title: Randomised controlled trial comparing efficacy and safety of high versus low Low-Molecular Weight Heparin dosages in hospitalized patients with severe COVID-19 pneumonia and coagulopathy not requiring invasive mechanical ventilation (COVID-19 HD): a structured summary of a study protocol

text: OBJECTIVES: a. 1. Death. 2. Acute Myocardial Infarction [AMI]. 3. Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]. 4. a. Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) or b. IMV in patients who at randomisation were receiving standard oxygen therapy. 5. IMV in patients who at randomisation were receiving non-invasive mechanical ventilation. b. Similar in terms of major bleeding risk. TRIAL DESIGN: Multicentre, randomised controlled, superiority, open label, parallel group, two arms (1:1 ratio), in-hospital study. PARTICIPANTS: Inpatients will be recruited from 7 Italian Academic and non-Academic Internal Medicine Units, 2 Infectious Disease Units and 1 Respiratory Disease Unit. INCLUSION CRITERIA (ALL REQUIRED): 1. Age > 18 and < 80 years. 2. Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material). 3. a. Respiratory Rate ≥25 breaths /min. b. Arterial oxygen saturation≤93% at rest on ambient air. c. PaO2/FiO2 ≤300 mmHg. 4. a. D-dimer >4 times the upper level of normal reference range. b. Sepsis-Induced Coagulopathy (SIC) score >4. 5. No need of IMV. EXCLUSION CRITERIA: 1. Age <18 and >80 years. 2. IMV. 3. Thrombocytopenia (platelet count < 80.000 mm3). 4. Coagulopathy: INR >1.5, aPTT ratio > 1.4. 5. Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation < 30 ml/min). 6. Known hypersensitivity to enoxaparin. 7. History of heparin induced thrombocytopenia. 8. Presence of an active bleeding or a pathology susceptible of bleeding in presence of anticoagulation (e.g. recent haemorrhagic stroke, peptic ulcer, malignant cancer at high risk of haemorrhage, recent neurosurgery or ophthalmic surgery, vascular aneurysms, arteriovenous malformations). 9. Concomitant anticoagulant treatment for other indications (e.g. atrial fibrillation, venous thromboembolism, prosthetic heart valves). 10. Concomitant double antiplatelet therapy. 11. Administration of therapeutic doses of LMWH, fondaparinux, or unfractionated heparin (UFH) for more than 72 hours before randomization; prophylactic doses are allowed. 12. Pregnancy or breastfeeding or positive pregnancy test. 13. Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition). 14. Lack or withdrawal of informed consent. INTERVENTION AND COMPARATOR: Control Group (Low-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at standard prophylactic dose (i.e., 4000 UI subcutaneously once day). Intervention Group (High-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at dose of 70 IU/kg every 12 hours, as reported in the following table. This dose is commonly used in Italy when a bridging strategy is required for the management of surgery or invasive procedures in patients taking anti-vitamin K oral anticoagulants The treatment with Enoxaparin will be initiated soon after randomization (maximum allowed starting time 12h after randomization). The treatment will be administered every 12 hours in the intervention group and every 24 hours in the control group. Treatments will be administered in the two arms until hospital discharge or the primary outcomes detailed below occur. MAIN OUTCOMES: Primary Efficacy Endpoint: 1. Death. 2. Acute Myocardial Infarction [AMI]. 3. Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]. 4. a. Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) or b. IMV in patients who at randomisation were in standard oxygen therapy by delivery interfaces. 5. Need for IMV, in patients who at randomisation were in Cpap or NIV. Time to the occurrence of each of these events will be recorded. Clinical worsening will be analysed as a binary outcome as well as a time-to-event one. Secondary Efficacy Endpoints: : 1. Death. 2. Acute Myocardial Infarction [AMI]. 3. Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]. 4. a. Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) or b. IMV in patients who at randomisation were in standard oxygen therapy by delivery interfaces. 5. Need for IMV in patients who at randomisation were in Cpap or NIV. 6. o D-dimer level; o Plasma fibrinogen levels; o Mean Platelet Volume; o Lymphocyte/Neutrophil ratio; o IL-6 plasma levels. MORTALITY AT 30 DAYS: Information about patients’ status will be sought in those who are discharged before 30 days on Day 30 from randomisation. Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. Primary safety endpoint: Decrease in haemoglobin of 2 g/dl or more; Transfusion of 2 or more units of packed red blood cells; Bleeding that occurs in at least one of the following critical sites [intracranial, intraspinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal]; Bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death); Bleeding that necessitates surgical intervention. Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. Secondary safety endpoint: 1. Any bleeding compromising hemodynamic. 2. Spontaneous hematoma larger than 25 cm2, or 100 cm2 if there was a traumatic cause. 3. Intramuscular hematoma documented by ultrasonography. 4. Epistaxis or gingival bleeding requiring tamponade or other medical intervention. 5. Bleeding from venipuncture for >5 minutes. 6. Haematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive procedures. 7. Haemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical intervention. 8. Any other bleeding requiring temporary cessation of a study drug. Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. RANDOMISATION: Randomisation (with a 1:1 randomisation ratio) will be centrally performed by using a secure, web-based system, which will be developed by the Methodological and Statistical Unit at the Azienda Ospedaliero-Universitaria of Modena. Randomisation stratified by 4 factors: 1) Gender (M/F); 2) Age (<75/≥75 years); 3) BMI (<30/≥30); 4) Comorbidities (0-1/>2) with random variable block sizes will be generated by STATA software. The web-based system will guarantee the allocation concealment. Blinding (masking) The study is conceived as open-label: patients and all health-care personnel involved in the study will be aware of the assigned group. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size is based on the hypothesis that LMWH administered at high doses versus low doses will significantly reduce the risk of clinical worsening. The overall sample size in this study is expected to be 300 with 150 in the Low-Dose LMWH control group and 150 in the High-Dose LMWH intervention group, recruited over 10-11 months. Assuming an alpha of 5% (two tailed) and a percentage of patients who experience clinical worsening in the control group being between 25% and 30%, the study will have 80% power to detect at least 50% relative reduction in the risk of death between low and high doses of heparin. TRIAL STATUS: Protocol version 1.2 of 11/05/2020. Recruitment start (expected): 08/06/2020 Recruitment finish (expected): 30/04/2021 Trial registration EudraCT 2020-001972-13, registered on April 17th, 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Path to Advanced Healthcare in the Wake of COVID-19


title: Relato histórico de la infectología española

text: En el presente manuscrito se hace un breve resumen de lo que ha sido la historia de la infectología en España. Se consideran cuatro secciones referidas, en primer lugar, a los orígenes de una especialidad fruto de la necesidad de contar con expertos que dieran solución de una forma práctica y moderna a los diferentes problemas planteados por los pacientes con enfermedades infecciosas. En segundo lugar, la aparición del sida al comienzo de los años ochenta dio lugar a un enorme florecimiento en el campo de las enfermedades infecciosas, que trajo consigo la creación de unidades específicas dedicadas no sólo al control de los problemas asociados directamente con la infección por el virus de la inmunodeficiencia humana, sino al tratamiento de las infecciones oportunistas concomitantes. En tercer lugar, en estos últimos años ha despuntado de forma alarmante el problema de la infección nosocomial, problema de plena actualidad que obliga a la presencia de infectólogos expertos en este campo. Finalmente, la emigración y los viajes han requerido de los especialistas en enfermedades infecciosas una formación especial en salud internacional, lo que acrecienta la importancia de la disciplina de infectología. This paper includes a brief summary of the clinical history of the diagnosis and treatment of infectious diseases in Spain. Firstly, the origins of a specialty arising from the need for specialists to attend to, in a practical and modern form, the different health problems of patients affected by infectious diseases, are described. Secondly, the appearance of AIDS, at the beginning of the 1980s, prompted the creation of specific units dedicated to the care of problems associated with human immunodeficiency virus (HIV) infection and the concomitant opportunistic infections arising from the immunodeficiency arising from the HIV infection. Thirdly, in the last decades and even today, nosocomial infections have appeared as an alarming problem, needing the presence of specialist physicians in this field. Finally, emigration and international travel require specialists in infectious diseases with specific expertise in international health, once more highlighting the importance of the specialty of Infectious Diseases.


title: Helminth Vaccines in Ruminants From Development to Application

text: This article summarizes the state of the art in vaccine research against parasitic helminths in sheep and cattle. Optimization of antigen production (eg, recombinant expression) and antigen delivery, followed by extensive field testing, is still required for further development of vaccines. Helminth vaccines should sufficiently reduce parasite transmission to protect vaccinated animals against parasite-induced disorders and production loss. Vaccine efficacy requirements depend on the parasite’s epidemiology and farm management, both of which vary in different geographic regions and are influenced by climate. Vaccination is likely to be part of integrated worm control, together with other worm control measures.


title: Genetic Characterization of Coronaviruses from Domestic Ferrets, Japan

text: We detected ferret coronaviruses in 44 (55.7%) of 79 pet ferrets tested in Japan and classified the viruses into 2 genotypes on the basis of genotype-specific PCR. Our results show that 2 ferret coronaviruses that cause feline infectious peritonitis–like disease and epizootic catarrhal enteritis are enzootic among ferrets in Japan.


title: Vaccines for Viral and Parasitic Diseases Produced with Baculovirus Vectors

text: Abstract The baculovirus–insect cell expression system is an approved system for the production of viral antigens with vaccine potential for humans and animals and has been used for production of subunit vaccines against parasitic diseases as well. Many candidate subunit vaccines have been expressed in this system and immunization commonly led to protective immunity against pathogen challenge. The first vaccines produced in insect cells for animal use are now on the market. This chapter deals with the tailoring of the baculovirus–insect cell expression system for vaccine production in terms of expression levels, integrity and immunogenicity of recombinant proteins, and baculovirus genome stability. Various expression strategies are discussed including chimeric, virus‐like particles, baculovirus display of foreign antigens on budded virions or in occlusion bodies, and specialized baculovirus vectors with mammalian promoters that express the antigen in the immunized individual. A historical overview shows the wide variety of viral (glyco)proteins that have successfully been expressed in this system for vaccine purposes. The potential of this expression system for antiparasite vaccines is illustrated. The combination of subunit vaccines and marker tests, both based on antigens expressed in insect cells, provides a powerful tool to combat disease and to monitor infectious agents.


title: Unprecedented disruption of lives and work: Health, distress and life satisfaction of working adults in China one month into the COVID-19 outbreak

text: Abstract We assess the health and wellbeing of normal adults living and working after one month of confinement to contain the COVID-19 outbreak in China. On Feb 20–21, 2020, we surveyed 369 adults in 64 cities in China that varied in their rates of confirmed coronavirus cases on their health conditions, distress and life satisfaction. 27% of the participants worked at the office, 38% resorted to working from home, and 25% stopped working due to the outbreak. Those who stopped working reported worse mental and physical health conditions as well as distress. The severity of COVID-19 in an individual's home city predicts their life satisfaction, and this relationship is contingent upon individuals’ existing chronic health issues and their hours of exercise. Our evidence supports the need to pay attention to the health of people who were not infected by the virus, especially for people who stopped working during the outbreak. Our results highlight that physically active people might be more susceptible to wellbeing issues during the lockdown. Policymakers who are considering introducing restrictive measures to contain COVID-19 may benefit from understanding such health and wellbeing implications.


title: Microbial proteinase inside human cells as anti-mitochondrial activity: A new virulence factor in infectious diseases?

text: Summary Both bacteria and fungi produce extracellular proteinases since they need aminoacids for optimal reproduction. This may also occur inside host cells. Viral proteinases are produced during propagation inside host cells to supply amino acids for rapid synthesis of viral proteins, and/or to split poly-protein molecules into single protein molecules, e.g., capside, and matrix and/or envelope proteins. In host cells the most profound, microbial proteinase-mediated effect is thought to be damage of the mitochondria, the site of oxidative energy generation. Two major effects can be imagined: (i) damage of proteinase-susceptible extra-mitochondrial membrane-associated proteins (razor blade effect), e.g., of mitochondrial transport proteins and of ATP:ADP translocase, and (ii) damage of intra-mitochondrial proteinase-susceptible proteins that are involved in the energy-generating processes. Although proteinases are not thought to invade and destroy mitochondria and essential intra-mitochondrial structures involved in energy generation, they can destroy non-mitochondrial encoded mitochondrial proteins during transport to the mitochondria, i.e., before incorporation inside the mitochondria in intra-mitochondrial structures. A secondary effect may be damage of liver cells that effect hepatic gluconeogenesis, the process that is involved in the synthesis of glucose from lactic acid. The proteinase may bring about inactivation of specific gluconeogenesis enzymes. This means that accumulated amounts of lactic acid cannot rapidly be reduced and consequently, such inactivation will increase intracellular and later even systemic acidification that may finally result in death. We postulate that both direct and indirect proteinase-mediated damage of mitochondria and gluconeogenesis enzymes, and consequently of human cellular energy generation, is an essential element in acute (e.g., influenza) and chronic (e.g., hepatitis B) intracellular infections.


title: Forsythoside a inhibits the avian infectious bronchitis virus in cell culture

text: Forsythoside A is a polyphenolic constituent of the fruits of Forsythia suspensa Vahl. which is widely used as an antiinflammatory agent in traditional Chinese medicine. In the present study, the effects of forsythoside A on cell infection by avian infectious bronchitis virus were assessed. A real‐time fluorescence quantitative PCR assay was used to determine mRNA content of IBV N gene. The pretreatment of cells with forsythoside A, adding forsythoside A post infection of cells, and treatment of virus with forsythoside A were analysed. The inhibitory effect of forsythoside A was confirmed by infecting primary chicken embryo kidney cells. Infected cells were inhibited by forsythoside A treatment. The data indicated that forsythoside A has the potential to prevent IBV infection in vitro. Copyright © 2010 John Wiley & Sons, Ltd.


title: Mortality of a pregnant patient diagnosed with COVID-19: A case report with clinical, radiological, and histopathological findings

text: Abstract This report highlights details on a pregnant case of COVID-19 who unfortunately did not survive. This 27-year-old woman at her 30 and 3/7 weeks’ gestation was referred to our center with fever, myalgia, and cough. The laboratory investigations showed leukopenia and lymphopenia as well as increased creatinine and CRP levels. The first chest X-ray (faint bilateral patchy opacities) and CT scan (some faint subpleural ground-glass opacities associated with pleural thickening) were not typical for initial COVID-19 pulmonary infection, however, the treatment for COVID-19 was started. Due to respiratory distress, she was intubated and put under mechanical ventilation. After a while, the fetus was born with Apgar score of 0 and did not react to the neonatal cardiopulmonary resuscitation protocol. Finally, due to deterioration in the clinical and imaging findings, the patient was expired as a result of multi-organ failure. Following the death, autopsy was performed and the histopathologic evaluations of the lungs showed evidence of viral pneumonia (viral cytopathic effect and a mild increase in alveolar wall thickness) and ARDS (hyaline membrane). Also, reverse transcription-polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infection in the lungs. To our knowledge, this is the first report of maternal death with confirmed COVID-19 infection.


title: Evaluation of pharmacodynamic activities of EPs® 7630, a special extract from roots of Pelargonium sidoides, in animals models of cough, secretolytic activity and acute bronchitis

text: Abstract Background EPs® 7630 is a proprietary aqueous-ethanolic extract from roots of Pelargonium sidoides DC and has been demonstrated to dispose among others of antibacterial, antiviral, immunomodulatory, antioxidant, and tissue-protective activity. It is an approved medicinal product in more than 50 countries for the treatment of airway infections such as acute bronchitis, common cold, and sinusitis. Purpose While the pharmacological effects of EPs® 7630 have extensively been evaluated in diverse in vitro test systems, the number of publications reporting results from in vivo models is limited. Study design In the present study antitussive, secretolytic, and anti-inflammatory effects of EPs® 7630 were assessed in animal experiments following oral administration at human equivalent doses. Methods Antitussive effects were evaluated using ammonia- and citric acid-induced models of cough in mice (20, 40, 120 mg/kg) and guinea pigs (10, 20, 45 mg/kg), respectively. For the determination of secretolytic activity tracheobronchial secretion of intraperitoneally injected phenol red was determined in mice, while antiinflammatory action was assessed in an acute bacterial bronchitis model in rats. Results A significant and dose-dependent reduction of cough frequency was observed in both cough models, which was accompanied by a prolongation of cough latency time. Similarly, the extract exerted a marked secretolytic activity in mice. Induction of acute bacterial bronchitis caused characteristic histopathological changes in lung tissue adjacent to trachea and bronchi. The degree of these lesions was significantly reduced in rats treated with EPs® 7630 at doses of 30 and 60 mg/kg. This protective effect at least partially seems to be mediated by an up-regulation of superoxide dismutase and a subsequent protective effect against oxidative stress as indicated by a reduced serum level of malondialdehyde. Conclusion The present data further support the therapeutic use of EPs® 7630 in respiratory tract infections and provide a basis for detailed studies on its bioactive constituents as well as their in vivo mode of action.


title: Estimating Potential Incidence of MERS-CoV Associated with Hajj Pilgrims to Saudi Arabia, 2014

text: Between March and June 2014 the Kingdom of Saudi Arabia (KSA) had a large outbreak of MERS-CoV, renewing fears of a major outbreak during the Hajj this October. Using KSA Ministry of Health data, the MERS-CoV Scenario and Modeling Working Group forecast incidence under three scenarios. In the expected incidence scenario, we estimate 6.2 (95% Prediction Interval [PI]: 1–17) pilgrims will develop MERS-CoV symptoms during the Hajj, and 4.0 (95% PI: 0–12) foreign pilgrims will be infected but return home before developing symptoms. In the most pessimistic scenario, 47.6 (95% PI: 32–66) cases will develop symptoms during the Hajj, and 29.0 (95% PI: 17–43) will be infected but return home asymptomatic. Large numbers of MERS-CoV cases are unlikely to occur during the 2014 Hajj even under pessimistic assumptions, but careful monitoring is still needed to detect possible mass infection events and minimize introductions into other countries.


Surveillance for Respiratory Infections in Low- and Middle-Income Countries: Experience From the Centers for Disease Control and Prevention's Global Disease Detection International Emerging Infections Program


title: 3D Tissue-Like Assemblies: A Novel Approach to Investigate Virus-Cell Interactions

text: Virus-host cell interactions are most commonly analyzed in cells maintained in vitro as two-dimensional tissue cultures. However, these in vitro conditions vary quite drastically from the tissues that are commonly infected in vivo. Over the years, a number of systems have been developed that allow the establishment of three-dimensional (3D) tissue structures that have properties similar to their in vivo 3D counterparts. These 3D systems have numerous applications including drug testing, maintenance of large tissue explants, monitoring migration of human lymphocytes in tissues, analysis of human organ tissue development and investigation of virus-host interactions including viral latency. Here, we describe the establishment of tissue-like assemblies for human lung and neuronal tissue that we infected with a variety of viruses including the respiratory pathogens human parainfluenza virus type 3 (PIV3), respiratory syncytial virus (RSV) and SARS corona virus (SARS-CoV) as well as the human neurotropic herpesvirus, varicella-zoster virus (VZV)


title: Special Article: Risk Communication During COVID-19

text: Abstract: During the unprecedented times caused by the novel coronavirus COVID-19, there is rapidly evolving information and guidance. However, a focus must also be on proper and effective risk communication. This is especially the case during pandemics that have high rates of infection, significant morbidity, lack of therapeutic measures, and rapid increases in cases, all of which apply to the current COVID-19 pandemic. A consequence of poor risk communication and heightened risk perception is hoarding behavior, which can lead to lack of medications and personal protective equipment. One potential way to ensure appropriate risk communication is utilizing social media channels, and ensuring an ongoing consistent media presence. Another important step is to include all stakeholders including members of the allergy community in broader public health messaging. As we continue to face unprecedented times in the allergy community, an understanding and appreciation of risk communication will be essential as we communicate with, and inform, our patients, and our colleagues, moving forward.


title: Stability of bovine coronavirus on lettuce surfaces under household refrigeration conditions

text: Fecal suspensions with an aerosol route of transmission were responsible for a cluster of severe acute respiratory syndrome (SARS) cases in 2003 in Hong Kong. Based on that event, the World Health Organization recommended that research be implemented to define modes of transmission of SARS coronavirus through sewage, feces, food and water. Environmental studies have shown that animal coronaviruses remain infectious in water and sewage for up to a year depending on the temperature and humidity. In this study, we examined coronavirus stability on lettuce surfaces. A cell culture adapted bovine coronavirus, diluted in growth media or in bovine fecal suspensions to simulate fecal contamination was used to spike romaine lettuce. qRT-PCR detected viral RNA copy number ranging from 6.6 × 10(4) to 1.7 × 10(6) throughout the experimental period of 30 days. Whereas infectious viruses were detected for at least 14 days, the amount of infectious virus varied, depending upon the diluent used for spiking the lettuce. UV and confocal microscopic observation indicated attachment of residual labeled virions to the lettuce surface after the elution procedure, suggesting that rates of inactivation or detection of the virus may be underestimated. Thus, it is possible that contaminated vegetables may be potential vehicles for coronavirus zoonotic transmission to humans.


title: Assurer les soins aux patients souffrant de troubles psychiques en France pendant l’épidémie à SARS-CoV-2

text: Résumé Objectif: L’absence de préparation du système de soins psychiatriques à l’épidémie de virus SARS-CoV-2 fait redouter fait redouter un scénario pessimiste pour la santé physique et mentale des patients suivis en psychiatrie. L’objectif de cet article est de proposer des éléments de guidance pour réorganiser les soins psychiatriques dans le contexte de pandémie COVID-19. Méthode: Les auteurs ont réalisé une synthèse de la littérature internationale combinée au partage des expériences locales françaises. Résultats: Les patients souffrant de troubles psychiques semblent particulièrement vulnérables à ce virus et à la pandémie : vulnérabilités liées aux comorbidités médicales, à l’âge, aux troubles cognitifs qui peuvent entraver le respect des consignes de confinement, et aux complications psychosociales. Plusieurs initiatives ont été prises pour assurer la continuité des soins et contenir l’épidémie : création en psychiatrie d’unité COVID+ co-supervisée par des médecins généralistes ou internistes, restriction des consultations aux cas sévères et redéploiement des soins en téléconsultation, accompagnement de type case-management pour les sorties précoces ou l’impossibilité d’hospitaliser, accompagnements spécifiques pour les complications psychiques du confinement. Les populations suivies en pédopsychiatrie, en psychiatrie du sujet âgé, en addictologie ou détenues en prison doivent bénéficier d’une attention particulière. Plusieurs questions restent en suspend : la question de l’interaction négative ou positive des traitements sur l’infection SARS-CoV-2, l’épidémiologie de l’infection chez les personnes souffrant de troubles psychiques, leur adaptation à un confinement long. Discussion: Une prise de conscience par les décideurs politiques de la grande vulnérabilité de ces populations et des institutions psychiatriques dans cette situation de catastrophe sanitaire est urgente. Abstract Objective: The lack of ressources and coordination to face the epidemic of coronavirus raises concerns for the health of patients with mental disorders in a country where we keep in memory the dramatic experience of famine in psychiatric hospitals during the Second World War. This article aims at proposing guidance to ensure mental health care during the SARS-CoV epidemy in France. Methods: authors performed a narrative review identifying relevant results in the scientific and medical literature and local initiatives in France. Results: We identified four types of major vulnerabilities in patients suffering from mental disorders during this pandemic: 1) medical comorbidities that are more frequently found in patients suffering from mental disorders (cardiovascular and pulmonary pathologies, diabetes, obesity, etc.) which represent risk factors for severe infections with covid-19; 2) age (the elderly constituting the population most vulnerable to coronavirus); 3) cognitive and behavioral troubles which can hamper compliance with confinement and hygiene measures and finally and 4) psychosocial vulnerability due to stigmatization and/or socio-economic difficulties. Furthermore, the mental health healthcare system is more vulnerable than other healthcare systems. Current government plans are poorly adapted to psychiatric establishments in a context of major shortage of organizational, material and human resources. In addition, a certain number of structural aspects make the psychiatric institution particularly vulnerable: many beds are closed, wards have a high density of patients, mental health community facilities are closed, medical teams are understaffed and poorly trained to face infectious diseases. We could also face major issues in referring patients with acute mental disorders to intensive care units. To maintain continuity of psychiatric care in this pandemic situation, several directions can be considered, in particular with the creation of COVID + units. These units are under the dual supervision of a psychiatrist and of an internist / infectious disease specialist; all new entrants should be placed in quarantine for 14 days; the nurse staff should benefit from specific training, from daily medical check-ups and from close psychological support. Family visits would be prohibited and replaced by videoconference. At the end of hospitalization, in particular for the population of patients in compulsory ambulatory care situations, specific case-management should be organized with the possibility of home visits, in order to support them when they get back home and to help them to cope with the experience of confinement, which is at risk to induce recurrences of mental disorders. The total or partial closure of mental health community facilities is particularly disturbing for patients but a regular follow-up is possible with telemedicine and should include the monitoring of the suicide risk and psychoeducation strategies; developing support platforms could also be very helpful in this context. Private psychiatrists have also a crucial role of information with their patients on confinement and barrier measures, but also on measures to prevent the psychological risks inherent to confinement: maintenance of sleep regularity, physical exercise, social interactions, stress management and coping strategies, prevention of addictions, etc. They should also be trained to prevent, detect and treat early warning symptoms of post-traumatic stress disorder, because their prevalence was high in the regions of China most affected by the pandemic. Discussion: French mental healthcare is now in a great and urgent need for reorganization and must also prepare in the coming days and weeks to face an epidemic of emotional disorders due to the containment of the general population.


title: Inhibition of SIRT1 by microRNA-9, the key point in process of LPS-induced severe inflammation

text: Abstract Severe inflammation may lead to multiple organs dysfunction syndrome, which has a high mortality. MicroRNA is found participated in this process. In this study we developed a lipopolysaccharide-induced inflammation cell model on macrophages and a lipopolysaccharide-induced inflammation mouse model. It was found that during inflammation, microRNA-9 was increased, accompanied with the up-regulation of pro-inflammatory cytokines and anti-inflammatory cytokines. Down-regulation of microRNA-9 inhibited the up-regulation of inflammatory cytokines, promoted the up-regulation of anti-inflammatory cytokines and induced the remission of organ damage, showing a protective effect in inflammation. Bioinformatics analysis combined with luciferase reporter assay showed that SIRT1 was the target gene of microRNA-9. Transfection of microRNA-9 inhibitor could increase the level of SIRT1 and decrease the activation of NF-κB pathway in macrophages. Myeloid specific sirt1 knockout mice were included and we found that lack of SIRT1 in mice macrophages led to aggravated inflammation, cell apoptosis and organ injury, and eliminated the protective property of microRNA-9 inhibitor. In conclusion, we demonstrated that inhibition of microRNA-9 could alleviate inflammation through the up-regulation of SIRT1 and then suppressed the activation of NF-κB pathway. This is a meaningful explore about the specific mechanism of microRNA-9 in inflammation.


title: Antibody responses against SARS-coronavirus and its nucleocaspid in SARS patients

text: Abstract Background: SARS-Cov is the etiologic agent of severe acute respiratory syndrome. An understanding of the antibody responses to the viral components is very important for diagnosis and vaccine development. Objective: The spectrum of SARS-specific antibody profiles in SARS patients was investigated from 7 to 210 days after the onset of the symptoms. Study design: Serial serum samples from 14 SARS patients were isolated from 7 to 210 days after the onset of the symptoms, and were tested for anti-viral IgG and IgM by indirect immunofluorescence tests (IFA), anti-nucleocaspid antibody by ELISA tests and viral neutralization. Results: Anti-viral (IgG) and anti-nucleocaspid antibodies were observed in 13 of 14 patients at 14 days after the onset of symptoms, and in all 14 patients at 30–210 days thereafter. Anti-viral antibody (IgM) was detected maximally at 30 days, later than that for the IgG class. IgM antibody declined and became undetectable between 60 to 180 days after the onset of the symptoms. Neutralizing viral antibodies were demonstrated in the sera from all of the patients with SARS symptoms. Conclusions: Anti-viral IgG, IgM, and anti-nucleocaspid antibodies were detected 7–30 days in patients after the onset of SARS symptoms. Anti-viral IgM antibodies disappeared earlier than IgG. Viral neutralization was demonstrated in the sera from the convalescent patients.


title: Clinical approach to the inflammatory etiology of cardiovascular diseases

text: Inflammation is an obligatory marker of arterial disease, both stemming from the inflammatory activity of cholesterol itself and from well-established molecular mechanisms. Raised progenitor cell recruitment after major events and clonal hematopoiesis related mechanisms have provided an improved understanding of factors regulating inflammatory phenomena. Trials with inflammation antagonists have led to an extensive evaluation of biomarkers such as the high sensitivity C reactive protein (hsCRP), not exerting a causative role, but frequently indicative of the individual cardiovascular (CV) risk. Aim of this review is to provide indication on the anti-inflammatory profile of agents of general use in CV prevention, i.e. affecting lipids, blood pressure, diabetes as well nutraceuticals such as n-3 fatty acids. A crucial issue in the evaluation of the benefit of the anti-inflammatory activity is the frequent discordance between a beneficial activity on a major risk factor and associated changes of hsCRP, as in the case of statins vs PCSK9 antagonists. In hypertension, angiotensin converting enzyme inhibitors exert an optimal anti-inflammatory activity, vs the case of sartans. The remarkable preventive activity of SLGT-2 inhibitors in heart failure is not associated with a clear anti-inflammatory mechanism. Finally, icosapent ethyl has been shown to reduce the CV risk in hypertriglyceridemia, with a 27% reduction of hsCRP. The inflammation-based approach to arterial disease has considerably gained from an improved understanding of the clinical diagnostic strategy and from a better knowledge on the mode of action of numerous agents, including nutraceuticals.


title: Early dynamics of transmission and control of COVID-19: a mathematical modelling study

text: BACKGROUND: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to 95 333 confirmed cases as of March 5, 2020. Understanding the early transmission dynamics of the infection and evaluating the effectiveness of control measures is crucial for assessing the potential for sustained transmission to occur in new areas. Combining a mathematical model of severe SARS-CoV-2 transmission with four datasets from within and outside Wuhan, we estimated how transmission in Wuhan varied between December, 2019, and February, 2020. We used these estimates to assess the potential for sustained human-to-human transmission to occur in locations outside Wuhan if cases were introduced. METHODS: We combined a stochastic transmission model with data on cases of coronavirus disease 2019 (COVID-19) in Wuhan and international cases that originated in Wuhan to estimate how transmission had varied over time during January, 2020, and February, 2020. Based on these estimates, we then calculated the probability that newly introduced cases might generate outbreaks in other areas. To estimate the early dynamics of transmission in Wuhan, we fitted a stochastic transmission dynamic model to multiple publicly available datasets on cases in Wuhan and internationally exported cases from Wuhan. The four datasets we fitted to were: daily number of new internationally exported cases (or lack thereof), by date of onset, as of Jan 26, 2020; daily number of new cases in Wuhan with no market exposure, by date of onset, between Dec 1, 2019, and Jan 1, 2020; daily number of new cases in China, by date of onset, between Dec 29, 2019, and Jan 23, 2020; and proportion of infected passengers on evacuation flights between Jan 29, 2020, and Feb 4, 2020. We used an additional two datasets for comparison with model outputs: daily number of new exported cases from Wuhan (or lack thereof) in countries with high connectivity to Wuhan (ie, top 20 most at-risk countries), by date of confirmation, as of Feb 10, 2020; and data on new confirmed cases reported in Wuhan between Jan 16, 2020, and Feb 11, 2020. FINDINGS: We estimated that the median daily reproduction number (R(t)) in Wuhan declined from 2·35 (95% CI 1·15–4·77) 1 week before travel restrictions were introduced on Jan 23, 2020, to 1·05 (0·41–2·39) 1 week after. Based on our estimates of R(t), assuming SARS-like variation, we calculated that in locations with similar transmission potential to Wuhan in early January, once there are at least four independently introduced cases, there is a more than 50% chance the infection will establish within that population. INTERPRETATION: Our results show that COVID-19 transmission probably declined in Wuhan during late January, 2020, coinciding with the introduction of travel control measures. As more cases arrive in international locations with similar transmission potential to Wuhan before these control measures, it is likely many chains of transmission will fail to establish initially, but might lead to new outbreaks eventually. FUNDING: Wellcome Trust, Health Data Research UK, Bill & Melinda Gates Foundation, and National Institute for Health Research.


La pandemia por la COVID-19: una oportunidad para cambiar la forma de atender a nuestros pacientes


title: Broad sarbecovirus neutralizing antibodies define a key site of vulnerability on the SARS-CoV-2 spike protein

text: Broadly protective vaccines against known and pre-emergent coronaviruses are urgently needed. Critical to their development is a deeper understanding of cross-neutralizing antibody responses induced by natural human coronavirus (HCoV) infections. Here, we mined the memory B cell repertoire of a convalescent SARS donor and identified 200 SARS-CoV-2 binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of pre-existing memory B cells (MBCs) elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a new target for the rational design of pan-sarbecovirus vaccines.


title: High prevalence of antibodies against polyomavirus WU, polyomavirus KI, and human bocavirus in German blood donors

text: BACKGROUND: DNA of the polyomaviruses WU (WUPyV) and KI (KIPyV) and of human bocavirus (HBoV) has been detected with varying frequency in respiratory tract samples of children. However, only little is known about the humoral immune response against these viruses. Our aim was to establish virus-specific serological assays and to determine the prevalence of immunoglobulin G (IgG) against these three viruses in the general population. METHODS: The capsid proteins VP1 of WUPyV and KIPyV and VP2 of HBoV were cloned into baculovirus vectors and expressed in Sf9 insect cells. IgG antibodies against WUPyV VP1, KIPyV VP1, and HBoV VP2 were determined by immunofluorescence assays in 100 plasma samples of blood donors. RESULTS: The median age of the blood donors was 31 years (range 20 - 66 yrs), 52% were male. 89% of the samples were positive for WUPyV IgG (median age 31 yrs, 49.4% male), 67% were positive for KIPyV IgG (median age 32 yrs, 46.3% male), and 76% were positive for HBoV IgG (median age 32 yrs, 51.3% male). For WUPyV and HBoV, there were no significant differences of the seropositivity rates with respect to age groups or gender. For KIPyV, the seropositivity rate increased significantly from 59% in the age group 20 - 29 years to 100% in the age group > 50 years. CONCLUSIONS: High prevalences of antibodies against WUPyV, KIPyV, and HBoV were found in plasma samples of healthy adults. The results indicate that primary infection with these viruses occurs during childhood or youth. For KIPyV, the seropositivity appears to increase further during adulthood.


title: Structure, physiological role, and specific inhibitors of human thymidine kinase 2 (TK2): Present and future

text: Human mitochondrial thymidine kinase (TK2) is a pyrimidine deoxynucleoside kinase (dNK) that catalyzes the phosphorylation of pyrimidine deoxynucleosides to their corresponding deoxynucleoside 5′‐monophosphates by γ‐phosphoryl transfer from ATP. In resting cells, TK2 is suggested to play a key role in the mitochondrial salvage pathway to provide pyrimidine nucleotides for mitochondrial DNA (mtDNA) synthesis and maintenance. However, recently the physiological role of TK2turned out to have direct clinical relevance as well. Point mutations in the gene encoding TK2 have been correlated to mtDNA disorders in a heterogeneous group of patients suffering from the so‐called mtDNA depletion syndrome (MDS). TK2 activity could also be involved in mitochondrial toxicity associated to prolonged treatment with antiviral nucleoside analogues like AZT and FIAU. Therefore, TK2 inhibitors can be considered as valuable tools to unravel the role of TK2 in the maintenance and homeostasis of mitochondrial nucleotide pools and mtDNA, and to clarify the contribution of TK2 activity to mitochondrial toxicity of certain antivirals. Highly selective TK‐2 inhibitors having an acyclic nucleoside structure and efficiently discriminating between TK‐2 and the closely related TK‐1 have already been reported. It is actually unclear whether these agents efficiently reach the inner mitochondrial compartment. In the present review article,structural features of TK2, MDS‐related mutations observed in TK2 and their role in MDS will be discussed. Also, an update on novel and selective TK2 inhibitors will be provided. © 2008 Wiley Periodicals, Inc. Med Res Rev, 28, No. 5, 797–820, 2008


title: Incidence of calf scours and associated risk factors in southern New South Wales beef herds

text: OBJECTIVE: The aim of this study was to identify the incidence of morbidity and mortality associated with calf scours in beef calves between birth and 14 days of age. Farm characteristics, animal factors and management practices were also assessed for any association with calf scours being present on the farm. METHODS: A questionnaire and return address envelope were distributed to 721 farms with at least 50 head of beef cattle in the Hume area of New South Wales, Australia. RESULTS: In total, 147 (20.4%) farmers responded to the survey, of which 76 (51.7%) indicated calf scours did occur on their farm. On average, farmers estimated the morbidity of calf scours was 4.5%, but only 0.2% of all calves died as a result of scours. Affected herds were more likely to have multiple breeds and a higher proportion of cows with mismothering problems or weak calves compared with unaffected herds. These differences were confirmed with regression analysis. A large proportion of farmers with affected herds reported the loss of many calves from ‘unexplained’ or ‘sudden’ death within the first 14 days of life. CONCLUSIONS: The incidence of calf morbidity was lower and mortality was within the same range compared with other studies on beef farms around the world. The high percentage of farms reporting losses from ‘unexplained’ or ‘sudden’ death of calves requires further monitoring and diagnostic and economic investigations.


title: Protective effects of hypericin against infectious bronchitis virus induced apoptosis and reactive oxygen species in chicken embryo kidney cells

text: ABSTRACT Avian infectious bronchitis virus (IBV), a coronavirus, causes infectious bronchitis leading to enormous economic loss in the poultry industry worldwide. Hypericin (HY) is an excellent compound that has been investigated in antiviral, antineoplastic, and antidepressant. To investigate the inhibition effect of HY on IBV infection in chicken embryo kidney (CEK) cells, 3 different experimental designs: pre-treatment of cells prior to IBV infection, direct treatment of IBV-infected cells, and pre-treatment of IBV prior to cell infection were used. Quantitative real-time PCR (qRT-PCR), immunofluorescence assay (IFA), flow cytometry, and fluorescence microscopy were performed and virus titer was determined by TCID50. The results revealed that HY had a good anti-IBV effect when HY directly treated the IBV-infected cells, and virus infectivity decreased in a dose-dependent manner. Furthermore, HY inhibited IBV-induced apoptosis in CEK cells, and significantly reduced the mRNA expression levels of Fas, FasL, JNK, Bax, Caspase 3, and Caspase 8, and significantly increased Bcl-2 mRNA expression level in CEK cells. In addition, HY treatment could decrease IBV-induced reactive oxygen species (ROS) generation in CEK cells. These results suggested that HY showed potential antiviral activities against IBV infection involving the inhibition of apoptosis and ROS generation in CEK cells.


Please cite this paper as: Arnott et al. (2013) Human bocavirus amongst an all‐ages population hospitalised with acute lower respiratory infections in Cambodia. Influenza and Other Respiratory Viruses 7(2) 201–210. Background Human bocavirus (HBoV) is a novel parvovirus that is associated with respiratory and gastrointestinal tract disease. Objectives To investigate the prevalence and genetic diversity of HBoV amongst hospitalized patients with acute lower respiratory infection (ALRI) in Cambodia. Study Design Samples were collected from 2773 patients of all ages hospitalised with symptoms of ALRI between 2007 and 2009. All samples were screened by multiplex RT‐PCR/PCR for 18 respiratory viruses. All samples positive for HBoV were sequenced and included in this study. Results Of the samples tested, 43 (1·5%) were positive for HBoV. The incidence of HBoV did not vary between the consecutive seasons investigated, and HBoV infections were detected year‐round. The incidence of HBoV infection was highest in patients aged <2 years, with pneumonia or bronchopneumonia the most common clinical diagnosis, regardless of age. A total of 19 patients (44%) were co‐infected with HBoV and an additional respiratory pathogen. All isolates were classified as HBoV type 1 (HBoV‐1). High conservation between Cambodian NP1 and V1V2 gene sequences was observed. Conclusions Human bocavirus infection can result in serious illness, however is frequently detected in the context of viral co‐infection. Specific studies are required to further understand the true pathogenesis of HBoV in the context of severe respiratory illness.


title: Acute Symptomatic Seizures in Critically Ill Patients with COVID-19: Is There an Association?

text: BACKGROUND: The coronavirus disease of 2019 (COVID-19) emerged as a global pandemic. Historically, the group of human coronaviruses can also affect the central nervous system leading to neurological symptoms; however, the causative mechanisms of the neurological manifestations of COVID-19 disease are not well known. Seizures have not been directly reported as a part of COVID-19 outside of patients with previously known brain injury or epilepsy. We report two cases of acute symptomatic seizures, in non-epileptic patients, associated with severe COVID-19 disease. CASE PRESENTATIONS: Two advanced-age, non-epileptic, male patients presented to our northeast Ohio-based health system with concern for infection in Mid-March 2020. Both had a history of lung disease and during their hospitalization tested positive for SARS-CoV-2. They developed acute encephalopathy days into their hospitalization with clinical and electrographic seizures. Resolution of seizures was achieved with levetiracetam. DISCUSSION: Patients with COVID-19 disease are at an elevated risk for seizures, and the mechanism of these seizures is likely multifactorial. Clinical (motor) seizures may not be readily detected in this population due to the expansive utilization of sedatives and paralytics for respiratory optimization strategies. Many of these patients are also not electrographically monitored for seizures due to limited resources, multifactorial risk for acute encephalopathy, and the risk of cross-contamination. Previously, several neurological symptoms were seen in patients with more advanced COVID-19 disease, and these were thought to be secondary to multi-system organ failure and/or disseminated intravascular coagulopathy-related brain injury. However, these patients may also have an advanced breakdown of the blood–brain barrier precipitated by pro-inflammatory cytokine reactions. The neurotropic effect and neuroinvasiveness of SARS-Coronavirus-2 have not been directly established. CONCLUSIONS: Acute symptomatic seizures are possible in patients with COVID-19 disease. These seizures are likely multifactorial in origin, including cortical irritation due to blood–brain barrier breakdown, precipitated by the cytokine reaction as a part of the viral infection. Patients with clinical signs of seizures or otherwise unexplained encephalopathy may benefit from electroencephalography monitoring and/or empiric anti-epileptic therapy. Further studies are needed to elucidate the risk of seizures and benefit of monitoring in this population.


title: A Versatile Sample Processing Workflow for Metagenomic Pathogen Detection

text: Metagenomics is currently the only generic method for pathogen detection. Starting from RNA allows the assessment of the whole sample community including RNA viruses. Here we present our modular concerted protocol for sample processing for diagnostic metagenomics analysis of human, animal, and food samples. The workflow does not rely on dedicated amplification steps at any stage in the process and, in contrast to published methods, libraries prepared accordingly will yield only minute amounts of unclassifiable reads. We confirmed the performance of the approach using a spectrum of pathogen/matrix-combinations showing it has the potential to become a commonly usable analytical framework.


Lung cancer patients and COVID-19 epidemic: an experience from an Italian university hospital


title: Accuracy of Emergency Department clinical findings for diagnostic of coronavirus disease-2019

text: Abstract: Objective We sought to describe the medical history and clinical findings of patients attending the ED with suspected COVID-19 and estimate the diagnostic accuracy of patients’ characteristics for predicting COVID-19. Methods We prospectively enrolled all patients tested for SARS-CoV-2 by RT-PCR in our ED from March 9, 2020 to April 4, 2020. We abstracted medical history, physical examination findings, and the clinical probability of COVID-19 (“low”, “moderate”, “high”) rated by emergency physicians depending on their clinical judgment. We assessed diagnostic accuracy of these characteristics for COVID-19 by calculating positive and negative likelihood ratios (LR+/LR-). Results We included 391 patients of whom 225 tested positive for SARS-CoV-2. RT-PCR was more likely to be negative when the emergency physician thought that clinical probability was low, and more likely to be positive when she or he thought that clinical probability was high. Patient-reported anosmia and the presence of bilateral B-lines on lung ultrasound had the highest LR+ for the diagnosis of COVID-19 (7.58; 95% CI 2.36–24.36 and 7.09; 95% CI 2.77–18.12 respectively). The absence of a high clinical probability determined by the emergency physician and the absence of bilateral B-lines on lung ultrasound had the lowest LR- for the diagnosis of COVID-19 (0.33; 95% CI 0.25–0.43 and 0.26; 95% CI 0.15–0.45 respectively). Conclusions Anosmia, emergency physician estimate of high clinical probability and bilateral B-lines on lung ultrasound increased the likelihood of identifying COVID-19 in patients presenting to the ED.


title: COVID-19 related suicide among hospital nurses; case study evidence from worldwide media reports

text: Nurses are acknowledged for their care and expertise on the front line of pandemics over the last century. The recent global impact of COVID-19 has been unprecedented and a parallel battle has also been fought by increasing numbers of nurses for their workplace mental health. Factors associated with nurses mental stress and consequence of suicide were identified from a retrospective analysis of six non-representative media case-reports in high and low resource countries. The need for a structured model of nursing workforce mental health preparation, monitoring, support and health care is essential to inform advocacy and timely intervention in pandemic response.


The importance of high-quality data and analytics during the pandemic


title: More than meets the I: the diverse antiviral and cellular functions of interferon-induced transmembrane proteins

text: The first responders of human antiviral immunity are components of the intrinsic immune response that reside within each and every one of our cells. This cell-autonomous arsenal consists of nucleic acid sensors and antiviral effectors strategically placed by evolution to detect and restrict invading viruses. While some factors are present at baseline to allow for constant surveillance of the cell interior, others are upregulated by cytokines (such as interferons) that signal a viral infection underway in neighboring cells. In this review, we highlight the multiple roles played by the interferon-induced transmembrane (IFITM) proteins during viral infection, with focuses on IFITM3 and HIV-1. Moreover, we discuss the cellular pathways in which IFITM proteins are intertwined and the various functions they have been ascribed outside the context of infection. While appreciated as broadly-acting, potent restriction factors that prevent virus infection and pathogenesis in cell culture and in vivo, questions remain regarding their precise mode of action and importance in certain viral contexts. Continued efforts to study IFITM protein function will further cement their status as critical host determinants of virus susceptibility and prioritize them in the development of new antiviral therapies.


title: A Role for IFITM Proteins in Restriction of Mycobacterium tuberculosis Infection

text: The interferon (IFN)-induced transmembrane (IFITM) proteins are critical mediators of the host antiviral response. Here, we expand the role of IFITM proteins to host defense against intracellular bacterial infection by demonstrating that they restrict Mycobacterium tuberculosis (MTb) intracellular growth. Simultaneous knockdown of IFITM1, IFITM2, and IFITM3 by RNAi significantly enhances MTb growth in human monocytic and alveolar/epithelial cells, whereas individual overexpression of each IFITM impairs MTb growth in these cell types. Furthermore, MTb infection, Toll-like receptor 2 and 4 ligands, and several proinflammatory cytokines induce IFITM1–3 gene expression in human myeloid cells. We find that IFITM3 co-localizes with early and, in particular, late MTb phagosomes, and overexpression of IFITM3 enhances endosomal acidification in MTb-infected monocytic cells. These findings provide evidence that the antiviral IFITMs participate in the restriction of mycobacterial growth, and they implicate IFITM-mediated endosomal maturation in its antimycobacterial activity.


title: Chapter 7 Infections and multiple sclerosis

text: Abstract Multiple sclerosis is a chronic inflammatory condition of unknown cause. Increasing evidence suggests that the disease develops as a result of interactions between the environment and the immune system in genetically susceptible individuals. It has long been recognized that infections may serve as environmental triggers for the disease, and a large number of pathogens have been proposed to be associated with multiple sclerosis. Here, we detail the historical basis linking infections to multiple sclerosis and review the epidemiology of the disease, which suggests a possible relationship with infectious agents. We also describe pathophysiologic studies in animals and other human demyelinating diseases that have demonstrated a variety of mechanisms by which infectious agents may induce chronic, relapsing central nervous system disease with myelin damage and relative preservation of axons, similar to multiple sclerosis. In addition, we discuss recent studies in individuals with multiple sclerosis indicating enhanced immune responses to infectious antigens, though not consistently demonstrating evidence for ongoing infection. Taken together, these studies suggest a role for infectious agents in the development of multiple sclerosis. Conclusive evidence, however, remains lacking.


title: The Impacts of Viral Inactivating Methods On Quantitative RT-PCR for COVID-19

text: Abstract Objective This paper aims to explore the effect of four virus inactivation methods on the rapid detection results of COVID-19 nucleic acid. Methods Collected samples of nasopharyngeal swabs from 2 patients diagnosed with COVID-19 at the First People's Hospital of Zhaoqing City, each of sample was divided into 5 groups (groupA∼E): A:Non-inactivated raw sample; B:75% ethanol inactivation; C:56 ℃ incubation for 30 min inactivation; D:65 ℃ incubation for 10 min inactivation; E:Pre-inactivation using RNA virus special preservation fluid added into the sampling tube to treated the nasopharyngeal swab sample separately, using real-time fluorescent RT-PCR to detect the N gene of COVID-19 and the ORF1ab gene simultaneously. All the groups are diluted in 1:2, 1:4, 1:8 ratios. The objectives are to compare the effect of the varied inactivation method on CT(Cycle Threshold)results in PCR, conduct correlation and Bland-Altman analysis. Results For the N gene and ORF1ab gene, the CT values of 4 inactivated and Non-inactivated treatment were correlated (P＜0.001). The results of the four treatment methods and specimens without inactivated treatment have shown good consistency. Conclusion The treatment of nasopharyngeal swab specimens using mentioned four inactivated methods had no significant effect on the subsequent detection of the new COVID-19 nucleic acid test. Lab test-persons can flexibly adopt pre-inactivation methods to ensure the accuracy of virus nucleic acid test results, meanwhile guarantee the safety of lab test-persons.


Melatonina, coronavirus, enfermedad cardiovascular y emergencia geriátrica: ¡usemos todo lo que tenemos!


title: Respiratory sampling for severe acute respiratory syndrome coronavirus 2: An Overview

text: The novel coronavirus disease 2019 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and was declared a pandemic in March 2020. A plethora of respiratory sampling methods for SARS‐CoV‐2 viral detection has been used and in the current evolving situation, there is no international consensus on the recommended method of respiratory sampling for diagnosis. Otolaryngologists deal intimately with the upper respiratory tract and a clear understanding of the respiratory sampling methods is of paramount importance. This article aims to provide an overview of the various methods and their evidence till date.


Virucidal Effect of a Newly Developed Nickel Alloy on Mouse Coronavirus


title: Comprehensive analysis of drugs to treat SARS-CoV-2 infection: Mechanistic insights into current COVID-19 therapies (Review)

text: The major impact produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) focused many researchers attention to find treatments that can suppress transmission or ameliorate the disease. Despite the very fast and large flow of scientific data on possible treatment solutions, none have yet demonstrated unequivocal clinical utility against coronavirus disease 2019 (COVID-19). This work represents an exhaustive and critical review of all available data on potential treatments for COVID-19, highlighting their mechanistic characteristics and the strategy development rationale. Drug repurposing, also known as drug repositioning, and target based methods are the most used strategies to advance therapeutic solutions into clinical practice. Current in silico, in vitro and in vivo evidence regarding proposed treatments are summarized providing strong support for future research efforts.


title: Genome-Wide Transcriptional Profiling Reveals Two Distinct Outcomes in Central Nervous System Infections of Rabies Virus

text: Rabies remains a major public health concern in many developing countries. The precise neuropathogenesis of rabies is unknown, though it is hypothesized to be due to neuronal death or dysfunction. Mice that received intranasal inoculation of an attenuated rabies virus (RABV) strain HEP-Flury exhibited subtle clinical signs, and eventually recovered, which is different from the fatal encephalitis caused by the virulent RABV strain CVS-11. To understand the neuropathogenesis of rabies and the mechanisms of viral clearance, we applied RNA sequencing (RNA-Seq) to compare the brain transcriptomes of normal mice vs. HEP-Flury or CVS-11 intranasally inoculated mice. Our results revealed that both RABV strains altered positively and negatively the expression levels of many host genes, including genes associated with innate and adaptive immunity, inflammation and cell death. It is found that HEP-Flury infection can activate the innate immunity earlier through the RIG-I/MDA-5 signaling, and the innate immunity pre-activated by HEP-Flury or Newcastle disease virus (NDV) infection can effectively prevent the CVS-11 to invade central nervous system (CNS), but fails to clear the CVS-11 after its entry into the CNS. In addition, following CVS-11 infection, genes implicated in cell adhesion, blood vessel morphogenesis and coagulation were mainly up-regulated, while the genes involved in synaptic transmission and ion transport were significantly down-regulated. On the other hand, several genes involved in the MHC class II-mediated antigen presentation pathway were activated to a greater extent after the HEP-Flury infection as compared with the CVS-11 infection suggesting that the collaboration of CD4(+) T cells and MHC class II-mediated antigen presentation is critical for the clearance of attenuated RABV from the CNS. The differentially regulated genes reported here are likely to include potential therapeutic targets for expanding the post-exposure treatment window for RABV infection.


title: Outside the Box and Into Thick Air: Implementation of an Exterior Mobile Pediatric Emergency Response Team for North American H1N1 (Swine) Influenza Virus in Houston, Texas

text: STUDY OBJECTIVE: We describe the implementation of a mobile pediatric emergency response team for mildly ill children with influenza-like illnesses during the H1N1 swine influenza outbreak. METHODS: This was a descriptive quality improvement study conducted in the Texas Children's Hospital (Houston, TX) pediatric emergency department (ED), covered, open-air parking lot from May 1, 2009, to May 7, 2009. Children aged 18 years or younger were screened for viral respiratory symptoms and sent to designated areas of the ED according to level of acuity, possibility of influenza-like illness, and the anticipated need for laboratory evaluation. RESULTS: The mobile pediatric emergency response team experienced 18% of the total ED volume, or a median of 48 patients daily, peaking at 83 patients treated on May 3, 2009. Although few children had positive rapid influenza assay results and the morbidity of disease in the community appeared to be minimal for the majority of children, anxiety about pandemic influenza drove a large number of ED visits, necessitating an increase in surge capacity. Surge capacity was augmented both through utilization of existing institutional resources and by creating a novel area in which to treat patients with potential airborne pathogens. Infection control procedures and patient safety were also maximized through patient cohorting and adaptation of social distancing measures to the ED setting. CONCLUSION: The mobile pediatric emergency response team and screening and triage algorithms were able to safely and effectively identify a group of low-acuity patients who could be rapidly evaluated and discharged, alleviating ED volume and potentially preventing transmission of H1N1 influenza.


What is COVID‐19?


title: Psychological impact of the 2003 severe acute respiratory syndrome outbreak on health care workers in a medium size regional general hospital in Singapore

text: Aims To describe the psychological impact of severe acute respiratory syndrome (SARS) on health care workers in a regional general hospital 2 months post-outbreak. Method Doctors and nurses were encouraged to participate. The survey consisted of self-report measures: demographics, the General Health Questionnaire (GHQ) 28 and Impact of Events Scale (IES). A questionnaire enquiring about changes in life's priorities due to SARS and circumstances that helped with coping was used. Participation was strictly voluntary and responses anonymous. Results In total 177 out of 661 (27%) participants [40 out of 113 (35%) doctors and 137 out of 544 (25%) nurses] had a GHQ 28 score ≥5. Doctors [P = 0.026, odds ratio (OR) = 1.6 and 95% confidence interval (CI) = 1.1–2.5] and single health care workers were at higher risk (P = 0.048, OR = 1.4 and 95% CI = 1.02–2.0) compared to nurses and those who were married. Approximately 20% of the participants had IES scores ≥30, indicating the presence of post-traumatic stress disorder (PTSD). Four areas were classified as more important using factor analysis: health and relationship with the family, relationship with friends/colleagues, work and spiritual. The areas for coping strategies were clear directives/precautionary measures, ability to give feedback to/obtain support from management, support from supervisors/colleagues, support from the family, ability to talk to someone and religious convictions. Support from supervisors/colleagues was a significant negative predictor for psychiatric symptoms and PTSD. Work and clear communication of directives/precautionary measures also helped reduce psychiatric symptoms. Conclusions Many health care workers were emotionally affected and traumatized during the SARS outbreak. Hence, it is important for health care institutions to provide psychosocial support and intervention for their health care workers.


title: Immunogenicity and protective efficacy of recombinant fusion proteins containing spike protein of infectious bronchitis virus and hemagglutinin of H3N2 influenza virus in chickens

text: Abstract Infectious bronchitis (IB) is an acute and highly contagious viral respiratory disease of chickens and vaccination is the main method for disease control. The S1 protein, which contains several virus neutralization epitopes, is considered to be a target site of vaccine development. However, although protective immune responses could be induced by recombinant S1 protein, the protection rate in chickens was still low (<50%). Here, we generated fused S1 proteins with HA2 protein (rS1-HA2) or transmembrane domain and cytoplasmic tail (rS1-H3(TM)) from hemagglutinin of H3N2 influenza virus. After immunization, animals vaccinated with fusion proteins rS1-HA2 and rS1-H3(TM) demonstrated stronger robust humoral and cellular immune responses than that of rS1 and inactivated M41 vaccine. The protection rates of groups immunized with rS1-HA2 (87%) were significantly higher than the groups inoculated with rS1 (47%) and inactivated M41 vaccine (53%). And chickens injected with rS1-H3(TM) had similar level of protection (73%) comparing to chickens vaccinated with rS1 (47%) (P=0.07). Our data suggest that S1 protein fused to the HA2 or TM proteins from hemagglutinin of H3N2 influenza virus may provide a new strategy for high efficacy recombinant vaccine development against IBV.


title: Prediction of the number of deaths in India due to SARS-CoV-2 at 5–6 weeks

text: Abstract Introduction and Aims: No valid treatment or preventative strategy has evolved till date to counter the SARS CoV 2 (Novel Coronavirus) epidemic that originated in China in late 2019 and have since wrought havoc on millions across the world with illness, socioeconomic recession and death. This analysis was aimed at tracing a trend related to death counts expected at the 5th and 6th week of the COVID-19 in India. Material and methods Validated database was used to procure global and Indian data related to coronavirus and related outcomes. Multiple regression and linear regression analyses were used interchangeably. Since the week 6 death count data was not correlated significantly with any of the chosen inputs, an auto-regression technique was employed to improve the predictive ability of the regression model. Results A linear regression analysis predicted average week 5 death count to be 211 with a 95% CI: 1.31–2.60). Similarly, week 6 death count, in spite of a strong correlation with input variables, did not pass the test of statistical significance. Using auto-regression technique and using week 5 death count as input the linear regression model predicted week 6 death count in India to be 467, while keeping at the back of our mind the risk of over-estimation by most of the risk-based models. Conclusion According to our analysis, if situation continue in present state; projected death rate (n) is 211 and467 at the end of the 5th and 6th week from now, respectively.


title: The neck-region polymorphism of DC-SIGNR in peri-centenarian from Han Chinese Population

text: BACKGROUND: DC-SIGNR (also called CD209L) has been extensively studied on its role in host genetic predisposition to viral infection. In particular, variable number tandem repeat (VNTR) of the neck-region of DC-SIGNR is highly polymorphic and the polymorphism has been investigated for genetic predisposition to various infectious diseases, though conflicting results had been reported. As infection is a major cause of human death and a mechanism of natural selection, we hypothesized that VNTR polymorphism of DC-SIGNR might have an effect on human life span. METHODS: Here we collected 361 peri-centenarian individuals (age ≥94 for female and age ≥90 for male) and 342 geographically matched controls (age 22-53, mean 35.0 ± 12.0) from Han Chinese. The VNTR polymorphism of the neck region was determined by PCR and genotype was called by separating the PCR products in agarose gel. RESULTS: A total of 11 genotypes and 5 alleles were found in our population. The genotype distribution, allele frequencies and homozygote proportion did not show a significant difference between peri-centenarian and control group. As gender differences in lifespan are ubiquitously observed throughout the animal kingdom, we then stratified the samples by gender. There was more 6/7 genotypes in female peri-centenarian group than that in female control group, at a marginal level of significance (5.56 vs. 1.28%, p = 0.041). The difference was not significant after correction by Bonferroni method. It suggests a possible differential effect of DC-SIGNR VNTR genotypes between sexes. Further studies are warranted to confirm our preliminary findings and investigate the mechanisms of the underlying functions. CONCLUSIONS: Our study indicated that there was absence of association between the neck region polymorphism of DC-SIGNR and longevity in Han Chinese population. But the question of whether the DC-SIGNR could affect longevity in a gender-specific pattern remains open.


title: Imaging Features of Coronavirus disease 2019 (COVID-19): Evaluation on Thin-Section CT

text: Rationale and Objectives To retrospectively analyze the chest imaging findings in patients with coronavirus disease 2019 (COVID-19) on thin-section CT. Materials and Methods Fifty-three patients with confirmed COVID-19 infection underwent thin-section CT examination. Two chest radiologists independently evaluated the imaging in terms of distribution, ground-glass opacity (GGO), consolidation, air bronchogram, stripe, enlarged mediastinal lymph node, and pleural effusion. Results Fourty-seven cases (88.7%) had findings of COVID-19 infection, and the other six (11.3%) were normal. Among the 47 cases, 78.7% involved both lungs, and 93.6% had peripheral infiltrates distributed along the subpleural area. All cases showed GGO, 59.6% of which were round and 40.4% patchy. Other imaging features included “crazy-paving pattern” (89.4%), consolidation (63.8%), and air bronchogram (76.6%). Air bronchograms were observed within GGO (61.7%) and consolidation (70.3%). Neither enlarged mediastinal lymph nodes nor pleural effusion were present. Thirty-three patients (62.3%) were followed an average interval of 6.2 ± 2.9 days. The lesions increased in 75.8% and resorbed in 24.2% of patients. Conclusion COVID-19 showed the pulmonary lesions in patients infected with COVID-19 were predominantly distributed peripherally in the subpleural area.


Macrophage subsets at the maternal-fetal interface


title: A Mobile Health Platform to Disseminate Validated Institutional Measurements During the COVID-19 Outbreak: Utilization-Focused Evaluation Study

text: BACKGROUND: As part of the response plans for the current outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), authorities are drafting and implementing containment measures across jurisdictions worldwide in the effort to slow down transmission and reduce the infection rate. A solid communication strategy is needed to increase the reach of valid information to health professionals, reduce misinformation, and efficiently implement recommended measures. OBJECTIVE: The aim of this paper is to describe the utilization of a dedicated mobile health (mHealth) platform to disseminate up-to-date and validated information about SARS-CoV-2 to all medical staff of the Children’s Hospital at the University Hospitals of Geneva. METHODS: Three documents containing institutional information concerning screening, local containment procedures, and frequently asked questions and answers for parents were made available to the staff through a mobile app developed in the University of Geneva, Switzerland. Using a third-party statistics tool, we anonymously monitored user activity as well as content utilization patterns since the diagnosis of the first case of SARS-CoV-2 in Switzerland on February 25, 2020. RESULTS: From February 25, 2020, to March 13, 2020 (18 days), information documents on SARS-CoV-2 were viewed 859 times, which accounted for 35.6% of the total content views (total views=332). User activity increased significantly with 50.8 (SD 14.4) users per day in this period as compared to the previous weeks (mean 26.4, SD 9.8; P<.001). In addition, session numbers per day more than doubled during the aforementioned period (P<.001). In a survey, medical staff found the information easy to find within the app. On a 10-point Likert scale, the ability of the app to reassure staff in clinical practice was rated as 7.6 (SD 2.1), time-saving ability was rated as 8.5 (SD 2.1), and the need to look for information from other sources was rated as 5.9 (SD 3.3). CONCLUSIONS: The use of an mHealth solution to disseminate novel coronavirus–related information seemed to be an effective and time-saving communication channel within our institution during the SARS-CoV-2 outbreak. Medical staff felt reassured and informed in daily practice. More research should be done on the clinical impact and outcomes of the integration of mHealth solutions as a communication channel of validated information within health institutions.


title: Respiratory nanoparticle-based vaccines and challenges associated with animal models and translation

text: Vaccine development has had a huge impact on human health. However, there is a significant need to develop efficacious vaccines for several existing as well as emerging respiratory infectious diseases. Several challenges need to be overcome to develop efficacious vaccines with translational potential. This review focuses on two aspects to overcome some barriers – 1) the development of nanoparticle-based vaccines, and 2) the choice of suitable animal models for respiratory infectious diseases that will allow for translation. Nanoparticle-based vaccines, including subunit vaccines involving synthetic and/or natural polymeric adjuvants and carriers, as well as those based on virus-like particles offer several key advantages to help overcome the barriers to effective vaccine development. These include the ability to deliver combinations of antigens, target the vaccine formulation to specific immune cells, enable cross-protection against divergent strains, act as adjuvants or immunomodulators, allow for sustained release of antigen, enable single dose delivery, and potentially obviate the cold chain. While mouse models have provided several important insights into the mechanisms of infectious diseases, they are often a limiting step in translation of new vaccines to the clinic. An overview of different animal models involved in vaccine research for respiratory infections, with advantages and disadvantages of each model, are discussed. Taken together, advances in nanotechnology, combined with the right animal models for evaluating vaccine efficacy, has the potential to revolutionize vaccine development for respiratory infections.


title: The Iterative Gramicidin S Thioesterase Catalyzes Peptide Ligation and Cyclization

text: Summary Here, we present a comprehensive in vitro characterization of the excised iterative, bimodular PCP-TE of the gramicidin S synthetase GrsB, which is able to act both as a ligation and a cyclization catalyst. Using the native pentapeptidyl-thioester substrates, GrsB PCP-TE catalyzes the dimerization and subsequent formation of the decapeptide lactam gramicidin S. Interestingly, the detection of linear decapeptidyl-SNAC as an enzyme-dependent intermediate supports the iterative mechanism in vivo, in which two pentapeptides, one bound as an ester to the active site serine of the TE domain and the second bound as a thioester to the adjacent pan-PCP, are ligated to a decapeptidyl-pan-PCP that subsequently transferred to the adjacent TE domain and cyclized. Moreover, GrsB PCP-TE can handle different substrates length, leading not only to dimerization, but also to trimerization and the formation of different ring sizes.


Commentary: House calls, Phone calls, Or Face Time! Post-Discharge Outcomes Are Improved By Education And Follow-Up.


Handy-Tracking als Maßnahme zur Bekämpfung der Covid-19-Pandemie


title: Role of the Spike Glycoprotein of Human Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Virus Entry and Syncytia Formation

text: Little is known about the biology of the emerging human group c betacoronavirus, Middle East Respiratory Syndrome coronavirus (MERS-CoV). Because coronavirus spike glycoproteins (S) mediate virus entry, affect viral host range, and elicit neutralizing antibodies, analyzing the functions of MERS-CoV S protein is a high research priority. MERS-CoV S on lentivirus pseudovirions mediated entry into a variety of cell types including embryo cells from New World Eptesicus fuscus bats. Surprisingly, a polyclonal antibody to the S protein of MHV, a group a murine betacoronavirus, cross-reacted in immunoblots with the S2 domain of group c MERS-CoV spike protein. MERS pseudovirions released from 293T cells contained only uncleaved S, and pseudovirus entry was blocked by lysosomotropic reagents NH(4)Cl and bafilomycin and inhibitors of cathepsin L. However, when MERS pseudovirions with uncleaved S protein were adsorbed at 4°C to Vero E6 cells, brief trypsin treatment at neutral pH triggered virus entry at the plasma membrane and syncytia formation. When 293T cells producing MERS pseudotypes co-expressed serine proteases TMPRSS-2 or -4, large syncytia formed at neutral pH, and the pseudovirions produced were non-infectious and deficient in S protein. These experiments show that if S protein on MERS pseudovirions is uncleaved, then viruses enter by endocytosis in a cathepsin L-dependent manner, but if MERS-CoV S is cleaved, either during virus maturation by serine proteases or on pseudovirions by trypsin in extracellular fluids, then viruses enter at the plasma membrane at neutral pH and cause massive syncytia formation even in cells that express little or no MERS-CoV receptor. Thus, whether MERS-CoV enters cells within endosomes or at the plasma membrane depends upon the host cell type and tissue, and is determined by the location of host proteases that cleave the viral spike glycoprotein and activate membrane fusion.


title: Peptide Nanoparticles as Novel Immunogens: Design and Analysis of a Prototypic Severe Acute Respiratory Syndrome Vaccine

text: Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel coronavirus that cost nearly 800 lives. While there have been no recent outbreaks of the disease, the threat remains as SARS coronavirus (SARS-CoV) like strains still exist in animal reservoirs. Therefore, the development of a vaccine against SARS is in grave need. Here, we have designed and produced a prototypic SARS vaccine: a self-assembling polypeptide nanoparticle that repetitively displays a SARS B-cell epitope from the C-terminal heptad repeat of the virus’ spike protein. Biophysical analyses with circular dichroism, transmission electron microscopy and dynamic light scattering confirmed the computational design showing α-helcial nanoparticles with sizes of about 25 nm. Immunization experiments with no adjuvants were performed with BALB/c mice. An investigation of the binding properties of the elicited antibodies showed that they were highly conformation specific for the coiled-coil epitope because they specifically recognized the native trimeric conformation of C-terminal heptad repeat region. Consequently, the antisera exhibited neutralization activity in an in vitro infection inhibition assay. We conclude that these peptide nanoparticles represent a promising platform for vaccine design, in particular for diseases that are characterized by neutralizing epitopes with coiled-coil conformation such as SARS-CoV or other enveloped viruses.


title: Correlation of Pandemic (H1N1) 2009 Viral Load with Disease Severity and Prolonged Viral Shedding in Children

text: Younger children may require a longer isolation period and more aggressive treatment.


title: Presence of SARS-Coronavirus-2 RNA in Sewage and Correlation with Reported COVID-19 Prevalence in the Early Stage of the Epidemic in The Netherlands

text: [Image: see text] In the current COVID-19 pandemic, a significant proportion of cases shed SARS-Coronavirus-2 (SARS-CoV-2) with their faeces. To determine if SARS-CoV-2 RNA was present in sewage during the emergence of COVID-19 in The Netherlands, sewage samples of six cities and the airport were tested using four qRT-PCR assays, three targeting the nucleocapsid gene (N1–N3) and one the envelope gene (E). No SARS-CoV-2 RNA was detected on February 6, 3 weeks before the first Dutch case was reported. On March 4/5, one or more gene fragments were detected in sewage of three sites, in concentrations of 2.6–30 gene copies per mL. In Amersfoort, N3 was detected in sewage 6 days before the first cases were reported. As the prevalence of COVID-19 in these cities increased in March, the RNA signal detected by each qRT-PCR assay increased, for N1–N3 up to 790–2200 gene copies per mL. This increase correlated significantly with the increase in reported COVID-19 prevalence. The detection of the virus RNA in sewage, even when the COVID-19 prevalence is low, and the correlation between concentration in sewage and reported prevalence of COVID-19, indicate that sewage surveillance could be a sensitive tool to monitor the circulation of the virus in the population.


title: Cutaneous manifestation of COVID‐19 in images: a case report

text: In December 2019, China reported the first group of pneumonia cases associated with a new coronavirus, 2019-SARS-CoV-21 . Currently, the novel coronavirus infection has become a pandemic2 . Significant research efforts are taking place around the world to better understand the transmission dynamics, the spectrum of clinical disease, possible treatment options, and prevention measures.


title: Revitalisation of industrial buildings in Hong Kong: New measures, new constraints?

text: Like many post-industrial cities around the world, Hong Kong has been experiencing de-industrialisation since the 1980s, and revitalisation of multi-storey industrial buildings within a high-density development context is necessary. Focussing on recent progress in revitalisation of industrial buildings in Hong Kong, this research investigates the Government regulations and market responses. It is found that simply relieving the regulations and institutional constraints in revitalisation does not work, either for the policy aim in a narrow sense or for the local economy in a broad sense. New revitalisation measures by the Government have led to new constraints in revitalisation. It is necessary to address the policy lag. This paper presents an opening statement of discussing effectiveness of revitalisation policy in terms of urban competitiveness. It advocates some general principles and goals been taken into account in making revitalisation policy, including industrial diversity, indigenously owned companies, social costs and quality of life.


title: School closure, COVID‐19 and lunch programme: Unprecedented undernutrition crisis in low‐middle income countries

text: The coronavirus disease 2019 pandemic has affected nearly 70% of children and teenagers around the world due to school closure policies. School closure is implemented widely in order to prevent viral transmission and its impact on the broader community, based on preliminary recommendations and evidence from influenza. However, there is debate with regard to the effectiveness of school closures. Growing evidence suggests that a child's SARS‐CoV‐2 infection is often mild or asymptomatic and that children may not be major SARS‐CoV‐2 transmitters; thus, it is questionable if school closures prevent transmission significantly. This question is important as a majority of children in low‐ and middle‐income countries depend on free school meals; unexpected long‐term school closure may adversely impact nutrition and educational outcomes. Food insecurity is expected to be higher during the pandemic. In this viewpoint, we argue for a more thorough exploration of potential adverse impacts of school closures in low‐ and middle‐income countries and recommend actions to ensure that the health and learning needs of vulnerable populations are met in this time of crisis.


title: Ouderen op reis

text: Ouderen reizen steeds meer, maar met de leeftijd neemt de kans toe om op reis te overlijden. De oorzaak hiervan is meestal een verergering van vooraf bestaande gezondheidsaandoeningen, eventueel uitgelokt door reisgerelateerde stress en vermoeidheid, infecties en hitte. Ook de hogere leeftijd zelf is echter verantwoordelijk voor een deel van de oversterfte, doordat de afweer afneemt met als gevolg meer kans op ernstige infecties. Daarnaast zijn ouderen gevoeliger voor diepveneuze trombose, dehydratie, temperatuurverschillen en jetlag. Een goede voorbereiding en rekening houden met de specifieke risico’s van een hogere leeftijd, zorgen ervoor dat ook ouderen in het algemeen veilig kunnen reizen.


title: Probiotic Use in Horses – What is the Evidence for Their Clinical Efficacy?

text: The gastrointestinal microbiota is extremely important for human and animal health. Investigations into the composition of the microbiota and its therapeutic modification have received increasing interest in human and veterinary medicine. Probiotics are a way of modifying the microbiota and have been tested to prevent and treat diseases. Probiotics are proposed to exert their beneficial effects through various pathways. Production of antimicrobial compounds targeting intestinal pathogens, general immune stimulation, and colonization resistance are among these mechanisms. Despite widespread availability and use, scientific, peer‐reviewed evidence behind commercial probiotic formulations in horses is limited. Additionally, quality control of commercial over‐the‐counter products is not tightly regulated. Although promising in vitro results have been achieved, in vivo health benefits have been more difficult to prove. Whether the ambiguous results are caused by strain selection, dosage selection or true lack of efficacy remains to be answered. Although these limitations exist, probiotics are increasingly used because of their lack of severe adverse effects, ease of administration, and low cost. This review summarizes the current evidence for probiotic use in equine medicine. It aims to provide veterinarians with evidence‐based information on when and why probiotics are indicated for prevention or treatment of gastrointestinal disease in horses. The review also outlines the current state of knowledge on the equine microbiota and the potential of fecal microbial transplantation, as they relate to the topic of probiotics.


title: SARS-CoV-2 pandemic on the activity and professionals of a General Surgery and Digestive Surgery Service in a tertiary hospital

text: Abstract Introduction The rapid spread of SARS-CoV-2 infection has led to a radical reorganization of healthcare resources. Surgical Departments need to adapt to this change. Patients and methods We performed a prospective descriptive observational study of the incidence of COVID-19 in patients and surgeons of a General Surgical Department in a high prevalence area, between the 1 st and 31 st of March 2020. Results Patients: The incidence of SARS-CoV-2 infection in elective surgery patients was 7% (mean age 59.5 years). All survived. Of 36 patients who underwent emergency surgery, two of them were SARS-CoV-2 positive and one was clinically highly suspicious of COVID-19 (11.1%). All three patients died of respiratory failure (mean age 81 years). Surgeons: There were a total of 12 confirmed SARS-CoV-2+ cases among the surgical department staff (24.4%) (8 out of 34 consultants and 4 out of 15 residents). Healthcare activity: The average number of daily emergency surgical interventions declined from 3.6 in February to 1.16 in March. 42% of the patients who underwent emergency surgery had peritonitis upon presentation. Conclusions The fast pace of COVID-19 pandemia, should alert surgical departments of the need of adopting early measures to ensure the safety of patients and staff.


title: Piloting forensic tele-mental health evaluations of asylum seekers

text: While the number of medical human rights programs has increased, there is substantial unmet need for forensic evaluations among asylum seekers throughout the United States. From September 2019 through May 2020, the Mount Sinai Human Rights Program has coordinated pro bono forensic mental health evaluations by telephone or video for individuals seeking protected immigration status who are unable to access in-person services. The national network clinicians conducted 32 forensic evaluations of individuals in eight U.S. states and Mexico seeking immigration relief. Remote forensic services have been a relevant solution for individuals in immigration detention, particularly during the COVID-19 pandemic.


title: Immediate and long‐term impact of the COVID‐19 pandemic on delivery of surgical services

text: BACKGROUND: The ongoing pandemic is having a collateral health effect on delivery of surgical care to millions of patients. Very little is known about pandemic management and effects on other services, including delivery of surgery. METHODS: This was a scoping review of all available literature pertaining to COVID‐19 and surgery, using electronic databases, society websites, webinars and preprint repositories. RESULTS: Several perioperative guidelines have been issued within a short time. Many suggestions are contradictory and based on anecdotal data at best. As regions with the highest volume of operations per capita are being hit, an unprecedented number of operations are being cancelled or deferred. No major stakeholder seems to have considered how a pandemic deprives patients with a surgical condition of resources, with patients disproportionally affected owing to the nature of treatment (use of anaesthesia, operating rooms, protective equipment, physical invasion and need for perioperative care). No recommendations exist regarding how to reopen surgical delivery. The postpandemic evaluation and future planning should involve surgical services as an essential part to maintain appropriate surgical care for the population during an outbreak. Surgical delivery, owing to its cross‐cutting nature and synergistic effects on health systems at large, needs to be built into the WHO agenda for national health planning. CONCLUSION: Patients are being deprived of surgical access, with uncertain loss of function and risk of adverse prognosis as a collateral effect of the pandemic. Surgical services need a contingency plan for maintaining surgical care in an ongoing or postpandemic phase.


title: Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2009–2010

text: This review is the sixth update of the original article published in 1999 on the application of MALDI mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2010. General aspects such as theory of the MALDI process, matrices, derivatization, MALDI imaging, arrays and fragmentation are covered in the first part of the review and applications to various structural typed constitutes the remainder. The main groups of compound that are discussed in this section are oligo and polysaccharides, glycoproteins, glycolipids, glycosides and biopharmaceuticals. Many of these applications are presented in tabular form. Also discussed are medical and industrial applications of the technique, studies of enzyme reactions and applications to chemical synthesis. © 2014 Wiley Periodicals, Inc. Mass Spec Rev 34: 268–422, 2015.


title: Fatal Invasive Aspergillosis and Coronavirus Disease in an Immunocompetent Patient

text: Invasive pulmonary aspergillosis is a complication in critically ill patients with acute respiratory distress syndrome, especially those with severe influenza pneumonia. We report a fatal case of invasive pulmonary aspergillosis in an immunocompetent patient in France who had severe coronavirus disease–associated pneumonia.


title: Seroprevalence of pathogens in domestic carnivores on the border of Madidi National Park, Bolivia

text: The importance of diseases of domestic animals in the conservation of wildlife is increasingly being recognised. Wild carnivores are susceptible to many of the pathogens carried by domestic dogs and cats and some of these pathogens have caused disease outbreaks and severe population declines in threatened species. The risk of disease spillover from domestic to wild carnivores in South America has not been extensively investigated. This study examined the disease exposure of domestic carnivores living near a protected area in Bolivia. Forty dogs and 14 cats living in three towns on the eastern border of Madidi National Park were sampled. High levels of exposure to canine distemper virus, canine parvovirus, Sarcoptes scabiei and Toxoplasma gondii were found among domestic dogs, with similarly high levels of exposure to feline parvovirus, feline calicivirus and T. gondii being found among domestic cats. If contact occurs between domestic and wild carnivores, disease spillover may represent an important risk for the persistence of wild carnivores in the region. Additional research is therefore necessary to determine if wild carnivores living in proximity to these domestic carnivore populations are being exposed to these pathogens.