various viruses are not only the most common causes of upper and lower respiratory infection but are also major causes of morbidity and mortality in children. In this study, we investigated the prevalence and clinical characteristics of children with virus-related ARTIs and determined the spectrum of respiratory viruses and their correlation with meteorological variables in Jiading District, Shanghai, China. Nasopharyngeal swabs from 2819 children with ARTIs were collected from August 2011 to December 2014, and used for detection of respiratory viruses by multiplex RT-PCR. Seventeen respiratory viruses were detected among 691 (24.5 %) of 2819 patients. The highest prevalence of respiratory viruses was detected in the age group of less than 1 year (29.0 %), and the prevalence decreased with age. This suggests that children less than one year old are the most susceptible to infection. Influenza virus (IFV) was the most frequently detected virus (5.8 %), followed by parainfluenza virus (PIV) (5.7 %), enterovirus (EV) (4.3 %), and respiratory syncytial virus (RSV) (3.6 %). Statistical analysis showed that epidemics of IFV, PIV and EV had distinct seasonal variations. Mean monthly temperature appeared to be the only meteorological factor associated with IFV and PIV infection. These findings will provide valuable information for decision-making, prevention and treatment of ARTIs in children. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-016-2866-z) contains supplementary material, which is available to authorized users.


title: 30-day mortality in patients hospitalized with COVID-19 during the first wave of the Italian epidemic: a prospective cohort study

text: Italy was the first European country hit by the COVID-19 pandemic and has the highest number of recorded COVID-19 deaths in Europe. This prospective cohort study of the correlates of the risk of death in COVID-19 patients was conducted at the Infectious Diseases and Intensive Care units of Luigi Sacco Hospital, Milan, Italy. The clinical characteristics of all the COVID-19 patients hospitalised in the early days of the epidemic (21 February -19 March 2020) were recorded upon admission, and the time-dependent probability of death was evaluated using the Kaplan-Meier method (censored as of 20 April 2020). Cox proportional hazard models were used to assess the factors independently associated with the risk of death. Forty-eight (20.6%) of the 233 patients followed up for a median of 40 days (interquartile range 33-47) died during the follow-up. Most were males (69.1%) and their median age was 61 years (IQR 50-72). The time-dependent probability of death was 19.7% (95% CI 14.6-24.9%) 30 days after hospital admission. Age (adjusted hazard ratio [aHR] 2.08, 95% CI 1.48-2.92 per ten years more) and obesity (aHR 3.04, 95% CI 1.42-6.49) were independently associated with an increased risk of death, which was also associated with critical disease (aHR 8.26, 95% CI 1.41-48.29), C-reactive protein levels (aHR 1.17, 95% CI 1.02-1.35 per 50 mg/L more) and creatinine kinase levels above 185 U/L (aHR 2.58, 95% CI 1.37-4.87) upon admission. Case-fatality rate of patients hospitalized with COVID-19 in the early days of the Italian epidemic was about 20%. Our study adds evidence to the notion that older age, obesity and more advanced illness are factors associated to an increased risk of death among patients hospitalized with COVID-19.


COVID-19 and concomitant neurological infections


title: Redesigning emergency department operations amidst a viral pandemic

text: Abstract As shown by the current COVID-19 pandemic, emergency departments (ED) are the front line for hospital-and-community-based care during viral respiratory disease outbreaks. As such, EDs must be able to reorganize and reformat operations to meet the changing needs and staggering patient volume. This paper addresses ways to adapt departmental operations to better manage in times of elevated disease burden, specifically identifying areas of intervention to help limit crowding and spread. Using experience from past outbreaks and the current COVID-19 pandemic, we advise strategies to increase surge capacity and limit patient inflow. Triage should identify and geographically cohort symptomatic patients within a designated unit to limit exposure early in an outbreak. Screening and PPE guidelines for both patient and staff should be followed closely, as determined by hospital administration and the CDC. Equipment needs are also greatly affected in an outbreak; we emphasis portable radiographic equipment to limit transport, and an upstocking of certain medications, respiratory supplies, and PPE.


title: Extensive diversity of coronaviruses in bats from China

text: Abstract To help reveal the diversity and evolution of bat coronaviruses we collected 1067 bats from 21 species in China. A total of 73 coronaviruses (32 alphacoronaviruses and 41 betacoronaviruses) were identified in these bats, with an overall prevalence of 6.84%. All newly-identified betacoronaviruses were SARS-related Rhinolophus bat coronaviruses (SARSr-Rh-BatCoV). Importantly, with the exception of the S gene, the genome sequences of the SARSr-Rh-BatCoVs sampled in Guizhou province were closely related to SARS-related human coronavirus. Additionally, the newly-identified alphacoronaviruses exhibited high genetic diversity and some may represent novel species. Our phylogenetic analyses also provided insights into the transmission of these viruses among bat species, revealing a general clustering by geographic location rather than by bat species. Inter-species transmission among bats from the same genus was also commonplace in both the alphacoronaviruses and betacoronaviruses. Overall, these data suggest that high contact rates among specific bat species enable the acquisition and spread of coronaviruses.


Navigating the COVID-19 Pandemic: Lessons From Global Surgery


title: Assembly of human severe acute respiratory syndrome coronavirus-like particles

text: Abstract Viral particles of human severe acute respiratory syndrome coronavirus (SARS CoV) consist of three virion structural proteins, including spike protein, membrane protein, and envelope protein. In this report, virus-like particles were assembled in insect cells by the co-infection with recombinant baculoviruses, which separately express one of these three virion proteins. We found that the membrane and envelope proteins are sufficient for the efficient formation of virus-like particles and could be visualized by electron microscopy. Sucrose gradient purification followed by Western blot analysis and immunogold labeling showed that the spike protein could be incorporated into the virus like particle also. The construction of engineered virus-like particles bearing resemblance to the authentic one is an important step towards the development of an effective vaccine against infection of SARS CoV.


title: Point-of-care testing for COVID-19 using SHERLOCK diagnostics

text: The recent outbreak of the novel coronavirus SARS-CoV-2, which causes COVID-19, can be diagnosed using RT-qPCR, but inadequate access to reagents and equipment has slowed disease detection and impeded efforts to mitigate viral spread. Alternative approaches based on combinations of isothermal amplification and CRISPR-mediated detection, such as the SHERLOCK (Specific High Sensitivity Enzymatic Reporter UnLOCKing) technique, offer reduced dependence on RT-qPCR equipment, but previously reported methods required multiple fluid handling steps, complicating their deployment outside clinical labs. Here we developed a simple test chemistry called STOP (SHERLOCK Testing in One Pot) for detecting SARS-CoV-2 in one hour that is suitable for point-of-care use. This simplified test, STOPCovid, provides sensitivity comparable to RT-qPCR-based SARS-CoV-2 tests and has a limit of detection of 100 copies of viral genome input in saliva or nasopharyngeal swabs per reaction. Using lateral flow readout, the test returns result in 70 minutes, and using fluorescence readout, the test returns result in 40 minutes. Moreover, we validated STOPCovid using nasopharyngeal swabs from COVID-19 patients and were able to correctly diagnose 12 positive and 5 negative patients out of 3 replicates. We envision that implementation of STOPCovid will significantly aid “test-trace-isolate” efforts, especially in low-resource settings, which will be critical for long-term public health safety and effective reopening of the society.


The prevalence of osteonecrosis in 448 SARS patients: a screening study with MRI


title: Online Developmental Science to Foster Innovation, Access, and Impact

text: We propose that developmental cognitive science should invest in an online CRADLE, a Collaboration for Reproducible and Distributed Large-Scale Experiments that crowdsources data from families participating on the internet. Here, we discuss how the field can work together to further expand and unify current prototypes for the benefit of researchers, science, and society.


Middle East Respiratory Syndrome Corona virus, MERS-CoV. Conclusions from the 2nd Scientific Advisory Board Meeting of the WHO Collaborating Center for Mass Gathering Medicine, Riyadh


Moving biochemistry and molecular biology courses online in times of disruption: Recommended practices and resources ‐ a collaboration with the faculty community and ASBMB


The American Board of Orthopaedic Surgery Response to COVID-19


title: Production of pharmaceutical proteins by transgenic animals

text: Abstract Proteins started being used as pharmaceuticals in the 1920s with insulin extracted from pig pancreas. In the early 1980s, human insulin was prepared in recombinant bacteria and it is now used by all patients suffering from diabetes. Several other proteins and particularly human growth hormone are also prepared from bacteria. This success was limited by the fact that bacteria cannot synthesize complex proteins such as monoclonal antibodies or coagulation blood factors which must be matured by post-translational modifications to be active or stable in vivo. These modifications include mainly folding, cleavage, subunit association, γ-carboxylation and glycosylation. They can be fully achieved only in mammalian cells which can be cultured in fermentors at an industrial scale or used in living animals. Several transgenic animal species can produce recombinant proteins but presently two systems started being implemented. The first is milk from farm transgenic mammals which has been studied for 20 years and which allowed a protein, human antithrombin III, to receive the agreement from EMEA (European Agency for the Evaluation of Medicinal Products) to be put on the market in 2006. The second system is chicken egg white which recently became more attractive after essential improvement of the methods used to generate transgenic birds. Two monoclonal antibodies and human interferon-β1a could be recovered from chicken egg white. A broad variety of recombinant proteins were produced experimentally by these systems and a few others. This includes monoclonal antibodies, vaccines, blood factors, hormones, growth factors, cytokines, enzymes, milk proteins, collagen, fibrinogen and others. Although these tools have not yet been optimized and are still being improved, a new era in the production of recombinant pharmaceutical proteins was initiated in 1987 and became a reality in 2006. In the present review, the efficiency of the different animal systems to produce pharmaceutical proteins are described and compared to others including plants and micro-organisms.


‘Shielded’ anaesthetists and intensivists during the COVID‐19 pandemic: a reply


Meeting report: the 4(th) symposium on animal models of non-human primates in Kunming, Yunnan, China


title: Emerging infectious diseases in southeast Asia: regional challenges to control

text: Southeast Asia is a hotspot for emerging infectious diseases, including those with pandemic potential. Emerging infectious diseases have exacted heavy public health and economic tolls. Severe acute respiratory syndrome rapidly decimated the region's tourist industry. Influenza A H5N1 has had a profound effect on the poultry industry. The reasons why southeast Asia is at risk from emerging infectious diseases are complex. The region is home to dynamic systems in which biological, social, ecological, and technological processes interconnect in ways that enable microbes to exploit new ecological niches. These processes include population growth and movement, urbanisation, changes in food production, agriculture and land use, water and sanitation, and the effect of health systems through generation of drug resistance. Southeast Asia is home to about 600 million people residing in countries as diverse as Singapore, a city state with a gross domestic product (GDP) of US$37 500 per head, and Laos, until recently an overwhelmingly rural economy, with a GDP of US$890 per head. The regional challenges in control of emerging infectious diseases are formidable and range from influencing the factors that drive disease emergence, to making surveillance systems fit for purpose, and ensuring that regional governance mechanisms work effectively to improve control interventions.


title: The prevalence of respiratory pathogens in adults with community-acquired pneumonia in an outpatient cohort

text: PURPOSE: Community-acquired pneumonia is a common illness worldwide. In adults, community-acquired bacterial pneumonia has been well studied, but viral pneumonia is less well understood. We designed this study to identify respiratory pathogens, including common pneumonia-causing bacteria, viruses and atypical pneumonia pathogens, using reverse transcription-polymerase chain reaction. PATIENTS AND METHODS: We conducted a retrospective study of outpatients with community-acquired pneumonia at the Fever Clinic of Peking University Third Hospital. We collected sputum or throat swabs from patients diagnosed with community-acquired pneumonia. Multiplex real-time reverse transcription-polymerase chain reaction was performed for 20 pathogens, including 9 viruses, 3 atypical pathogens and 8 bacteria. RESULTS: There were 232 outpatients enrolled in our study, and 153 patients (65.9%) had positive test results, of which 26.7% were viruses, 19.4% were atypical pathogens and 19.8% were bacteria. Mycoplasma pneumoniae infection was detected at the highest frequency (19.0%), exceeding Streptococcus pneumoniae infection. The most commonly identified viral pathogens were IFVs (15.1%), PIVs (3.4%) and RhV (2.6%). The most commonly identified bacteria were Streptococcus pneumoniae (9.1%), Haemophilus influenza (6.5%) and Klebsiella pneumoniae (2.6%). CONCLUSION: Our study suggests that viruses were commonly detected in outpatients with CAP, and IFVs were the most common viruses, especially during flu season. Patients with viral infection were prone to viral-bacterial coinfection. Mycoplasma pneumoniae was the leading pathogen in the outpatients with CAP. Viral infection occurs in a large number of outpatients with CAP, and it should receive greater attention in clinical work.


title: Mxra8 is a receptor for multiple arthritogenic alphaviruses

text: Arthritogenic alphaviruses comprise a group of enveloped RNA viruses that are transmitted to humans by mosquitoes and cause debilitating acute and chronic musculoskeletal disease(1). The host factors required for alphavirus entry remain poorly characterized(2). Using a genome-wide CRISPR/Cas9-based screen, we identified the cell adhesion molecule Mxra8 as an entry mediator for multiple emerging arthritogenic alphaviruses including chikungunya (CHIKV), Ross River, Mayaro, and O’nyong nyong (ONNV) viruses. Gene editing of mouse Mxra8 or human MXRA8 resulted in reduced viral infection of cells, and reciprocally, ectopic expression resulted in increased infection. Mxra8 bound directly to CHIKV particles and enhanced virus attachment and internalization into cells. Consistent with these findings, Mxra8-Fc protein or anti-Mxra8 monoclonal antibodies blocked CHIKV infection in multiple cell types including primary human synovial fibroblasts, osteoblasts, chondrocytes, and skeletal muscle cells. Mutagenesis experiments suggest that Mxra8 binds to a surface-exposed region across the A and B domains of CHIKV E2, a speculated site of attachment. Finally, administration of Mxr8a-Fc protein or anti-Mxra8 blocking antibodies reduced CHIKV or ONNV infection and associated foot swelling in mice. Pharmacological targeting of Mxra8 could form a strategy for mitigating infection and disease by multiple arthritogenic alphaviruses.


title: Spontaneous Pneumomediastinum: Descriptive Study of Our Experience With 36 Cases

text: Spontaneous pneumomediastinum is defined as a primary process characterized by the presence of air or gas in the mediastinum. We report all the cases of spontaneous pneumomediastinum diagnosed in our hospital between January 1996 and December 2004. We developed a protocol for data collection that included the following: medical history, triggers, signs, radiology, treatment, hospital stay, and complications. During this period we diagnosed 36 cases—25 men (69.4%) and 11 women (30.6%)—with a mean age of 36.8 years (range, 11-90 years) and a mean hospital stay of 8.56 days (range, 1-53 days). The most common clinical presentation was chest pain, either isolated (27%) or with associated dyspnea (19.4%). A triggering factor was identified for 14 patients (38.8%). There was no associated morbidity or mortality. In view of our findings, we concluded that spontaneous pneumomediastinum is an uncommon entity with considerable clinical variability and that correct diagnosis requires a high level of suspicion. Radiography provides the best evidence for diagnosis.


title: Reverse transcriptase loop-mediated isothermal amplification for the detection of feline coronavirus

text: Abstract The Feline coronavirus (FCoV) is the etiological agent of feline infectious peritonitis (FIP), a lethal disease of felids. The role of molecular methods is controversial for the diagnosis of FIP, while essential for the identification of the shedders. Thus, a fast and inexpensive method for the detection of FCoV could be beneficial, especially in multicat environments. A reverse transcription loop mediated isothermal amplification (RT-LAMP) assay was developed. RNA extraction and RT-nPCR for FCoV were performed on thirty-two samples (11 faeces, 9 blood, 8 effusions, and 4 lymph nodes) collected from 27 cats. Six RT-LAMP primers were designed from the same conserved region of RT-nPCR, and the assay was run at 63°C for one hour. Results were evaluated through both agarose gel run and hydroxynapthol blue (HNB) dye and then compared with RT-nPCR results for the assessment of sensitivity and specificity. The overall specificity was 100%, but the sensitivity was 50% and 54.5% for agarose gel and HNB respectively. Therefore, RT-LAMP seems optimal to confirm the presence of the virus, but not applicable to exclude it.


title: A Population Health Surveillance Theory

text: OBJECTIVES: Despite its extensive use, the term "Surveillance" often takes on various meanings in the scientific literature pertinent to public health and animal health. A critical appraisal of this literature also reveals ambiguities relating to the scope and necessary structural components underpinning the surveillance process. The authors hypothesized that these inconsistencies translate to real or perceived deficiencies in the conceptual framework of population health surveillance. This paper presents a population health surveillance theory framed upon an explicit conceptual system relative to health surveillance performed in human and animal populations. METHODS: The population health surveillance theory reflects the authors' system of thinking and was based on a creative process. RESULTS: Population health surveillance includes two broad components: one relating to the human organization (which includes expertise and the administrative program), and one relating to the system per se (which includes elements of design and method) and which can be viewed as a process. The population health surveillance process is made of five sequential interrelated steps: 1) a trigger or need, 2) problem formulation, 3) surveillance planning, 4) surveillance implementation, and 5) information communication and audit. CONCLUSIONS: The population health surveillance theory provides a systematic way of understanding, organizing and evaluating the population health surveillance process.


title: Complete genome analysis of equine coronavirus isolated in Japan

text: Equine coronavirus has been responsible for several outbreaks of disease in the United States and Japan. Only one complete genome sequence (NC99 isolated in the US) had been reported for this pathogenic RNA virus. Here, we report the complete genome sequences of three equine coronaviruses isolated in 2009 and 2012 in Japan. The genome sequences of Tokachi09, Obihiro12-1 and Obihiro12-2 were 30,782, 30,916 and 30,916 nucleotides in length, respectively, excluding the 3’-poly (A) tails. All three isolates were genetically similar to NC99 (98.2–98.7 %), but deletions and insertions were observed in the genes nsp3 of ORF1a, NS2 and p4.7. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-015-2565-1) contains supplementary material, which is available to authorized users.


title: Reversal of Infected Host Gene Expression Identifies Repurposed Drug Candidates for COVID-19

text: Repurposing existing drugs is a timely option to cope with COVID-19. We predicted therapeutic candidates that could reverse the gene expression of coronavirus-infected host cells. Thirteen expression signatures computed from various experimental conditions and preclinical models could be reversed by those compounds known to be effective against SARS- or MERS-CoV, as well as the drug candidates recently shown to be effective against SARS-CoV-2. We selected ten novel candidates to further evaluate their in vitro efficacy against SARS-CoV-2 infection. Four compounds bortezomib, dactolisib, alvocidib and methotrexate inhibited the formation of virus infection-induced cytopathic effect in Vero E6 cells at 1 μM, yet such a concentration seems toxic to the cells as well. While the evaluation in other permissive cells and the prediction of toxicity are needed to optimize and minimize their antiviral activity and cytotoxicity, respectively, this computational approach has the potential to rapidly and rationally identify drug candidates against COVID-19.


The emergence of methemoglobinemia amidst the COVID‐19 pandemic


title: The biological potential of the raccoon dog (Nyctereutes procyonoides, Gray 1834) as an invasive species in Europe—new risks for disease spread?

text: Invasive wildlife species have the potential to act as additional host and vector species for infectious diseases. The raccoon dog (Nyctereutes procyonides), a carnivore species that has its origin in Asia, was taken as an example to demonstrate biological and ecological prerequisites which enables an invasive species to occupy a new habitat permanently. Studies conducted during the last 20 years identified a total of 35 species of endoparasites, five ectoparasites, six bacterial or protozoan species, and five viruses found in the subspecies Nyctereutes procyonoides ussuriensis in its original and newly occupied habitat or in Nyctereutes procyonoides koreensis in its original habitat, respectively. With reference to raccoon dogs impact as vector species and the relevance for human and animal health, we selected Trichinella spp., Echinococcus multilocularis, Francisella tularensis, rabies virus, and canine distemper virus for detailed description. Results of studies from Finland and Germany furthermore showed that biological characteristics of the raccoon dog make this carnivore an ideal host and vector for a variety of pathogens. This may result in a growing importance of this invasive species concerning the epidemiology of some transmissible diseases in Europe, including the hazard that the existence of autochthonous wildlife, particularly small populations, is endangered. Potential adverse effects on human and animal health in the livestock sector must also be taken into account. Especially with regard to its potential as a reservoir for zoonotic diseases, the raccoon dog should receive more attention in disease prevention and eradication strategies.


title: An interferon-beta promoter reporter assay for high throughput identification of compounds against multiple RNA viruses

text: Virus infection of host cells is sensed by innate pattern recognition receptors (PRRs) and induces production of type I interferons (IFNs) and other inflammatory cytokines. These cytokines orchestrate the elimination of the viruses but are occasionally detrimental to the hosts. The outcomes and pathogenesis of viral infection are largely determined by the specific interaction between the viruses and their host cells. Therefore, compounds that either inhibit viral infection or modulate virus-induced cytokine response should be considered as candidates for managing virus infection. The aim of the study was to identify compounds in both categories, using a single cell-based assay. Our screening platform is a HEK293 cell-based reporter assay where the expression of a firefly luciferase is under the control of a human IFN-β promoter. We have demonstrated that infection of the reporter cell line with a panel of RNA viruses activated the reporter gene expression that correlates quantitatively with the levels of virus replication and progeny virus production, and could be inhibited in a dose-dependent manner by known antiviral compound or inhibitors of PRR signal transduction pathways. Using Dengue virus as an example, a pilot screening of a small molecule library consisting of 26,900 compounds proved the concept that the IFN-β promoter reporter assay can serve as a convenient high throughput screening platform for simultaneous discovery of antiviral and innate immune response modulating compounds. A representative antiviral compound from the pilot screening, 1-(6-ethoxybenzo[d]thiazol-2-yl)-3-(3-methoxyphenyl) urea, was demonstrated to specifically inhibit several viruses belonging to the family of flaviviridae.


title: COVID‐19 vaccines: knowing the unknown

text: Vaccine development against SARS‐CoV‐2 has drawn attention around the globe due to the exploding pandemic. Although COVID‐19 is caused by a new coronavirus, SARS‐CoV‐2, previous research on other coronavirus vaccines, such as FIPV, SARS and MERS, has provided valuable information for the rapid development of COVID‐19 vaccine. However, important knowledge gaps remain – some are specific to SARS‐CoV‐2, others are fundamental to immunology and vaccinology. Here we discuss areas that need to be addressed for COVID‐19 vaccine development, and what can be learned from examples of vaccine development in the past. Since the beginning of the outbreak, the research progress on COVID‐19 has been remarkable. We are therefore optimistic about the rapid development of COVID‐19 vaccine. This article is protected by copyright. All rights reserved


title: Understanding Viral Transmission Behavior via Protein Intrinsic Disorder Prediction: Coronaviruses

text: Besides being a common threat to farm animals and poultry, coronavirus (CoV) was responsible for the human severe acute respiratory syndrome (SARS) epidemic in 2002–4. However, many aspects of CoV behavior, including modes of its transmission, are yet to be fully understood. We show that the amount and the peculiarities of distribution of the protein intrinsic disorder in the viral shell can be used for the efficient analysis of the behavior and transmission modes of CoV. The proposed model allows categorization of the various CoVs by the peculiarities of disorder distribution in their membrane (M) and nucleocapsid (N). This categorization enables quick identification of viruses with similar behaviors in transmission, regardless of genetic proximity. Based on this analysis, an empirical model for predicting the viral transmission behavior is developed. This model is able to explain some behavioral aspects of important coronaviruses that previously were not fully understood. The new predictor can be a useful tool for better epidemiological, clinical, and structural understanding of behavior of both newly emerging viruses and viruses that have been known for a long time. A potentially new vaccine strategy could involve searches for viral strains that are characterized by the evolutionary misfit between the peculiarities of the disorder distribution in their shells and their behavior.


title: ‘No Ebola…still doomed’ – The Ebola-induced tourism crisis

text: Abstract Many recent crisis and disasters affecting tourism have been studied, but few explicitly explore health related crisis in developing countries. This study analyses the effect of the Ebola Virus Disease Epidemic (EVDE) on The Gambia, where, despite no reported cases, EVDE had devastating consequences. A Rapid Situation Analysis is used to gain insights into responses to the EVDE, encompassing interviews with key stakeholders, field observations and follow up meetings with those involved in managing the crisis over 21 months. A crisis and disaster framework is used to understand the challenges encountered. Findings highlight the importance of consumer perception and preparedness and management failures’ consequences, contributing to the broader debate on the indirect threat of epidemics on tourism in developing countries.


Authors’ Reply to: Tocilizumab, Adipokines and Severe Complications of COVID-19


Can a Paper-Based Device Trace COVID-19 Sources with Wastewater-Based Epidemiology?


title: Development of a one step real time RT-PCR assay to detect and quantify Dugbe virus

text: Abstract A one-step real time quantitative RT-PCR (qRT-PCR) assay was developed to detect all published Dugbe virus (DUGV) genomes of the Nairovirus genus. Primers and probes were designed to detect specific sequences on the most conserved regions of the S segment. The limit of detection of the assay was 10 copies per reaction which is an improvement of 3log10 FFU/mL over the sensitivity of conventional RT-PCR. The specificity of the primers and probe was confirmed with the closely related Nairoviruses CCHFV and Hazara virus, and on the non-related viruses Coronavirus and Influenza A virus. This qRT-PCR assay was used to screen nucleic acids extracted from 498 ticks collected in the Republic of Chad. One sample was found positive suggesting that DUGV is present in this part of the world. The molecular assay developed in this study is sensitive, specific and rapid and can be used for research and epidemiological studies.


title: Modified management mode for colorectal cancer during COVID-19 outbreak – a single-center experience

text: During the epidemic of COVID-19, the management model of colorectal cancer has to be changed at our center due to relatively limited medical resources. Outpatient visits are reduced under well protected after appointment, and rigorous investigation of epidemiological history and clinical symptoms are needed. We prefer a simple and convenient treatment regimen, which may also be postponed appropriately. Minimally invasive CRC surgery combined with a perioperative program of enhanced recovery after surgery should be recommended. We also focus on mental health treatments and healthy lifestyle education. In addition, routine follow-up can be moderately delayed. In total, adequate doctor-patient communication is also recommended throughout the treatment.


title: Non‐invasive imaging of mouse hepatitis coronavirus infection reveals determinants of viral replication and spread in vivo

text: Bioluminescence imaging (BLI) is a powerful new method to study virus dissemination in the live animal. Here we used this method to monitor the spatial and temporal progression of mouse hepatitis coronavirus (MHV) infection in mice using luciferase‐expressing viruses. Upon intranasal inoculation, virus replication could initially be observed in the nasal cavity and the cervical lymph nodes, after which the infection spread to the brain and frequently to the eyes. The kinetics of virus spread to and clearance from the brain appeared to depend on the inoculation dose. After intraperitoneal inoculation, virus replication was predominantly observed in the liver and occasionally in the intestines, but interestingly also in the tail and paws. BLI thus elucidated new anatomic locations of virus replication. Furthermore, MHV dissemination was shown to be critically depended on the viral spike protein, but also on the mouse strain used. Widespread dissemination was observed in mice lacking a functional type I interferon response. The importance of the type I interferon system in limiting viral spread was also demonstrated by the administration of type I interferons to mice. Our results provide new insights in coronavirus pathogenesis and demonstrate the potential of BLI to study coronavirus–host interactions in vivo.


Polypill for Population-Level Primary Cardiovascular Prevention in Underserved Populations at Heterogeneous Risk — A Social Epidemiology Counterargument


title: Comparison of the Elecsys® Anti-SARS-CoV-2 immunoassay with the EDI(TM) enzyme linked immunosorbent assays for the detection of SARS-CoV-2 antibodies in human plasma

text: BACKGROUND: Here, we report on a head-to-head comparison of the fully-automated Elecsys® Anti-SARS-CoV-2 immunoassay with the EDI(TM) enzyme linked immunosorbent assays (ELISA) for the detection of SARS-CoV-2 antibodies in human plasma. METHODS: SARS-CoV-2 antibodies were measured with the Elecsys® assay and the EDI(TM) ELISAs (IgM and IgG) in 64 SARS-CoV-2 RT-PCR confirmed COVID-19 patients with serial blood samples (n=104) collected at different time points from symptom onset. Blood samples from 200 healthy blood donors and 256 intensive care unit (ICU) patients collected before the COVID-19 outbreak were also used. RESULTS: In COVID-19 patients, the percentage of positive results rose with time from symptom onset, peaking to positivity rates after 15-22 days of 100% for the Elecsys® assay, of 94% for the EDI(TM) IgM-ELISA and of 100% for the EDI(TM) IgG ELISA. In the 104 blood samples, the agreement between positive/negative classifications of the Elecsys® assay and the EDI(TM) ELISAs (IgM or IgG) was 90%. The false positivity rates in the healthy blood donors and the ICU patients were <1% for the Elecsys® assay and <3% for the EDI(TM) ELISAs. CONCLUSIONS: Our results indicate a high sensitivity and specificity for the Elecsys® assay and an acceptable agreement with the EDI(TM) ELISAs.


title: Structure-Based Design and Synthesis of Triazole-based Macrocyclic Inhibitors of Norovirus Protease: Structural, Biochemical, Spectroscopic, and Antiviral Studies

text: Outbreaks of acute gastroenteritis caused by noroviruses constitute a public health concern worldwide. To date, there are no approved drugs or vaccines for the management and prophylaxis of norovirus infections. A potentially effective strategy for the development of norovirus therapeutics entails the discovery of inhibitors of norovirus 3CL protease, an enzyme essential for noroviral replication. We describe herein the structure-based design of the first class of permeable, triazole-based macrocyclic inhibitors of norovirus 3C-like protease, as well as pertinent X-ray crystallographic, biochemical, spectroscopic, and antiviral studies.


title: Stop making sense or Regulation at the level of termination in eukaryotic protein synthesis

text: Abstract An increasing number of examples of translational regulation at the level of termination has been recently reported in eukaryotes. This paper reviews our present knowledge on this topic and proposes an understanding of these regulations by relating the study of viral gene expression to a comprehensive view of the mechanisms and components of the translational process.


title: A Mixed Methods Evaluation of a Digital Intervention to Improve Sedentary Behaviour Across Multiple Workplace Settings

text: Background: Prolonged sedentary behaviour (SB) is associated with risk of chronic diseases. Digital interventions in SB require mixed method evaluations to understand potential for impact in real-world settings. In this study, the RE-AIM QuEST evaluation framework will be used to understand the potential of a digital health promotion application which targets reducing and breaking up SB across multiple workplace settings. Methods: Four companies and 80 employees were recruited to use a digital application. Questionnaires were used to measure SB, and additional health and work-related outcomes at baseline, one month, three month and six month follow-up. Qualitative data was collected through focus groups with employees and interviews with stakeholders. Questionnaire data was analysed using Wilcoxon Sign Rank tests and qualitative data was thematically analysed. Results: The digital application significantly increased standing time at one month for the total group and transitions per hour in one of the companies. Facilitators and barriers were identified across RE-AIM. Conclusions: Addressing the barriers which have been identified, while maintaining the positive attributes will be critical to producing an effective digital application which also has the potential for impact in the real world.


title: Establishment of a reference panel for the detection of anti-SARS-CoV antibodies

text: Abstract The immunological assays for detection of antibodies against SARS-CoV were developed in-house and some of them are available commercially. However, the antigens used in these assays differed. In order to validate the reliability of these assays, the standard panel should be established. In this study, we have expressed and purified severe acute respiratory syndrome (SARS) structural proteins and their fragments and developed indirect enzyme-linked immunosorbent assays (ELISAs) that detect antibodies against the SARS N, N1, N2, S1, SC, S2, and M proteins as well as the human coronavirus OC43 and 229E N proteins. These assays were used to screen 58 samples from SARS convalescent patients, 40 serial serum specimens from patients at different phases of SARS infection, and 88 plasma specimens from normal blood donors. The samples from normal blood donors were also tested for antibodies against other respiratory virus. The representative samples were chosen to comprise a reference panel of SARS antibodies that may be used for the detection of SARS. The panel is composed of 25 positive samples, 25 negative samples, 7 diluted samples for anti-N antibody, 6 diluted samples for anti-S antibody, and one sample for validating precision. Comparison of detection results with different SARS antibody assays indicated that our panel should differentiate the specificity and sensitivity of different assays.


title: Connectedness and systemic risk spillovers analysis of Chinese sectors based on tail risk network

text: Abstract This paper investigates the systemic risk spillovers and connectedness in the sectoral tail risk network of Chinese stock market, and explores the transmission mechanism of systemic risk spillovers by block models. Based on conditional value at risk (CoVaR) and single index model (SIM) quantile regression technique, we analyse the tail risk connectedness and find that during market crashes, stock market exposes to more systemic risk and more connectedness. Further, the orthogonal pulse function shows that Herfindahl-Hirschman Index (HHI) of edges has a significant positive effect on systemic risk, but the impact shows a certain lagging feature. Besides, the directional connectedness of sectors shows that systemic risk receivers and transmitters vary across time, and we adopt PageRank index to identify systemically important sector released by utilities and financial sectors. Finally, by block model we find that the tail risk network of Chinese sectors can be divided into four different spillover function blocks. The role of blocks and the spatial spillover transmission path between risk blocks are time-varying. Our results provide useful and positive implications for market participants and policy makers dealing with investment diversification and tracing the paths of risk shock transmission.


title: Arbidol/IFN-α2b Therapy for Patients With Corona Virus Disease 2019: A Retrospective Multicenter Cohort Study

text: The spread of COVID-19 is accelerating. At present, there is no specific antiviral drugs for COVID-19 outbreak. This is a multicenter retrospective cohort study of patients with laboratory-confirmed COVID-19 infection pneumonia from 3 hospitals in Hubei and Guangdong province, 141 adults (aged ≥18 years) without ventilation were included. Combined group patients were given Arbidol and IFN-α2b, monotherapy group patients inhaled IFN-α2b for 10-14 days. Of 141 COVID-19 patients, baseline clinical and laboratory characteristics were similar between combined group and monotherapy group, that 30% of the patients leucocytes counts were below the normal range and 36.4% of the patients experienced lymphocytopenia. The duration of viral RNA of respiratory tract in the monotherapy group was not longer than that in the combined therapy group. There was no significant differences between two groups. The absorption of pneumonia in the combined group was faster than that in the monotherapy group. We inferred that Arbidol/IFN - 2b therapy can be used as an effective method to improve the COVID-19 pneumonia of mild patients, although it helpless with accelerating the virus clearance. These results should be verified in a larger prospective randomized environment.


title: BHV4 (bovine herpes virus 4) related disorders in Belgian cattle: A study of two problem herds

text: Two cattle farms, with a ten year history of BHV4 related postpartum metritis accompanied by fertility problems, were monitored during the winter season 1985–1986. BHV4 was isolated from the lochia from 55% of the animals on farm A and 66% of those on farm B. Respectively 59% and 30% of the animals presented postpartum metritis. In some animals virus multiplication was followed by severe leucopenia lasting several weeks. Indirect immunofluorescence (IIF) BHV4 seropositive as well as IIF seronegative animals were affected. The latter responded with a rapid or late IIF antibody reaction. No BHV4 seroneutralizing antibodies could be detected. The authors also suggest a possible role of BHV4 in the respiratory problems observed during the study.


title: T-lymphocyte recognition of a portion of myelin basic protein encoded by an exon expressed during myelination

text: Abstract The major isoform of myelin basic protein (MBP) in the healthy adult central nervous system is the 18.5-kDa protein which is produced by mRNA derived from exons 1, 3, 4, 5, 6 and 7 of the MBP gene. Since isoforms containing exon 2-encoded protein (X2MBP) are expressed during myelin formation, we examined T cell ractivity specific for X2MBP in a disease characterized by remyelination subsequent to demyelination, multiple sclerosis (MS). T cell lines specific for X2MBP were derived from three MS patients as well as one healthy control. This suggests that candidate autoantigens in demyelinating/remyelinating diseases should include not only the major isoforms of myelin proteins, but also isoforms expressed aberrantly during a disease process since they too may be the target of a T cell-mediated autoimmune process.


title: Epidemiological and clinical features of 125 Hospitalized Patients with COVID-19 in Fuyang, Anhui, China

text: Abstract Objective To investigate the epidemiological and clinical features of patients with COVID-19 in Anhui province of China. Method In this descriptive study, we obtained epidemiological, demographic, manifestations, laboratory data and radiological findings of patients confirmed by real-time RT-PCR in the NO.2 People’s Hospital of Fuyang City from Jan 20 to Feb 9, 2020. Clinical outcomes were followed up to Feb 18, 2020. Results Of 125 patients infected SARS-CoV-2, the mean age was 38.76 years (SD, 13.799) and 71(56.8%) were male. Common symptoms include fever [116 (92.8%)], cough [102(81.6%)], and shortness of breath [57(45.6%)]. Lymphocytopenia developed in 48(38.4%) patients. 100(80.0%) patients showed bilateral pneumonia, 26(20.8%) patients showed multiple mottling and ground-glass opacity. All patients were given antiviral therapy. 19(15.2%) patients were transferred to the intensive care unit. By February 18, 47(37.6%) patients were discharged and none of patients died. Among the discharged patients, the median time of length of stay was 14.8 days (SD 4.16). Conclusion In this single-center, retrospective, descriptive study, fever is the most common symptom. Old age, chronic underlying diseases and smoking history may be risk factors to worse condition. Certain laboratory inspection may contribute to the judgment of the severity of illness.


title: Free DNA, a reason for severe COVID-19 infection?

text: Abstract The fast-growing outbreak of 2019 novel coronaviruses (SARS-CoV-2) reached all continents except the Antarctica in merely three months. Severe SARS-CoV-2 infection (COVID-19) has a bad clinical outcome, and some reports emphasized the role of cytokine storm and dysfunctions of multiple organs. However, the etiology of severe COVID-19 has been largely unknown. Similar as SARS-CoV and MERS-CoV, SARS-CoV-2 is also thought derived from bat coronaviruses. However, it is not pathogenic for bat at all, because free DNA in cytoplasm or blood cannot bring up violent immune response in bat; but it can produce severe inflammations in human. I hypothesized that the damage induced by free DNA is a reason for severe COVID-19, which can explain many symptoms of this disease, such as cytokine storm, ARDS and muscus plug, acute injuries of heart, liver and kidney, and some special symptoms of COVID-19. My hypothesis will be helpful for better understand the etiology of severe COVID-19.


Rapid Diagnosis of a Coronavirus Associated with Severe Acute Respiratory Syndrome (SARS)


title: Assessing the welfare of kennelled dogs—A review of animal-based measures

text: Abstract Hundreds of thousands of dogs are housed in kennels worldwide, yet there are no standard protocols for assessing the welfare of dogs in these environments. Animal science is focusing increasingly on the importance of animal-based measures for determining welfare states, and those measures that have been used with kennelled dogs are reviewed in this paper with particular focus on their validity and practicality. From a physiological standpoint, studies using cortisol, heart rate and heart rate variability, temperature changes, and immune function are discussed. Behavioural measures are also of great relevance when addressing canine welfare, thus studies on fear and anxiety behaviours, abnormal behaviours like stereotypies, as well as responses to strangers and novel objects are reviewed. Finally, a limited number of studies attempting to use cognitive bias and learning ability are also mentioned as cognitive measures. The literature to date provides a strong background for which measures may be useful in determining the welfare of kennelled canines, however more research is needed to further assess the value of using these methods, particularly in regard to the large degree of individual differences that exist between dogs.


title: Asteltoxins with Antiviral Activities from the Marine Sponge-Derived Fungus Aspergillus sp. SCSIO XWS02F40

text: Two new asteltoxins named asteltoxin E (2) and F (3), and a new chromone (4), together with four known compounds were isolated from a marine sponge–derived fungus, Aspergillus sp. SCSIO XWS02F40. The structures of the compounds (1–7) were determined by the extensive 1D- and 2D-NMR spectra, and HRESIMS spectrometry. All the compounds were tested for their antiviral (H1N1 and H3N2) activity. Compounds 2 and 3 showed significant activity against H3N2 with the prominent IC(50) values of 6.2 ± 0.08 and 8.9 ± 0.3 μM, respectively. In addition, compound 2 also exhibited inhibitory activity against H1N1 with an IC(50) value of 3.5 ± 1.3 μM.


title: Multiple Family Members With Delayed Cord Separtion and Combined Immunodeficiency With Novel Mutation in IKBKB

text: Background: Inhibitor of kappa kinase 2 (IKK2) deficiency is a recently described combined immunodeficiency. It undermines the nuclear factor-kappa B (NF-κB) activation pathway. Methods: The clinical and immunological data of four patients diagnosed with combined immunodeficiency (CID) from two related Saudi families were collected. Autozygosity mapping of all available members and whole exome sequencing of the index case were performed to define the genetic etiology. Results: The patients had early onset (2–4 months of age) severe infections caused by viruses, bacteria, mycobacteria, and fungi. They all had hypogammaglobulinemia and low absolute lymphocyte count. Their lymphocytes failed to respond to PHA mitogen stimulation. A novel homozygous non-sense mutation in the IKBKB gene, c.850C>T (p. Arg284*) was identified in the index patient and segregated with the disease in the rest of the family. He underwent hematopoietic stem cell transplantation (HSCT) from a fully matched sibling with no conditioning. The other three patients succumbed to their disease. Interestingly, all patients had delayed umbilical cord separation. Conclusion: IKK2 deficiency causes CID with high mortality. Immune reconstitution with HSCT should be considered as early as possible. Delayed umbilical cord separation in CID patients may be a clue to IKK2 deficiency.


title: A family cluster of Middle East Respiratory Syndrome Coronavirus infections related to a likely unrecognized asymptomatic or mild case

text: Abstract Background Ninety confirmed cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) have been reported to the World Health Organization. We report the details of a second family cluster of MERS-CoV infections from Riyadh, Saudi Arabia. Methods We present the clinical, laboratory and epidemiological details of 3 patients from a family cluster of MERS-CoV infections. Results The first patient developed respiratory symptoms and fever 14 days after admission to hospital for an unrelated reason. He died 11 days later with multi-organ failure. Two of his brothers presented later to another hospital with respiratory symptoms and fever. MERS-CoV infection in the latter 2 patients was confirmed by reverse transcriptase polymerase chain reaction testing. All 3 patients had fever, cough, shortness of breath, bilateral infiltrates on chest x-ray, thrombocytopenia, lymphopenia and rises in serum creatinine kinase and alanine transaminase. No hospital or other social contacts are known to have acquired the infection. It appears that the index patient in this cluster acquired MERS-CoV infection whilst in hospital from an unrecognized mild or asymptomatic case. Conclusion MERS-CoV acquisition from unrecognized mild or asymptomatic cases may be a more important contributor to ongoing transmission than previously appreciated.


title: Utilization of the Emergency Department and Predicting Factors Associated With Its Use at the Saudi Ministry of Health General Hospitals

text: Overuse of emergency rooms (ER) is a public health problem. To investigate this issue, a cross-sectional survey was conducted at the ERs of King Abdul-Aziz Hospital, King Fahd Hospital, and Al-Thaghor Hospital in November 2013 with the aims of estimating emergency service utilization for non-urgent cases, identifying the predictors of ER utilization for non-urgent cases, and measuring patients’ knowledge of primary healthcare centers (PHCCs). Patients were interviewed using a structured questionnaire and the data were analyzed using the Statistical Package for the Social Sciences. We recruited 300 patients; males comprised 50.7% of the sample. A higher proportion of patients with non-urgent cases visited the ER three to four times a year (P=0.001). A higher proportion of patients without emergencies had not attempted to visit an outpatient clinic before the ER (P=0.003). Most patients without emergencies thought the ER was the first place to consult in case of illness. Most patients who visited the ER were single, < 15 years, and had lower incomes. Patients requested ER services for primary care-treatable conditions because of limited services and resources as well as limited working hours at PHCCs. Most patients (90.0%) were knowledgeable about PHCCs, with those of lower education being more knowledgeable. Patients reported long ER waiting times (≥ 3 hours), no organization (85.9%), and lack of medical staff. Overall, overuse of ER services is high at the Ministry of Health hospitals in Jeddah. The risk factors for ER overuse are age < 15 years, singlehood, and low incomes. Policy makers and health providers have a challenging task to control ER overuse. We recommend developing strategies to implement policies aimed at reducing non-urgent ER use as well as making healthcare services more available to the population.


title: Conversion of operating theatre from positive to negative pressure environment

text: Summary The severe acute respiratory syndrome (SARS) crisis led to the construction of a negative pressure operating theatre at a hospital in Hong Kong. It is currently used for treatment of suspected or confirmed airborne infection cases, and was built in anticipation of a return of SARS, an outbreak of avian influenza or other respiratory epidemics. This article describes the physical conversion of a standard positive pressure operating theatre into a negative pressure environment, problems encountered, airflow design, and evaluation of performance. Since entering regular service, routine measurements and observations have indicated that the airflow performance has been satisfactory. This has also been confirmed by regular air sampling checks. Computational fluid dynamics, a computer modelling technique, was used to compare the distribution of room air before and after the design changes from positive to negative pressure. The simulation results show that the physical environment and the dispersion pattern of bacteria in the negative pressure theatre were as good as, if not better than, those in the original positive pressure design.


Genes 3 and 5 of Infectious Bronchitis Virus are Accessory Protein Genes


A25 Phylogenetic analysis of the nucleocapsid and RNA-dependent RNA polymerase fragments of the first imported case of middle east respiratory syndrome coronavirus (MERS-CoV) infection in the Philippines from Saudi Arabia, February 2015


title: Standardization of elective tracheostomies at the Central Institute of the Hospital das Clinicas in Sao Paulo during the COVID-19 pandemic

text: The COVID-19 Pandemic has resulted in a high number of hospital admissions and some of those patients need ventilatory support in intensive care units The viral pneumonia secondary to Sars-cov-2 infection may lead to acute respiratory distress syndrome (ARDS) and longer mechanical ventilation needs, resulting in a higher demand for tracheostomies Due to the high aerosolization potential of such procedure, and the associated risks of staff and envoirenment contamination, it is necesseray to develop a specific standardization of the of the whole process involving tracheostomies This manuscript aims to demonstrate the main steps of the standardization created by a tracheostomy team in a tertiary hospital dedicated to providing care for patients with COVID-19


title: New real time and conventional RT-PCRs for updated molecular diagnosis of infectious bronchitis virus infection (IBV) in chickens in Egypt associated with frequent co-infections with avian influenza and Newcastle Disease viruses

text: Abstract In Egypt, currently two geographically restricted genotypes of the infectious bronchitis coronavirus (IBV) are circulating with detrimental effects for poultry industry. A sensitive real-time RT-PCR assay targeting the IBV nucleocapsid gene (N) was developed to screen clinical samples for presence of IBV. Conventional RT-PCRs amplifying hypervariable regions (HVRs 1–2 and 3) of the IBV S1 gene were developed and amplificates used for nucleotide sequence-based typing of IBV field strains in Egyptian chickens directly from clinical samples.


title: Patient and health system delays before registration among migrant patients with tuberculosis who were transferred out in China

text: BACKGROUND: Early diagnosis and treatment is vital for effective tuberculosis (TB) management especially among migrant populations who are a vulnerable group. We aimed to study factors associated with delay before registration at country level among registered migrant TB patients in China (2014–15) who were transferred out (during treatment) through web-based TB information management system (TBIMS). METHODS: This was a cross sectional study involving review of TBIMS data. Delays (in days) were classified as follows: patient delay (from symptom onset to first doctor visit), health system delay (from first doctor visit to treatment initiation, divided into health system diagnosis and treatment delay before and after date of diagnosis respectively), diagnosis delay (from symptom onset to diagnosis) and total delay (from symptom onset to treatment initiation). Linear regression was used to build a predictive model (forward stepwise) for the socio-demographic, clinical and health system related factors associated with delay: one model for each type of delay. Delays were log transformed and included in the model. RESULTS: The median (IQR) patient delay, health system delay and total delay was 16 (6, 34), two (0, 6) and 22 (11, 41) days respectively. Factors associated with long patient, diagnosis and total delay were: female gender, age ≥ 65 years, sputum smear positive pulmonary TB and registration at referral hospital. Treatment initiation delay was significantly higher among those registered in referral hospitals, unemployed and previously treated. Among migrant patients having permanent residence out of province, health system diagnosis delay was significantly higher while treatment initiation delay after diagnosis was significantly lower when compared to patients having permanent residence within the prefecture. CONCLUSION: Among migrant population with TB, patient delay contributed to the total delay. The factors identified including the need for improved coordination between referral hospitals and national programme have to be addressed if China has to end TB. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12913-018-3583-y) contains supplementary material, which is available to authorized users.


title: Current and future therapeutical approaches for COVID-19

text: • COVID-19, an alarming pandemic outbreak of 2020. • Amelioration of the clinical understanding of COVID-19 and its potential targets. • Adapted clinical strategies based on merits and demerits of COVID-19 treatment. • Current clinical manifestations and the proposed prospects against COVID-19. Coronavirus 2019 (COVID-19), the WHO-classified novel coronavirus of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a global pandemic. To tackle both its spread and virulence, research is ongoing worldwide to develop an effective anti-COVID-19 drug or vaccine. In this review, we explore the clinical understanding and severity of COVID-19 emergence across the world, with a focus on China. We also discuss potential therapeutic targets, either host virus based, that could be used to tackle the COVID-19 outbreak.