title: Adherence to social distancing and use of personal protective equipment and the risk of Sars-COV-2 infection in a cohort of patients with Multiple Sclerosis

text: Background Aiming to safeguard its population from COVID19 infection, Italian government provided specific advices, especially to fragile individuals such those affected by Multiple Sclerosis (MS), to respect social distancing, to arrange remote work and to use personal protective equipment (PPE). The aim of this study is to investigate real adherence to these measures among MS patients and to evaluate its impact on exposure to infection. Methods MS patients followed at the MS centre of Tor Vergata University hospital, Rome, Italy were asked to complete an anonymous 35-items web-survey exploring demographics, residency, employment, social distancing habits, use of PPE, MS features and COVID19 infection data, including self-reported information about contact with SARS-CoV-2 positive/presumed positive person. In order to estimate adherence to social distancing and use of PPE, an overall ‘Lockdown Score’ (LS) on 0-10 scale was created analyzing four main domains (Working (0 - 4), Social distancing and PPE use (0 - 4), Assistance for shopping needs (0 - 2), Residency (-2 - 0)). Mean scores for several pre-defined subgroups of patients were compared using both univariable and multivariable analyses. Accuracy of the score in discriminating subjects at higher risk of coming in contact with SARS-CoV-2 positive/presumed positive individuals was calculated as the area under the receiver-operator characteristic curve (AUC). The optimal cut-off was identified and used to dichotomize LS (high/ low). Logistic regression model was applied to estimate the characteristics of individuals associated to high/low LS and the odds ratio of coming in contact with SARS-CoV-2 positive/presumed positive individuals based on continous and dichotomised LS. Results Respondents (N=551) had a mean(±SD) overall LS of 6.52±2.11 (Working 3.16±1.19, Social distancing and PPE use 2.69±1.33, Assistance 0.66± 0.62, Residency penalty applied in 4 cases). Females, disabled and unemployed individuals had significantly higher mean LS (p<0.05). The AUC of the LS was 0.68 (95% CI, 0.59-0.77) and the optimal LS cut-off for discrimination was 6.0. Consistently, females, disabled and unemployed individuals had higher odd of getting a high LS (≥ 6) compared to males, independent and employed (p<0.05). Odd of coming in contact with SARS-CoV-2 positive/presumed positive individuals was significantly reduced for one-unit increase in LS (0.74 (95% CI: 0.64-0.85)) and among individuals with high LS (0.37 (95% CI: 0.19-0.72)). Only one subject among respondents declared to have been diagnosed with COVID19. Conclusions MS patients, especially those with social unfavorable conditions, demonstrated good adherence to social distancing and use of protection equipment. Implementing domains, such as social assistance, may improve protection from infection. LS score is potentially able to identify subjects with behaviors at greater risk of infection, although it needs to be validated against MS population living in higher incidence areas.


Interpreting Results From Environmental Contamination Studies of Middle East Respiratory Syndrome Coronavirus


title: Unprecedented Challenges, Familiar Paradoxes: COVID‐19 and Governance in a New Normal State of Risks

text: Through the lens of paradoxes, this essay understands China's COVID‐19 responses, focusing on normal and non‐normal governance, competing values, expertise and politics, centralization and decentralization, public and private, and technology and institution. Preliminary lessons are drawn regarding pandemic governance: embedding resilience into all aspects of governance; developing a public value framework for pandemic governance and improving individuals' ethical capacity; institutionalizing policy capacity on pandemic governance and requiring expertise in relevant positions; balancing centralized coordination and decentralized responses with a stable and ready‐to‐work commanding center; enabling businesses and nonprofits for pandemic governance but regulating them appropriately; and enacting technologies to revolutionize pandemic governance with proper institutional safeguards. This article is protected by copyright. All rights reserved.


title: How Can Viral Dynamics Models Inform Endpoint Measures in Clinical Trials of Therapies for Acute Viral Infections?

text: Acute viral infections pose many practical challenges for the accurate assessment of the impact of novel therapies on viral growth and decay. Using the example of influenza A, we illustrate how the measurement of infection-related quantities that determine the dynamics of viral load within the human host, can inform investigators on the course and severity of infection and the efficacy of a novel treatment. We estimated the values of key infection-related quantities that determine the course of natural infection from viral load data, using Markov Chain Monte Carlo methods. The data were placebo group viral load measurements collected during volunteer challenge studies, conducted by Roche, as part of the oseltamivir trials. We calculated the values of the quantities for each patient and the correlations between the quantities, symptom severity and body temperature. The greatest variation among individuals occurred in the viral load peak and area under the viral load curve. Total symptom severity correlated positively with the basic reproductive number. The most sensitive endpoint for therapeutic trials with the goal to cure patients is the duration of infection. We suggest laboratory experiments to obtain more precise estimates of virological quantities that can supplement clinical endpoint measurements.


title: CHAPTER 2 Classification and Nomenclature of Viruses

text: Publisher Summary Viral taxonomists have developed a system of classification and nomenclature that embraces all viruses. From the operational point of view, viruses are divided into those that affect vertebrate animals, insects, plants, and bacteria. The chapter discusses the viruses of vertebrate animals, although some of these viruses, the arthropod-borne viruses (arboviruses), also replicate in insects or other arthropods. Several hundred species of viruses have been recovered from humans, who are the best-studied vertebrate hosts and new ones are still occasionally discovered. Somewhat fewer have been recovered from each of the common species of farm and companion animals and from the commonly used laboratory animals. To simplify the study of this vast number of infectious agents, these are sorted into groups that share certain common properties. The most important criteria for classification are the physical and chemical characteristics of the virion and the mode of replication of the virus. The chapter explains a formal viral taxonomy, which is based on these criteria.


title: Posttraumatic stress, anxiety, and depression in survivors of severe acute respiratory syndrome (SARS)

text: This study examines the psychological impact of severe acute respiratory syndrome (SARS) in 195 adult patients in Hong Kong. The Impact of Event Scale—Revised and Hospital Anxiety and Depression Scale were administered to patients 1 month after their discharge. Of the participants 10% to 18% reported symptoms related to posttraumatic stress disorder, anxiety, and depression. Symptom severity was associated with high perceived life threat and low emotional support. Women and participants who had low education level were more likely to have symptoms of avoidance. Participants who personally knew someone who had SARS were more likely to be affected by depressive symptoms.


title: Welche Bedeutung hat die Bindehaut als möglicher Übertragungsweg für eine SARS-CoV-2-Infektion?

text: Recent studies have described conjunctivitis in approximately 1% of COVID-19 patients and speculated that SARS-CoV‑2 can be transmitted via the conjunctiva. In this article we recapitulate the molecular mechanisms of host cell entry of SARS-CoV‑2 and discuss the current evidence for a potential conjunctival transmission of SARS-CoV‑2. The current body of evidence indicates that SARS-CoV‑2 requires the membrane-bound angiotensin-converting enzyme 2 (ACE2) and the membrane-bound serine protease TMPRSS2 to enter cells. Recent studies suggest that COVID-19 patients rarely exhibit viral RNA in tear film and conjunctival smears and that, ACE2 and TMPRSS2 are only expressed in very small amounts in the conjunctiva, making conjunctival infection with SARS-CoV‑2 via these mediators unlikely. Nevertheless, we consider the current evidence to be still too limited to provide a conclusive statement and recommend appropriate protective measures for healthcare personnel who are in close contact with suspected and confirmed COVID-19 patients.


title: Case Study: Control of respiratory disease in male Holstein calves with tildipirosin and effect on health and growth from 0 to 4 months of age

text: ABSTRACT In trial 1, phase 1, 48 male Holstein calves initially 2 to 4 d of age were transported 3.5 h to the research facility. Calves were randomly selected to either receive a s.c. injection of Zuprevo (Merck Animal Health, Summit, NJ; 4 mg of tildipirosin/kg of BW; TIL) the day after arrival (d 0) and again at weaning (d 42) or receive no injections (CON). Calves were fed 0.66 kg of milk replacer DM daily for 39 d and then 0.33 kg daily for 3 d. A starter was fed free choice for the 56 d of phase 1. In trial 1, phase 2, the same calves from phase 1 grouped by CON and TIL were moved to group pens (4 pens per treatment, 4 calves per pen) for the next 56 d. The starter was blended with 5% chopped grass hay and fed free choice. Trial 2 was similar to trial 1, phase 2 and used 48 two-month-old male Holstein calves. Calves were randomly selected to receive either a s.c. injection of Zuprevo (4 mg of tildipirosin/kg of BW; TIL) on d 0 or no injections (CON). In trial 1, phase 1, preweaning ADG and BCS change; postweaning starter intake and hip width change; overall starter intake, ADG, and hip width change; final hip width; and final BCS were greater for TIL than CON. During phase 2 of trial 1 and trial 2, calf ADG and hip width change were greater for TIL than CON. Overall, in transported Holstein calves, TIL improved ADG and structural growth by approximately 13%.


title: Animal models for emerging coronavirus: progress and new insights

text: The emergences of coronaviruses have caused a serious global public health problem because their infection in humans caused the severe acute respiratory disease and deaths. The outbreaks of lethal coronaviruses have taken place for three times within recent two decades (SARS-CoV in 2002, MERS-CoV in 2012 and SARS-CoV-2 in 2019). Much more serious than SARS-CoV in 2002, the current SARS-CoV-2 infection has been spreading to more than 213 countries, areas or territories and causing more than two million cases up to date (17 April 2020). Unfortunately, no vaccine and specific anti-coronavirus drugs are available at present time. Current clinical treatment at hand is inadequate to suppress viral replication and inflammation, and reverse organ failure. Intensive research efforts have focused on increasing our understanding of viral biology of SARS-CoV-2, improving antiviral therapy and vaccination strategies. The animal models are important for both the fundamental research and drug discovery of coronavirus. This review aims to summarize the animal models currently available for SARS-CoV and MERS-CoV, and their potential use for the study of SARS-CoV-2. We will discuss the benefits and caveats of these animal models and present critical findings that might guide the fundamental studies and urgent treatment of SARS-CoV-2-caused diseases.


title: Immunogenicity, safety, and protective efficacy of an inactivated SARS-associated coronavirus vaccine in rhesus monkeys

text: An inactivated vaccine for severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) was evaluated in rhesus monkeys. The monkeys were inoculated intramuscularly (i.m.) with 0.5, 5, 50, or 5000 μg of vaccine, or PBS as control, and boosted on day 7. After 3 weeks, they were challenged with the NS-1 strain of SARS-CoV. The humoral and mucosal immune responses, clinical signs, chemical indices and viremia were monitored following the immunization and challenge. The control animals who received PBS developed atypical SAR-CoV infection after viral challenge, according to clinical, virological and pathological findings. No systematic side effects were observed in vaccinated animals post-immunization, even in at the high dose of 5000 μg. The 50 μg dosage of vaccine elicited SARS-CoV specific immune responses against viral infection as compared to the partial immunity elicited by 0.5 and 5 μg doses. The results show that this inactivated vaccine can induce effective concomitant humoral and mucosal immunity against SARS-CoV infection, is safe in monkeys, and the vaccine maybe a good candidate for clinical trials.


title: Zoonotic Vectorborne Pathogens and Ectoparasites of Dogs and Cats in Eastern and Southeast Asia

text: To provide data that can be used to inform treatment and prevention strategies for zoonotic pathogens in animal and human populations, we assessed the occurrence of zoonotic pathogens and their vectors on 2,381 client-owned dogs and cats living in metropolitan areas of 8 countries in eastern and Southeast Asia during 2017–2018. Overall exposure to ectoparasites was 42.4% in dogs and 31.3% in cats. Our data cover a wide geographic distribution of several pathogens, including Leishmania infantum and zoonotic species of filariae, and of animals infested with arthropods known to be vectors of zoonotic pathogens. Because dogs and cats share a common environment with humans, they are likely to be key reservoirs of pathogens that infect persons in the same environment. These results will help epidemiologists and policy makers provide tailored recommendations for future surveillance and prevention strategies.


title: Prevalence and phylogenetic analysis of porcine diarrhea associated viruses in southern China from 2012 to 2018

text: BACKGROUND: In China, large-scale outbreaks of severe diarrhea caused by viruses have occurred in pigs since late 2010. To investigate the prevalence and genetic evolution of diarrhea-associated viruses responsible for the outbreaks, a total of 2987 field diarrheal samples collected from 168 pig farms in five provinces in Southern China during 2012–2018 were tested. RESULTS: Porcine epidemic diarrhea virus (PEDV) was most frequently detected virus with prevalence rates between 50.21 and 62.10% in samples, and 96.43% (162/168) in premises, respectively. Porcine deltacoronavirus (PDCoV) was the second prevalent virus with prevalence rates ranging from 19.62 to 29.19% in samples, and 70.24% (118/168) in premises, respectively. Both transmissible gastroenteritis virus (TGEV) and porcine rotavirus (PoRV) were detected at low prevalence rates of < 3% in samples and 10.12% in premises. In this study, we identified a newly emerged swine acute diarrhea syndrome coronavirus (SADS-CoV) in diarrheal samples of piglets from Fujian province in Southern China, and the prevalence rate of SADS-CoV was 10.29% (7/68). Co-infections of these diarrhea-associated viruses were common. The most frequent co-infection was PEDV with PDCoV, with an average detection rate of 12.72% (380/2987, ranging from 8.26–17.33%). Phylogenetic analysis revealed that PEDVs circulating in Southern China during the last 7 years were clustered with the variant strains of PEDV in genotype IIa. The most frequent mutations were present in the collagenase equivalent (COE) and epitope regions of the spike gene of the PEDVs currently circulating in the field. Genetic relationships of PDCoVs were closely related with Chinese strains, other than those present in the USA, South Korea, Thailand and Lao’s public. CONCLUSIONS: The findings of this study indicated that variant PEDV, PDCoV, and SADS-CoV were leading etiologic agents of porcine diarrhea, and either mono-infections or co-infections of pathogenic enteric CoVs were common in pigs in Southern China during 2012–2018. Thus, significant attention should be paid in order to effectively prevent and control porcine viral diarrhea.


title: Risk reduction through family therapy (RRFT): Protocol of a randomized controlled efficacy trial of an integrative treatment for co-occurring substance use problems and posttraumatic stress disorder symptoms in adolescents who have experienced interpersonal violence and other traumatic events

text: Abstract Decades of research demonstrate that childhood exposure to traumatic events, particularly interpersonal violence experiences (IPV; sexual abuse, physical abuse, witnessing violence), increases risk for negative behavioral and emotional outcomes, including substance use problems (SUP) and posttraumatic stress disorder (PTSD). Despite this well-established link—including empirical support for shared etiological and functional connections between SUP and PTSD –the field has been void of a gold standard treatment for adolescent populations. To address this gap, our team recently completed a large randomized controlled trial to evaluate the efficacy of Risk Reduction through Family Therapy (RRFT), an integrative and exposure-based risk-reduction and treatment approach for adolescents who have experienced IPV and other traumatic events. The purpose of this paper is to provide a detailed description of the design and methods of this RCT designed to reduce SUP, PTSD symptoms, and related risk behaviors, with outcomes measured from pre-treatment through 18 months post-entry. Specifically, the recruitment and sampling procedures, assessment measures and methods, description of the intervention, and planned statistical approaches to evaluating the full range of outcomes are detailed. Clinical and research implications of this work are also discussed.


title: Smoking Upregulates Angiotensin-Converting Enzyme-2 Receptor: A Potential Adhesion Site for Novel Coronavirus SARS-CoV-2 (Covid-19)

text: The epicenter of the original outbreak in China has high male smoking rates of around 50%, and early reported death rates have an emphasis on older males, therefore the likelihood of smokers being overrepresented in fatalities is high. In Iran, China, Italy, and South Korea, female smoking rates are much lower than males. Fewer females have contracted the virus. If this analysis is correct, then Indonesia would be expected to begin experiencing high rates of Covid-19 because its male smoking rate is over 60% (Tobacco Atlas). Smokers are vulnerable to respiratory viruses. Smoking can upregulate angiotensin-converting enzyme-2 (ACE2) receptor, the known receptor for both the severe acute respiratory syndrome (SARS)-coronavirus (SARS-CoV) and the human respiratory coronavirus NL638. This could also be true for new electronic smoking devices such as electronic cigarettes and “heat-not-burn” IQOS devices. ACE2 could be a novel adhesion molecule for SARS-CoV-2 causing Covid-19 and a potential therapeutic target for the prevention of fatal microbial infections, and therefore it should be fast tracked and prioritized for research and investigation. Data on smoking status should be collected on all identified cases of Covid-19.


title: Travelling to scientific meetings is a mission, not a vacation

text: University accountants and administrators should support scientists going to meetings, not further burden them with bureaucratic hurdles, expense claims or unnecessary auditing.[Image: see text]


title: Clinical and epidemiological characteristics of 320 deceased Covid‐19 patients in an Italian Province: a retrospective observational study

text: BACKGROUND: Studies have described clinical features of Covid‐19 patients. However, limited data concerning the clinical characteristics of the Italian deaths are available. We aim to describe the clinical and epidemiological characteristics of 320 deceased from the Italian experience. METHODS: We retrospectively collected all consecutive non‐survivor patients with laboratory‐confirmed Covid‐19 infection admitted to the Emergency Rooms (ER) Piacenza Hospital Network during the first month of Covid‐19 pandemic in Italy. Clinical history, comorbidities, laboratory findings and treatment were recorded for each patient. RESULTS: A total of 1050 patients with confirmed Covid‐19 pneumonia were admitted to the ERs between 24 February,2020, and 22 March,2020. 320 (30.5%) patients died with a median age of 78.0 years, 205 (64%) non‐survivors were above 65 years old, 230 (71.9 %) were male. Non‐survivor patients showed frequently several coexisting medical conditions, with hypertension being the most common comorbidity (235 patients, 73.4%). The in‐hospital mortality did not change during the progression of the pandemic. CONCLUSION: In this retrospective Italian study, most of Covid‐19 deceased patients were elderly male aged over than 65 years. Hypertension was the most common coexisting disease. In‐hospital mortality was high and showed no variation during the first month of the Covid‐19 italian epidemic. This article is protected by copyright. All rights reserved.


title: Limited Utility of Polymerase Chain Reaction in Induced Sputum Specimens for Determining the Causes of Childhood Pneumonia in Resource-Poor Settings: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study

text: BACKGROUND. Sputum examination can be useful in diagnosing the cause of pneumonia in adults but is less well established in children. We sought to assess the diagnostic utility of polymerase chain reaction (PCR) for detection of respiratory viruses and bacteria in induced sputum (IS) specimens from children hospitalized with severe or very severe pneumonia. METHODS. Among children aged 1–59 months, we compared organism detection by multiplex PCR in IS and nasopharyngeal/oropharyngeal (NP/OP) specimens. To assess whether organism presence or density in IS specimens was associated with chest radiographic evidence of pneumonia (radiographic pneumonia), we compared prevalence and density in IS specimens from children with radiographic pneumonia and children with suspected pneumonia but without chest radiographic changes or clinical or laboratory findings suggestive of pneumonia (nonpneumonia group). RESULTS. Among 4232 cases with World Health Organization–defined severe or very severe pneumonia, we identified 1935 (45.7%) with radiographic pneumonia and 573 (13.5%) with nonpneumonia. The organism detection yield was marginally improved with IS specimens (96.2% vs 92.4% for NP/OP specimens for all viruses combined [P = .41]; 96.9% vs 93.3% for all bacteria combined [P = .01]). After accounting for presence in NP/OP specimens, no organism was detected more frequently in the IS specimens from the radiographic pneumonia compared with the nonpneumonia cases. Among high-quality IS specimens, there were no statistically significant differences in organism density, except with cytomegalovirus, for which there was a higher quantity in the IS specimens from cases with radiographic pneumonia compared with the nonpneumonia cases (median cycle threshold value, 27.9 vs 28.5, respectively; P = .01). CONCLUSIONS. Using advanced molecular methods with IS specimens provided little additional diagnostic information beyond that obtained with NP/OP swab specimens.


title: Infectious Disease Externalities

text: Abstract In the presence of infectious diseases, people's actions have consequences for others but not ones that they take into account in making their choices. These externalities arise for individuals' decisions about both prevention and therapy and condition the design of government interventions. Subsidies are one form of intervention but may be constrained by circumstances to be less than optimal.


title: Low prevalence of equine coronavirus in foals in the largest thoroughbred horse breeding region of Japan, 2012–2014

text: BACKGROUND: Equine coronavirus (ECoV) is considered to be a diarrheic pathogen in foals. In central Kentucky in the United States, it has been shown that approximately 30 % of thoroughbred foals are infected with ECoV and thus it is considered widely prevalent. In contrast, the epidemiology of ECoV and its relationship to diarrhea in foals are poorly understood in Japan. We investigated ECoV in rectal swabs collected from thoroughbred foals in Japan. RESULTS: We collected 337 rectal swabs from 307 diarrheic foals in the Hidaka district of Hokkaido, the largest thoroughbred horse breeding region in Japan, between 2012 and 2014. In addition, 120 rectal swabs were collected from 120 healthy foals in 2012. These samples were tested by reverse transcription loop-mediated isothermal amplification and a real-time reverse transcription-polymerase chain reaction. All samples collected from diarrheic foals were negative, and only three samples (2.5 %) collected from healthy foals were positive for ECoV. Compared with central Kentucky, ECoV is not prevalent among thoroughbred foals in the Hidaka district of Hokkaido. CONCLUSION: ECoV is not prevalent and was not related to diarrhea in thoroughbred foals in the Hidaka district of Hokkaido between 2012 and 2014.


title: Characterization of a Novel Influenza Virus in Cattle and Swine: Proposal for a New Genus in the Orthomyxoviridae Family

text: We have recently reported the isolation of a novel virus, provisionally designated C/swine/Oklahoma/1334/2011 (C/OK), with 50% overall homology to human influenza C viruses (ICV), from a pig in Oklahoma. Deep RNA sequencing of C/OK virus found a matrix 1 (M1) protein expression strategy that differed from that of ICV. The novelty of C/OK virus prompted us to investigate whether C/OK virus could exist in a nonswine species. Significantly, we found that C/OK virus was widespread in U.S. bovine herds, as demonstrated by reverse transcription (RT)-PCR and serological assays. Genome sequencing of three bovine viruses isolated from two herds in different states further confirmed these findings. To determine whether swine/bovine C/OK viruses can undergo reassortment with human ICV, and to clarify the taxonomic status of C/OK, in vitro reassortment and serological typing by agar gel immunodiffusion (AGID) were conducted. In vitro reassortment using two human ICV and two swine and bovine C/OK viruses demonstrated that human ICV and C/OK viruses were unable to reassort and produce viable progeny. Antigenically, no cross-recognition of detergent split virions was observed in AGID between human and nonhuman viruses by using polyclonal antibodies that were reactive to cognate antigens. Taken together, these results demonstrate that C/OK virus is genetically and antigenically distinct from ICV. The classification of the new virus in a separate genus of the Orthomyxoviridae family is proposed. The finding of C/OK virus in swine and bovine indicates that this new virus may spread and establish infection in other mammals, including humans.


title: Chapter 34 Antiviral Drugs

text: Abstract Viruses are major pathogenic agents causing a variety of serious diseases in humans, other animals, and plants. Drugs that combat viral infections are called antiviral drugs. There are no effective antiviral drugs for many viral infections. However, there are several drugs for influenza, a couple of drugs for herpesviruses, and some new antiviral drugs for treatment of HIV and hepatitis C infections. The arsenal of antivirals is complex. As of March 2014, it consists of approximately 50 drugs approved by the FDA, approximately half of which are directed against HIV. Antiviral drug creation strategies are focused on two different approaches: targeting the viruses themselves or targeting host cell factors. Direct virus-targeting antiviral drugs include attachment inhibitors, entry inhibitors, uncoating inhibitors, protease inhibitors, polymerase inhibitors, nucleoside and nucleotide reverse transcriptase inhibitors, nonnucleoside reverse-transcriptase inhibitors, and integrase inhibitors. Protease inhibitors (darunavir, atazanavir, and ritonavir), viral DNA polymerase inhibitors (acyclovir, valacyclovir, valganciclovir, and tenofovir), and an integrase inhibitor (raltegravir) are included in the list of Top 200 Drugs by sales for the 2010s.


title: Respiratory infectious phenotypes in acute exacerbation of COPD: an aid to length of stay and COPD Assessment Test

text: PURPOSE: To investigate the respiratory infectious phenotypes and their impact on length of stay (LOS) and the COPD Assessment Test (CAT) Scale in acute exacerbation of COPD (AECOPD). PATIENTS AND METHODS: We categorized 81 eligible patients into bacterial infection, viral infection, coinfection, and non-infectious groups. The respiratory virus examination was determined by a liquid bead array xTAG Respiratory Virus Panel in pharyngeal swabs, while bacterial infection was studied by conventional sputum culture. LOS and CAT as well as demographic information were recorded. RESULTS: Viruses were detected in 38 subjects, bacteria in 17, and of these, seven had both. Influenza virus was the most frequently isolated virus, followed by enterovirus/rhinovirus, coronavirus, bocavirus, metapneumovirus, parainfluenza virus types 1, 2, 3, and 4, and respiratory syncytial virus. Bacteriologic analyses of sputum showed that Pseudomonas aeruginosa was the most common bacteria, followed by Acinetobacter baumannii, Klebsiella, Escherichia coli, and Streptococcus pneumoniae. The longest LOS and the highest CAT score were detected in coinfection group. CAT score was positively correlated with LOS. CONCLUSION: Respiratory infection is a common causative agent of exacerbations in COPD. Respiratory coinfection is likely to be a determinant of more severe acute exacerbations with longer LOS. CAT score may be a predictor of longer LOS in AECOPD.


title: The use of complementary and alternative medicine by patients with cancer: a cross-sectional survey in Saudi Arabia

text: BACKGROUND: A significant proportion of cancer patients use complementary and alternative medicine (CAM) along with conventional therapies (CT), whereas a smaller proportion delay or defer CT in favor of CAM. Previous studies exploring CAM use among cancer patients in the Middle East region have shown discrepant results. This study investigates the prevalence and pattern of CAM use by Saudi cancer patients. It also discusses the possible benefits and harm related to CAM use by cancer patients, and it explores the beliefs patients hold and their transparency with health care providers regarding their CAM use. METHODS: A cross-sectional study was conducted in oncology wards and outpatient clinics by using face-to-face interviews with the participants. RESULTS: A total of 156 patients with a median age of 50 years (18–84) participated in the study. The prevalence of CAM use was 69.9%; the most prominent types of CAM were those of a religious nature, such as supplication (95.4%), Quran recitation (88.1%), consuming Zamzam water (84.4%), and water upon which the Quran has been read (63.3%). Drinking camel milk was reported by 24.1% of CAM users, whereas camel urine was consumed by 15.7%. A variety of reasons were given for CAM use: 75% reported that they were using CAM to treat cancer, enhance mood (18.3%),control pain (11.9%), enhance the immune system (11%),increase physical fitness (6.4%), and improve appetite (4.6%). Thirty percent of CAM users had discussed the issue with their doctors; only 7.7% had done so with their nurses. CONCLUSIONS: The use of CAM, including camel products, is highly prevalent among cancer patients in the Middle East, but these patients do not necessarily divulge their CAM use to their treating physicians and nurses. Although CAM use can be beneficial, some can be very harmful, especially for cancer patients. Association is known between camel products and brucellosis and Middle East respiratory syndrome coronavirus (MERS-CoV). Both can lead to tremendous morbidity in immune-compromised patients. Doctor–patient communication regarding CAM use is of paramount importance in cancer care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12906-018-2150-8) contains supplementary material, which is available to authorized users.


title: Respiratory infections: A current and future threat

text: Despite all the medical progress in the last 50 years pulmonary infections continue to exact and extremely high human and economic cost. This review will focus on the human, pathogen and environmental factors that contribute to the continued global burden or respiratory diseases with a particular focus on areas where we might hope to see some progress in the coming decades.


title: Clinical Characteristics and Outcomes of Type 2 Diabetes Patients Infected with COVID-19: A Retrospective Study

text: Diabetes and its related metabolic disorders have been reported as the leading comorbidities in patients with coronavirus disease 2019 (COVID-19). This clinical study aims to investigate the clinical features, radiographic and laboratory tests, complications, treatments, and clinical outcomes in COVID-19 patients with or without diabetes. This retrospective study included 208 hospitalized patients (≥ 45 years old) with laboratory-confirmed COVID-19 during the period between 12 January and 25 March 2020. Information from the medical record, including clinical features, radiographic and laboratory tests, complications, treatments, and clinical outcomes, were extracted for the analysis. 96 (46.2%) patients had comorbidity with type 2 diabetes. In COVID-19 patients with type 2 diabetes, the coexistence of hypertension (58.3% vs. 31.2%), coronary heart disease (17.1% vs. 8.0%), and chronic kidney diseases (6.2% vs. 0%) was significantly higher than in COVID-19 patients without type 2 diabetes. The frequency and degree of abnormalities in computed tomography (CT) chest scans in COVID-19 patients with type 2 diabetes were markedly increased, including ground-glass opacity (85.6% vs. 64.9%, P < 0.001) and bilateral patchy shadowing (76.7% vs. 37.8%, P < 0.001). In addition, the levels of blood glucose (7.23 mmol·L(-1) (interquartile range (IQR): 5.80–9.29) vs. 5.46 mmol·L(-1) (IQR: 5.00–6.46)), blood low-density lipoprotein cholesterol (LDL-C) (2.21 mmol·L(-1) (IQR: 1.67–2.76) vs. 1.75 mmol·L(-1) (IQR: 1.27–2.01)), and systolic pressure (130 mmHg (IQR: 120–142) vs. 122 mmHg (IQR: 110–137), P = 0.001) in COVID-19 patients with diabetes were significantly higher than in patients without diabetes (P < 0.001). The coexistence of type 2 diabetes and other metabolic disorders is common in patients with COVID-19, which may potentiate the morbidity and aggravate COVID-19 progression. Optimal management of the metabolic hemostasis of glucose and lipids is the key to ensuring better clinical outcomes. Increased clinical vigilance is warranted for COVID-19 patients with diabetes and other metabolic diseases that are fundamental and chronic conditions.


Practical implementation of COVID-19 patient flags into an antimicrobial stewardship program’s prospective review


title: Head and neck oncologic surgery in the COVID‐19 pandemic: Our experience in a deep south tertiary care center

text: INTRODUCTION: The ongoing worldwide pandemic due to COVID‐19 has forced drastic changes on the daily lives of the global population. This is most notable within the health care sector. The current paper outlines the response of the head and neck oncologic surgery (HNS) division within our academic otolaryngology department in the state of Alabama. METHODS: Data with regard to case numbers and types were obtained during the pandemic and compared with time matched data. Our overall approach to managing previously scheduled and new cases, personal protective equipment (PPE) utilization, outpatient clinic, and resident involvement is summarized. DISCUSSION: Our HNS division saw a 55% reduction in surgical volume during the peak of the COVID‐19 pandemic. We feel that an early and cohesive strategy to triaging surgical cases, PPE usage, and minimizing exposure of personnel is essential to providing care for HNS patients during this pandemic.


Responsabilité de l’employeur dans le cadre de la pandémie Covid 19


Ten diseases you need to know if you want to be a critical care specialist in Hong Kong


title: Accuracy of parents in measuring body temperature with a tympanic thermometer

text: BACKGROUND: It is now common for parents to measure tympanic temperatures in children. The objective of this study was to assess the diagnostic accuracy of these measurements. METHODS: Parents and then nurses measured the temperature of 60 children with a tympanic thermometer designed for home use (home thermometer). The reference standard was a temperature measured by a nurse with a model of tympanic thermometer commonly used in hospitals (hospital thermometer). A difference of ≥ 0.5 °C was considered clinically significant. A fever was defined as a temperature ≥ 38.5 °C. RESULTS: The mean absolute difference between the readings done by the parent and the nurse with the home thermometer was 0.44 ± 0.61 °C, and 33% of the readings differed by ≥ 0.5 °C. The mean absolute difference between the readings done by the parent with the home thermometer and the nurse with the hospital thermometer was 0.51 ± 0.63 °C, and 72 % of the readings differed by ≥ 0.5 °C. Using the home thermometer, parents detected fever with a sensitivity of 76% (95% CI 50–93%), a specificity of 95% (95% CI 84–99%), a positive predictive value of 87% (95% CI 60–98%), and a negative predictive value of 91% (95% CI 79–98 %). In comparing the readings the nurse obtained from the two different tympanic thermometers, the mean absolute difference was 0.24 ± 0.22 °C. Nurses detected fever with a sensitivity of 94% (95 % CI 71–100 %), a specificity of 88% (95% CI 75–96 %), a positive predictive value of 76% (95% CI 53–92%), and a negative predictive value of 97% (95%CI 87–100 %) using the home thermometer. The intraclass correlation coefficient for the three sets of readings was 0.80, and the consistency of readings was not affected by the body temperature. CONCLUSIONS: The readings done by parents with a tympanic thermometer designed for home use differed a clinically significant amount from the reference standard (readings done by nurses with a model of tympanic thermometer commonly used in hospitals) the majority of the time, and parents failed to detect fever about one-quarter of the time. Tympanic readings reported by parents should be interpreted with great caution.


title: Introducing E-learning in Epidemiology Course for Undergraduate Medical Students at the Faculty of Medicine, University of Belgrade: A Pilot Study

text: The aim of this study was to determine whether e-learning as a new teaching concept was acceptable for second-year undergraduates and to compare attitudes and exam results of students who followed electronic compared with classroom seminars. The electronic seminars (e-seminars) were developed several months prior to start of the epidemiology course for second-year students at the Faculty of Medicine, University of Belgrade. The students who applied for e-seminars accessed their content during summer semester (February–May) 2014. E-seminars were set according to the existing topics in practical workbook and designed using Moodle, a free, open-source, personal home page web application for producing modular internet-based courses. To evaluate the motives for enrollment and satisfaction with seminars, two surveys (pre- and post-course) were administered. Students’ exam grades were registered over 4 exam sessions (June–October 2014) and compared according to seminar program. Out of 516 students in the second year, 60 (11.6 %) applied for e-seminars (mean age 21 years). Students considered the reason “It’s easier to do assignments from home” as the strongest motive to participate. When compared to classroom seminars, students in e-seminars had significantly more fun (p = 0.003), thought that e-seminars were better mode to learn epidemiology (p = 0.030) and would recommend them to other colleagues (p = 0.001). There was no significant difference in average grade received at the oral exam in epidemiology (t = 0.071, p = 0.944). E-seminars in undergraduate epidemiology course add a novel, easy-to-follow and amusing mode of learning. Based on this pilot study, e-seminars in epidemiology will be available for next generations of students, while further improvement of e-seminars could include expansion of seminar syllabus and development of discussion fora.


title: Whole-genome Sequencing for Tracing the Transmission Link between Two ARD Outbreaks Caused by a Novel HAdV Serotype 7 Variant, China

text: From December 2012 to February 2013, two outbreaks of acute respiratory disease caused by HAdV-7 were reported in China. We investigated possible transmission links between these two seemingly unrelated outbreaks by integration of epidemiological and whole-genome sequencing (WGS) data. WGS analyses showed that the HAdV-7 isolates from the two outbreaks were genetically indistinguishable; however, a 12 bp deletion in the virus-associated RNA gene distinguished the outbreak isolates from other HAdV-7 isolates. Outbreak HAdV-7 isolates demonstrated increased viral replication compared to non-outbreak associated HAdV-7 isolate. Epidemiological data supported that the first outbreak was caused by introduction of the novel HAdV-7 virus by an infected recruit upon arrival at the training base. Nosocomial transmission by close contacts was the most likely source leading to onset of the second HAdV-7 outbreak, establishing the apparent transmission link between the outbreaks. Our findings imply that in-hospital contact investigations should be encouraged to reduce or interrupt further spread of infectious agents when treating outbreak cases, and WGS can provide useful information guiding infection-control interventions.


title: Vascular skin symptoms in COVID‐19: a french observational study

text: Coronavirus 19 (COVID‐19) was declared as a pandemic viral infection by the World Health organization on March 11(th) 2020. Usual clinical manifestations of COVID‐19 infection include fever, fatigue, myalgia, headache, diarrhea, dry cough, dyspnea that may lead to acute respiratory distress syndrome and death (1). Skin symptoms of COVID‐19 have been poorly described but may include erythematous rash, urticaria and chicken pox like lesions (2‐7). Angiotensin‐converting enzyme 2 (ACE2) is a cellular receptor for COVID‐19.


Serratia marcescens outbreak in the intensive care unit during the COVID-19 pandemic: a paradoxical risk?


title: Sensitive Detection of Viral Transcripts in Human Tumor Transcriptomes

text: In excess of [Image: see text]% of human cancer incidents have a viral cofactor. Epidemiological studies of idiopathic human cancers indicate that additional tumor viruses remain to be discovered. Recent advances in sequencing technology have enabled systematic screenings of human tumor transcriptomes for viral transcripts. However, technical problems such as low abundances of viral transcripts in large volumes of sequencing data, viral sequence divergence, and homology between viral and human factors significantly confound identification of tumor viruses. We have developed a novel computational approach for detecting viral transcripts in human cancers that takes the aforementioned confounding factors into account and is applicable to a wide variety of viruses and tumors. We apply the approach to conducting the first systematic search for viruses in neuroblastoma, the most common cancer in infancy. The diverse clinical progression of this disease as well as related epidemiological and virological findings are highly suggestive of a pathogenic cofactor. However, a viral etiology of neuroblastoma is currently contested. We mapped [Image: see text] transcriptomes of neuroblastoma as well as positive and negative controls to the human and all known viral genomes in order to detect both known and unknown viruses. Analysis of controls, comparisons with related methods, and statistical estimates demonstrate the high sensitivity of our approach. Detailed investigation of putative viral transcripts within neuroblastoma samples did not provide evidence for the existence of any known human viruses. Likewise, de-novo assembly and analysis of chimeric transcripts did not result in expression signatures associated with novel human pathogens. While confounding factors such as sample dilution or viral clearance in progressed tumors may mask viral cofactors in the data, in principle, this is rendered less likely by the high sensitivity of our approach and the number of biological replicates analyzed. Therefore, our results suggest that frequent viral cofactors of metastatic neuroblastoma are unlikely.


title: Development of a consensus microarray method for identification of some highly pathogenic viruses

text: Some highly pathogenic viruses, such as Chikungunya virus, Japanese encephalitis virus, Yellow fever virus, Dengue virus, Hanta virus, SARS‐CoV, and H5N1 avian influenza virus can cause severe infectious diseases. However, the consensus method for detecting these viruses has not been well established. A rapid and sensitive microarray approach for detection of these viruses and a panel of specific probes covering nine genera and 16 virus species were designed. 70‐mer oligonucleotides were used at the genus level and 50‐mer oligonucleotides were at the species level, respectively. To decrease the interference of the host genome in hybridization, the consensus genus primers were designed and used to reverse transcribe only virus genome. The synthesis of the second strand was carried out with a random primer sequence (5′‐GTTTCCCAGTAGGTCTCNNNNNNNN‐3′). The amplified products were labeled and processed for microarray analyses. This microarray‐based method used the highly conserved consensus primers to synthesize specifically the virus cDNA and could identify effectively Chikungunya virus, Japanese encephalitis virus, Yellow fever virus, Dengue virus, Tick borne encephalitis virus, and H5N1 avian influenza virus. Using this method, one unknown virus isolated from pig brain in Shanxi Province, China was identified. This method may have an important potential application for the diagnosis of virus infection. J. Med. Virol. 81:1945–1950, 2009. © 2009 Wiley‐Liss, Inc.


title: Analysis of dermatologic conditions in Turkey and Italy by using Google Trends analysis in the era of the COVID‐19 pandemic

text: Many areas of life including patterns of dermatological diseases that patient attend to the hospital were tremendously affected by implementing stay‐at‐home orders during the COVID‐19 pandemic. We aimed to identify the dermatologic interest of the public during the COVID‐19 pandemic by using Google Trends. The terms “acne”, “hair loss”, “eczema”, “genital warts”, “molluscum contagiosum”, “botox”, “skin cancer”, “sunscreen” were analyzed on first April, first May, first June 2020, and the corresponding period of the previous year in Turkey and Italy by using Google Trends. The searching spectrum was between 3first March 2019‐first June 2020. The relative change of search term “acne” was +10, +29, +13/ ‐1, +17,+33, “hair loss” was +14, +40, +16/+3, +16, +15, and “eczema” was +2, +34, −4/ +3, +25, +18, on the other hand, the relative change of the “genital warts” was −15, −48, +10/ ‐44, −30, +18 and “molluscum contagiosum” was −12, −2, −4/ ‐4, −1, −12 while “botox” was, −10, −43, −8/ ‐41, −31, +4, “skin cancer” was −27, −38, −38/−22,+33, −7 and sunscreen was −6, −25, −71/−13,0,‐45 in Turkey/Italy on 1 st April, 1 st May, and 1 st June, 2020, respectively. A statistically significant positive correlation was found between the number of COVID‐19 cases in Turkey and search terms of the general dermatology group during the COVID‐19 pandemic (P < 0.05). The search terms including “acne”, “eczema”, “hair loss” appears to be increasing while “molluscum contagiosum”, “genital warts” “botox”, “skin cancer”, and “sunscreen” decreasing in the era of the COVID‐19 pandemic. Understanding the trends and impacts of dermatologic diseases on public perceptions during the COVID‐19 pandemic will allow for better preparation of dermatologists. This article is protected by copyright. All rights reserved.


Síndrome de Guillain-Barré asociado a infección por Covid-19


title: Rapid implementation and validation of a cold-chain free SARS-CoV-2 diagnostic testing workflow to support surge capacity

text: BACKGROUND: In January 2020 reports of unidentified severe respiratory illness were described in Wuhan, China. A rapid expansion in cases affecting most countries around the globe led to major changes in the way people live their daily lives. In the United Kingdom, the Department of Health and Social Care directed healthcare providers to establish additional resources to manage the anticipated surge in cases that could overwhelm the health services. A priority area was testing for SARS-CoV-2 RNA and its detection by qualitative RT-PCR. DESIGN: A laboratory workflow twinning research environment with clinical laboratory capabilities was implemented and validated in the University of Birmingham within 4 days of the project initiation. The diagnostic capability was centred on an IVD CE-marked RT-PCR kit and designed to provide surge capacity to the nearby Queen Elizabeth Hospital. The service was initially tasked with testing healthcare workers (HCW) using throat swabs, and subsequently the process investigated the utility of using saliva as an alternative sample type. RESULTS: Between the 8(th) April 2020 and the 30(th) April 2020, the laboratory tested a total of 1282 HCW for SARS-CoV-2 RNA in throat swabs. RNA was detected in 54% of those who reported symptoms compatible with COVID-19, but in only 4% who were asymptomatic. CONCLUSION: This capability was established rapidly and utilised a cold-chain free methodology, applicable to a wide range of settings, and which can provide surge capacity and support to clinical laboratories facing increasing pressure during periods of national crisis.


title: “The COVID-19 outbreak”—An empirical phenomenological study on perceptions and psychosocial considerations surrounding the immediate incorporation of final-year Spanish nursing and medical students into the health system

text: The COVID-19 pandemic has caused an unprecedented health crisis worldwide, with the numbers of infections and deaths worldwide multiplying alarmingly in a matter of weeks. Accordingly, governments have been forced to take drastic actions such as the confinement of the population and the suspension of face-to-face teaching. In Spain, due to the collapse of the health system the government has been forced to take a series of important measures such as requesting the voluntary incorporation of final-year nursing and medical students into the health system. The objective of the present work is to study, using a phenomenological qualitative approach, the perceptions of students in this exceptional actual situation. A total of 62 interviews were carried out with final-year nursing and medicine students from Jaime I University (Spain), with 85% reporting having voluntarily joined the health system for ethical and moral reasons. Results from the inductive analysis of the descriptions highlighted two main categories and a total of five sub-categories. The main feelings collected regarding mood were negative, represented by uncertainty, nervousness, and fear. This study provides a description of the perceptions of final-year nursing and medical students with respect to their immediate incorporation into a health system aggravated by a global crisis.


title: Electron microscopic reporting of gastrointestianal viruses in the United Kingdom, 1985–1987

text: We examined some epidemiological features of the viruses associated with gastrointestinal illness, using national data reported by electron microscopists in the United Kingdom. During the 3 years analyzed (1985–1987), a total of 1,993 positive detections of astroviruses, caliciviruses, coronaviruses, and small round structured viruses (SRSVs) were reported. In 1 year of this period, 8,210 rotaviruses were reported. More than 90% of the astroviruses and caliciviruses were detected in children under 5 years of age, while coronaviruses and SRSVs were detected in adults as well as children. Detections of astroviruses increased in the winter and were infrequent during the summer, a seasonal pattern similar to that observed for rotaviruses. There was some variability between reporting regions in rates of detection of fecal viruses. We have attempted to identify the reasons for this. We make suggestions for improving the detection of human fecal viruses, and we recognize the need for continued surveillance of these agents.


title: Infecciones agudas traqueales y del árbol bronquial

text: Resumen Las infecciones agudas del tracto respiratorio son una de las principales causas de inflamación de la vía aérea, siendo especialmente frecuentes las de origen vírico. Las infecciones de la vía aérea superior son más frecuentes en niños, y es la principal causa de hospitalización en pacientes menores de 4 años. Sin embargo, la infección aguda de los bronquios es más frecuente en adultos, siendo una de las principales causas por las que consultan en las urgencias y centros de salud. La afectación puede ir desde una en fermedad autolimitada de pocos días de evolución, hasta una obstrucción de la vía aérea potencialmente mortal. Abstract Acute respiratory tract infections are one of the main causes of airway inflammation, frequently triggered by viruses. Upper airway infections are highly prevalent in children, causing hospitalization in patients under 4 years of age. On the contrary acute bronchial infections are more frequent in adults and they are one of the major causes of consultation in emergency units and health centers. They include a wide spectrum of diseases ranging from self-limited diseases of short duration, to an airway obstruction potentially fatal.


Introducing the Videocall to facilitate the communication between health care providers and families of patients in the intensive care unit during COVID-19 pandemia


title: Clinical Factors, Preventive Behaviours and Temporal Outcomes Associated with COVID-19 Infection in Health Professionals at a Spanish Hospital

text: The novel coronavirus disease (COVID-19) outbreak has quickly spread around the world, with Spain being one of the most severely affected countries. Healthcare professionals are an important risk group given their exposure. The aims of this study were to determine the prevalence of symptoms, main concerns as patients, preventive behaviours of healthcare professionals, and the different temporal outcomes associated with the negativization of PCR results. A total of 238 professionals were analysed and follow-up was conducted from 11 March to 21 April 2020 through clinical records, in-depth surveys, and telephone interviews. Symptoms, concerns, and preventive measures were documented, and temporal outcomes (start and end of symptoms, first positive PCR, and negativization of PCR) were analysed through survival analyses. A high prevalence of gastrointestinal symptoms (especially in women and older professionals), fever, cough, and fatigue were reported. The main concern was contagion in the work and home environment. Professionals (especially men) reported low use of face masks before the pandemic. Our analysis indicates that the median times for the negativization of PCR testing to confirm the resolution of infection is 15 days after the end of symptoms, or 25 days after the first positive PCR test. Our results suggest that these times are longer for women and for professionals aged ≥55 years, therefore follow-up strategies should be optimized in light of both variables. This is the first study we are aware of to report factors associated with the time to negativization of PCR results. We present the first rigorous estimates of time outcomes and hope that these data can be valuable to continue feeding the prediction models that are currently being developed. Similar studies are required to corroborate our results.


title: The interplay of autophagy and enterovirus

text: Abstract Autophagy, an evolutional conserved lysosomal degradation process, has been implicated to play an important role in cellular defense against a variety of microbial infection. Interestingly, numerous studies found that some pathogens, especially positive-single-strand RNA viruses, actually hijacked autophagy machinery to promote virus infection within host cells, facilitating different stages of viral life cycle, from replication, assembly to egress. Enterovirus, a genus of positive-strand RNA virus, can cause various human diseases and is one of main public health threat globally, yet no effective clinical intervention is available for enterovirus infection. Here we summarized recent literature on how enteroviruses regulate and utilize autophagy process to facilitate their propagation in the host cells. The studies on the interplay between enterovirus and autophagy not only shed light on the molecular mechanisms underlying how enterovirus hijacks cellular components and pathway for its own benefits, but also provide therapeutic option against enterovirus infection.


title: Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after SARS-CoV-2 infection

text: Abstract Covid-19 is a new coronavirus disease first described in December 2019. This respiratory illness is severe and potentially fatal. Severe cases make up to 15%, lethality ranges between 1.5 and more than 10 %. What is urgently needed is an efficient pharmacological treatment for the treatment of severe cases. During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. Starting inhibition at 0.1 µM, CQ completely prevented in vitro infections at 10 µM, suggesting a prophylactic effect and preventing the virus spread 5 hours after infection. In a first clinical trial, CQ was effective in inhibiting exacerbation of pneumonia, improving lung imaging findings, promotion of virus-negative conversion, and shortening the disease. In addition, HCQ, which is three times more potent than CQ in SARS-CoV-2 infected cells (EC50 0.72 µM), was significantly associated with viral load reduction/disappearance in COVID-19 patients compared to controls. Theoretically, CQ and HCQ could thus be effectively used in the treatment of SARS-CoV pneumonia. From a pharmacological standpoint, however, the major problems of oral treatment with these drugs are possible severe side effects and toxicity. Concretely, this relates to (a) the inconsistent individual bioavailability of these drugs at the alveolar target cells, depending on intestinal resorption, hepatic first-pass metabolism and accumulation in liver, spleen and lung, and (b) the need for a relatively high concentration of 1-5 µM at the alveolar surface. Therefore, we propose in a first dose estimation the use of HCQ as an aerosol in a dosage of 2-4 mg per inhalation in order to reach sufficient therapeutic levels at the alveolar epithelial cells. By using a low-dose non-systemic aerosol, adverse drug reactions will markedly be reduced compared with oral application. This increase in tolerability enables a broader use for prevention and after contact with an infected person, which would be an advantage especially for the high-risk, often multi-morbid and elderly patients. Empirical data on self-medication with a one-week aerosol application by two of the authors is presented. Inhalation was well tolerated without relevant side effects.


title: The prevalance of respiratory viruses among healthcare workers serving pilgrims in Makkah during the 2009 influenza A (H1N1) pandemic

text: Summary Despite the high risk of acquiring respiratory infections, healthcare workers who treat pilgrims at Hajj have not been studied in previous research on respiratory diseases during Hajj. The objective of this study was to determine the prevalence of different respiratory viruses among healthcare workers who treated pilgrims during Hajj 2009, the year of the influenza A H1N1 pandemic. A cross-sectional study was performed just before and after Hajj (25–29 November, 2009). Nasal and throat swabs were tested for 18 respiratory virus types and subtypes. A total of 184 healthcare workers were examined. Most were men (85%) with an average age of 41 years. Before the Hajj, rates of seasonal influenza vaccination were higher (51%) than rates of pandemic influenza A H1N1 vaccination (22%). After the Hajj, participants reported high rates of maintaining hand hygiene (98%), cough etiquette (89%), and wearing a face mask (90%). Among all the viruses tested, only two were detected: rhinovirus was detected in 12.6% and Coronavirus 229E in 0.6%. Rhinovirus was detected in 21% of those who had respiratory symptoms during Hajj. Influenza A (including H1N1), influenza B. respiratory syncytial virus, other coronaviruses, parainfluenza viruses, human metapneumovirus, adenovirus, and human bocavirus were not detected. The finding of high rates of rhinovirus infection corresponds to their frequent occurrence in adults. None of the participants had influenza A H1N1 2009, possibly because it was also infrequent among the 2009 pilgrims.


Telemedicine in the face of the COVID-19 pandemic


Virus Taxonomy: One Step Forward, Two Steps Back


title: The role of human Metapneumovirus genetic diversity and nasopharyngeal viral load on symptom severity in adults

text: BACKGROUND: Human metapneumovirus (HMPV) is established as one of the causative agents of respiratory tract infections. To date, there are limited reports that describe the effect of HMPV genotypes and/or viral load on disease pathogenesis in adults. This study aims to determine the role of HMPV genetic diversity and nasopharyngeal viral load on symptom severity in outpatient adults with acute respiratory tract infections. METHODS: Severity of common cold symptoms of patients from a teaching hospital was assessed by a four-category scale and summed to obtain the total symptom severity score (TSSS). Association between the fusion and glycoprotein genes diversity, viral load (quantified using an improved RT-qPCR assay), and symptom severity were analyzed using bivariate and linear regression analyses. RESULTS: Among 81/3706 HMPV-positive patients, there were no significant differences in terms of demographics, number of days elapsed between symptom onset and clinic visit, respiratory symptoms manifestation and severity between different HMPV genotypes/sub-lineages. Surprisingly, elderly patients (≥65 years old) had lower severity of symptoms (indicated by TSSS) than young and middle age adults (p = 0.008). Nasopharyngeal viral load did not correlate with nor predict symptom severity of HMPV infection. Interestingly, at 3–5 days after symptom onset, genotype A-infected patients had higher viral load compared to genotype B (4.4 vs. 3.3 log(10) RNA copies/μl) (p = 0.003). CONCLUSIONS: Overall, HMPV genetic diversity and viral load did not impact symptom severity in adults with acute respiratory tract infections. Differences in viral load dynamics over time between genotypes may have important implications on viral transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1005-8) contains supplementary material, which is available to authorized users.


title: Achilles' heel of the killer virus: the highly important molecular targets for hitting SARS-CoV-2 that causes COVID-19

text: As an immediate priority, finding a solution for the new coronavirus (SARS-CoV-2) pandemic is on the agenda of scientists of the world. Herein, we summarize all the suggested global solutions proposed by scientists and physicians so far to stop this dangerous virus. Also, the important molecular targets for hitting the killer virus are highlighted.


title: Zika Virus Infection, Basic and Clinical Aspects: A Review Article

text: BACKGROUND: Zika virus infection has recently attracted the attention of medical community. While clinical manifestations of the infection in adult cases are not severe and disease is not associated with high mortality rates, Zika virus infection can have an impact on fetal development and lead to severe neurodevelopmental abnormalities. METHODS: To gain insight into different aspects of Zika virus infection, a comprehensive literature review was performed. With regard to epidemiology and geographical distribution of Zika virus infection, relevant information was extracted from CDC and WHO websites. RESULTS: In this review, we discuss different basic and clinical aspects of Zika virus infection including virology, epidemiology and pathogenesis of disease. Laboratory methods required for the diagnosis of disease together with ethical issues associated with Zika virus infection will also be discussed in detail. CONCLUSION: Herein, we have tried to provide a multi-faceted view of Zika virus infection, with greater emphasis on disease status in Eastern Mediterranean Region.


title: Covid‐19 related IgA vasculitis

text: IgA vasculitis is a systemic small‐vessel vasculitis which may be triggered by different microorganisms. IgA vasculitis cases have been reported in patients with immune‐mediated inflammatory disorders treated with TNF inhibitors. Here we report the case of a young Crohn’s disease patient in clinical remission under adalimumab admitted for an IgA vasculitis, with an extended ileitis, and a positive PCR testing for Covid‐19. Serum IgA levels were markedly increased and serology for Covid‐19 was weakly positive for IgA. Even if we cannot prove the causality of Covid‐19, it is remarkable to note that this case of IgA vasculitis was associated with high IgA levels in the serum and the Covid‐19 serology was positive only for IgA.


title: Detection of bovine coronavirus in nasal swab of non‐captive wild water deer, Korea

text: Bovine coronavirus (BCoV) is a causative agent of respiratory and enteric diseases in cattle and calves. BCoV infection was also evident in captive wild ruminants. Recently, water deer are recognized as the most common wildlife to approach farmhouses and livestock barns in Korea. Therefore, we investigated 77 nasal swab samples from non‐captive wild water deer (Hydropotes inermis) between November 2016 and September 2017 and identified three samples positive for coronavirus, indicating potential for respiratory shedding. The full genomic sequences of the water deer coronavirus were closely related to BCoV (>98%). Therefore, effective biosecurity system in bovine farms would be necessary to prevent contact between farm ruminants and free‐ranging wild water deer.


title: Implications of respiratory pathogen transmission dynamics on prevention and testing

text: • Respiratory droplets can travel beyond current physical distancing recommendations. • Limited evidence of air pollution linked to respiratory transmission. • COVID close contact and testing criteria may need to consider these findings. • Universal masking may provide a viable option against these transmission dynamics.


title: Identification and location of the structural glycoproteins of a tissue culture-adapted turkey enteric coronavirus

text: The Minnesota strain of turkey enteric coronavirus (TCV) was grown on a human rectal tumor (HRT-18) cell line in the presence of radiolabeled amino acids and glucosamine to analyse virion structural proteins. In addition to the 52,000 unglycosylated nucleocapsid protein, three major glycoprotein species were found to be associated with the viral envelope. A predominant glycosylated protein with a molecular weight of 22–24,000 represented the transmembrane matrix protein. Larger glycoproteins with apparent molecular weights of 180–200,000 (gp 200), 120–125,000 (gp 120) and 95–100,000 (gp 100) were associated to the characteristic large bulbous projections (peplomers) located at the surface of the virion. The gp 100 and gp 120 species apparently arose from a proteolytic cleavage of gp 200, as suggested by digestion studies with trypsin and chymotrypsin. An additional large glycoprotein with mol.wt. of 140,000 (gp 140), that behaved as a disulfide-linked dimer of a 66,000 molecule, was found to be associated to granular projections located near the base of the large peplomers. Digestion studies with trypsin, bromelain and pronase demonstrated that gp 140 was related to the hemagglutinating activity of the virus. An inner membranous sac or tongue-shaped structure could be visualized in the interior of the viral particles following treatment with pronase. In contrast, trypsin or chymotrypsin treatments resulted in evaginations (“budding”) on the virus surface. Progeny viral particles produced in TCV-infected cell cultures in the presence of tunicamycin lacked both types of surface projections, as demonstrated by electron microscopy and electrophoresis. The matrix protein also appeared to be reduced to its unglycosylated form, concomitant with a considerable loss of its antigenicity. Thus, with respect to its morphological and biochemical characteristics, TCV resembles viruses belonging to the group of mammalian hemagglutinating coronaviruses, but differs in that both types of envelope glycoproteins are N-glycosylated as in case of the avian infectious bronchitis virus.


title: Xenotransplantation, Xenogeneic Infections, Biotechnology, and Public Health

text: Xenotransplantation is the attempt to use living biological material from nonhuman animal species in humans for therapeutic purposes. Clinical trials and preclinical studies have suggested that living cells and tissue from other species have the potential to be used in humans to ameliorate disease. However, the potential for successful xenotransplantation to cure human disease is coupled with the risk that therapeutic use of living nonhuman cells in humans may also serve to introduce xenogeneic infections of unpredictable significance. Animal husbandry practices and xenotransplantation product preparation may eliminate most exogenous infectious agents prior to transplantation. However, endogenous retroviruses are present in the genomes of all mammalian cells, have an inadequately defined ability to infect human cells, and have generated public health concern. The history of xenotransplantation, the implications for public health, the global consensus on public safeguards necessary to accompany clinical trials, and the future direction of xenotransplantation are discussed in the context of public health. Mt Sinai J Med 76:435–441, 2009. © 2009 Mount Sinai School of Medicine


title: Incidence and predisposing factors for severe disease in previously healthy term infants experiencing their first episode of bronchiolitis

text: Aim: To determine the incidence and predisposing factors for severe bronchiolitis in previously healthy term infants <12 months of age experiencing their first episode of bronchiolitis. Methods: Epidemiological, clinical and virological data were prospectively collected. Severity was assessed by the need for ventilatory support. Results: Of the 310 infants enrolled, 16 (5.1%) presented with severe bronchiolitis requiring ventilatory support (11 since admission). Compared with infants with less severe bronchiolitis, infants with severe disease presented with lower birth weight, gestational age, postnatal weight and postnatal age, and were more likely to be born by cesarian section. C‐reactive protein positive results (>0.8 mg/dL) and pulmonary consolidation on chest X‐ray were more common among infants with severe disease. Severity was independently associated with younger age on admission <30 days, respiratory syncytial virus (RSV) infection and lymphocyte counts <3200/μL. No significant differences were found between epidemiologic variables. Conclusions: Severe bronchiolitis is uncommon in previously healthy term infants <12 months of age and when present develops soon after disease onset. Severity is predicted by young age and RSV carriage, whereas epidemiologic variables seem less likely to intervene.


title: [Analysis of bronchoscope-guided tracheal intubation in 12 cases with COVID-19 under the personal protective equipment with positive pressure protective hood].

text: Endotracheal intubation is an independent risk factor for respiratory infectious diseases. We conducted a retrospective study in 12 cases with COVID-19 who underwent endotracheal intubation at ICU of the Guangzhou eighth hospital from January 20 to February 10, 2020. The intubation procedure, anesthetic regimen, and complication were collected and analyzed. The 9 healthcare workers who involved in intubation received virus nucleic acid test and 14 days temperature monitoring. All 12 patients were successfully intubated under the guidance of bronchoscope, without any complications. Midazolam, Propofol and Morphine or fentanyl were used for sedation and analgesia, avoiding patients cough and agitated during the procedure. The 9 healthcare workers were protected under the Personal Protective Equipment(PPE) with positive pressure protective hood. The detection of oropharyngeal swab virus nucleic acid were negative in all 9 healthcare workers, none of them had fever or any respiratory symptoms. The PPE with positive pressure protective hood should be needed to perform bronchoscope-guided endotracheal intubation in patients with COVID-19, it could strengthen to protect healthcare workers from virus exposure.


title: A pandemic in all but name

text: The spread of the coronavirus beyond China is entering a critical new phase


SARS-like virus in the Middle East: A truly bat-related coronavirus causing human diseases


title: Osteoporosis Management in the Era of COVID‐19

text: Osteoporosis is a chronic condition that reflects reduced bone strength and an associated increased risk for fracture. As a chronic condition, osteoporosis generally requires sustained medical intervention(s) to limit the risks for additional bone loss, compromise of skeletal integrity, and fracture occurrence. Further complicating this issue is the fact that the abrupt cessation of some therapies can be associated with an increased risk for harm. It is in this context that the COVID‐19 pandemic has brought unprecedented disruption to the provision of health care globally, including near universal requirements for social distancing. In this Perspective, we provide evidence, where available, regarding the general care of patients with osteoporosis in the COVID‐19 era and provide clinical recommendations based primarily on expert opinion when data are absent. Particular emphasis is placed on the transition from parenteral osteoporosis therapies. It is hoped that these recommendations can be used to safely guide care for patients with osteoporosis until a return to routine clinical care standards is available. © 2020 American Society for Bone and Mineral Research.


title: Global funding for local health issues

text: Jeremy Farrar tells Fiona Fleck why global health research must go local to respond to social needs.


title: Battling COVID-19: using old weapons for a new enemy

text: Coronavirus disease-19 (COVID-19) has reached pandemic proportions. Most of the drugs that are being tried for the treatment have not been evaluated in any randomized controlled trials. The purpose of this review was to summarize the in-vitro and in-vivo efficacy of these drugs on Severe Acute Respiratory Syndrome (SARS-CoV-2) and related viruses (SARS and Middle East Respiratory Syndrome) and evaluate their potential for re-purposing them in the management of COVID-19.


title: IT applications in healthcare management: a survey

text: Healthcare management is currently undergoing substantial changes, and reshaping our perception of the medical field. One spectrum is that of the considerable changes that we see in surgical machines and equipment, and the way the procedures are performed. Computing power, Internet and associated technologies are transforming surgical operations into model based procedures. The other spectrum is the management side of healthcare, which is equally critical to the medical profession. In particular, recent advances in the field of Information Technology (IT) is assisting in better management of health appointments and record management. With the proliferation of IT and management, data is now playing a vital role in diagnostics, drug administration and management of healthcare services. With the advancement in data processing, large amounts of medical data collected by medical centres and providers, can now be mined and analysed to assist in planning and making appropriate decisions. In this article, we shall provide an overview of the role of IT that have been reshaping the healthcare management, hospital, health profession and industry.


title: Circulation of human metapneumovirus among children with influenza‐like illness in Wuhan, China

text: Human metapneumovirus (HMPV) is a worldwide distributed pathogen of the respiratory tract. The objectives of this study were to identify HMPV infections among children with influenza‐like illness (ILI) in Wuhan and to assess circulation patterns and molecular diversity of HMPV in this area. From July 2008 to December 2013, a total of 3,883 throat swab samples were collected from ILI outpatients under 16 years old. HMPV RNA was detected in 171 samples (4.40%). All the four subtypes of HMPV were identified, among which A2 was the most common subtype (61/145, 42.1%), followed by B1, B2, and A1. During the study period, HMPV circulation presented a biennial alternation between high and low incidence in Wuhan and the seasonal peak also shift between winter and spring in two continuous seasons. Subtype A2, B1, and B2 co‐circulated during the study period, with genotype A prevailing in epidemic season 2008–2009 and 2012–2013, and genotype B prevailing during other periods. This large‐scale analysis of HMPV prevalence in ILI outpatient children improves the understanding of local HMPV circulation patterns and provides molecular epidemic evidence for comparative analysis of HMPV infection. J. Med. Virol. 88:774–781, 2016. © 2015 Wiley Periodicals, Inc.


title: Will the COVID-19 pandemic change national security and health care in the spectrum of cardiovascular disease?

text: COVID-19 pandemic changed the current state of healthcare, especially in terms of reorganization of resources. Chief complaints of patients admitted to hospitals changed drastically in the proceeding months, which worsened the treatment of many acute and chronic conditions involving cardiovascular system pathologies and resources were moved in order to fight COVID-19. Moreover, the pandemic had long-term effects not only on healthcare but also national security on global scale. The COVID-19 drastically changed perception of global health and safety, trust in healthcare professionals as well as patients’ willingness to seek medical help. The long-term effect of the epidemic, in terms of its impact cardiovascular disease progression and prognosis remain to be observed. The current paper discusses the impact of COVID-19 on healthcare an national security based on the currently available data.


title: Radiation therapy considerations during the COVID‐19 Pandemic: Literature review and expert opinions

text: COVID-19 is an unprecedented pandemic that has already reached over 2 million confirmed cases globally, with at least 140,000 deaths as reported by the World Health Organization (WHO) as of April 16, 2020 1 . More than 662,000 cases have been reported in the United States with more than 29,000 deaths2 . The overall crude mortality rate now stands at 6.6% (may possibly be lower due to under-testing and under-reporting of total confirmed cases), and is highly dependent on age group, comorbidities, and the locoregional resources medically1 . A report from the United States presented age-stratified COVID-19 associated hospitalization rates among 1,482 patients during March 1-28, 2020, highlighting an alarmingly high rate of 74.5% at age > 50 years with underlining medical conditions3 . Based on a data summary report provided by New York City Health, as of April 14, 2020, the shares of a total of 6839 deaths reached 0.04%, 4.5%, 23.1%, 24.6%, and 47.7% for the age groups of 0-17, 18-44, 45-64, 65-74, and 75+ years old4 . All data suggest that adults at a more advanced age group are facing higher morbidity and mortality risks.


title: Infectious diseases spreading on a metapopulation network coupled with its second-neighbor network

text: Abstract Traditional infectious diseases models on metapopulation networks focus on direct transportations (e.g., direct flights), ignoring the effect of indirect transportations. Based on global aviation network, we turn the problem of indirect flights into a question of second neighbors, and propose a susceptible-infectious-susceptible model to study disease transmission on a connected metapopulation network coupled with its second-neighbor network (SNN). We calculate the basic reproduction number, which is independent of human mobility, and we prove the global stability of disease-free and endemic equilibria of the model. Furthermore, the study shows that the behavior that all travelers travel along the SNN may hinder the spread of disease if the SNN is not connected. However, the behavior that individuals travel along the metapopulation network coupled with its SNN contributes to the spread of disease. Thus for an emerging infectious disease, if the real network and its SNN keep the same connectivity, indirect transportations may be a potential threat and need to be controlled. Our work can be generalized to high-speed train and rail networks, which may further promote other research on metapopulation networks.


Telemedicine in nursing homes during the COVID‐19 outbreak: A star is born (again)


title: Chikungunya as a paradigm for emerging viral diseases: Evaluating disease impact and hurdles to vaccine development

text: Chikungunya fever (CHIKF) is an emerging infectious disease caused by an alphavirus transmitted by Aedes spp. mosquitoes. Because mosquito control programs are not highly efficient for outbreak containment, vaccines are essential to reduce the burden of disease. Although no licensed vaccine against CHIKF is yet available, many highly promising candidates are undergoing preclinical studies, and a few of them have been tested in human trials of phase 1 or 2. Here, we review recent findings regarding the need for a CHIKF vaccine and provide an update on vaccines nearing or having entered clinical trials. We also address needs to tackle bottlenecks to vaccine development—including scientific and financial barriers—and to accelerate the development of vaccines; several actions should be taken: (i) design efficacy trials to be conducted during the course of outbreaks; (ii) evaluate the opportunity for adopting the “animal rule”for demonstration of efficacy for regulatory purposes; (iii) strengthen the collective commitment of nations, international organizations, potential donors and industry; (iv) stimulate public and/or private partnerships to invest in vaccine development and licensure; and (v) identify potential markets for an effective and safe CHIKF vaccine.


title: Serological Diagnosis of Feline Coronavirus Infection by Immunochromatographic Test

text: The immunochromatographic assay (ICA) is a simple antibody–antigen detection method, the results of which can be rapidly obtained at a low cost. We designed an ICA to detect anti-feline coronavirus (FCoV) antibodies. A colloidal gold-labeled recombinant FCoV nucleocapsid protein (rNP) is used as a conjugate. The Protein A and affinity-purified cat anti-FCoV IgG are blotted on the test line and the control line, respectively, of the nitrocellulose membrane. The specific detection of anti-FCoV antibodies was possible in all heparin-anticoagulated plasma, serum, whole blood, and ascitic fluid samples from anti-FCoV antibody positive cats, and nonspecific reaction was not noted in samples from anti-FCoV antibody negative cats.


title: Chapter 8 Reproduction and Breeding of Nonhuman Primates

text: This chapter provides an overview of reproductive biology and husbandry and management of captive nonhuman primates for breeding purposes. The reproductive biology section includes overviews of hypothalamic-pituitary-gonadal function and puberty as well as specific sections on female and male reproductive physiology. The breeding overview is generally limited to taxonomic groups most commonly bred for use in research facilities: macaques, baboons, squirrel monkeys, owl monkeys, and marmosets. For each of these taxonomic groups, the review provides information on typical group compositions; enclosure types; factors used in decisions regarding retention or removal of offspring and breeders; island/semi-free ranging production systems, if relevant; Specific-Pathogen-Free colony production and management, if relevant; and population management, including expected production figures. Pregnancy management is described in more detail, primarily for macaques and marmosets, including methods to detect ovulation and pregnancy, tracking of prenatal growth and development, maternal changes during pregnancy, and prevalence and causes of prenatal mortality. Finally, an overview of acquisition of nonhuman primates from foreign breeding programs is provided.


title: Global animal disease surveillance

text: Abstract Development and implementation of global animal disease surveillance has been limited by the lack of information systems that enable near real-time data capturing, sharing, analysis, and related decision- and policy-making. The objective of this paper is to describe requirements for global animal disease surveillance, including design and functionality of tools and methods for visualization and analysis of animal disease data. The paper also explores the potential application of techniques for spatial and spatio-temporal analysis on global animal disease surveillance, including for example, landscape genetics, social network analysis, and Bayesian modeling. Finally, highly pathogenic avian influenza data from Denmark and Sweden are used to illustrate the potential application of a novel system (Disease BioPortal) for data sharing, visualization, and analysis for regional and global surveillance efforts.


title: Prefusion structure of a human coronavirus spike protein

text: HKU1 is a human betacoronavirus that causes mild yet prevalent respiratory disease(1) and is related to the zoonotic SARS(2) and MERS(3) betacoronaviruses that have high fatality rates and pandemic potential. Cell tropism and host range is determined in part by the coronavirus spike (S) protein(4), which binds cellular receptors and mediates membrane fusion. As the largest known class I fusion protein, its size and extensive glycosylation have hindered structural studies of the full ectodomain, thus preventing a molecular understanding of its function and limiting development of effective interventions. Here we present the 4.0 Å resolution structure of the trimeric HKU1 S protein determined using single-particle cryo-electron microscopy. In the prefusion conformation, the receptor-binding subunits, S1, rest atop the fusion-mediating subunits, S2, preventing their conformational rearrangement. Surprisingly, the S1 C-terminal domains are interdigitated and form extensive quaternary interactions that occlude surfaces known to bind protein receptors in other coronaviruses. These features, along with the location of the two protease sites known to be important for coronavirus entry, provide a structural basis to support a model of membrane fusion mediated by progressive S protein destabilization through receptor binding and proteolytic cleavage. Additionally, these studies should serve as a foundation for the structure-based design of betacoronavirus vaccine immunogens.


title: A large outbreak of acute encephalitis with high fatality rate in children in Andhra Pradesh, India, in 2003, associated with Chandipura virus

text: Summary Background An outbreak of acute encephalitis of unknown origin with high case fatality (183 of 329 cases) was reported in children from Andhra Pradesh state in southern India during 2003. We investigated the causative agent. Methods Cell lines and peripheral blood lymphocyte co-cultures were used to isolate the causative agent from clinical samples. Identity of the agent was established by electron microscopy and serological and molecular assays. Findings Clinical samples tested negative for IgM antibodies to Japanese encephalitis, West Nile, dengue, and measles viruses, and for RNA of coronavirus, paramyxovirus, enterovirus, and influenza viruses. Virus was isolated from six patients with encephalitis and was identified as Chandipura virus by electron microscopy, complement fixation, and neutralisation tests. Chandipura virus RNA was detected in clinical samples from nine patients. Sequencing of five of these RNA samples showed 96·7–97·5% identity with the reference strain of 1965. Chandipura viral antigen and RNA were detected in brain tissue of a deceased child by immunofluorescent antibody test and PCR. Neutralising, IgG, and IgM antibodies to Chandipura virus were present in some patients' serum samples. Serum samples obtained after 4 days of illness were more frequently positive for IgM to Chandipura virus than were those obtained earlier (p<0·001). A similar trend was noted for neutralising antibodies. Interpretation Our findings suggest that this outbreak of acute encephalitis in Andhra Pradesh was associated with Chandipura virus, adding to the evidence suggesting that this virus should be considered as an important emerging pathogen.


title: Hepatitis C Virus Infection as a Traumatic Experience

text: OBJECTIVE: The purpose of this study was to evaluate whether individuals consider their HCV infection to be a potentially traumatic experience. Additionally, we investigated its association with Post-Traumatic Stress Disorder (PTSD) and the impact of PTSD diagnosis on health-related quality of life (HRQoL) in HCV infected subjects. METHODS: We conducted a cross-sectional survey of 127 HCV-infected outpatients recruited at a University Hospital in Salvador, Brazil. All subjects answered an orally-administered questionnaire to gather clinical and socio-demographic data. We investigated traumatic experiences and the subject's perception of the disease using the Trauma History Questionnaire. PTSD and other psychiatric diagnoses were assessed through the Mini International Neuropsychiatric Interview-Brazilian Version 5.0.0 (M.I.N.I. PLUS). HRQoL was assessed using Short-Form 36 (SF-36). RESULTS: Approximately 38.6% of the patients considered hepatitis C to be a traumatic experience. Of these, 60.7% had a PTSD diagnosis. PTSD was associated with significant impairment in quality of life for individuals in seven SF-36 domains as shown bymultivariate analysis: Role-Physical (β: −24.85; 95% CI: −42.08; −7.61), Bodily Pain (β: −19.36; 95% CI: −31.28; −7.45), General Health (β: −20.79; 95% CI: −29.65; −11.92), Vitality (β: −11.92; 95% CI: −20.74; −3.1), Social Functioning (β: −34.73; 95% CI: −46.79; −22.68), Role-Emotional (β: −26.07; 95% CI: −44.61; −7.53), Mental Health (β: −17.46; 95% CI: −24.38; −10.54). CONCLUSION: HCV is frequently a traumatic experience and it is strongly associated with PTSD diagnosis. PTSD significantly impaired HRQoL.


title: Moving Forward: Recent Developments for the Ferret Biomedical Research Model

text: Since the initial report in 1911, the domestic ferret has become an invaluable biomedical research model. While widely recognized for its utility in influenza virus research, ferrets are used for a variety of infectious and noninfectious disease models due to the anatomical, metabolic, and physiological features they share with humans and their susceptibility to many human pathogens. However, there are limitations to the model that must be overcome for maximal utility for the scientific community. Here, we describe important recent advances that will accelerate biomedical research with this animal model.


title: Subcellular fractionation method to study endosomal trafficking of Kaposi’s sarcoma-associated herpesvirus

text: BACKGROUND: Virus entry involves multiple steps and is a highly orchestrated process on which successful infection collectively depends. Entry processes are commonly analyzed by monitoring internalized virus particles via Western blotting, polymerase chain reaction, and imaging techniques that allow scientist to track the intracellular location of the pathogen. Such studies have provided abundant direct evidence on how viruses interact with receptor molecules on the cell surface, induce cell signaling at the point of initial contact with the cell to facilitate internalization, and exploit existing endocytic mechanisms of the cell for their ultimate infectious agenda. However, there is dearth of knowledge in regards to trafficking of a virus via endosomes. Herein, we describe an optimized laboratory procedure to isolate individual organelles during different stages of endocytosis by performing subcellular fractionation. This methodology is established using Kaposi’s sarcoma-associated herpesvirus (KSHV) infection of human foreskin fibroblast (HFF) cells as a model. With KSHV and other herpesviruses alike, envelope glycoproteins have been widely reported to physically engage target cell surface receptors, such as integrins, in interactions leading to entry and subsequent infection. RESULTS: Subcellular fractionation was used to isolate early and late endosomes (EEs and LEs) by performing a series of centrifugations steps. Specifically, a centrifugation step post-homogenization was utilized to obtain the post-nuclear supernatant containing intact intracellular organelles in suspension. Successive fractionation via sucrose density gradient centrifugation was performed to isolate specific organelles including EEs and LEs. Intracellular KSHV trafficking was directly traced in the isolated endosomal fractions. Additionally, the subcellular fractionation approach demonstrates a key role for integrins in the endosomal trafficking of KSHV. The results obtained from fractionation studies corroborated those obtained by traditional imaging studies. CONCLUSIONS: This study is the first of its kind to employ a sucrose flotation gradient assay to map intracellular KSHV trafficking in HFF cells. We are confident that such an approach will serve as a powerful tool to directly study intracellular trafficking of a virus, signaling events occurring on endosomal membranes, and dynamics of molecular events within endosomes that are crucial for uncoating and virus escape into the cytosol.


Covid-19 and EU Competition Law: Bring the Informal Guidance On


title: Lessons Learned from Emergency Response Vaccination Efforts for Cholera, Typhoid, Yellow Fever, and Ebola

text: Countries must be prepared to respond to public health threats associated with emergencies, such as natural disasters, sociopolitical conflicts, or uncontrolled disease outbreaks. Rapid vaccination of populations vulnerable to epidemic-prone vaccine-preventable diseases is a major component of emergency response. Emergency vaccination planning presents challenges, including how to predict resource needs, expand vaccine availability during global shortages, and address regulatory barriers to deliver new products. The US Centers for Disease Control and Prevention supports countries to plan, implement, and evaluate emergency vaccination response. We describe work of the Centers for Disease Control and Prevention in collaboration with global partners to support emergency vaccination against cholera, typhoid, yellow fever, and Ebola, diseases for which a new vaccine or vaccine formulation has played a major role in response. Lessons learned will help countries prepare for future emergencies. Integration of vaccination with emergency response augments global health security through reducing disease burden, saving lives, and preventing spread across international borders.


Emerging respiratory infections: influenza, MERS-CoV, and extensively drug-resistant tuberculosis


Pulmonary intravascular coagulopathy in COVID-19 pneumonia – Authors' reply


title: Chapter 7 Commonly Used Animal Models

text: Abstract This chapter provides an introduction to animals that are commonly used for research. It presents information on basic care topics such as biology, behavior, housing, feeding, sexing, and breeding of these animals. The chapter provides some insight into the reasons why these animals are used in research. It also gives an overview of techniques that can be utilized to collect blood or to administer drugs or medicine. Each section concludes with a brief description of how to recognize abnormal signs, in addition to lists of various diseases.